(data stored in ACNUC8465 zone)

HOGENOM: HS15_PE968

ID   HS15_PE968                           STANDARD;      PRT;   393 AA.
AC   HS15_PE968; Q02750;
DT   00-JAN-0000 (Rel. 1, Created)
DT   00-JAN-0000 (Rel. 2, Last sequence update)
DT   00-JAN-0000 (Rel. 3, Last annotation update)
DE   RecName: Full=Dual specificity mitogen-activated protein kinase kinase 1;
DE   Short=MAP kinase kinase 1; Short=MAPKK 1; Short=MKK1; EC=2.7.12
DE   2;AltName: Full=ERK activator kinase 1;AltName: Full=MAPK/ERK kinase 1;
DE   Short=MEK 1; (HS15.PE968).
GN   Name=MAP2K1; Synonyms=MEK1, PRKMK1;
OS   HOMO SAPIENS.
OC   Eukaryota; Metazoa; Eumetazoa; Bilateria; Coelomata; Deuterostomia;
OC   Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi;
OC   Sarcopterygii; Tetrapoda; Amniota; Mammalia; Theria; Eutheria;
OC   Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini;
OC   Hominoidea; Hominidae; Homininae; Homo.
OX   NCBI_TaxID=9606;
RN   [0]
RP   -.;
RG   -.;
RL   -.;
CC   -!- SEQ. DATA ORIGIN: Translated from the HOGENOM CDS HS15.PE968.
CC       Homo sapiens chromosome 15 GRCh37  sequence 1..102521392 annotated by
CC       Ensembl
CC   -!- ANNOTATIONS ORIGIN:MP2K1_HUMAN
CC   -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine
CC       and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP
CC       kinases. Activates ERK1 and ERK2 MAP kinases.
CC   -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC   -!- ENZYME REGULATION: Activated by phosphorylation.
CC   -!- SUBUNIT: Interacts with MORG1. Interacts with ARRB2. Found in a
CC       complex with at least BRAF, HRAS1, MAP2K1, MAPK3 and RGS14 (By
CC       similarity). Interacts with Yersinia yopJ.
CC   -!- INTERACTION:
CC       Q9NR09:BIRC6; NbExp=2; IntAct=EBI-492564, EBI-1765160;
CC       P04049:RAF1; NbExp=2; IntAct=EBI-492564, EBI-365996;
CC       Q86Y07:VRK2; NbExp=2; IntAct=EBI-492564, EBI-1207615;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=MKK1a;
CC         IsoId=Q02750-1; Sequence=Displayed;
CC       Name=2; Synonyms=MKK1b;
CC         IsoId=Q02750-2; Sequence=VSP_040500;
CC   -!- TISSUE SPECIFICITY: Widely expressed, with extremely low levels in
CC       brain.
CC   -!- PTM: Phosphorylation on Ser/Thr by MAP kinase kinase kinases (RAF
CC       or MEKK1) regulates positively the kinase activity.
CC   -!- PTM: Acetylation by Yersinia yopJ prevents phosphorylation and
CC       activation, thus blocking the MAPK signaling pathway.
CC   -!- DISEASE: Defects in MAP2K1 are a cause of cardiofaciocutaneous
CC       syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio-
CC       cutaneous syndrome. CFC syndrome is characterized by a distinctive
CC       facial appearance, heart defects and mental retardation. Heart
CC       defects include pulmonic stenosis, atrial septal defects and
CC       hypertrophic cardiomyopathy. Some affected individuals present
CC       with ectodermal abnormalities such as sparse, friable hair,
CC       hyperkeratotic skin lesions and a generalized ichthyosis-like
CC       condition. Typical facial features are similar to Noonan syndrome.
CC       They include high forehead with bitemporal constriction,
CC       hypoplastic supraorbital ridges, downslanting palpebral fissures,
CC       a depressed nasal bridge, and posteriorly angulated ears with
CC       prominent helices. The inheritance of CFC syndrome is autosomal
CC       dominant.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC       protein kinase family. MAP kinase kinase subfamily.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MAP2K1";
CC   -!- GENE_FAMILY: HOG000234206 [ FAMILY / ALN / TREE ]
DR   HOGENOM:Homo_sapiens;ENSG00000169032;ENST00000307102;ENSP00000302486.
DR   EMBL; AK291500; - ;
DR   EMBL; AK294322; - ;
DR   EMBL; BC137459; - ;
DR   EMBL; BC139729; - ;
DR   EMBL; CH471082; - ;
DR   EMBL; L05624; - ;
DR   EMBL; L11284; - ;
DR   UniProtKB/Swiss-Prot; Q02750; -.
DR   EMBL; L05624; AAA36318.1; -; mRNA.
DR   EMBL; L11284; -; NOT_ANNOTATED_CDS; mRNA.
DR   IPI; IPI00219604; -.
DR   IPI; IPI00797850; -.
DR   PIR; A45100; A45100.
DR   RefSeq; NP_002746.1; NM_002755.3.
DR   UniGene; Hs.145442; -.
DR   PDB; 1S9J; X-ray; 2.40 A; A=62-392.
DR   PDB; 2P55; X-ray; 2.80 A; A=62-393.
DR   PDB; 3DV3; X-ray; 2.30 A; A=62-382.
DR   PDB; 3DY7; X-ray; 2.70 A; A=62-393.
DR   PDB; 3E8N; X-ray; 2.50 A; A=62-393.
DR   PDB; 3EQB; X-ray; 2.62 A; A=62-393.
DR   PDB; 3EQC; X-ray; 1.80 A; A=35-393.
DR   PDB; 3EQD; X-ray; 2.10 A; A=35-393.
DR   PDB; 3EQF; X-ray; 2.70 A; A=35-393.
DR   PDB; 3EQG; X-ray; 2.50 A; A=35-393.
DR   PDB; 3EQH; X-ray; 2.00 A; A=35-393.
DR   PDB; 3EQI; X-ray; 1.90 A; A=35-393.
DR   PDB; 3MBL; X-ray; 2.60 A; A=62-382.
DR   PDB; 3ORN; X-ray; 2.80 A; A=62-393.
DR   PDB; 3PP1; X-ray; 2.70 A; A=62-382.
DR   PDBsum; 1S9J; -.
DR   PDBsum; 2P55; -.
DR   PDBsum; 3DV3; -.
DR   PDBsum; 3DY7; -.
DR   PDBsum; 3E8N; -.
DR   PDBsum; 3EQB; -.
DR   PDBsum; 3EQC; -.
DR   PDBsum; 3EQD; -.
DR   PDBsum; 3EQF; -.
DR   PDBsum; 3EQG; -.
DR   PDBsum; 3EQH; -.
DR   PDBsum; 3EQI; -.
DR   PDBsum; 3MBL; -.
DR   PDBsum; 3ORN; -.
DR   PDBsum; 3PP1; -.
DR   ProteinModelPortal; Q02750; -.
DR   SMR; Q02750; 39-381.
DR   DIP; DIP-201N; -.
DR   IntAct; Q02750; 18.
DR   MINT; MINT-99632; -.
DR   STRING; Q02750; -.
DR   PhosphoSite; Q02750; -.
DR   PeptideAtlas; Q02750; -.
DR   PRIDE; Q02750; -.
DR   Ensembl; ENST00000307102; ENSP00000302486; ENSG00000169032.
DR   GeneID; 5604; -.
DR   KEGG; hsa:5604; -.
DR   UCSC; uc010bhq.1; human.
DR   CTD; 5604; -.
DR   GeneCards; GC15P043515; -.
DR   H-InvDB; HIX0038157; -.
DR   HGNC; HGNC:6840; MAP2K1.
DR   HPA; CAB003834; -.
DR   HPA; HPA026430; -.
DR   MIM; 115150; phenotype.
DR   MIM; 176872; gene.
DR   neXtProt; NX_Q02750; -.
DR   Orphanet; 1340; Cardiofaciocutaneous syndrome.
DR   eggNOG; prNOG13928; -.
DR   GeneTree; ENSGT00570000078767; -.
DR   InParanoid; Q02750; -.
DR   OMA; DIAGWVC; -.
DR   OrthoDB; EOG4SF965; -.
DR   PhylomeDB; Q02750; -.
DR   BRENDA; 2.7.12.2; 2681.
DR   Pathway_Interaction_DB; bcr_5pathway; BCR signaling pathway.
DR   Pathway_Interaction_DB; anthraxpathway; Cellular roles of Anthrax toxin.
DR   Pathway_Interaction_DB; ceramidepathway; Ceramide signaling pathway.
DR   Pathway_Interaction_DB; pi3kcibpathway; Class IB PI3K non-lipid kinase events.
DR   Pathway_Interaction_DB; cd8tcrdownstreampathway; Downstream signaling in naive CD8+ T cells.
DR   Pathway_Interaction_DB; endothelinpathway; Endothelins.
DR   Pathway_Interaction_DB; ephbfwdpathway; EPHB forward signaling.
DR   Pathway_Interaction_DB; fcer1pathway; Fc-epsilon receptor I signaling in mast cells.
DR   Pathway_Interaction_DB; foxm1pathway; FOXM1 transcription factor network.
DR   Pathway_Interaction_DB; hedgehog_glipathway; Hedgehog signaling events mediated by Gli proteins.
DR   Pathway_Interaction_DB; ifngpathway; IFN-gamma pathway.
DR   Pathway_Interaction_DB; il2_1pathway; IL2-mediated signaling events.
DR   Pathway_Interaction_DB; trkrpathway; Neurotrophic factor-mediated Trk receptor signaling.
DR   Pathway_Interaction_DB; tcrraspathway; Ras signaling in the CD4+ TCR pathway.
DR   Pathway_Interaction_DB; met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
DR   Pathway_Interaction_DB; kitpathway; Signaling events mediated by Stem cell factor receptor (c-Kit).
DR   Pathway_Interaction_DB; mapktrkpathway; Trk receptor signaling mediated by the MAPK pathway.
DR   Reactome; REACT_11061; Signalling by NGF.
DR   Reactome; REACT_16888; Signaling by PDGF.
DR   Reactome; REACT_18266; Axon guidance.
DR   Reactome; REACT_498; Signaling by Insulin receptor.
DR   Reactome; REACT_6900; Immune System.
DR   Reactome; REACT_9417; Signaling by EGFR.
DR   NextBio; 21776; -.
DR   PMAP-CutDB; Q02750; -.
DR   ArrayExpress; Q02750; -.
DR   Bgee; Q02750; -.
DR   CleanEx; HS_MAP2K1; -.
DR   Genevestigator; Q02750; -.
DR   GermOnline; ENSG00000169032; Homo sapiens.
DR   GO; GO:0005829; C:cytosol; EXP:Reactome.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004708; F:MAP kinase kinase activity; TAS:ProtInc.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; EXP:Reactome.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0000187; P:activation of MAPK activity; TAS:Reactome.
DR   GO; GO:0000186; P:activation of MAPKK activity; TAS:Reactome.
DR   GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR   GO; GO:0007050; P:cell cycle arrest; IMP:BHF-UCL.
DR   GO; GO:0090398; P:cellular senescence; IMP:BHF-UCL.
DR   GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR   GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; EXP:Reactome.
DR   GO; GO:0002756; P:MyD88-independent toll-like receptor signaling pathway; EXP:Reactome.
DR   GO; GO:0008285; P:negative regulation of cell proliferation; IDA:BHF-UCL.
DR   GO; GO:0048011; P:nerve growth factor receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0007265; P:Ras protein signal transduction; EXP:Reactome.
DR   GO; GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
DR   GO; GO:0008063; P:Toll signaling pathway; TAS:Reactome.
DR   GO; GO:0034130; P:toll-like receptor 1 signaling pathway; TAS:Reactome.
DR   GO; GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
DR   GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
DR   GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR   InterPro; IPR011009; Kinase-like_dom.
DR   InterPro; IPR000719; Prot_kinase_cat_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR017442; Se/Thr_kinase-like_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR002290; Ser/Thr_kinase_dom.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Kinase_like; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   HOGENOMDNA; HS15.PE968; -.
KW   ENSG000001690321755old_1320000031; ENSP000003024867901old_1320000031;
KW   A4QPA9_HUMAN; B4DFY5_HUMAN; AK291500; AK294322; BC137459; BC139729;
KW   L05624; L11284;
KW   3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW   Complete proteome; Direct protein sequencing; Disease mutation;
KW   Kinase; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
SQ   SEQUENCE   393 AA;  UNKNOWN MW;  UNKNOWN CRC64;
     MPKKKPTPIQ LNPAPDGSAV NGTSSAETNL EALQKKLEEL ELDEQQRKRL EAFLTQKQKV
     GELKDDDFEK ISELGAGNGG VVFKVSHKPS GLVMARKLIH LEIKPAIRNQ IIRELQVLHE
     CNSPYIVGFY GAFYSDGEIS ICMEHMDGGS LDQVLKKAGR IPEQILGKVS IAVIKGLTYL
     REKHKIMHRD VKPSNILVNS RGEIKLCDFG VSGQLIDSMA NSFVGTRSYM SPERLQGTHY
     SVQSDIWSMG LSLVEMAVGR YPIPPPDAKE LELMFGCQVE GDAAETPPRP RTPGRPLSSY
     GMDSRPPMAI FELLDYIVNE PPPKLPSGVF SLEFQDFVNK CLIKNPAERA DLKQLMVHAF
     IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA AGV
//

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