REACTOME REACT 1866 6
type: UnificationXref
id: REACT_1866
db: Reactome
id version: 6
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1866.6

REACTOME REACT 2741 1
type: UnificationXref
id: REACT_2741
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2741.1

CHEBI CHEBI:13236
type: UnificationXref
id: CHEBI:13236
db: chebi

REACTOME_112374
type: UnificationXref
id: 112374
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112374

CHEBI CHEBI:13342
type: UnificationXref
id: CHEBI:13342
db: chebi

UNIPROT Q14971
type: UnificationXref
id: Q14971
db: uniprot

ENTREZ+GENE 5781
type: RelationshipXref
id: 5781
db: Entrez Gene

Adenosine 5'-triphosphate
type: SmallMolecule
entity reference: Adenosine triphosphate
data source: Reactome
xref: REACTOME REACT 2812 1
xref: REACTOME_113592
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#SmallMolecule5
comment: Reactome DB_ID: 113592
display name: ATP

REACTOME REACT 27630 1
type: UnificationXref
id: REACT_27630
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27630.1

Activated JAK2
type: Protein
entity reference: Janus kinase 2
data source: Reactome
name: p-JAK2 (Y1007)
xref: REACTOME REACT 26044 2
xref: REACTOME_873799
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature217
cellular location: cytosol
comment: Reactome DB_ID: 873799
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1639
display name: p(Y1007)-JAK2

REACTOME_1112594
type: UnificationXref
id: 1112594
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112594

CDK1
type: ProteinReference
name: Cell division protein kinase 1
name: Cell division control protein 2 homolog
name: p34 protein kinase
name: 2.7.11.23
name: 2.7.11.22
xref: UNIPROT P06493
xref: UNIPROT C9J497
xref: UNIPROT A8K7C4
xref: UNIPROT O60764
xref: REFSEQ NP 001777
xref: ENTREZ+GENE 983
xref: REFSEQ NP 203698
xref: HGNC CDK1
display name: CDK1_HUMAN
standard name: Cyclin-dependent kinase 1
comment: FUNCTION: Plays a key role in the control of the eukaryotic cell cycle. It is required in higher cells for entry into S-phase and mitosis. p34 is a component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CATALYTIC ACTIVITY: ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate. ENZYME REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it. SUBUNIT: Forms a stable but non-covalent complex with a regulatory subunit and with a cyclin. Interacts with DLGAP5. Isoform 2 is unable to complex with cyclin B1 and also fails to bind to the CDK inhibitor p21. Interacts with catalytically active CCNB1 and RALBP1 during mitosis to form an endocytotic complex during interphase. SUBCELLULAR LOCATION: Nucleus (By similarity). ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P06493-1; Sequence=Displayed; Name=2; Synonyms=CDC2deltaT; IsoId=P06493-2; Sequence=VSP_021375; TISSUE SPECIFICITY: Isoform 2 is found in breast cancer tissues. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdc2/"; GENE SYNONYMS: CDC2. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
organism: Homo sapiens

REACTOME_1112596
type: UnificationXref
id: 1112596
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112596

CHEBI CHEBI:13222
type: UnificationXref
id: CHEBI:13222
db: chebi

REACTOME_1112598
type: UnificationXref
id: 1112598
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112598

ENTREZ+GENE 7529
type: RelationshipXref
id: 7529
db: Entrez Gene

Adenosine 5'-diphosphate
type: SmallMolecule
entity reference: 5'-adenylphosphoric acid
data source: Reactome
xref: REACTOME_29370
xref: REACTOME REACT 2741 1
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#SmallMolecule6
comment: Reactome DB_ID: 29370
display name: ADP

Protein 1054
type: ProteinReference
name: 14-3-3 protein beta/alpha, N-terminally processed
name: Protein kinase C inhibitor protein 1
name: KCIP-1
xref: UNIPROT E1P616
xref: ENTREZ+GENE 7529
xref: REFSEQ NP 647539
xref: HGNC YWHAB
xref: UNIPROT P31946
xref: UNIPROT A8K9K2
xref: REFSEQ NP 003395
display name: 1433B_HUMAN
standard name: 14-3-3 protein beta/alpha
comment: FUNCTION: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathway. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. SUBUNIT: Homodimer. Interacts with SSH1 and TORC2/CRTC2. Interacts with ABL1; the interaction results in cytoplasmic location of ABL1 and inhition of cABL-mediated apoptosis. Interacts with ROR2 (dimer); the interaction results in phosphorylation of YWHAB on tyrosine residues. Interacts with GAB2 and YAP1 (phosphorylated form). SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. ALTERNATIVE PRODUCTS: Event=Alternative initiation; Named isoforms=2; Name=Long; IsoId=P31946-1; Sequence=Displayed; Name=Short; IsoId=P31946-2; Sequence=VSP_018632; Note=Acetylated on Met-1 (By similarity); PTM: The alpha, brain-specific form differs from the beta form in being phosphorylated (By similarity). PTM: Isoform Short contains a N-acetylmethionine at position 1 (By similarity). SIMILARITY: Belongs to the 14-3-3 family. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
organism: Homo sapiens

chebi_15996
type: ChemicalStructure
structure format: InChI

REACTOME REACT 5391 2
type: UnificationXref
id: REACT_5391
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5391.2

REACTOME REACT 2607 1
type: UnificationXref
id: REACT_2607
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2607.1

p21 RAS:GTP
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry2971
component stoichiometry: Stoichiometry2972
component: Guanosine 5'-triphosphate
component: p21 RAS
xref: REACTOME_109783
xref: REACTOME REACT 4782 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex1116
comment: Reactome DB_ID: 109783

UNIPROT P05231
type: UnificationXref
id: P05231
db: uniprot

REACTOME_447100
type: UnificationXref
id: 447100
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=447100

REACTOME_1067638
type: UnificationXref
id: 1067638
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1067638

Protein kinase C inhibitor protein-1
type: Protein
entity reference: Protein 1054
data source: Reactome
name: Protein 1054
name: 143B protein
name: 14-3-3 protein beta/alpha
xref: REACTOME REACT 2686 2
xref: REACTOME_48888
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein2357
comment: Reactome DB_ID: 48888
display name: KCIP-1

REACTOME_112398
type: UnificationXref
id: 112398
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112398

Dissociation of phospho-ERK-2:MEK2
type: BiochemicalReaction
data source: Reactome
xref: REACTOME_109864
xref: REACTOME REACT 1019 3
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
left: phospho-ERK-2:MEK2
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction703
comment: Authored: Charalambous, M, 2005-02-04 06:50:22
comment: MEK2 dissociates from phospho-ERK2, allowing phospho-ERK2 to dimerise with another phospho-ERK2.
comment: Reviewed: Gillespie, ME, 2010-11-24
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: MAP kinase 2
right: MAPK/ERK kinase 2

REFSEQ NP 109587
type: RelationshipXref
id: NP_109587
db: RefSeq

HGNC RAF1
type: RelationshipXref
id: Raf1
db: HGNC

PATHWAYSTEP897 1 9606
type: PathwayStep
step process: ERK activation
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep897

REACTOME REACT 2275 1
type: UnificationXref
id: REACT_2275
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2275.1

phospho-ERK-1:MEK1
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1948
component stoichiometry: Stoichiometry1947
component: MAPK/ERK kinase 1
component: p44-MAPK
xref: REACTOME REACT 2796 1
xref: REACTOME_109843
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex679
comment: Reactome DB_ID: 109843

p44-MAPK
type: Protein
entity reference: Microtubule-associated protein 2 kinase
data source: Reactome
name: MAP kinase 1
name: Microtubule- associated protein-2 kinase
name: p44-ERK1
name: Activated ERK1
name: Extracellular signal-regulated kinase 1
name: phospho-ERK-1
name: ERK-1
name: MAPK 1
name: Mitogen-activated protein kinase 3
name: Insulin-stimulated MAP2 kinase
xref: REACTOME REACT 3037 2
xref: REACTOME_109842
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature210
feature: ModificationFeature211
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1632
comment: Reactome DB_ID: 109842
display name: ERT2

UNIPROT Q02750
type: UnificationXref
id: Q02750
db: uniprot

REACTOME REACT 143 6
type: UnificationXref
id: REACT_143
db: Reactome
id version: 6
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_143.6

REACTOME_48888
type: UnificationXref
id: 48888
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=48888

REACTOME_62725
type: UnificationXref
id: 62725
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=62725

PATHWAYSTEP1231 1 9606
type: PathwayStep
step process: CATALYSIS583 1 9606
step process: RAF1 phosphorylates MEK2
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep1231
next step: PATHWAYSTEP891 1 9606

BSF-2
type: ProteinReference
name: CTL differentiation factor
name: IL-6
name: B-cell stimulatory factor 2
name: CDF
name: IFN-beta-2
name: Hybridoma growth factor
name: Interferon beta-2
xref: UNIPROT Q9UCU2
xref: ENTREZ+GENE 3569
xref: UNIPROT Q9UCU3
xref: UNIPROT P05231
xref: HGNC IL6
xref: REFSEQ NP 000591
xref: UNIPROT Q9UCU4
display name: IL6_HUMAN
standard name: Interleukin-6
comment: FUNCTION: Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig- secreting cells Involved in lymphocyte and monocyte differentiation. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation Acts on B-cells, T-cells, hepatocytes, hematopoeitic progenitor cells and cells of the CNS. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. SUBCELLULAR LOCATION: Secreted. PTM: N- and O-glycosylated. POLYMORPHISM: Genetic variations in IL6 may be correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disrutption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture. DISEASE: Genetic variations in IL6 are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]. An inflammatory articular disorder with systemic- onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. DISEASE: Note=A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men. SIMILARITY: Belongs to the IL-6 superfamily. WEB RESOURCE: Name=R&D Systems' cytokine mini-reviews: IL-6; URL="http://www.rndsystems.com/molecule_detail.aspx?m=1648"; WEB RESOURCE: Name=Wikipedia; Note=Interleukin-6 entry; URL="http://en.wikipedia.org/wiki/Interleukin_6"; WEB RESOURCE: Name=Seatt…
organism: Homo sapiens

ENTREZ+GENE 5894
type: RelationshipXref
id: 5894
db: Entrez Gene

CHEBI CHEBI:22249
type: UnificationXref
id: CHEBI:22249
db: chebi

CHEBI CHEBI:22244
type: UnificationXref
id: CHEBI:22244
db: chebi

REACTOME_1112563
type: UnificationXref
id: 1112563
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112563

REFSEQ NP 002218
type: RelationshipXref
id: NP_002218
db: RefSeq

Interleukin-6 receptor subunit alpha long transmembrane form
type: Protein
entity reference: IL-6R-alpha
data source: Reactome
name: IL6RA_HUMAN
name: IL6RA
xref: REACTOME REACT 27516 1
xref: REACTOME_1067672
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: FragmentFeature575
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1636
comment: Reactome DB_ID: 1067672
display name: IL6R

REFSEQ NP 001777
type: RelationshipXref
id: NP_001777
db: RefSeq

extracellular region
type: CellularLocationVocabulary
xref: GENE+ONTOLOGY GO:0005576
comment: cPath2-generated

PATHWAYSTEP887 1 9606
type: PathwayStep
step process: Dissociation of phospho-ERK-1:MEK1
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep887
next step: PATHWAYSTEP888 1 9606

REACTOME REACT 3571 1
type: UnificationXref
id: REACT_3571
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3571.1

9632795
type: PublicationXref
id: 9632795
db: PubMed

UNIPROT Q5FWG2
type: UnificationXref
id: Q5FWG2
db: uniprot

REFSEQ NP 852004
type: RelationshipXref
id: NP_852004
db: RefSeq

REACTOME_1067661
type: UnificationXref
id: 1067661
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1067661

REACTOME REACT 3932 1
type: UnificationXref
id: REACT_3932
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3932.1

REACTOME REACT 3339 1
type: UnificationXref
id: REACT_3339
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3339.1

8388392
type: PublicationXref
id: 8388392
author: Guan, KL
author: Zheng, CF
db: PubMed
title: Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2.
source: J Biol Chem 268:11435-9
year: 1993

p44-MAPK
type: Protein
entity reference: Microtubule-associated protein 2 kinase
data source: Reactome
name: MAP kinase 1
name: Microtubule- associated protein-2 kinase
name: p44-ERK1
name: Extracellular signal-regulated kinase 1
name: phospho-ERK-1
name: MAPK 1
name: ERK-1
name: Mitogen-activated protein kinase 3
name: Insulin-stimulated MAP2 kinase
xref: REACTOME_112359
xref: REACTOME REACT 3346 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature213
feature: ModificationFeature212
cellular location: nucleoplasm
comment: Reactome DB_ID: 112359
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1633
display name: ERT2

ENTREZ+GENE 5604
type: RelationshipXref
id: 5604
db: Entrez Gene

ENTREZ+GENE 5605
type: RelationshipXref
id: 5605
db: Entrez Gene

Inactivation of MEK1 by p34cdc2
type: BiochemicalReaction
data source: Reactome
EC number: 2.7.11
xref: REACTOME_112342
xref: REACTOME REACT 1836 2
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
participant stoichiometry: Stoichiometry1942
participant stoichiometry: Stoichiometry1943
left: Adenosine 5'-triphosphate
left: MEK1
comment: At the beginning of this reaction, 2 molecules of 'ATP', and 1 molecule of 'MEK1' are present. At the end of this reaction, 1 molecule of 'phospho_MEK1', and 2 molecules of 'ADP' are present. This reaction takes place in the 'cytosol' and is mediated by the 'protein serine/threonine kinase activity' of 'phospho-Cdc2 (Thr 161)'.
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction695
right: Adenosine 5'-diphosphate
right: phospho_MEK1

SequenceSite1160
type: SequenceSite
position status: EQUAL
sequence position: 365

chebi_16761
type: ChemicalStructure
structure format: InChI

REACTOME_1112580
type: UnificationXref
id: 1112580
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112580

UNIPROT A8K8Z5
type: UnificationXref
id: A8K8Z5
db: uniprot

REACTOME_1112585
type: UnificationXref
id: 1112585
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112585

REACTOME_1112584
type: UnificationXref
id: 1112584
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112584

UNIPROT P01118
type: UnificationXref
id: P01118
db: uniprot

REACTOME REACT 3199 1
type: UnificationXref
id: REACT_3199
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3199.1

UNIPROT P31946
type: UnificationXref
id: P31946
db: uniprot

Dimerisation of phospho-ERK-1
type: BiochemicalReaction
data source: Reactome
xref: REACTOME REACT 1289 6
xref: REACTOME_109865
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
participant stoichiometry: Stoichiometry1950
left: p44-MAPK
comment: Two phospho-ERK1 molecules dimerise and enter the nucleus, where they may phosphorylate downstream targets.
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction699
comment: Authored: Charalambous, M, 2005-02-04 06:50:22
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: phospho-ERK-1 dimer

UNIPROT P01116
type: UnificationXref
id: P01116
db: uniprot

REACTOME REACT 4906 3
type: UnificationXref
id: REACT_4906
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4906.3

REFSEQ NP 002737
type: RelationshipXref
id: NP_002737
db: RefSeq

PATHWAYSTEP888 1 9606
type: PathwayStep
step process: Dimerisation of phospho-ERK-1
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep888
next step: PATHWAYSTEP889 1 9606

REACTOME_1067672
type: UnificationXref
id: 1067672
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1067672

MEK activation
type: Pathway
data source: Reactome
pathway component: RAF phosphorylates MEK
pathway component: Activated RAF1 complex binds MEK
xref: REACTOME_110049
xref: GENE+ONTOLOGY GO:0000186
xref: REACTOME REACT 962 4
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
pathway order: PATHWAYSTEP1415 1 9606
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Pathway270
comment: MEK is phosphorylated and activated by RAF.
comment: Authored: Charalambous, M, 2004-04-29 09:21:24
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
organism: Homo sapiens

TAXONOMY 9606
type: UnificationXref
id: 9606
db: taxonomy

SequenceSite1155
type: SequenceSite
position status: EQUAL
sequence position: 1

REFSEQ NP 002736
type: RelationshipXref
id: NP_002736
db: RefSeq

SequenceSite1156
type: SequenceSite
position status: EQUAL
sequence position: 1187

SequenceSite1157
type: SequenceSite
position status: EQUAL
sequence position: 23

REFSEQ NP 203698
type: RelationshipXref
id: NP_203698
db: RefSeq

SequenceSite1158
type: SequenceSite
position status: EQUAL
sequence position: 918

REACTOME REACT 27429 1
type: UnificationXref
id: REACT_27429
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27429.1

SequenceSite1159
type: SequenceSite
position status: EQUAL
sequence position: 20

SequenceSite1945
type: SequenceSite
position status: EQUAL
sequence position: 1

UNIPROT P01112
type: UnificationXref
id: P01112
db: uniprot

SequenceSite1946
type: SequenceSite
position status: EQUAL
sequence position: 186

UNIPROT P01111
type: UnificationXref
id: P01111
db: uniprot

REACTOME REACT 1482 4
type: UnificationXref
id: REACT_1482
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1482.4

SequenceSite1150
type: SequenceSite
position status: EQUAL
sequence position: 212

SequenceSite1154
type: SequenceSite
position status: EQUAL
sequence position: 1154

Guanosine 5'-triphosphate
type: SmallMolecule
entity reference: guanosine 5'-triphosphoric acid
data source: Reactome
xref: REACTOME_29438
xref: REACTOME REACT 2875 1
cellular location: cytosol
comment: Reactome DB_ID: 29438
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#SmallMolecule84
display name: GTP

SequenceSite1153
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite1152
type: SequenceSite
position status: EQUAL
sequence position: 468

SequenceSite1151
type: SequenceSite
position status: EQUAL
sequence position: 20

Transforming protein N-Ras
type: Protein
entity reference: Transforming protein N-Ras
data source: Reactome
xref: REACTOME_62725
xref: REACTOME REACT 3280 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: FragmentFeature953
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein2356
comment: Reactome DB_ID: 62725
display name: p21/N-Ras

REACTOME_1112570
type: UnificationXref
id: 1112570
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112570

REACTOME REACT 4992 1
type: UnificationXref
id: REACT_4992
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4992.1

PATHWAYSTEP894 1 9606
type: PathwayStep
step process: Dimerisation of phospho-ERK-2
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep894
next step: PATHWAYSTEP895 1 9606

REACTOME REACT 3906 1
type: UnificationXref
id: REACT_3906
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3906.1

UNIPROT P04049
type: UnificationXref
id: P04049
db: uniprot

REACTOME REACT 4863 1
type: UnificationXref
id: REACT_4863
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4863.1

CHEBI CHEBI:10841
type: UnificationXref
id: CHEBI:10841
db: chebi

CATALYSIS485 1 9606
type: Catalysis
data source: Reactome
controlled: Inactivation of MEK1 by p34cdc2
control type: ACTIVATION
xref: REACTOME_112341
xref: GENE+ONTOLOGY GO:0004674
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
controller: phospho-Cdc2 (Thr 161)
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Catalysis485

REACTOME_1067687
type: UnificationXref
id: 1067687
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1067687

REFSEQ NP 002746
type: RelationshipXref
id: NP_002746
db: RefSeq

SequenceSite1149
type: SequenceSite
position status: EQUAL
sequence position: 30

UNIPROT Q9UQ41
type: UnificationXref
id: Q9UQ41
db: uniprot

IL6ST
type: Protein
entity reference: CD130
data source: Reactome
name: Tyrosine phosphorylated Interleukin-6 receptor subunit beta long transmembrane form
name: IL6RB_HUMAN
xref: REACTOME REACT 27647 1
xref: REACTOME_1112580
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature222
feature: ModificationFeature223
feature: FragmentFeature578
feature: ModificationFeature220
feature: ModificationFeature219
feature: ModificationFeature221
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1641
comment: Reactome DB_ID: 1112580
display name: gp130

Tyrosine-protein kinase JAK1
type: Protein
entity reference: Janus kinase 1
data source: Reactome
name: p(Y1034)-JAK1
name: Janus kinase 1
xref: REACTOME_1112543
xref: REACTOME REACT 27963 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: FragmentFeature576
feature: ModificationFeature216
cellular location: cytosol
comment: Reactome DB_ID: 1112543
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1638
display name: JAK1_HUMAN

UNIPROT B5BUA0
type: UnificationXref
id: B5BUA0
db: uniprot

17993263
type: PublicationXref
id: 17993263
author: Dance, M
author: Salles, JP
author: Montagner, A
author: Raynal, P
author: Yart, A
db: PubMed
title: The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway
source: Cell Signal 20:453-9
year: 2008

REACTOME REACT 27564 1
type: UnificationXref
id: REACT_27564
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27564.1

GENE+ONTOLOGY GO:0000189
type: RelationshipXref
id: GO:0000189
db: Gene Ontology

GENE+ONTOLOGY GO:0000187
type: RelationshipXref
id: GO:0000187
db: Gene Ontology

GENE+ONTOLOGY GO:0000186
type: RelationshipXref
id: GO:0000186
db: Gene Ontology

Activated JAK1, JAK2, TYK2
type: Protein
data source: Reactome
member physical entity: p(Y1054)-TYK2
member physical entity: Activated JAK2
member physical entity: Tyrosine-protein kinase JAK1
xref: REACTOME REACT 27853 1
xref: REACTOME_1112596
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 1112596
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1637

REFSEQ NP 002871
type: RelationshipXref
id: NP_002871
db: RefSeq

UNIPROT P28482
type: UnificationXref
id: P28482
db: uniprot

REACTOME REACT 634 5
type: UnificationXref
id: REACT_634
db: Reactome
id version: 5
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_634.5

REACTOME REACT 2822 1
type: UnificationXref
id: REACT_2822
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2822.1

p21A (K-Ras 2A)
type: Protein
entity reference: K-Ras 2
data source: Reactome
name: Transforming protein p21A
name: c-K-ras
name: K-Ras 2A
xref: REACTOME_62719
xref: REACTOME REACT 4992 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Reactome DB_ID: 62719
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein2355
display name: Ki-Ras

HGNC IL6
type: RelationshipXref
id: Il6
db: HGNC

IS CONJUGATE ACID OF CHEBI:57600
type: RelationshipXref
id: 57600
db: CHEBI

REACTOME REACT 2196 5
type: UnificationXref
id: REACT_2196
db: Reactome
id version: 5
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2196.5

MEK1
type: Protein
data source: Reactome
member physical entity: MAPK/ERK kinase 1
member physical entity: Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1)
xref: REACTOME_112336
xref: REACTOME REACT 2607 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Reactome DB_ID: 112336
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1624
comment: Converted from EntitySet in Reactome

REACTOME REACT 5485 2
type: UnificationXref
id: REACT_5485
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5485.2

REACTOME REACT 2640 2
type: UnificationXref
id: REACT_2640
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2640.2

Activated RAF1 complex:MEK
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry2978
component stoichiometry: Stoichiometry2979
component: Activated RAF1 complex
component: MEK
xref: REACTOME_112406
xref: REACTOME REACT 3953 2
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex1117
comment: Reactome DB_ID: 112406

REACTOME_59504
type: UnificationXref
id: 59504
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=59504

REACTOME_59502
type: UnificationXref
id: 59502
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=59502

MAPK/ERK kinase 2
type: Protein
entity reference: MEK 2
data source: Reactome
name: ERK activator kinase 2
name: phospho-MEK2
name: Dual specificity mitogen-activated protein kinase kinase 2
name: MAPKK 2
name: MAP kinase kinase 2
xref: REACTOME REACT 3571 1
xref: REACTOME_109848
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature225
feature: ModificationFeature224
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1643
comment: Reactome DB_ID: 109848
display name: MEK2

ENTREZ+GENE 3265
type: RelationshipXref
id: 3265
db: Entrez Gene

REACTOME_162573
type: UnificationXref
id: 162573
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=162573

phospho-ERK-1 dimer
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1952
component: p44-MAPK
xref: REACTOME REACT 3152 1
xref: REACTOME_109845
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: nucleoplasm
comment: Reactome DB_ID: 109845
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex681

REFSEQ NP 005334
type: RelationshipXref
id: NP_005334
db: RefSeq

UNIPROT Q15104
type: UnificationXref
id: Q15104
db: uniprot

REACTOME_112411
type: UnificationXref
id: 112411
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112411

REACTOME_1112543
type: UnificationXref
id: 1112543
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112543

REACTOME REACT 4782 1
type: UnificationXref
id: REACT_4782
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4782.1

REACTOME_29438
type: UnificationXref
id: 29438
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29438

REFSEQ NP 004976
type: RelationshipXref
id: NP_004976
db: RefSeq

cRaf
type: ProteinReference
name: Proto-oncogene c-RAF
name: 2.7.11.1
name: Raf-1
xref: HGNC RAF1
xref: UNIPROT P04049
xref: REFSEQ NP 002871
xref: UNIPROT B2R5N3
xref: UNIPROT B0LPH8
xref: UNIPROT Q9UC20
xref: UNIPROT Q15278
xref: ENTREZ+GENE 5894
display name: RAF1_HUMAN
standard name: RAF proto-oncogene serine/threonine-protein kinase
comment: FUNCTION: Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Part of the Ras-dependent signaling pathway from receptors to the nucleus. Protects cells from apoptosis mediated by STK3. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Binds 2 zinc ions per subunit. SUBUNIT: Forms a multiprotein complex with Ras (M-Ras/MRAS), SHOC2 and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC). Interacts with Ras proteins; the interaction is antagonized by RIN1. Weakly interacts with RIT1 (By similarity). Interacts with STK3; the interaction inhibits its pro-apoptotic activity. Interacts (when phosphorylated at Ser-259) with YWHAZ (unphosphorylated at 'Thr- 232'). ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=6C; IsoId=P04049-1; Sequence=Displayed; Name=2; Synonyms=1A; IsoId=P04049-2; Sequence=VSP_034649; TISSUE SPECIFICITY: In skeletal muscle, isoform 1 is more abundant than isoform 2. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylation at Thr-269 increases its kinase activity. Phosphorylation at Ser-259 induces the interaction with YWHAZ and inactivates kinase activity. Dephosphorylation of Ser-259 by the complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves inactivation, leading to stimulate RAF1 activity. DISEASE: Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:611553]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. DISEASE: Defects in RAF1 are the cause of LEOPARD syndrome type 2 (LEOPARD2) [MIM:611554]. LEOPARD syndrome is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnor…
organism: Homo sapiens

phospho-ERK-2:MEK2
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1970
component stoichiometry: Stoichiometry1971
component: MAP kinase 2
component: MAPK/ERK kinase 2
xref: REACTOME REACT 3199 1
xref: REACTOME_109854
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex691
comment: Reactome DB_ID: 109854

phospho-ERK-2 dimer
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1973
component: MAP kinase 2
xref: REACTOME_109855
xref: REACTOME REACT 3688 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Reactome DB_ID: 109855
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex692

Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1)
type: Protein
entity reference: MEK 1
data source: Reactome
name: MAPK/ERK kinase 1
name: ERK activator kinase 1
name: Dual specificity mitogen-activated protein kinase kinase 1
name: phospho-MEK1
name: MAP kinase kinase 1
name: MAPKK 1
xref: REACTOME_112374
xref: REACTOME REACT 2822 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature207
feature: ModificationFeature208
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1629
comment: Reactome DB_ID: 112374
display name: MEK1

UNIPROT Q9UCE2
type: UnificationXref
id: Q9UCE2
db: uniprot

PATHWAYSTEP886 1 9606
type: PathwayStep
step process: CATALYSIS486 1 9606
step process: 'phospho_MEK1 [cytosol]' negatively regulates 'MEK1 phosphorylates ERK-1'
step process: MEK1 phosphorylates ERK-1
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep886
next step: PATHWAYSTEP887 1 9606

Shp2
type: ProteinReference
name: Protein-tyrosine phosphatase 1D
name: Protein-tyrosine phosphatase 2C
name: PTP-2C
name: SH-PTP2
name: SHP-2
name: SH-PTP3
name: PTP-1D
name: 3.1.3.48
xref: UNIPROT A8K1D9
xref: HGNC PTPN11
xref: UNIPROT Q96HD7
xref: ENTREZ+GENE 5781
xref: UNIPROT Q06124
xref: REFSEQ NP 002825
display name: PTN11_HUMAN
standard name: Tyrosine-protein phosphatase non-receptor type 11
comment: FUNCTION: Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. SUBUNIT: Interacts with phosphorylated LIME1 and BCAR3. Interacts with SHB and INPP5D/SHIP1 (By similarity). Interacts with MCA32 (tyrosine-phosphorylated) (By similarity). Interacts with PTPNS1 and CD84. Interacts with phosphorylated SIT1 and MPZL1. Interacts with FCRL3, FCRL4, FCRL6 and ANKHD1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts with GAB2. Interacts with TERT; the interaction retains TERT in the nucleus. Interacts with PECAM1. SUBCELLULAR LOCATION: Cytoplasm. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; Synonyms=PTP2Ci; IsoId=Q06124-1; Sequence=Displayed; Name=2; Synonyms=PTP2C; IsoId=Q06124-2; Sequence=VSP_016672; Name=3; IsoId=Q06124-3; Sequence=VSP_016672, VSP_016673, VSP_016674; TISSUE SPECIFICITY: Widely expressed, with highest levels in heart, brain, and skeletal muscle. DOMAIN: The SH2 domains repress phosphatase activity. Binding of these domains to phosphotyrosine-containing proteins relieves this auto-inhibition, possibly by inducing a conformational change in the enzyme. PTM: Phosphorylated on Tyr-546 and Tyr-584 upon receptor protein tyrosine kinase activation; which creates a binding site for GRB2 and other SH2-containing proteins. DISEASE: Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:151100]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness. DISEASE: Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:163950]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial …
organism: Homo sapiens

HGNC NRAS
type: RelationshipXref
id: Nras
db: HGNC

UNIPROT Q14080
type: UnificationXref
id: Q14080
db: uniprot

HGNC TYK2
type: RelationshipXref
id: Tyk2
db: HGNC

CHEBI CHEBI:5234
type: UnificationXref
id: CHEBI:5234
db: chebi

IL6_HUMAN
type: Protein
entity reference: BSF-2
data source: Reactome
name: Interleukin-6
xref: REACTOME REACT 27735 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
xref: REACTOME_447100
feature: FragmentFeature574
cellular location: extracellular region
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1635
comment: Reactome DB_ID: 447100
display name: IL6

CATALYSIS486 1 9606
type: Catalysis
data source: Reactome
controlled: MEK1 phosphorylates ERK-1
control type: ACTIVATION
xref: GENE+ONTOLOGY GO:0004674
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
xref: REACTOME_109859
controller: MEK1:ERK-1
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Catalysis486

CHEBI CHEBI:2342
type: UnificationXref
id: CHEBI:2342
db: chebi

REACTOME_62719
type: UnificationXref
id: 62719
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=62719

REFSEQ NP 002825
type: RelationshipXref
id: NP_002825
db: RefSeq

REACTOME_112339
type: UnificationXref
id: 112339
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112339

UNIPROT B0LPG3
type: UnificationXref
id: B0LPG3
db: uniprot

REFSEQ NP 004963
type: RelationshipXref
id: NP_004963
db: RefSeq

REACTOME_62717
type: UnificationXref
id: 62717
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=62717

REACTOME REACT 1836 2
type: UnificationXref
id: REACT_1836
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1836.2

IL-6R-alpha
type: ProteinReference
name: Membrane glycoprotein 80
name: gp80
name: IL-6R 1
name: IL-6 receptor subunit alpha
name: IL-6R subunit alpha
name: IL-6RA
name: CD126
xref: REFSEQ NP 000556
xref: UNIPROT P08887
xref: UNIPROT A8KAE8
xref: UNIPROT Q5FWG2
xref: UNIPROT Q53EQ7
xref: REFSEQ NP 852004
xref: ENTREZ+GENE 3570
xref: UNIPROT B2R6V4
xref: UNIPROT Q5VZ23
xref: UNIPROT Q16202
xref: HGNC IL6R
display name: IL6RA_HUMAN
standard name: Interleukin-6 receptor subunit alpha
comment: FUNCTION: Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation may lead to the regulation of the immune response, acute-phase reactions and hematopoiesis. FUNCTION: Low concentration of a soluble form of IL6 receptor acts as an agonist of IL6 activity. SUBUNIT: Hexamer of two molecules each of IL6, IL6R and IL6ST. SUBCELLULAR LOCATION: Isoform 1: Basolateral cell membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: Isoform 2: Secreted. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=Long; IsoId=P08887-1; Sequence=Displayed; Name=2; Synonyms=Short; IsoId=P08887-2; Sequence=VSP_001682, VSP_001683; TISSUE SPECIFICITY: Isoform 2 is expressed in peripheral blood mononuclear cells and weakly found in urine and serum. DOMAIN: The two fibronectin type-III-like domains, contained in the N-terminal part, form together a cytokine-binding domain. DOMAIN: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell- surface receptor binding. PTM: A short soluble form may also be released from the membrane by proteolysis. SIMILARITY: Belongs to the type I cytokine receptor family. Type 3 subfamily. SIMILARITY: Contains 1 fibronectin type-III domain. SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like) domain. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
organism: Homo sapiens

CHEBI CHEBI:42934
type: UnificationXref
id: CHEBI:42934
db: chebi

REACTOME_112336
type: UnificationXref
id: 112336
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112336

IL6:IL6RA
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1955
component stoichiometry: Stoichiometry1954
component: IL6_HUMAN
component: Interleukin-6 receptor subunit alpha long transmembrane form
xref: REACTOME_1067638
xref: REACTOME REACT 27964 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex686
comment: Reactome DB_ID: 1067638

Homo sapiens
type: BioSource
xref: TAXONOMY 9606

UNIPROT B0LPF9
type: UnificationXref
id: B0LPF9
db: uniprot

UNIPROT Q6QB10
type: UnificationXref
id: Q6QB10
db: uniprot

REACTOME REACT 962 4
type: UnificationXref
id: REACT_962
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_962.4

REFSEQ NP 002175
type: RelationshipXref
id: NP_002175
db: RefSeq

UNIPROT P36507
type: UnificationXref
id: P36507
db: uniprot

REACTOME REACT 2875 1
type: UnificationXref
id: REACT_2875
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2875.1

HGNC IL6R
type: RelationshipXref
id: Il6r
db: HGNC

REACTOME_112340
type: UnificationXref
id: 112340
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112340

RAF1 phosphorylates MEK2
type: BiochemicalReaction
data source: Reactome
xref: REACTOME REACT 1727 5
xref: REACTOME_109852
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
participant stoichiometry: Stoichiometry2982
participant stoichiometry: Stoichiometry2983
left: Adenosine 5'-triphosphate
left: Activated RAF1 complex:MEK2
comment: Active Raf-1 phosphorylates MEK-1/2 on Serine residues, converting ATP to ADP. The MEK-1/2 kinase is now active.
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction981
comment: Authored: Charalambous, M, 2005-01-07 11:17:43
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: Adenosine 5'-diphosphate
right: Activated RAF1 complex
right: MAPK/ERK kinase 2

REACTOME_112342
type: UnificationXref
id: 112342
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112342

IS CONJUGATE ACID OF CHEBI:456216
type: RelationshipXref
id: 456216
db: CHEBI

REACTOME_112343
type: UnificationXref
id: 112343
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112343

REACTOME REACT 1289 6
type: UnificationXref
id: REACT_1289
db: Reactome
id version: 6
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1289.6

CHEBI CHEBI:2359
type: UnificationXref
id: CHEBI:2359
db: chebi

GENE+ONTOLOGY GO:0005576
type: UnificationXref
id: GO:0005576
db: Gene Ontology

Mitogen-activated protein kinase 1 (EC 2.7.1.-) (Extracellular signal- regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1)
type: Protein
entity reference: MAPK 2
data source: Reactome
name: MAP kinase 2
name: Extracellular signal-regulated kinase 2
name: ERK-2
name: MAPK 2
name: ERT1
name: Mitogen-activated protein kinase 1
name: p42-MAPK
name: Mitogen-activated protein kinase 2
xref: REACTOME REACT 5485 2
xref: REACTOME_59282
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein207
comment: Reactome DB_ID: 59282
display name: ERK2

REACTOME REACT 3346 1
type: UnificationXref
id: REACT_3346
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3346.1

UNIPROT A8K9K2
type: UnificationXref
id: A8K9K2
db: uniprot

ERK activation
type: Pathway
data source: Reactome
pathway component: ERK2 activation
pathway component: ERK1 activation
xref: REACTOME REACT 1482 4
xref: REACTOME_112409
xref: GENE+ONTOLOGY GO:0000187
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
pathway order: PATHWAYSTEP890 1 9606
pathway order: PATHWAYSTEP896 1 9606
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Pathway192
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Activated MEK phosphorylates and activates ERK.
organism: Homo sapiens

p44-MAPK
type: Protein
entity reference: Microtubule-associated protein 2 kinase
data source: Reactome
name: MAP kinase 1
name: Mitogen-activated protein kinase 3 (EC 2.7.1.-) (Extracellular signal- regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase)
name: Microtubule- associated protein-2 kinase
name: p44-ERK1
name: Extracellular signal-regulated kinase 1
name: ERK-1
name: MAPK 1
name: Mitogen-activated protein kinase 3
name: Insulin-stimulated MAP2 kinase
name: ERT2
xref: REACTOME REACT 4130 1
xref: REACTOME_59284
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1631
comment: Reactome DB_ID: 59284
display name: ERK1

CHEBI CHEBI:24451
type: UnificationXref
id: CHEBI:24451
db: chebi

RAF phosphorylates MEK
type: Pathway
data source: Reactome
pathway component: RAF1 phosphorylates MEK1
pathway component: RAF1 phosphorylates MEK2
xref: REACTOME REACT 614 4
xref: REACTOME_112407
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
pathway order: PATHWAYSTEP1230 1 9606
pathway order: PATHWAYSTEP1231 1 9606
comment: Active Raf-1 phosphorylates MEK-1/2 on Serine residues, converting ATP to ADP. The MEK-1/2 kinase is now active.
comment: Authored: Charalambous, M, 2005-01-07 11:17:43
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Pathway250
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
organism: Homo sapiens

UNIPROT B2R6V4
type: UnificationXref
id: B2R6V4
db: uniprot

UNIPROT O75297
type: UnificationXref
id: O75297
db: uniprot

GENE+ONTOLOGY GO:0070371
type: RelationshipXref
id: GO:0070371
db: Gene Ontology

UNIPROT A8K1D9
type: UnificationXref
id: A8K1D9
db: uniprot

REACTOME_112359
type: UnificationXref
id: 112359
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112359

ENTREZ+GENE 7297
type: RelationshipXref
id: 7297
db: Entrez Gene

REACTOME_112354
type: UnificationXref
id: 112354
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112354

c-H-ras
type: ProteinReference
name: GTPase HRas, N-terminally processed
name: H-Ras-1
name: p21ras
name: Transforming protein p21
name: Ha-Ras
xref: UNIPROT Q9UCE2
xref: REFSEQ NP 001123914
xref: REFSEQ NP 005334
xref: UNIPROT Q14080
xref: UNIPROT P01112
xref: UNIPROT Q6FHV9
xref: HGNC HRAS
xref: UNIPROT B5BUA0
xref: ENTREZ+GENE 3265
display name: RASH_HUMAN
standard name: GTPase HRas
comment: FUNCTION: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. ENZYME REGULATION: Alternate between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase- activating protein (GAP). SUBUNIT: In its GTP-bound form interacts with PLCE1. Interacts with TBC1D10C. Interacts with RGL3. Interacts with HSPD1 (By similarity). Forms a signaling complex with RASGRP1 and DGKZ. Interacts with RASSF5. Interacts with HRAS. SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic side. Golgi apparatus membrane; Lipid-anchor. Note=Shuttles between the plasma membrane and the Golgi apparatus. PTM: Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi. PTM: S-nitrosylated; critical for redox regulation. Important for stimulating guanine nucleotide exchange. No structural perturbation on nitrosylation. MASS SPECTROMETRY: Mass=6223; Mass_error=2; Method=Electrospray; Range=112-166; Source=PubMed:9020151; MASS SPECTROMETRY: Mass=6253; Mass_error=2; Method=Electrospray; Range=112-166; Note=Includes one nitric oxide molecule; Source=PubMed:9020151; DISEASE: Defects in HRAS are the cause of Costello syndrome (COSTS) [MIM:218040]; also known as faciocutaneoskeletal syndrome. Costello syndrome is a rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities. DISEASE: Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]. CMEMS is a variant of Costello syndrome. DISEASE: Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma (HCTC) [MIM:607464]. Hurthle cell th…
organism: Homo sapiens

Transforming protein N-Ras
type: ProteinReference
xref: HGNC NRAS
xref: UNIPROT Q15104
xref: UNIPROT Q14971
xref: UNIPROT Q15282
xref: ENTREZ+GENE 4893
xref: UNIPROT P01111
xref: REFSEQ NP 002515
display name: RASN_HUMAN
standard name: GTPase NRas
comment: FUNCTION: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. ENZYME REGULATION: Alternate between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase- activating protein (GAP). SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic side. Golgi apparatus membrane; Lipid-anchor. Note=Shuttles between the plasma membrane and the Golgi apparatus. PTM: Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi. DISEASE: Defects in NRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. DISEASE: Defects in NRAS are the cause of Noonan syndrome type 6 (NS6) [MIM:613224]. A syndrome characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits. MISCELLANEOUS: Mutations which change AA 12, 13 or 61 activate the potential of Ras to transform cultured cells and are implicated in a variety of human tumors. SIMILARITY: Belongs to the small GTPase superfamily. Ras family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NRASID92.html"; WEB RESOURCE: Name=NRASbase; Note=NRAS mutation db; URL="http://bioinf.uta.fi/NRASbase/"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/nras/"; WEB RESOURCE: Name=Wikipedia; Note=RAS proteins entry; URL="http://en.wikipedia.org/wiki/RAS_proteins"; GENE SYNONYMS: HRAS1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.u…
organism: Homo sapiens

HAS ROLE CHEBI:50733
type: RelationshipXref
id: 50733
db: CHEBI

K-Ras 2
type: ProteinReference
name: c-Ki-ras
name: c-K-ras
name: GTPase KRas, N-terminally processed
name: Ki-Ras
xref: ENTREZ+GENE 3845
xref: REFSEQ NP 004976
xref: UNIPROT B0LPF9
xref: REFSEQ NP 203524
xref: HGNC KRAS
xref: UNIPROT A8K8Z5
xref: UNIPROT P01116
xref: UNIPROT Q96D10
xref: UNIPROT P01118
display name: RASK_HUMAN
standard name: GTPase KRas
comment: FUNCTION: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. ENZYME REGULATION: Alternate between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase- activating protein (GAP). SUBUNIT: Interacts with PHLPP (By similarity). SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic side. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Comment=Isoforms differ in the C-terminal region which is encoded by two alternative exons (IVA and IVB); Name=2A; IsoId=P01116-1; Sequence=Displayed; Name=2B; IsoId=P01116-2, P01118-1; Sequence=VSP_011140, VSP_011141; Note=Variant in position: 153:D->V (in CFC syndrome and NS3), exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein. Variant in position: 156: F->I (in NS3/CFC syndrome). Variant in position: 156: F->L (found in a patient with Costello syndrome), exhibits an increase in intrinsic and guanine nucleotide exchange factor catalyzed nucleotide exchange in combination with an impaired GTPase-activating protein-stimulated GTP hydrolysis but functional in interaction with effectors; DISEASE: Defects in KRAS are a cause of acute myelogenous leukemia (AML) [MIM:601626]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. DISEASE: Defects in KRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte- macrophage colony stimulating factor. DISEASE: Defects in KRAS are the cause of Noonan syndrome type 3 (NS3) [MIM:609942]. Noonan syndrome (NS) [MIM:163950] is a disorder characterized by dysmorphic facial features…
organism: Homo sapiens

UNIPROT Q6FHV9
type: UnificationXref
id: Q6FHV9
db: uniprot

REACTOME REACT 26044 2
type: UnificationXref
id: REACT_26044
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_26044.2

REACTOME REACT 3037 2
type: UnificationXref
id: REACT_3037
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3037.2

HGNC IL6ST
type: RelationshipXref
id: Il6st
db: HGNC

PUBCHEM_8144912
type: UnificationXref
id: 8144912
db: PubChem

PATHWAYSTEP892 1 9606
type: PathwayStep
step process: CATALYSIS487 1 9606
step process: MEK2 phosphorylates ERK-2
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep892
next step: PATHWAYSTEP893 1 9606

GENE+ONTOLOGY GO:0000165
type: RelationshipXref
id: GO:0000165
db: Gene Ontology

REFSEQ NP 001035145
type: RelationshipXref
id: NP_001035145
db: RefSeq

REACTOME REACT 2247 5
type: UnificationXref
id: REACT_2247
db: Reactome
id version: 5
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2247.5

REACTOME REACT 27964 1
type: UnificationXref
id: REACT_27964
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27964.1

REFSEQ NP 001123914
type: RelationshipXref
id: NP_001123914
db: RefSeq

REACTOME REACT 27963 1
type: UnificationXref
id: REACT_27963
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27963.1

UNIPROT B0LPH8
type: UnificationXref
id: B0LPH8
db: uniprot

UNIPROT P23458
type: UnificationXref
id: P23458
db: uniprot

UNIPROT P08887
type: UnificationXref
id: P08887
db: uniprot

MAP kinase 2
type: Protein
entity reference: MAPK 2
data source: Reactome
name: Extracellular signal-regulated kinase 2
name: MAPK 2
name: ERK-2
name: phospho-ERK-2
name: Mitogen-activated protein kinase 1
name: p42-MAPK
name: Mitogen-activated protein kinase 2
xref: REACTOME REACT 2688 1
xref: REACTOME_112354
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature226
feature: ModificationFeature227
cellular location: nucleoplasm
comment: Reactome DB_ID: 112354
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1644
display name: ERT1

MAPK/ERK kinase 1
type: Protein
entity reference: MEK 1
data source: Reactome
name: ERK activator kinase 1
name: Dual specificity mitogen-activated protein kinase kinase 1
name: phospho-MEK1
name: MAP kinase kinase 1
name: MAPKK 1
xref: REACTOME_112339
xref: REACTOME REACT 4863 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature206
feature: ModificationFeature203
feature: ModificationFeature204
feature: ModificationFeature205
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1628
comment: Reactome DB_ID: 112339
display name: MEK1

MEK1 phosphorylates ERK-1
type: BiochemicalReaction
data source: Reactome
EC number: 2.7.11
xref: REACTOME_109860
xref: REACTOME REACT 136 4
xref: 8388392
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
participant stoichiometry: Stoichiometry1949
participant stoichiometry: Stoichiometry1946
left: Adenosine 5'-triphosphate
left: MEK1:ERK-1
comment: MEK1 phosphorylates the critical Tyrosine and Threonine on ERK1, converting two ATP to ADP. Phosphorylation of ERK-1 activates its kinase activity.
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction697
comment: Authored: Charalambous, M, 2005-02-04 06:50:22
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: Adenosine 5'-diphosphate
right: phospho-ERK-1:MEK1

GENE+ONTOLOGY GO:0016301
type: RelationshipXref
id: GO:0016301
db: Gene Ontology

REFSEQ NP 786943
type: RelationshipXref
id: NP_786943
db: RefSeq

GENE+ONTOLOGY GO:0005654
type: UnificationXref
id: GO:0005654
db: Gene Ontology

REACTOME REACT 136 4
type: UnificationXref
id: REACT_136
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_136.4

REACTOME REACT 3688 1
type: UnificationXref
id: REACT_3688
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3688.1

UNIPROT Q16202
type: UnificationXref
id: Q16202
db: uniprot

REFSEQ NP 003395
type: RelationshipXref
id: NP_003395
db: RefSeq

MEK 2
type: ProteinReference
name: ERK activator kinase 2
name: MAPK/ERK kinase 2
name: 2.7.12.2
name: MAPKK 2
name: MAP kinase kinase 2
xref: REFSEQ NP 109587
xref: HGNC MAP2K2
xref: UNIPROT P36507
xref: ENTREZ+GENE 5605
display name: MP2K2_HUMAN
standard name: Dual specificity mitogen-activated protein kinase kinase 2
comment: FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. SUBUNIT: Interacts with MORG1 (By similarity). PTM: MAPKK is itself dependent on Ser/Thr phosphorylation for activity catalyzed by MAP kinase kinase kinases (RAF or MEKK1). PTM: Acetylation of Ser-222 and Ser-226 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway. DISEASE: Defects in MAP2K2 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio- cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MAP2K2"; GENE SYNONYMS: MEK2 MKK2 PRKMK2. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
organism: Homo sapiens

UNIPROT P06493
type: UnificationXref
id: P06493
db: uniprot

UNIPROT O60764
type: UnificationXref
id: O60764
db: uniprot

Dissociation of phospho-ERK-1:MEK1
type: BiochemicalReaction
data source: Reactome
xref: REACTOME REACT 1740 3
xref: REACTOME_109863
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
left: phospho-ERK-1:MEK1
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction698
comment: MEK1 dissociates from phospho-ERK1, allowing phospho-ERK1 to dimerise with another phospho-ERK1.
comment: Authored: Charalambous, M, 2005-02-04 06:50:22
comment: Reviewed: Gillespie, ME, 2010-11-24
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: MAPK/ERK kinase 1
right: p44-MAPK

UNIPROT Q15278
type: UnificationXref
id: Q15278
db: uniprot

PATHWAYSTEP885 1 9606
type: PathwayStep
step process: MEK1 binds ERK-1
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep885
next step: PATHWAYSTEP886 1 9606

REACTOME_873799
type: UnificationXref
id: 873799
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=873799

CD130
type: ProteinReference
name: CDw130
name: Membrane glycoprotein 130
name: IL-6R subunit beta
name: Interleukin-6 signal transducer
name: IL-6R-beta
name: IL-6RB
name: gp130
name: Oncostatin-M receptor subunit alpha
name: IL-6 receptor subunit beta
xref: UNIPROT A0N0L4
xref: UNIPROT P40189
xref: UNIPROT Q9UQ41
xref: REFSEQ NP 786943
xref: HGNC IL6ST
xref: ENTREZ+GENE 3572
xref: REFSEQ NP 002175
display name: IL6RB_HUMAN
standard name: Interleukin-6 receptor subunit beta
comment: FUNCTION: Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize gp130 for initiating signal transmission. Binds to IL6/IL6R (alpha chain) complex, resulting in the formation of high-affinity IL6 binding sites, and transduces the signal. Does not bind IL6. May have a role in embryonic development (By similarity). The type I OSM receptor is capable of transducing OSM-specific signaling events. SUBUNIT: Interacts with INPP5D/SHIP1 (By similarity). Forms heterodimers composed of LIPR and IL6ST (type I OSM receptor). Also forms heterodimers composed of OSMR and IL6ST (type II OSM receptor). Homodimer. The homodimer binds two molecules of herpes virus IL6. Component of a hexamer of two molecules each of IL6, IL6R and IL6ST. SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: Isoform 2: Secreted. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P40189-1; Sequence=Displayed; Name=2; Synonyms=GP130-RAPS; IsoId=P40189-2; Sequence=VSP_001684, VSP_001685; TISSUE SPECIFICITY: Found in all the tissues and cell lines examined. Expression not restricted to IL6 responsive cells. INDUCTION: Leukemia inhibitory factor (LIF) and Oncostatin-M (OSM) activate the type I OSM receptor while only OSM can activate the type II OSM receptor. DOMAIN: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell- surface receptor binding. DOMAIN: The box 1 motif is required for JAK interaction and/or activation. PTM: Phosphorylation of Ser-782 down-regulates cell surface expression. PTM: Heavily N-glycosylated. SIMILARITY: Belongs to the type I cytokine receptor family. Type 2 subfamily. SIMILARITY: Contains 5 fibronectin type-III domains. SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like) domain. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/…
organism: Homo sapiens

CHEBI CHEBI:15996
type: UnificationXref
id: CHEBI:15996
db: chebi

MAPK 2
type: ProteinReference
name: MAPK 1
name: 2.7.11.24
name: ERT1
name: p42-MAPK
name: MAP kinase 1
name: MAP kinase 2
name: Extracellular signal-regulated kinase 2
name: ERK-2
name: MAP kinase isoform p42
name: Mitogen-activated protein kinase 2
xref: UNIPROT P28482
xref: REFSEQ NP 620407
xref: ENTREZ+GENE 5594
xref: HGNC MAPK1
xref: REFSEQ NP 002736
display name: MK01_HUMAN
standard name: Mitogen-activated protein kinase 1
comment: FUNCTION: Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1 (By similarity). Phosphorylates heat shock factor protein 4 (HSF4) and ARHGEF2. FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: Activated by phosphorylation on tyrosine and threonine in response to insulin and NGF. Both phosphorylations are required for activity (By similarity). SUBUNIT: Interacts with MORG1 (By similarity). Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine- kinase activity. Interacts with its substrates HSF4 and ARHGEF2. Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation (By similarity). Interacts with NISCH. Interacts with ARRB2. Interacts with ADAM15. SUBCELLULAR LOCATION: Nucleus. DOMAIN: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. PTM: Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. Dephosphorylated by PTPRJ at Tyr-187. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=CAA77753.1; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=Wikipedia; No…
organism: Homo sapiens

p21 RAS
type: Protein
data source: Reactome
member physical entity: Transforming protein N-Ras
member physical entity: p21A (K-Ras 2A)
member physical entity: Transforming protein p21/H-Ras-1
xref: REACTOME_109782
xref: REACTOME REACT 4582 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Converted from EntitySet in Reactome
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein2354
comment: Reactome DB_ID: 109782

REACTOME REACT 5701 2
type: UnificationXref
id: REACT_5701
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5701.2

REACTOME_113592
type: UnificationXref
id: 113592
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592

UNIPROT A8K7C4
type: UnificationXref
id: A8K7C4
db: uniprot

C-RAF
type: Protein
entity reference: cRaf
data source: Reactome
name: RAF proto-oncogene serine/threonine-protein kinase
name: Raf-1
name: phospho-Raf1 (multiple sites)
xref: REACTOME REACT 3645 2
xref: REACTOME_109792
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature421
feature: ModificationFeature423
feature: ModificationFeature420
feature: ModificationFeature422
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein2358
comment: Reactome DB_ID: 109792
display name: cRaf

ENTREZ+GENE 3717
type: RelationshipXref
id: 3717
db: Entrez Gene

UNIPROT P27361
type: UnificationXref
id: P27361
db: uniprot

ENTREZ+GENE 3716
type: RelationshipXref
id: 3716
db: Entrez Gene

IL6:sIL6R
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1960
component stoichiometry: Stoichiometry1961
component: IL6_HUMAN
component: sIL6R
xref: REACTOME_1067687
xref: REACTOME REACT 27493 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: extracellular region
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex689
comment: Reactome DB_ID: 1067687

REACTOME REACT 4223 3
type: UnificationXref
id: REACT_4223
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4223.3

HGNC PTPN11
type: RelationshipXref
id: Ptpn11
db: HGNC

UNIPROT O14636
type: UnificationXref
id: O14636
db: uniprot

chebi_15422
type: ChemicalStructure
structure format: InChI

REFSEQ NP 620407
type: RelationshipXref
id: NP_620407
db: RefSeq

MEK2 binds ERK-2
type: BiochemicalReaction
data source: Reactome
xref: REACTOME REACT 495 5
xref: REACTOME_109858
xref: 8388392
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
left: Mitogen-activated protein kinase 1 (EC 2.7.1.-) (Extracellular signal- regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1)
left: MAPK/ERK kinase 2
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction701
comment: Authored: Charalambous, M, 2005-02-04 06:50:22
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
comment: In the cytoplasm activated MEK2 (Serine phosphorylated) may encounter monomeric, inactive ERK2. ERK2 in its inactive form is not phosphorylated on a critical Threonine (T183) and a critical Tyrosine (Y185).
right: MEK2:ERK-2

Adenosine triphosphate
type: SmallMoleculeReference
structure: chebi_15422
chemical formula: C10H16N5O13P3
name: H4atp
name: adenosine 5'-(tetrahydrogen triphosphate)
xref: CHEBI CHEBI:22249
xref: CHEBI CHEBI:13236
xref: IS CONJUGATE ACID OF CHEBI:57299
xref: PUBCHEM_8143180
xref: HAS ROLE CHEBI:50733
xref: INCHI ZKHQWZAMYRWXGA-KQYNXXCUSA-N
xref: CHEBI CHEBI:10789
xref: CHEBI CHEBI:40938
xref: CHEBI CHEBI:10841
xref: CHEBI CHEBI:15422
xref: CHEBI CHEBI:2359
display name: ATP

REACTOME REACT 6097 2
type: UnificationXref
id: REACT_6097
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_6097.2

MAP kinase 2
type: Protein
entity reference: MAPK 2
data source: Reactome
name: Extracellular signal-regulated kinase 2
name: Activated ERK2
name: MAPK 2
name: ERK-2
name: phospho-ERK-2
name: Mitogen-activated protein kinase 1
name: p42-MAPK
name: Mitogen-activated protein kinase 2
xref: REACTOME_109853
xref: REACTOME REACT 2640 2
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature14
feature: ModificationFeature13
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein208
comment: Reactome DB_ID: 109853
display name: ERT1

PATHWAYSTEP884 1 9606
type: PathwayStep
step process: Inactivation of MEK1 by p34cdc2
step process: CATALYSIS485 1 9606
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep884

REACTOME REACT 27735 1
type: UnificationXref
id: REACT_27735
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27735.1

ENTREZ+GENE 3845
type: RelationshipXref
id: 3845
db: Entrez Gene

'phospho_MEK1 [cytosol]' negatively regulates 'MEK1 phosphorylates ERK-1'
type: Control
data source: Reactome
xref: REACTOME REACT 6097 2
xref: REACTOME_112343
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
controlled: MEK1 phosphorylates ERK-1
control type: INHIBITION
controller: phospho_MEK1
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Control46

REACTOME_112341
type: RelationshipXref
id: 112341
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112341

REACTOME REACT 5046 1
type: UnificationXref
id: REACT_5046
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5046.1

plasma membrane
type: CellularLocationVocabulary
xref: GENE+ONTOLOGY GO:0005886
comment: cPath2-generated

GENE+ONTOLOGY GO:0004674
type: RelationshipXref
id: GO:0004674
db: Gene Ontology

UNIPROT A0N0L4
type: UnificationXref
id: A0N0L4
db: uniprot

UNIPROT Q59GQ2
type: UnificationXref
id: Q59GQ2
db: uniprot

ERK1 activation
type: Pathway
data source: Reactome
pathway component: Dimerisation of phospho-ERK-1
pathway component: Dissociation of phospho-ERK-1:MEK1
pathway component: Inactivation of MEK1 by p34cdc2
pathway component: Nuclear translocation of phospho-ERK-1 dimer
pathway component: MEK1 binds ERK-1
pathway component: MEK1 phosphorylates ERK-1
xref: REACTOME REACT 1391 3
xref: REACTOME_110056
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
pathway order: PATHWAYSTEP885 1 9606
pathway order: PATHWAYSTEP887 1 9606
pathway order: PATHWAYSTEP889 1 9606
pathway order: PATHWAYSTEP888 1 9606
pathway order: PATHWAYSTEP884 1 9606
pathway order: PATHWAYSTEP886 1 9606
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Pathway193
comment: Activated MEK1 phosphorylates and activates ERK1.
comment: Authored: Charalambous, M, 2005-02-04 06:50:22
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
organism: Homo sapiens

GENE+ONTOLOGY GO:0005886
type: UnificationXref
id: GO:0005886
db: Gene Ontology

Microtubule-associated protein 2 kinase
type: ProteinReference
name: MAP kinase isoform p44
name: MAPK 1
name: 2.7.11.24
name: MAPK 3
name: Insulin-stimulated MAP2 kinase
name: ERT2
name: p44-MAPK
name: MAP kinase 1
name: MAP kinase 3
name: p44-ERK1
name: Extracellular signal-regulated kinase 1
name: ERK-1
name: Mitogen-activated protein kinase 1
xref: UNIPROT P27361
xref: REFSEQ NP 001103361
xref: UNIPROT B0LPG3
xref: ENTREZ+GENE 5595
xref: REFSEQ NP 001035145
xref: HGNC MAPK3
xref: REFSEQ NP 002737
display name: MK03_HUMAN
standard name: Mitogen-activated protein kinase 3
comment: FUNCTION: Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK-1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1 (By similarity). Phosphorylates heat shock factor protein 4 (HSF4). CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: Activated by tyrosine phosphorylation in response to insulin and NGF. SUBUNIT: Interacts with MORG1 (By similarity). Binds to HIV-1 Nef. This interaction inhibits its kinase activity. Interacts with HSF4 and NISCH. Interacts with ARRB2. Interacts with ADAM15. DOMAIN: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. PTM: Dually phosphorylated on Thr-202 and Tyr-204, which activates the enzyme. Dephosphorylated by PTPRJ at Tyr-204. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. GENE SYNONYMS: ERK1 PRKM3. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
organism: Homo sapiens

Stoichiometry1966
type: Stoichiometry
physical entity: Mitogen-activated protein kinase 1 (EC 2.7.1.-) (Extracellular signal- regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1)
stoichiometric coefficient: 1.0

ENTREZ+GENE 4893
type: RelationshipXref
id: 4893
db: Entrez Gene

7871433
type: PublicationXref
id: 7871433
author: Stahl, N
author: Darnell JE, Jr
author: Farruggella, TJ
author: Zhong, Z
author: Boulton, TG
author: Yancopoulos, GD
db: PubMed
title: Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors
source: Science 267:1349-53
year: 1995

Stoichiometry1965
type: Stoichiometry
physical entity: IL-6:Tyrosine phosphorylated hexameric IL-6 receptor:Activated JAKs
stoichiometric coefficient: 1.0

Stoichiometry1968
type: Stoichiometry
physical entity: Adenosine 5'-triphosphate
stoichiometric coefficient: 2.0

REFSEQ NP 203524
type: RelationshipXref
id: NP_203524
db: RefSeq

Stoichiometry1967
type: Stoichiometry
physical entity: MAPK/ERK kinase 2
stoichiometric coefficient: 1.0

Stoichiometry1962
type: Stoichiometry
physical entity: IL6:sIL6R
stoichiometric coefficient: 1.0

Stoichiometry1961
type: Stoichiometry
physical entity: IL6_HUMAN
stoichiometric coefficient: 1.0

Stoichiometry1964
type: Stoichiometry
physical entity: IL6:Tyrosine phosphorylated trimeric IL-6 receptor:Activated JAKs
stoichiometric coefficient: 2.0

CATALYSIS583 1 9606
type: Catalysis
data source: Reactome
controlled: RAF1 phosphorylates MEK2
control type: ACTIVATION
xref: GENE+ONTOLOGY GO:0016301
xref: REACTOME_109834
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
controller: Activated RAF1 complex:MEK
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Catalysis583

Stoichiometry1963
type: Stoichiometry
physical entity: Tyrosine phosphorylated IL6RB:Activated JAKs
stoichiometric coefficient: 1.0

Stoichiometry1960
type: Stoichiometry
physical entity: sIL6R
stoichiometric coefficient: 1.0

UNIPROT O60674
type: UnificationXref
id: O60674
db: uniprot

REACTOME_112406
type: UnificationXref
id: 112406
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112406

PATHWAYSTEP1230 1 9606
type: PathwayStep
step process: RAF1 phosphorylates MEK1
step process: CATALYSIS582 1 9606
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep1230
next step: PATHWAYSTEP885 1 9606

Phosphorylated SHP2
type: Protein
entity reference: Shp2
data source: Reactome
xref: REACTOME REACT 21811 1
xref: REACTOME_162573
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature214
feature: ModificationFeature215
cellular location: cytosol
comment: Reactome DB_ID: 162573
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1634

PATHWAYSTEP890 1 9606
type: PathwayStep
step process: 'IL6:Tyrosine phosphorylated hexameric IL-6 receptor:Activated JAKs:p-SHP2 [plasma membrane]' positively regulates 'ERK1 activation'
step process: ERK1 activation
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep890

REACTOME_112409
type: UnificationXref
id: 112409
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112409

REACTOME_112407
type: UnificationXref
id: 112407
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112407

REACTOME REACT 3953 2
type: UnificationXref
id: REACT_3953
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3953.2

REACTOME REACT 3280 1
type: UnificationXref
id: REACT_3280
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3280.1

Stoichiometry1969
type: Stoichiometry
physical entity: Adenosine 5'-diphosphate
stoichiometric coefficient: 2.0

REACTOME REACT 27855 1
type: UnificationXref
id: REACT_27855
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27855.1

'IL6:Tyrosine phosphorylated hexameric IL-6 receptor:Activated JAKs:p-SHP2 [plasma membrane]' positively regulates 'ERK2 activation'
type: Control
data source: Reactome
xref: 9488469
xref: 7871433
xref: 17993263
xref: REACTOME REACT 28018 1
xref: 9632795
xref: 8934572
xref: 10409724
xref: REACTOME_1112769
xref: 19050043
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
controlled: ERK2 activation
control type: ACTIVATION
controller: IL6:Tyrosine phosphorylated hexameric IL-6 receptor:Activated JAKs:p-SHP2
comment: IL-6-type receptor activation leads to induction of the MAPK cascade. Experiments using gp130 identified that the gp130 SHP2 (SH2-domain-containing tyrosine phosphatase)-binding site Tyr-759 (Stahl et al. 1995) is required for this activation. Mutation of gp130 Tyr-759 impairs IL-6 induced activation of the MAPK cascade (Kim et al. 1998). While there is a consensus that SHP2 is involved in IL-6-induced activation of the MAPK pathway, the molecular details are uncertain. One proposed mechanism suggests SHP2 acts as an adaptor for Grb2-Sos recruitment (Fukada et al. 1996, Kim & Baumann 1999). IL-6 induced SHP2 recruitment to p-Tyr-759 of gp130 was demonstrated but relatively little of the SHP2 remained associated with gp130, suggesting that SHP2 dissociates from the receptor when phosphorylated. This seems inconsistent with a Grb2-Sos recruitment role for SHP2, though it is possible that only low levels or transient recruitment are required. IL-6 induced ERK activation was not inhibited in cells transfected with a phosphatase inactive mutant of SHP2, whereas an SHP2 mutant missing the Grb2 interaction region significantly suppressed ERK activation. This suggests phosphatase activity is not required for ERK activation while SHP-2 interaction with Grb2 is important. However, overexpression studies can generate artefactual interactions and this interpretation has been questioned (Dance et al. 2008). An alternative proposal suggests that SHP2 and the adaptor protein Gab1 couple gp130 signalling to Erk activation. In this proposal phosphorylated SHP2 dissociates from gp130 and becomes associated with membrane associated Gab1 in a complex with PI3-kinase (Takahashi-Tezuka et al. 1998, Eulenfeld & Schaper 2009). SHP2 interaction is suggested to induce a conformational change in Gab1 that permits Gab1-PI3-kinase activation and enhancement of IL-6-induced Erk pathway activation. However this is speculative, the role of SHP2 phosphatase activity is unclear. Other possible mecha…
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Control48

Activated RAF1 complex:MEK1
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry2976
component stoichiometry: Stoichiometry2970
component: Activated RAF1 complex
component: Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1)
xref: REACTOME REACT 4256 3
xref: REACTOME_109794
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex1114
comment: Reactome DB_ID: 109794

Stoichiometry1974
type: Stoichiometry
physical entity: MAP kinase 2
stoichiometric coefficient: 2.0

Stoichiometry1973
type: Stoichiometry
physical entity: MAP kinase 2
stoichiometric coefficient: 2.0

Stoichiometry1972
type: Stoichiometry
physical entity: MAP kinase 2
stoichiometric coefficient: 2.0

Stoichiometry1971
type: Stoichiometry
physical entity: MAPK/ERK kinase 2
stoichiometric coefficient: 1.0

Stoichiometry1970
type: Stoichiometry
physical entity: MAP kinase 2
stoichiometric coefficient: 1.0

CHEBI CHEBI:15422
type: UnificationXref
id: CHEBI:15422
db: chebi

Janus kinase 2
type: ProteinReference
name: JAK-2
name: 2.7.10.2
xref: UNIPROT O14636
xref: UNIPROT O75297
xref: ENTREZ+GENE 3717
xref: HGNC JAK2
xref: UNIPROT O60674
xref: REFSEQ NP 004963
display name: JAK2_HUMAN
standard name: Tyrosine-protein kinase JAK2
comment: FUNCTION: Non-receptor tyrosine kinase involved in various processes such as cell cycle progression, apoptosis, mitotic recombination, genetic instability and histone modifications. In the cytoplasm, plays a pivotal role in signal transduction via its association with cytokine receptors, which constitutes an initiating step in signaling for many members of the cytokine receptor superfamily including the receptors for growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), granulocyte-macrophage colony-stimulating factor (CSF2), thrombopoietin (THPO) and multiple interleukins. Following stimulation with erythropoietin (EPO) during erythropoiesis, it is autophosphorylated and activated, leading to its association with erythropoietin receptor (EPOR) and tyrosine phosphorylation of residues in the EPOR cytoplasmic domain. Also involved in promoting the localization of EPOR to the plasma membrane. Also acts downstream of some G-protein coupled receptors. Plays a role in the control of body weight (By similarity). Mediates angiotensin-2-induced ARHGEF1 phosphorylation. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Regulated by autophosphorylation, can both activate or decrease activity (By similarity). Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr- 1008. SUBUNIT: Interacts with EPOR, SIRPA and SH2B1 (By similarity). Interacts with IL23R, SKB1 and STAM2. SUBCELLULAR LOCATION: Endomembrane system; Peripheral membrane protein (By similarity). Nucleus. TISSUE SPECIFICITY: Expressed in blood, bone marrow and lymph node. DOMAIN: Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences sugg…
organism: Homo sapiens

ENTREZ+GENE 983
type: RelationshipXref
id: 983
db: Entrez Gene

MAPK/ERK kinase 1
type: Protein
entity reference: MEK 1
data source: Reactome
name: ERK activator kinase 1
name: Dual specificity mitogen-activated protein kinase kinase 1
name: phospho-MEK1
name: MAP kinase kinase 1
xref: REACTOME REACT 5701 2
xref: REACTOME_109837
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature201
feature: ModificationFeature202
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1626
comment: Reactome DB_ID: 109837
display name: MAPKK 1

CATALYSIS487 1 9606
type: Catalysis
data source: Reactome
controlled: MEK2 phosphorylates ERK-2
control type: ACTIVATION
xref: GENE+ONTOLOGY GO:0004674
xref: REACTOME_109861
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
controller: MEK2:ERK-2
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Catalysis487

INCHI XTWYTFMLZFPYCI-KQYNXXCUSA-N
type: UnificationXref
id: XTWYTFMLZFPYCI-KQYNXXCUSA-N
db: InChI

REACTOME REACT 1019 3
type: UnificationXref
id: REACT_1019
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1019.3

AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
type: RelationshipXref
id: urn:miriam:taxonomy:9606
db: auto-generated
comment: auto-generated

UNIPROT Q5VZ23
type: UnificationXref
id: Q5VZ23
db: uniprot

UNIPROT A8KAE8
type: UnificationXref
id: A8KAE8
db: uniprot

Stoichiometry1942
type: Stoichiometry
physical entity: Adenosine 5'-triphosphate
stoichiometric coefficient: 2.0

Stoichiometry1944
type: Stoichiometry
physical entity: MAPK/ERK kinase 1
stoichiometric coefficient: 1.0

Stoichiometry1943
type: Stoichiometry
physical entity: Adenosine 5'-diphosphate
stoichiometric coefficient: 2.0

REACTOME REACT 27336 1
type: UnificationXref
id: REACT_27336
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27336.1

Stoichiometry1946
type: Stoichiometry
physical entity: Adenosine 5'-triphosphate
stoichiometric coefficient: 2.0

Stoichiometry1945
type: Stoichiometry
physical entity: p44-MAPK
stoichiometric coefficient: 1.0

REACTOME REACT 1740 3
type: UnificationXref
id: REACT_1740
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1740.3

REACTOME_109795
type: UnificationXref
id: 109795
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109795

UNIPROT P29597
type: UnificationXref
id: P29597
db: uniprot

REACTOME_109794
type: UnificationXref
id: 109794
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109794

REACTOME_1112753
type: UnificationXref
id: 1112753
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112753

REACTOME_109793
type: UnificationXref
id: 109793
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109793

REACTOME_109792
type: UnificationXref
id: 109792
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109792

REACTOME REACT 1727 5
type: UnificationXref
id: REACT_1727
db: Reactome
id version: 5
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1727.5

CHEBI CHEBI:40938
type: UnificationXref
id: CHEBI:40938
db: chebi

UNIPROT Q53EQ7
type: UnificationXref
id: Q53EQ7
db: uniprot

CHEBI CHEBI:40553
type: UnificationXref
id: CHEBI:40553
db: chebi

Stoichiometry1947
type: Stoichiometry
physical entity: MAPK/ERK kinase 1
stoichiometric coefficient: 1.0

Stoichiometry1948
type: Stoichiometry
physical entity: p44-MAPK
stoichiometric coefficient: 1.0

INCHI ZKHQWZAMYRWXGA-KQYNXXCUSA-N
type: UnificationXref
id: ZKHQWZAMYRWXGA-KQYNXXCUSA-N
db: InChI

Stoichiometry1949
type: Stoichiometry
physical entity: Adenosine 5'-diphosphate
stoichiometric coefficient: 2.0

UNIPROT C9J497
type: UnificationXref
id: C9J497
db: uniprot

INCHI XKMLYUALXHKNFT-UUOKFMHZSA-N
type: UnificationXref
id: XKMLYUALXHKNFT-UUOKFMHZSA-N
db: InChI

MEK1:ERK-1
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1944
component stoichiometry: Stoichiometry1945
component: MAPK/ERK kinase 1
component: p44-MAPK
xref: REACTOME_109838
xref: REACTOME REACT 5539 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex678
comment: Reactome DB_ID: 109838

phospho-ERK-2 dimer
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1974
component: MAP kinase 2
xref: REACTOME REACT 5046 1
xref: REACTOME_109856
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: nucleoplasm
comment: Reactome DB_ID: 109856
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex693

nucleoplasm
type: CellularLocationVocabulary
xref: GENE+ONTOLOGY GO:0005654
comment: cPath2-generated

Activated RAF1 complex
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry2973
component stoichiometry: Stoichiometry2975
component stoichiometry: Stoichiometry2974
component: p21 RAS:GTP
component: Protein kinase C inhibitor protein-1
component: C-RAF
xref: REACTOME REACT 4906 3
xref: REACTOME_109793
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex1115
comment: Reactome DB_ID: 109793

UNIPROT Q15282
type: UnificationXref
id: Q15282
db: uniprot

Stoichiometry1953
type: Stoichiometry
physical entity: Phosphorylated SHP2
stoichiometric coefficient: 1.0

Stoichiometry1952
type: Stoichiometry
physical entity: p44-MAPK
stoichiometric coefficient: 2.0

Dimerisation of phospho-ERK-2
type: BiochemicalReaction
data source: Reactome
xref: REACTOME REACT 2196 5
xref: REACTOME_109866
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
participant stoichiometry: Stoichiometry1972
left: MAP kinase 2
comment: Two phospho-ERK2 molecules dimerise and enter the nucleus, where they may phosphorylate downstream targets.
comment: Authored: Charalambous, M, 2005-02-04 06:50:22
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction704
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: phospho-ERK-2 dimer

Stoichiometry1951
type: Stoichiometry
physical entity: p44-MAPK
stoichiometric coefficient: 2.0

Stoichiometry1950
type: Stoichiometry
physical entity: p44-MAPK
stoichiometric coefficient: 2.0

Stoichiometry1957
type: Stoichiometry
physical entity: Activated JAK1, JAK2, TYK2
stoichiometric coefficient: 1.0

Stoichiometry1956
type: Stoichiometry
physical entity: IL6:IL6RA
stoichiometric coefficient: 1.0

Stoichiometry1955
type: Stoichiometry
physical entity: Interleukin-6 receptor subunit alpha long transmembrane form
stoichiometric coefficient: 1.0

Stoichiometry1954
type: Stoichiometry
physical entity: IL6_HUMAN
stoichiometric coefficient: 1.0

REACTOME_1112769
type: UnificationXref
id: 1112769
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112769

REACTOME_1112768
type: UnificationXref
id: 1112768
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1112768

IL6:sIL6R:Tyrosine phosphorylated IL6RB:Activated JAKs
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1962
component stoichiometry: Stoichiometry1963
component: IL6:sIL6R
component: Tyrosine phosphorylated IL6RB:Activated JAKs
xref: REACTOME REACT 27784 1
xref: REACTOME_1112570
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex688
comment: Reactome DB_ID: 1112570

UNIPROT Q96CH0
type: UnificationXref
id: Q96CH0
db: uniprot

REFSEQ NP 001103361
type: RelationshipXref
id: NP_001103361
db: RefSeq

REACTOME_109783
type: UnificationXref
id: 109783
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109783

REACTOME_109782
type: UnificationXref
id: 109782
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109782

Nuclear translocation of phospho-ERK-2 dimer
type: BiochemicalReaction
data source: Reactome
xref: REACTOME REACT 487 6
xref: REACTOME_109868
xref: GENE+ONTOLOGY GO:0000189
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
left: phospho-ERK-2 dimer
comment: Phospho-ERK-2 dimer is translocated from cytosol to nucleoplasm.
comment: Authored: Charalambous, M, 2004-04-29 09:21:24
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction705
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: phospho-ERK-2 dimer

HGNC KRAS
type: RelationshipXref
id: Kras
db: HGNC

REACTOME REACT 4795 1
type: UnificationXref
id: REACT_4795
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4795.1

REFSEQ NP 647539
type: RelationshipXref
id: NP_647539
db: RefSeq

Stoichiometry1958
type: Stoichiometry
physical entity: IL6ST
stoichiometric coefficient: 1.0

Stoichiometry1959
type: Stoichiometry
physical entity: Tyrosine phosphorylated IL6RB:Activated JAKs
stoichiometric coefficient: 1.0

REACTOME REACT 28018 1
type: UnificationXref
id: REACT_28018
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_28018.1

PATHWAYSTEP896 1 9606
type: PathwayStep
step process: 'IL6:Tyrosine phosphorylated hexameric IL-6 receptor:Activated JAKs:p-SHP2 [plasma membrane]' positively regulates 'ERK2 activation'
step process: ERK2 activation
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep896

PATHWAYSTEP1415 1 9606
type: PathwayStep
step process: Activated RAF1 complex binds MEK
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep1415
next step: PATHWAYSTEP1230 1 9606
next step: PATHWAYSTEP1231 1 9606

MAPK/ERK kinase 2
type: Protein
entity reference: MEK 2
data source: Reactome
name: ERK activator kinase 2
name: Dual specificity mitogen-activated protein kinase kinase 2
name: Dual specificity mitogen-activated protein kinase kinase 2 (EC 2.7.1.-) (MAP kinase kinase 2) (MAPKK 2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK2)
name: MAPKK 2
name: MAP kinase kinase 2
xref: REACTOME_59504
xref: REACTOME REACT 3918 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein2360
comment: Reactome DB_ID: 59504
display name: MEK2

UNIPROT Q9UCU3
type: UnificationXref
id: Q9UCU3
db: uniprot

19050043
type: PublicationXref
id: 19050043
author: Eulenfeld, R
author: Schaper, F
db: PubMed
title: A new mechanism for the regulation of Gab1 recruitment to the plasma membrane
source: J Cell Sci 122:55-64
year: 2009

UNIPROT Q9UCU4
type: UnificationXref
id: Q9UCU4
db: uniprot

UNIPROT Q9UCU2
type: UnificationXref
id: Q9UCU2
db: uniprot

UNIPROT Q9UC20
type: UnificationXref
id: Q9UC20
db: uniprot

REACTOME_109834
type: RelationshipXref
id: 109834
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109834

REACTOME REACT 4256 3
type: UnificationXref
id: REACT_4256
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4256.3

PROTEIN+MODIFICATION+ONTOLOGY MOD:00048
type: UnificationXref
id: MOD:00048
db: Protein Modification Ontology

10409724
type: PublicationXref
id: 10409724
db: PubMed

PROTEIN+MODIFICATION+ONTOLOGY MOD:00046
type: UnificationXref
id: MOD:00046
db: Protein Modification Ontology

PROTEIN+MODIFICATION+ONTOLOGY MOD:00047
type: UnificationXref
id: MOD:00047
db: Protein Modification Ontology

Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1)
type: Protein
entity reference: MEK 1
data source: Reactome
name: MAPK/ERK kinase 1
name: ERK activator kinase 1
name: Dual specificity mitogen-activated protein kinase kinase 1
name: MAP kinase kinase 1
name: MAPKK 1
xref: REACTOME_59502
xref: REACTOME REACT 3906 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1625
comment: Reactome DB_ID: 59502
display name: MEK1

REACTOME_110056
type: UnificationXref
id: 110056
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=110056

Transforming protein p21/H-Ras-1
type: Protein
entity reference: c-H-ras
data source: Reactome
name: p21/H-RAS-1
xref: REACTOME REACT 4795 1
xref: REACTOME_62717
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein2350
comment: Reactome DB_ID: 62717
display name: c-H-ras

Nuclear translocation of phospho-ERK-1 dimer
type: BiochemicalReaction
data source: Reactome
xref: REACTOME_109867
xref: REACTOME REACT 1866 6
xref: GENE+ONTOLOGY GO:0000189
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
left: phospho-ERK-1 dimer
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction700
comment: Phospho-ERK-1 dimer is translocated from cytosol to nucleoplasm.
comment: Authored: Charalambous, M, 2004-04-29 09:21:24
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: phospho-ERK-1 dimer

PATHWAYSTEP889 1 9606
type: PathwayStep
step process: Nuclear translocation of phospho-ERK-1 dimer
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep889

REACTOME REACT 21811 1
type: UnificationXref
id: REACT_21811
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_21811.1

REACTOME REACT 5435 1
type: UnificationXref
id: REACT_5435
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5435.1

REACTOME REACT 27710 1
type: UnificationXref
id: REACT_27710
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27710.1

REACTOME_109869
type: UnificationXref
id: 109869
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109869

REACTOME REACT 487 6
type: UnificationXref
id: REACT_487
db: Reactome
id version: 6
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_487.6

REACTOME_109867
type: UnificationXref
id: 109867
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109867

REACTOME_109868
type: UnificationXref
id: 109868
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109868

cytosol
type: CellularLocationVocabulary
xref: GENE+ONTOLOGY GO:0005829
comment: cPath2-generated

REACTOME_109865
type: UnificationXref
id: 109865
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109865

REFSEQ NP 000591
type: RelationshipXref
id: NP_000591
db: RefSeq

REACTOME_109866
type: UnificationXref
id: 109866
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109866

REACTOME_109863
type: UnificationXref
id: 109863
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109863

REACTOME_109864
type: UnificationXref
id: 109864
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109864

REACTOME_109862
type: UnificationXref
id: 109862
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109862

REACTOME_157415
type: UnificationXref
id: 157415
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=157415

PATHWAYSTEP891 1 9606
type: PathwayStep
step process: MEK2 binds ERK-2
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep891
next step: PATHWAYSTEP892 1 9606

REACTOME_109860
type: UnificationXref
id: 109860
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109860

REFSEQ NP 003322
type: RelationshipXref
id: NP_003322
db: RefSeq

PUBCHEM_17487135
type: UnificationXref
id: 17487135
db: PubChem

phospho_MEK1
type: Protein
data source: Reactome
member physical entity: Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1)
member physical entity: MAPK/ERK kinase 1
xref: REACTOME_112340
xref: REACTOME REACT 3339 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 112340
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1627

MEK2 phosphorylates ERK-2
type: BiochemicalReaction
data source: Reactome
EC number: 2.7.11
xref: REACTOME_109862
xref: 8388392
xref: REACTOME REACT 2247 5
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
participant stoichiometry: Stoichiometry1968
participant stoichiometry: Stoichiometry1969
left: Adenosine 5'-triphosphate
left: MEK2:ERK-2
comment: MEK2 phosphorylates the critical Tyrosine and Threonine on ERK2, converting two ATP to ADP. Phosphorylation of ERK-2 activates its kinase activity.
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction702
comment: Authored: Charalambous, M, 2005-02-04 06:50:22
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: phospho-ERK-2:MEK2
right: Adenosine 5'-diphosphate

MEK2:ERK-2
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1967
component stoichiometry: Stoichiometry1966
component: Mitogen-activated protein kinase 1 (EC 2.7.1.-) (Extracellular signal- regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1)
component: MAPK/ERK kinase 2
xref: REACTOME_109849
xref: REACTOME REACT 5435 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Reactome DB_ID: 109849
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex690

UNIPROT P40189
type: UnificationXref
id: P40189
db: uniprot

ENTREZ+GENE 5594
type: RelationshipXref
id: 5594
db: Entrez Gene

ENTREZ+GENE 5595
type: RelationshipXref
id: 5595
db: Entrez Gene

REACTOME REACT 27516 1
type: UnificationXref
id: REACT_27516
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27516.1

IL-6:Tyrosine phosphorylated hexameric IL-6 receptor:Activated JAKs
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1964
component: IL6:Tyrosine phosphorylated trimeric IL-6 receptor:Activated JAKs
xref: REACTOME REACT 27710 1
xref: REACTOME_1112594
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Reactome DB_ID: 1112594
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex683

UNIPROT B2R5N3
type: UnificationXref
id: B2R5N3
db: uniprot

HGNC HRAS
type: RelationshipXref
id: HRAS
db: HGNC

REACTOME_109859
type: RelationshipXref
id: 109859
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109859

O4'-phospho-L-tyrosine
type: SequenceModificationVocabulary
xref: PROTEIN+MODIFICATION+ONTOLOGY MOD:00048
comment: cPath2-generated

REACTOME_109854
type: UnificationXref
id: 109854
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109854

REACTOME_109855
type: UnificationXref
id: 109855
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109855

REACTOME REACT 4582 1
type: UnificationXref
id: REACT_4582
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4582.1

REACTOME_109856
type: UnificationXref
id: 109856
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109856

REACTOME_109861
type: RelationshipXref
id: 109861
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109861

REACTOME_109857
type: UnificationXref
id: 109857
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109857

REACTOME_109858
type: UnificationXref
id: 109858
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109858

HGNC MAP2K1
type: RelationshipXref
id: Map2k1
db: HGNC

Activated RAF1 complex binds MEK
type: BiochemicalReaction
data source: Reactome
xref: REACTOME REACT 143 6
xref: REACTOME_109830
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
left: Activated RAF1 complex
left: MEK
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction1144
comment: Authored: Charalambous, M, 2005-01-07 11:17:43
comment: MEK-1/2 have a proline rich domain (P) and critical Serine residues (MEK-1 S218/222, MEK-2 unknown, S) upon which the molecules may be phosphorylated. MEK1/2 are found in the cytoplasm of unstimulated cells. MEK-1/2 bind to active Raf-1 via the proline-rich domain. Active Raf-1 is able to phosphorylate target Serine and Threonine residues in the presence of ATP.
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: Activated RAF1 complex:MEK

HGNC MAP2K2
type: RelationshipXref
id: Map2k2
db: HGNC

PATHWAYSTEP1416 1 9606
type: PathwayStep
step process: MEK activation
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep1416

guanosine 5'-triphosphoric acid
type: SmallMoleculeReference
structure: chebi_15996
chemical formula: C10H16N5O14P3
name: guanosine 5'-(tetrahydrogen triphosphate)
name: H4gtp
name: guanosine triphosphate
name: 5'-GTP
xref: CHEBI CHEBI:24451
xref: IS CONJUGATE ACID OF CHEBI:57600
xref: CHEBI CHEBI:15996
xref: PUBCHEM_17487135
xref: CHEBI CHEBI:13342
xref: CHEBI CHEBI:5234
xref: CHEBI CHEBI:42934
xref: INCHI XKMLYUALXHKNFT-UUOKFMHZSA-N
molecular weight: 523.181
display name: GTP

REACTOME REACT 2812 1
type: UnificationXref
id: REACT_2812
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2812.1

REACTOME_109852
type: UnificationXref
id: 109852
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109852

REACTOME REACT 27518 1
type: UnificationXref
id: REACT_27518
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27518.1

REACTOME_109853
type: UnificationXref
id: 109853
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109853

REACTOME_110049
type: UnificationXref
id: 110049
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=110049

'IL6:Tyrosine phosphorylated hexameric IL-6 receptor:Activated JAKs:p-SHP2 [plasma membrane]' positively regulates 'ERK1 activation'
type: Control
data source: Reactome
xref: 9488469
xref: 7871433
xref: 17993263
xref: REACTOME_1112768
xref: 9632795
xref: 8934572
xref: 10409724
xref: 19050043
xref: REACTOME REACT 28015 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
controlled: ERK1 activation
control type: ACTIVATION
controller: IL6:Tyrosine phosphorylated hexameric IL-6 receptor:Activated JAKs:p-SHP2
comment: IL-6-type receptor activation leads to induction of the MAPK cascade. Experiments using gp130 identified that the gp130 SHP2 (SH2-domain-containing tyrosine phosphatase)-binding site Tyr-759 (Stahl et al. 1995) is required for this activation. Mutation of gp130 Tyr-759 impairs IL-6 induced activation of the MAPK cascade (Kim et al. 1998). While there is a consensus that SHP2 is involved in IL-6-induced activation of the MAPK pathway, the molecular details are uncertain. One proposed mechanism suggests SHP2 acts as an adaptor for Grb2-Sos recruitment (Fukada et al. 1996, Kim & Baumann 1999). IL-6 induced SHP2 recruitment to p-Tyr-759 of gp130 was demonstrated but relatively little of the SHP2 remained associated with gp130, suggesting that SHP2 dissociates from the receptor when phosphorylated. This seems inconsistent with a Grb2-Sos recruitment role for SHP2, though it is possible that only low levels or transient recruitment are required. IL-6 induced ERK activation was not inhibited in cells transfected with a phosphatase inactive mutant of SHP2, whereas an SHP2 mutant missing the Grb2 interaction region significantly suppressed ERK activation. This suggests phosphatase activity is not required for ERK activation while SHP-2 interaction with Grb2 is important. However, overexpression studies can generate artefactual interactions and this interpretation has been questioned (Dance et al. 2008). An alternative proposal suggests that SHP2 and the adaptor protein Gab1 couple gp130 signalling to Erk activation. In this proposal phosphorylated SHP2 dissociates from gp130 and becomes associated with membrane associated Gab1 in a complex with PI3-kinase (Takahashi-Tezuka et al. 1998, Eulenfeld & Schaper 2009). SHP2 interaction is suggested to induce a conformational change in Gab1 that permits Gab1-PI3-kinase activation and enhancement of IL-6-induced Erk pathway activation. However this is speculative, the role of SHP2 phosphatase activity is unclear. Other possible mecha…
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Control47

ENTREZ+GENE 3570
type: RelationshipXref
id: 3570
db: Entrez Gene

ENTREZ+GENE 3572
type: RelationshipXref
id: 3572
db: Entrez Gene

REFSEQ NP 002515
type: RelationshipXref
id: NP_002515
db: RefSeq

IS CONJUGATE ACID OF CHEBI:57299
type: RelationshipXref
id: 57299
db: CHEBI

REACTOME_109845
type: UnificationXref
id: 109845
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109845

REACTOME REACT 1391 3
type: UnificationXref
id: REACT_1391
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1391.3

REACTOME_109843
type: UnificationXref
id: 109843
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109843

O-phospho-L-threonine
type: SequenceModificationVocabulary
xref: PROTEIN+MODIFICATION+ONTOLOGY MOD:00047
comment: cPath2-generated

O-phospho-L-serine
type: SequenceModificationVocabulary
xref: PROTEIN+MODIFICATION+ONTOLOGY MOD:00046
comment: cPath2-generated

REACTOME_109844
type: UnificationXref
id: 109844
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109844

REACTOME_109849
type: UnificationXref
id: 109849
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109849

REACTOME_109848
type: UnificationXref
id: 109848
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109848

REACTOME REACT 5539 1
type: UnificationXref
id: REACT_5539
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5539.1

REACTOME REACT 3152 1
type: UnificationXref
id: REACT_3152
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3152.1

REACTOME REACT 495 5
type: UnificationXref
id: REACT_495
db: Reactome
id version: 5
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_495.5

REACTOME_109841
type: UnificationXref
id: 109841
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109841

REACTOME_109842
type: UnificationXref
id: 109842
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109842

REACTOME REACT 28015 1
type: UnificationXref
id: REACT_28015
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_28015.1

PATHWAYSTEP895 1 9606
type: PathwayStep
step process: Nuclear translocation of phospho-ERK-2 dimer
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep895

REACTOME_29370
type: UnificationXref
id: 29370
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29370

REACTOME REACT 2686 2
type: UnificationXref
id: REACT_2686
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2686.2

MAP kinase cascade
type: Pathway
data source: Reactome
pathway component: ERK activation
pathway component: MEK activation
xref: REACTOME REACT 634 5
xref: REACTOME_109869
xref: GENE+ONTOLOGY GO:0000165
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
pathway order: PATHWAYSTEP897 1 9606
pathway order: PATHWAYSTEP1416 1 9606
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Pathway269
comment: The MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a common 'module' in the transmission of an extracellular signal into the nucleus.
comment: Authored: Charalambous, M, 2004-04-29 09:21:24
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
organism: Homo sapiens

ERK2 activation
type: Pathway
data source: Reactome
pathway component: MEK2 binds ERK-2
pathway component: Dimerisation of phospho-ERK-2
pathway component: MEK2 phosphorylates ERK-2
pathway component: Nuclear translocation of phospho-ERK-2 dimer
pathway component: Dissociation of phospho-ERK-2:MEK2
xref: REACTOME REACT 1183 4
xref: GENE+ONTOLOGY GO:0070371
xref: REACTOME_112411
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
pathway order: PATHWAYSTEP895 1 9606
pathway order: PATHWAYSTEP892 1 9606
pathway order: PATHWAYSTEP894 1 9606
pathway order: PATHWAYSTEP891 1 9606
pathway order: PATHWAYSTEP893 1 9606
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Pathway194
comment: Activated MEK2 phosphorylates and activates ERK2.
comment: Authored: Charalambous, M, 2005-02-04 06:50:22
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
organism: Homo sapiens

Tyrosine phosphorylated IL6RB:Activated JAKs
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1958
component stoichiometry: Stoichiometry1957
component: IL6ST
component: Activated JAK1, JAK2, TYK2
xref: REACTOME REACT 27630 1
xref: REACTOME_1112563
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Reactome DB_ID: 1112563
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex687

REACTOME REACT 27493 1
type: UnificationXref
id: REACT_27493
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27493.1

UNIPROT Q9UD26
type: UnificationXref
id: Q9UD26
db: uniprot

REACTOME REACT 27784 1
type: UnificationXref
id: REACT_27784
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27784.1

CHEBI CHEBI:10789
type: UnificationXref
id: CHEBI:10789
db: chebi

UNIPROT Q96HD7
type: UnificationXref
id: Q96HD7
db: uniprot

Reactome
type: Provenance
comment: cPath2-generated. Data loaded from:
comment: cPath2-generated. Data version: 20110323, March 23, 2011
comment: http://www.reactome.org
comment: cPath2-generated. Data (internal) id: REACTOME_HUMAN
comment: cPath2-generated. Data type: BIOPAX

ENTREZ+GENE 3569
type: RelationshipXref
id: 3569
db: Entrez Gene

REACTOME_109830
type: UnificationXref
id: 109830
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109830

REACTOME_109837
type: UnificationXref
id: 109837
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109837

IL6:Tyrosine phosphorylated trimeric IL-6 receptor:Activated JAKs
type: Complex
data source: Reactome
member physical entity: IL6:IL6RA:Tyrosine phosphorylated IL6RB:Activated JAKs
member physical entity: IL6:sIL6R:Tyrosine phosphorylated IL6RB:Activated JAKs
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
xref: REACTOME_1112584
xref: REACTOME REACT 27564 1
cellular location: plasma membrane
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 1112584
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex684

HGNC JAK2
type: RelationshipXref
id: Jak2
db: HGNC

REACTOME REACT 27853 1
type: UnificationXref
id: REACT_27853
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27853.1

REACTOME REACT 4130 1
type: UnificationXref
id: REACT_4130
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4130.1

REACTOME_109838
type: UnificationXref
id: 109838
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109838

REACTOME REACT 2796 1
type: UnificationXref
id: REACT_2796
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2796.1

HGNC JAK1
type: RelationshipXref
id: Jak1
db: HGNC

phospho-ERK-1 dimer
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1951
component: p44-MAPK
xref: REACTOME REACT 3932 1
xref: REACTOME_109844
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Reactome DB_ID: 109844
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex680

PUBCHEM_8143180
type: UnificationXref
id: 8143180
db: PubChem

PATHWAYSTEP893 1 9606
type: PathwayStep
step process: Dissociation of phospho-ERK-2:MEK2
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#PathwayStep893
next step: PATHWAYSTEP894 1 9606

REACTOME REACT 545 5
type: UnificationXref
id: REACT_545
db: Reactome
id version: 5
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_545.5

MEK
type: Protein
data source: Reactome
member physical entity: Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1)
member physical entity: MAPK/ERK kinase 2
xref: REACTOME REACT 2275 1
xref: REACTOME_112398
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: cytosol
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 112398
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein2359

8934572
type: PublicationXref
id: 8934572
author: Hibi, M
author: Fukada, T
author: Fujitani, Y
author: Nakajima, K
author: Yamaguchi, T
author: Yamanaka, Y
author: Hirano, T
author: Takahashi-Tezuka, M
db: PubMed
title: Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in anti-apoptosis
source: Immunity 5:449-60
year: 1996

IL6:IL6RA:Tyrosine phosphorylated IL6RB:Activated JAKs
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1959
component stoichiometry: Stoichiometry1956
component: IL6:IL6RA
component: Tyrosine phosphorylated IL6RB:Activated JAKs
xref: REACTOME REACT 27518 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
xref: REACTOME_1112585
cellular location: plasma membrane
comment: Reactome DB_ID: 1112585
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex685

CATALYSIS582 1 9606
type: Catalysis
data source: Reactome
controlled: RAF1 phosphorylates MEK1
control type: ACTIVATION
xref: GENE+ONTOLOGY GO:0016301
xref: REACTOME_109834
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
controller: Activated RAF1 complex:MEK
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Catalysis582

REACTOME REACT 2688 1
type: UnificationXref
id: REACT_2688
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2688.1

5'-adenylphosphoric acid
type: SmallMoleculeReference
structure: chebi_16761
chemical formula: C10H15N5O10P2
name: H3adp
name: adenosine 5'-(trihydrogen diphosphate)
xref: INCHI XTWYTFMLZFPYCI-KQYNXXCUSA-N
xref: CHEBI CHEBI:22244
xref: CHEBI CHEBI:2342
xref: CHEBI CHEBI:40553
xref: CHEBI CHEBI:13222
xref: CHEBI CHEBI:16761
xref: IS CONJUGATE ACID OF CHEBI:456216
xref: PUBCHEM_8144912
display name: ADP
comment: A purine ribonucleoside 5'-diphosphate having adenine as the nucleobase.

REACTOME REACT 1780 6
type: UnificationXref
id: REACT_1780
db: Reactome
id version: 6
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1780.6

GENE+ONTOLOGY GO:0005829
type: UnificationXref
id: GO:0005829
db: Gene Ontology

Stoichiometry2969
type: Stoichiometry
physical entity: Adenosine 5'-triphosphate
stoichiometric coefficient: 2.0

CHEBI CHEBI:16761
type: UnificationXref
id: CHEBI:16761
db: chebi

RAF1 phosphorylates MEK1
type: BiochemicalReaction
data source: Reactome
xref: REACTOME_109841
xref: REACTOME REACT 545 5
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
participant stoichiometry: Stoichiometry2969
participant stoichiometry: Stoichiometry2977
left: Adenosine 5'-triphosphate
left: Activated RAF1 complex:MEK1
comment: Active Raf-1 phosphorylates MEK-1/2 on Serine residues, converting ATP to ADP. The MEK-1/2 kinase is now active.
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction980
comment: Authored: Charalambous, M, 2005-01-07 11:17:43
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: Adenosine 5'-diphosphate
right: MAPK/ERK kinase 1
right: Activated RAF1 complex

REFSEQ NP 000556
type: RelationshipXref
id: NP_000556
db: RefSeq

HGNC CDK1
type: RelationshipXref
id: Cdk1
db: HGNC

REACTOME REACT 614 4
type: UnificationXref
id: REACT_614
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_614.4

UNIPROT E1P616
type: UnificationXref
id: E1P616
db: uniprot

p(Y1054)-TYK2
type: Protein
entity reference: 2.7.10.2
data source: Reactome
name: Non-receptor tyrosine-protein kinase TYK2
xref: REACTOME_1112598
xref: REACTOME REACT 27336 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature218
feature: FragmentFeature577
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1640
comment: Reactome DB_ID: 1112598
display name: TYK2_HUMAN

9488469
type: PublicationXref
id: 9488469
author: Baumann, H
author: Hawley, TS
author: Kim, H
author: Hawley, RG
db: PubMed
title: Protein tyrosine phosphatase 2 (SHP-2) moderates signaling by gp130 but is not required for the induction of acute-phase plasma protein genes in hepatic cells
source: Mol Cell Biol 18:1525-33
year: 1998

MEK1 binds ERK-1
type: BiochemicalReaction
data source: Reactome
xref: REACTOME REACT 1780 6
xref: 8388392
xref: REACTOME_109857
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
left: MAPK/ERK kinase 1
left: p44-MAPK
comment: In the cytoplasm activated MEK1 (Serine phosphorylated) may encounter monomeric, inactive ERK1. ERK1 in its inactive form is not phosphorylated on a critical Threonine (T) and a critical Tyrosine (Y).
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#BiochemicalReaction696
comment: Authored: Charalambous, M, 2005-02-04 06:50:22
comment: Reviewed: Greene, LA, 2007-11-08 15:39:37
comment: Edited: Schmidt, EE, 0000-00-00 00:00:00
right: MEK1:ERK-1

Stoichiometry2970
type: Stoichiometry
physical entity: Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.1.-) (MAP kinase kinase 1) (MAPKK 1) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK1)
stoichiometric coefficient: 1.0

Stoichiometry2971
type: Stoichiometry
physical entity: Guanosine 5'-triphosphate
stoichiometric coefficient: 1.0

REACTOME REACT 1183 4
type: UnificationXref
id: REACT_1183
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1183.4

Stoichiometry2972
type: Stoichiometry
physical entity: p21 RAS
stoichiometric coefficient: 1.0

REACTOME REACT 3645 2
type: UnificationXref
id: REACT_3645
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3645.2

HGNC MAPK3
type: RelationshipXref
id: Mapk3
db: HGNC

Stoichiometry2977
type: Stoichiometry
physical entity: Adenosine 5'-diphosphate
stoichiometric coefficient: 2.0

Stoichiometry2978
type: Stoichiometry
physical entity: Activated RAF1 complex
stoichiometric coefficient: 1.0

HGNC MAPK1
type: RelationshipXref
id: Mapk1
db: HGNC

Stoichiometry2979
type: Stoichiometry
physical entity: MEK
stoichiometric coefficient: 1.0

phospho-Cdc2 (Thr 161)
type: Protein
entity reference: CDK1
data source: Reactome
xref: REACTOME_157415
xref: REACTOME REACT 5391 2
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: ModificationFeature209
cellular location: cytosol
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1630
comment: Reactome DB_ID: 157415

Stoichiometry2973
type: Stoichiometry
physical entity: p21 RAS:GTP
stoichiometric coefficient: 1.0

UNIPROT Q06124
type: UnificationXref
id: Q06124
db: uniprot

Stoichiometry2974
type: Stoichiometry
physical entity: Protein kinase C inhibitor protein-1
stoichiometric coefficient: 1.0

Stoichiometry2975
type: Stoichiometry
physical entity: C-RAF
stoichiometric coefficient: 1.0

2.7.10.2
type: ProteinReference
xref: UNIPROT P29597
xref: UNIPROT Q6QB10
xref: REFSEQ NP 003322
xref: HGNC TYK2
xref: ENTREZ+GENE 7297
xref: UNIPROT Q96CH0
display name: TYK2_HUMAN
standard name: Non-receptor tyrosine-protein kinase TYK2
comment: FUNCTION: Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. SUBUNIT: Interacts with JAKMIP1. TISSUE SPECIFICITY: Observed in all cell lines analyzed. Expressed in a variety of lymphoid and non-lymphoid cell lines. DOMAIN: The FERM domain mediates interaction with JAKMIP1. DISEASE: Defects in TYK2 are the cause of protein-tyrosine kinase 2 deficiency (TYK2 deficiency) [MIM:611521]; also known as autosomal recessive hyper-IgE syndrome (HIES) with atypical mycobacteriosis. TYK2 deficiency consists of a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. SIMILARITY: Contains 1 FERM domain. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain. WEB RESOURCE: Name=TYK2base; Note=TYK2 mutation db; URL="http://bioinf.uta.fi/TYK2base/"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/tyk2/"; COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
organism: Homo sapiens

MEK 1
type: ProteinReference
name: MKK1
name: MAPK/ERK kinase 1
name: ERK activator kinase 1
name: 2.7.12.2
name: MAP kinase kinase 1
name: MAPKK 1
xref: REFSEQ NP 002746
xref: ENTREZ+GENE 5604
xref: UNIPROT Q02750
xref: HGNC MAP2K1
display name: MP2K1_HUMAN
standard name: Dual specificity mitogen-activated protein kinase kinase 1
comment: FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates ERK1 and ERK2 MAP kinases. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Activated by phosphorylation. SUBUNIT: Interacts with MORG1. Interacts with ARRB2 (By similarity). Interacts with Yersinia yopJ. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=MKK1a; IsoId=Q02750-1; Sequence=Displayed; Name=2; Synonyms=MKK1b; IsoId=Q02750-2; Sequence=VSP_040500; TISSUE SPECIFICITY: Widely expressed, with extremely low levels in brain. PTM: Phosphorylation on Ser/Thr by MAP kinase kinase kinases (RAF or MEKK1) regulates positively the kinase activity. PTM: Acetylation by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway. DISEASE: Defects in MAP2K1 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio- cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MAP2K1"; GENE SYNONYMS: MEK1 …
organism: Homo sapiens

Stoichiometry2976
type: Stoichiometry
physical entity: Activated RAF1 complex
stoichiometric coefficient: 1.0

Janus kinase 1
type: ProteinReference
name: JAK-1
name: 2.7.10.2
xref: HGNC JAK1
xref: UNIPROT Q59GQ2
xref: REFSEQ NP 002218
xref: ENTREZ+GENE 3716
xref: UNIPROT P23458
xref: UNIPROT Q9UD26
display name: JAK1_HUMAN
standard name: Tyrosine-protein kinase JAK1
comment: FUNCTION: Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. SUBUNIT: Interacts with IL31RA, IFNAR2, JAKMIP1 and SHB. SUBCELLULAR LOCATION: Endomembrane system; Peripheral membrane protein. Note=Wholly intracellular, possibly membrane associated. TISSUE SPECIFICITY: Expressed at higher levels in primary colon tumors than in normal colon tissue. The expression level in metastatic colon tumors is comparable to the expression level in normal colon tissue. DOMAIN: Possesses two phosphotransferase domains. The second one probably contains the catalytic domain (By similarity), while the presence of slight differences suggest a different role for domain 1. DOMAIN: The FERM domain mediates interaction with JAKMIP1. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. SIMILARITY: Contains 1 FERM domain. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain. SEQUENCE CAUTION: Sequence=AAA36527.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAA36527.1; Type=Frameshift; Positions=858, 862; GENE SYNONYMS: JAK1A JAK1B. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
organism: Homo sapiens

Activated RAF1 complex:MEK2
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry2981
component stoichiometry: Stoichiometry2980
component: Activated RAF1 complex
component: MAPK/ERK kinase 2
xref: REACTOME REACT 4223 3
xref: REACTOME_109795
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex1118
comment: Reactome DB_ID: 109795

IL6:Tyrosine phosphorylated hexameric IL-6 receptor:Activated JAKs:p-SHP2
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry1953
component stoichiometry: Stoichiometry1965
component: IL-6:Tyrosine phosphorylated hexameric IL-6 receptor:Activated JAKs
component: Phosphorylated SHP2
xref: REACTOME_1112753
xref: REACTOME REACT 27855 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
cellular location: plasma membrane
comment: Reactome DB_ID: 1112753
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Complex682

REACTOME REACT 3918 1
type: UnificationXref
id: REACT_3918
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3918.1

UNIPROT Q96D10
type: UnificationXref
id: Q96D10
db: uniprot

sIL6R
type: Protein
entity reference: IL-6R-alpha
data source: Reactome
name: Interleukin-6 receptor subunit alpha short soluble form
name: IL6RA_HUMAN
xref: REACTOME_1067661
xref: REACTOME REACT 27429 1
xref: AUTO-GENERATED URN:MIRIAM:TAXONOMY:9606
feature: FragmentFeature579
cellular location: extracellular region
comment: Original RDFId (before applying ReactomeCleaner): http://www.reactome.org/biopax/48887#Protein1642
comment: Reactome DB_ID: 1067661
display name: IL6R

Stoichiometry2982
type: Stoichiometry
physical entity: Adenosine 5'-triphosphate
stoichiometric coefficient: 2.0

HGNC YWHAB
type: RelationshipXref
id: Ywhab
db: HGNC

Stoichiometry2983
type: Stoichiometry
physical entity: Adenosine 5'-diphosphate
stoichiometric coefficient: 2.0

Stoichiometry2980
type: Stoichiometry
physical entity: Activated RAF1 complex
stoichiometric coefficient: 1.0

Stoichiometry2981
type: Stoichiometry
physical entity: MAPK/ERK kinase 2
stoichiometric coefficient: 1.0

REACTOME REACT 27647 1
type: UnificationXref
id: REACT_27647
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27647.1

REACTOME_59282
type: UnificationXref
id: 59282
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=59282

REACTOME_59284
type: UnificationXref
id: 59284
db: Reactome
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=59284