MAP3K7
entrez
6885
canonical
uniprot
O43318
canonical
ensembl
ENSG00000135341
resolver
ensp
ENSP00000358331
resolver
ensp
ENSP00000358333
resolver
ensp
ENSP00000358335
resolver
ensp
ENSP00000358338
resolver
genesymbol
MAP3K7
resolver
genesymbol_syn
TAK1
resolver
hgnc
HGNC:6859
resolver
uniprot
B2RE27
resolver
uniprot
E1P523
resolver
uniprot
O43317
resolver
uniprot
O43319
resolver
uniprot
Q5TDN2
resolver
uniprot
Q5TDN3
resolver
uniprot
Q5TDT7
resolver
uniprot
Q9NTR3
resolver
uniprot
Q9NZ70
resolver
uniprot_entry
M3K7_HUMAN
resolver
uniprot_sec
B2RE27
resolver
uniprot_sec
E1P523
resolver
uniprot_sec
O43317
resolver
uniprot_sec
O43319
resolver
uniprot_sec
Q5TDN2
resolver
uniprot_sec
Q5TDN3
resolver
uniprot_sec
Q5TDT7
resolver
uniprot_sec
Q9NTR3
resolver
uniprot_sec
Q9NZ70
resolver
activity_regulation
ACTIVITY REGULATION: Activated by pro-inflammatory cytokines and in response to physical and chemical stresses, including osmotic stress, oxidative stress, arsenic and ultraviolet light irradiation (PubMed:16893890). Activated by 'Lys-63'-linked polyubiquitination and by autophosphorylation (PubMed:10702308, PubMed:11460167, PubMed:12242293, PubMed:29291351). Association with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 promotes activation through autophosphorylation, whereas PPM1B/PP2CB, PP2A and PPP6C dephosphorylation leads to inactivation (PubMed:11104763, PubMed:17079228, PubMed:37832545). Ceramides are also able to activate MAP3K7/TAK1 (PubMed:9079627). {ECO:0000269|PubMed:10702308, ECO:0000269|PubMed:11104763, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12242293, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:17079228, ECO:0000269|PubMed:29291351, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:9079627}.
uniprot
proteins
amino_acid_sequence
MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDVAIKQIESESERKAFIVELRQLSRVNHPNIVKLYGACLNPVCLVMEYAEGGSLYNVLHGAEPLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTACDIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIMWAVHNGTRPPLIKNLPKPIESLMTRCWSKDPSQRPSMEEIVKIMTHLMRYFPGADEPLQYPCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQSESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTAYSKPKRGHRKTASFGNILDVPEIVISGNGQPRRRSIQDLTVTGTEPGQVSSRSSSPSVRMITTSGPTSEKPTRSHPWTPDDSTDTNGSDNSIPMAYLTLDHQLQPLAPCPNSKESMAVFEQHCKMAQEYMKVQTEIALLLQRKQELVAELDQDEKDQQNTSRLVQEHKKLLDENKSLSTYYQQCKKQLEVIRSQQQKRQGTS
uniprot
proteins
disease_involvement
DISEASE: Frontometaphyseal dysplasia 2 (FMD2) [MIM:617137]: A form of frontometaphyseal dysplasia, a progressive sclerosing skeletal dysplasia affecting the long bones and skull. Characteristic features include supraorbital hyperostosis, cranial hyperostosis, undermodeling of the small bones, flared metaphyses, and digital anomalies. Extra-skeletal manifestations include hearing loss, cardiac malformations, and stenosis, particularly of the upper airway and urinary tract. FMD2 inheritance is autosomal dominant. {ECO:0000269|PubMed:27426733}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cardiospondylocarpofacial syndrome (CSCF) [MIM:157800]: A syndrome characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion and extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations. CSCF transmission pattern is consistent with autosomal dominant inheritance. {ECO:0000269|PubMed:27426734}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.25
uniprot
proteins
function
FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Plays an important role in the cascades of cellular responses evoked by changes in the environment (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR) (PubMed:16893890, PubMed:9079627). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7 (PubMed:11460167, PubMed:8663074). These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs); both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1) (PubMed:11460167, PubMed:12589052, PubMed:8663074). Independently of MAP2Ks and p38 MAPKs, acts as a key activator of NF-kappa-B by promoting activation of the I-kappa-B-kinase (IKK) core complex (PubMed:12589052, PubMed:8663074). Mechanistically, recruited to polyubiquitin chains of RIPK2 and IKBKG/NEMO via TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3, and catalyzes phosphorylation and activation of IKBKB/IKKB component of the IKK complex, leading to NF-kappa-B activation (PubMed:10094049, PubMed:11460167). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B (PubMed:16893890). Promotes TRIM5 capsid-specific restriction activity (PubMed:21512573). Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity). Phosphorylates STING1 in response to cGAMP-activation, promoting association between STEEP1 and STING1 and STING1 translocation to COPII vesicles (PubMed:37832545). {ECO:0000250|UniProtKB:Q62073, ECO:0000269|PubMed:10094049, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9079627}.
uniprot
proteins
mass_dalton
67196
uniprot
proteins
mutagenesis
MUTAGEN 34; /note="K->R: No effect on ubiquitination."; /evidence="ECO:0000269|PubMed:29291351"; MUTAGEN 63; /note="K->W: Loss of kinase activity. Loss of autophosphorylation."; /evidence="ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:22802624"; MUTAGEN 158; /note="K->R: Abolishes ubiquitination."; /evidence="ECO:0000269|PubMed:29291351"; MUTAGEN 209; /note="K->R: Strongly decreases ubiquitination."; /evidence="ECO:0000269|PubMed:29291351"; MUTAGEN 512; /note="P->R,A: Enhances autophosphorylation; Alters MAPK signaling."; /evidence="ECO:0000269|PubMed:27426733
uniprot
proteins
post_translational_modification
PTM: Association with TAB1/MAP3K7IP1 promotes autophosphorylation at Ser-192 and subsequent activation. Association with TAB2/MAP3K7IP2, itself associated with free unanchored Lys-63 polyubiquitin chain, promotes autophosphorylation and subsequent activation of MAP3K7. Dephosphorylation at Ser-192 by PPM1B/PP2CB and at Thr-187 by PP2A and PPP6C leads to inactivation. {ECO:0000269|PubMed:10702308, ECO:0000269|PubMed:10838074, ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:17548520, ECO:0000269|PubMed:19675569, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:37832545}.; PTM: 'Lys-48'-linked polyubiquitination at Lys-72 is induced by TNFalpha, and leads to proteasomal degradation. Undergoes 'Lys-48'-linked polyubiquitination catalyzed by ITCH (By similarity). Requires 'Lys-63'-linked polyubiquitination for autophosphorylation and subsequent activation. 'Lys-63'-linked ubiquitination does not lead to proteasomal degradation. Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains. Deubiquitinated by Y.enterocolitica YopP. Deubiquitinated by USP19; leading to negative regulation of TNF- and IL-1beta-triggered NF-kappa-B activation (PubMed:24356957). {ECO:0000250|UniProtKB:Q62073, ECO:0000269|PubMed:17548520, ECO:0000269|PubMed:22406003, ECO:0000269|PubMed:24356957}.; PTM: (Microbial infection) Cleaved and inactivated by the proteases 3C of coxsackievirus A16 and human enterovirus D68, allowing the virus to disrupt TRAF6-triggered NF-kappa-B induction. {ECO:0000269|PubMed:28424289}.; PTM: (Microbial infection) Acetylation of Thr-184 and Thr-187 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway. {ECO:0000269|PubMed:22520462, ECO:0000269|PubMed:22802624}.
uniprot
proteins
protein_family
MAP kinase kinase kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
STE Ser/Thr protein kinase family
uniprot
proteins
pubmed
10094049
uniprot
proteins
pubmed
10702308
uniprot
proteins
pubmed
10838074
uniprot
proteins
pubmed
11104763
uniprot
proteins
pubmed
11118615
uniprot
proteins
pubmed
11460167
uniprot
proteins
pubmed
12242293
uniprot
proteins
pubmed
12589052
uniprot
proteins
pubmed
12804775
uniprot
proteins
pubmed
12874243
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14670075
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15894542
uniprot
proteins
pubmed
16289117
uniprot
proteins
pubmed
16845370
uniprot
proteins
pubmed
16893890
uniprot
proteins
pubmed
17079228
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17449468
uniprot
proteins
pubmed
17496917
uniprot
proteins
pubmed
17548520
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18286207
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18758450
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19521662
uniprot
proteins
pubmed
19675569
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20060931
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21512573
uniprot
proteins
pubmed
22084099
uniprot
proteins
pubmed
22406003
uniprot
proteins
pubmed
22520462
uniprot
proteins
pubmed
22802624
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23776175
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24356957
uniprot
proteins
pubmed
26334375
uniprot
proteins
pubmed
27426733
uniprot
proteins
pubmed
27426734
uniprot
proteins
pubmed
28397838
uniprot
proteins
pubmed
28424289
uniprot
proteins
pubmed
28827540
uniprot
proteins
pubmed
29291351
uniprot
proteins
pubmed
37832545
uniprot
proteins
pubmed
8638164
uniprot
proteins
pubmed
8663074
uniprot
proteins
pubmed
9079627
uniprot
proteins
pubmed
9480845
uniprot
proteins
sequence_length
606
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12242293}. Cell membrane {ECO:0000269|PubMed:12242293}; Peripheral membrane protein {ECO:0000269|PubMed:12242293}; Cytoplasmic side {ECO:0000269|PubMed:12242293}. Note=Although the majority of MAP3K7/TAK1 is found in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2, it is also localized at the cell membrane.
uniprot
proteins