GENERAL INFORMATIONi
Gene namei MAP3K7
Synonyms MEKK7, TAK1
Gene descriptioni Mitogen-activated protein kinase kinase kinase 7
Protein classi Disease related genes
Enzymes
Human disease related genes
Potential drug targets
Predicted locationi Intracellular
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi
Chromosome 6
Cytoband q15
Chromosome location (bp) 90513573 - 90587086
Number of transcriptsi 8
Ensembl ENSG00000135341 (version 109)
Entrez gene 6885
HGNC HGNC:6859
UniProt O43318 (UniProt - Evidence at protein level)
neXtProt NX_O43318
GeneCards MAP3K7
Antibodypedia MAP3K7 antibodies


PROTEIN FUNCTION
Protein function (UniProt)i Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway 1, 2, 3, 4, 5, 6, 7, 8. Plays an important role in the cascades of cellular responses evoked by changes in the environment 9, 10, 11, 12, 13, 14, 15, 16. 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) 17, 18. 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 19, 20. 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) 21, 22, 23. 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 24, 25. 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 26, 27. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B 28. Promotes TRIM5 capsid-specific restriction activity 29. 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 30. show less
Molecular function (UniProt)i Kinase, Serine/threonine-protein kinase, Transferase
Biological process (UniProt)i Apoptosis, Host-virus interaction, Stress response, Transcription, Transcription regulation
Ligand (UniProt)i ATP-binding, Magnesium, Metal-binding, Nucleotide-binding
Gene summary (Entrez)i The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008] show less
PROTEIN INFORMATIONi
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)		 Transmembrane regions
(predicted)
MAP3K7-202
ENSP00000358331
ENST00000369325
O43318
[Direct mapping] Mitogen-activated protein kinase kinase kinase 7
Show all
Enzymes
   ENZYME proteins
   Transferases
   Kinases
   STE Ser/Thr protein kinases
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Disease related genes
Potential drug targets
Human disease related genes
   Congenital malformations
   Congenital malformations of the musculoskeletal system
   Other congenital malformations
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000165 [MAPK cascade]
GO:0000166 [nucleotide binding]
GO:0000287 [magnesium ion binding]
GO:0002223 [stimulatory C-type lectin receptor signaling pathway]
GO:0002726 [positive regulation of T cell cytokine production]
GO:0002753 [cytoplasmic pattern recognition receptor signaling pathway]
GO:0002755 [MyD88-dependent toll-like receptor signaling pathway]
GO:0004672 [protein kinase activity]
GO:0004674 [protein serine/threonine kinase activity]
GO:0004707 [MAP kinase activity]
GO:0004709 [MAP kinase kinase kinase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005634 [nucleus]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0005886 [plasma membrane]
GO:0006468 [protein phosphorylation]
GO:0006915 [apoptotic process]
GO:0007165 [signal transduction]
GO:0007179 [transforming growth factor beta receptor signaling pathway]
GO:0007249 [I-kappaB kinase/NF-kappaB signaling]
GO:0007250 [activation of NF-kappaB-inducing kinase activity]
GO:0007252 [I-kappaB phosphorylation]
GO:0007254 [JNK cascade]
GO:0008349 [MAP kinase kinase kinase kinase activity]
GO:0008385 [IkappaB kinase complex]
GO:0010008 [endosome membrane]
GO:0016020 [membrane]
GO:0016239 [positive regulation of macroautophagy]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016740 [transferase activity]
GO:0030971 [receptor tyrosine kinase binding]
GO:0032743 [positive regulation of interleukin-2 production]
GO:0038066 [p38MAPK cascade]
GO:0038095 [Fc-epsilon receptor signaling pathway]
GO:0042802 [identical protein binding]
GO:0043123 [positive regulation of I-kappaB kinase/NF-kappaB signaling]
GO:0043276 [anoikis]
GO:0043507 [positive regulation of JUN kinase activity]
GO:0043966 [histone H3 acetylation]
GO:0046872 [metal ion binding]
GO:0050852 [T cell receptor signaling pathway]
GO:0050896 [response to stimulus]
GO:0051092 [positive regulation of NF-kappaB transcription factor activity]
GO:0051403 [stress-activated MAPK cascade]
GO:0070423 [nucleotide-binding oligomerization domain containing signaling pathway]
GO:0070498 [interleukin-1-mediated signaling pathway]
GO:0097110 [scaffold protein binding]
GO:0106310 [protein serine kinase activity]
GO:0140672 [ATAC complex]
Show all
 518 aa
56.7 kDa 		No 0
MAP3K7-203
ENSP00000358333
ENST00000369327
O43318
[Direct mapping] Mitogen-activated protein kinase kinase kinase 7
Show all
Enzymes
   ENZYME proteins
   Transferases
   Kinases
   STE Ser/Thr protein kinases
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Disease related genes
Potential drug targets
Human disease related genes
   Congenital malformations
   Congenital malformations of the musculoskeletal system
   Other congenital malformations
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000165 [MAPK cascade]
GO:0000166 [nucleotide binding]
GO:0000287 [magnesium ion binding]
GO:0002223 [stimulatory C-type lectin receptor signaling pathway]
GO:0002726 [positive regulation of T cell cytokine production]
GO:0002753 [cytoplasmic pattern recognition receptor signaling pathway]
GO:0002755 [MyD88-dependent toll-like receptor signaling pathway]
GO:0004672 [protein kinase activity]
GO:0004674 [protein serine/threonine kinase activity]
GO:0004707 [MAP kinase activity]
GO:0004709 [MAP kinase kinase kinase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005634 [nucleus]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0005886 [plasma membrane]
GO:0006468 [protein phosphorylation]
GO:0006915 [apoptotic process]
GO:0007165 [signal transduction]
GO:0007179 [transforming growth factor beta receptor signaling pathway]
GO:0007249 [I-kappaB kinase/NF-kappaB signaling]
GO:0007250 [activation of NF-kappaB-inducing kinase activity]
GO:0007252 [I-kappaB phosphorylation]
GO:0007254 [JNK cascade]
GO:0008349 [MAP kinase kinase kinase kinase activity]
GO:0008385 [IkappaB kinase complex]
GO:0010008 [endosome membrane]
GO:0016020 [membrane]
GO:0016239 [positive regulation of macroautophagy]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016740 [transferase activity]
GO:0030971 [receptor tyrosine kinase binding]
GO:0032743 [positive regulation of interleukin-2 production]
GO:0038066 [p38MAPK cascade]
GO:0038095 [Fc-epsilon receptor signaling pathway]
GO:0042802 [identical protein binding]
GO:0043123 [positive regulation of I-kappaB kinase/NF-kappaB signaling]
GO:0043276 [anoikis]
GO:0043507 [positive regulation of JUN kinase activity]
GO:0043966 [histone H3 acetylation]
GO:0046872 [metal ion binding]
GO:0050852 [T cell receptor signaling pathway]
GO:0050896 [response to stimulus]
GO:0051092 [positive regulation of NF-kappaB transcription factor activity]
GO:0051403 [stress-activated MAPK cascade]
GO:0070423 [nucleotide-binding oligomerization domain containing signaling pathway]
GO:0070498 [interleukin-1-mediated signaling pathway]
GO:0097110 [scaffold protein binding]
GO:0106310 [protein serine kinase activity]
GO:0140672 [ATAC complex]
Show all
 491 aa
53.7 kDa 		No 0
MAP3K7-204
ENSP00000358335
ENST00000369329
O43318
[Direct mapping] Mitogen-activated protein kinase kinase kinase 7
Show all
Enzymes
   ENZYME proteins
   Transferases
   Kinases
   STE Ser/Thr protein kinases
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Disease related genes
Potential drug targets
Human disease related genes
   Congenital malformations
   Congenital malformations of the musculoskeletal system
   Other congenital malformations
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000165 [MAPK cascade]
GO:0000166 [nucleotide binding]
GO:0000287 [magnesium ion binding]
GO:0002223 [stimulatory C-type lectin receptor signaling pathway]
GO:0002726 [positive regulation of T cell cytokine production]
GO:0002753 [cytoplasmic pattern recognition receptor signaling pathway]
GO:0002755 [MyD88-dependent toll-like receptor signaling pathway]
GO:0004672 [protein kinase activity]
GO:0004674 [protein serine/threonine kinase activity]
GO:0004707 [MAP kinase activity]
GO:0004709 [MAP kinase kinase kinase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005634 [nucleus]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0005886 [plasma membrane]
GO:0006468 [protein phosphorylation]
GO:0006915 [apoptotic process]
GO:0007165 [signal transduction]
GO:0007179 [transforming growth factor beta receptor signaling pathway]
GO:0007249 [I-kappaB kinase/NF-kappaB signaling]
GO:0007250 [activation of NF-kappaB-inducing kinase activity]
GO:0007252 [I-kappaB phosphorylation]
GO:0007254 [JNK cascade]
GO:0008349 [MAP kinase kinase kinase kinase activity]
GO:0008385 [IkappaB kinase complex]
GO:0010008 [endosome membrane]
GO:0016020 [membrane]
GO:0016239 [positive regulation of macroautophagy]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016740 [transferase activity]
GO:0030971 [receptor tyrosine kinase binding]
GO:0032743 [positive regulation of interleukin-2 production]
GO:0038066 [p38MAPK cascade]
GO:0038095 [Fc-epsilon receptor signaling pathway]
GO:0042802 [identical protein binding]
GO:0043123 [positive regulation of I-kappaB kinase/NF-kappaB signaling]
GO:0043276 [anoikis]
GO:0043410 [positive regulation of MAPK cascade]
GO:0043507 [positive regulation of JUN kinase activity]
GO:0043966 [histone H3 acetylation]
GO:0046872 [metal ion binding]
GO:0050852 [T cell receptor signaling pathway]
GO:0050896 [response to stimulus]
GO:0051092 [positive regulation of NF-kappaB transcription factor activity]
GO:0051403 [stress-activated MAPK cascade]
GO:0070423 [nucleotide-binding oligomerization domain containing signaling pathway]
GO:0070498 [interleukin-1-mediated signaling pathway]
GO:0097110 [scaffold protein binding]
GO:0106310 [protein serine kinase activity]
GO:0140672 [ATAC complex]
Show all
 606 aa
67.2 kDa 		No 0
MAP3K7-205
ENSP00000358338
ENST00000369332
O43318
[Direct mapping] Mitogen-activated protein kinase kinase kinase 7
Show all
Enzymes
   ENZYME proteins
   Transferases
   Kinases
   STE Ser/Thr protein kinases
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Disease related genes
Potential drug targets
Human disease related genes
   Congenital malformations
   Congenital malformations of the musculoskeletal system
   Other congenital malformations
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000165 [MAPK cascade]
GO:0000166 [nucleotide binding]
GO:0000287 [magnesium ion binding]
GO:0002223 [stimulatory C-type lectin receptor signaling pathway]
GO:0002726 [positive regulation of T cell cytokine production]
GO:0002753 [cytoplasmic pattern recognition receptor signaling pathway]
GO:0002755 [MyD88-dependent toll-like receptor signaling pathway]
GO:0004672 [protein kinase activity]
GO:0004674 [protein serine/threonine kinase activity]
GO:0004707 [MAP kinase activity]
GO:0004709 [MAP kinase kinase kinase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005634 [nucleus]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0005886 [plasma membrane]
GO:0006468 [protein phosphorylation]
GO:0006915 [apoptotic process]
GO:0007165 [signal transduction]
GO:0007179 [transforming growth factor beta receptor signaling pathway]
GO:0007249 [I-kappaB kinase/NF-kappaB signaling]
GO:0007250 [activation of NF-kappaB-inducing kinase activity]
GO:0007252 [I-kappaB phosphorylation]
GO:0007254 [JNK cascade]
GO:0008349 [MAP kinase kinase kinase kinase activity]
GO:0008385 [IkappaB kinase complex]
GO:0010008 [endosome membrane]
GO:0016020 [membrane]
GO:0016239 [positive regulation of macroautophagy]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016740 [transferase activity]
GO:0030971 [receptor tyrosine kinase binding]
GO:0032743 [positive regulation of interleukin-2 production]
GO:0038066 [p38MAPK cascade]
GO:0038095 [Fc-epsilon receptor signaling pathway]
GO:0042802 [identical protein binding]
GO:0043123 [positive regulation of I-kappaB kinase/NF-kappaB signaling]
GO:0043276 [anoikis]
GO:0043507 [positive regulation of JUN kinase activity]
GO:0043966 [histone H3 acetylation]
GO:0046872 [metal ion binding]
GO:0050852 [T cell receptor signaling pathway]
GO:0050896 [response to stimulus]
GO:0051092 [positive regulation of NF-kappaB transcription factor activity]
GO:0051403 [stress-activated MAPK cascade]
GO:0070423 [nucleotide-binding oligomerization domain containing signaling pathway]
GO:0070498 [interleukin-1-mediated signaling pathway]
GO:0097110 [scaffold protein binding]
GO:0106310 [protein serine kinase activity]
GO:0140672 [ATAC complex]
Show all
 579 aa
64.2 kDa 		No 0
MAP3K7-218
ENSP00000515082
ENST00000700591
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Human disease related genes
   Congenital malformations
   Congenital malformations of the musculoskeletal system
   Other congenital malformations
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000287 [magnesium ion binding]
GO:0004672 [protein kinase activity]
GO:0004709 [MAP kinase kinase kinase activity]
GO:0005524 [ATP binding]
GO:0006468 [protein phosphorylation]
GO:0007165 [signal transduction]
Show all
 557 aa
61.7 kDa 		No 0
MAP3K7-219
ENSP00000515083
ENST00000700592
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Human disease related genes
   Congenital malformations
   Congenital malformations of the musculoskeletal system
   Other congenital malformations
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000287 [magnesium ion binding]
GO:0004672 [protein kinase activity]
GO:0004709 [MAP kinase kinase kinase activity]
GO:0005524 [ATP binding]
GO:0006468 [protein phosphorylation]
GO:0007165 [signal transduction]
Show all
 604 aa
66.8 kDa 		No 0
MAP3K7-220
ENSP00000515084
ENST00000700593
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Human disease related genes
   Congenital malformations
   Congenital malformations of the musculoskeletal system
   Other congenital malformations
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000287 [magnesium ion binding]
GO:0004672 [protein kinase activity]
GO:0004709 [MAP kinase kinase kinase activity]
GO:0005524 [ATP binding]
GO:0006468 [protein phosphorylation]
GO:0007165 [signal transduction]
Show all
 476 aa
53 kDa 		No 0
MAP3K7-224
ENSP00000515169
ENST00000703101
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Human disease related genes
   Congenital malformations
   Congenital malformations of the musculoskeletal system
   Other congenital malformations
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000287 [magnesium ion binding]
GO:0004709 [MAP kinase kinase kinase activity]
GO:0007165 [signal transduction]
Show all
 194 aa
21.8 kDa 		No 0

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