| Tag | Content |
|---|---|
| Uniprot ID | Q62073 |
| Entrez ID | 26409 |
| Genbank protein ID | BAA11184.1 |
| Genbank nucleotide ID | NM_172688.3 |
| Ensembl protein ID | ENSMUSP00000079734 |
| Ensembl nucleotide ID | ENSMUSG00000028284 |
| Gene name | Mitogen-activated protein kinase kinase kinase 7 |
| Gene symbol | Map3k7 |
| Organism | Mus musculus |
| NCBI taxa ID | 10090 |
| Cleft type | CPO |
| Developmental stage | |
| Data sources | Manually collected |
| Reference | 25523394; 23460641; 23546880; |
| Functional description | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. 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:10748100, PubMed:16157589, PubMed:21183079, PubMed:29291351). Ceramides are also able to activate MAP3K7/TAK1. 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. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK (PubMed:16157589, PubMed:8533096, PubMed:29291351). MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis (PubMed:10748100). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity (By similarity). 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 (PubMed:28842570). |
| Sequence | MSTASAASSS SSSSASEMIE APSQVLNFEE IDYKEIEVEE VVGRGAFGVV CKAKWRAKDV 60 AIKQIESESE RKAFIVELRQ LSRVNHPNIV KLYGACLNPV CLVMEYAEGG SLYNVLHGAE 120 PLPYYTAAHA MSWCLQCSQG VAYLHSMQPK ALIHRDLKPP NLLLVAGGTV LKICDFGTAC 180 DIQTHMTNNK GSAAWMAPEV FEGSNYSEKC DVFSWGIILW EVITRRKPFD EIGGPAFRIM 240 WAVHNGTRPP LIKNLPKPIE SLMTRCWSKD PSQRPSMEEI VKIMTHLMRY FPGADEPLQY 300 PCQYSDEGQS NSATSTGSFM DIASTNTSNK SDTNMEQVPA TNDTIKRLES KLLKNQAKQQ 360 SESGRLSLGA SRGSSVESLP PTSEGKRMSA DMSEIEARIV ATAGNGQPRR RSIQDLTVTG 420 TEPGQVSSRS SSPSVRMITT SGPTSEKPAR SHPWTPDDST DTNGSDNSIP MAYLTLDHQL 480 QPLAPCPNSK ESMAVFEQHC KMAQEYMKVQ TEIALLLQRK QELVAELDQD EKDQQNTSRL 540 VQEHKKLLDE NKSLSTYYQQ CKKQLEVIRS QQQKRQGTS 579 |
Abbreviation :
CLO : cleft lip only. CPO : cleft palate only.
CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0000287 | magnesium ion binding | IEA |
| GO:0004674 | protein serine/threonine kinase activity | IDA |
| GO:0004674 | protein serine/threonine kinase activity | TAS |
| GO:0004708 | MAP kinase kinase activity | IDA |
| GO:0004709 | MAP kinase kinase kinase activity | ISS |
| GO:0004709 | MAP kinase kinase kinase activity | IBA |
| GO:0005515 | protein binding | IPI |
| GO:0005524 | ATP binding | IEA |
| GO:0030971 | receptor tyrosine kinase binding | IPI |
| GO:0097110 | scaffold protein binding | ISO |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0000165 | MAPK cascade | IDA |
| GO:0000186 | activation of MAPKK activity | IEA |
| GO:0000187 | activation of MAPK activity | IEA |
| GO:0001525 | angiogenesis | IMP |
| GO:0001841 | neural tube formation | IMP |
| GO:0006468 | protein phosphorylation | IDA |
| GO:0007179 | transforming growth factor beta receptor signaling pathway | IMP |
| GO:0007252 | I-kappaB phosphorylation | ISS |
| GO:0007252 | I-kappaB phosphorylation | IGI |
| GO:0007254 | JNK cascade | IBA |
| GO:0007254 | JNK cascade | IDA |
| GO:0016239 | positive regulation of macroautophagy | IMP |
| GO:0018107 | peptidyl-threonine phosphorylation | IDA |
| GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB signaling | IGI |
| GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB signaling | IBA |
| GO:0043276 | anoikis | IMP |
| GO:0043507 | positive regulation of JUN kinase activity | ISS |
| GO:0046330 | positive regulation of JNK cascade | IGI |
| GO:0060546 | negative regulation of necroptotic process | IMP |
| GO:1902443 | negative regulation of ripoptosome assembly involved in necroptotic process | IGI |
| GO:2000377 | regulation of reactive oxygen species metabolic process | IMP |
| GO:2000378 | negative regulation of reactive oxygen species metabolic process | IMP |
| GO:2001234 | negative regulation of apoptotic signaling pathway | IGI |
| GO:2001234 | negative regulation of apoptotic signaling pathway | IMP |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0005829 | cytosol | TAS |
| GO:0005886 | plasma membrane | IEA |
| GO:0014069 | postsynaptic density | IDA |
| Reactome ID | Reactome Term | Evidence |
|---|---|---|
| R-MMU-1280215 | Cytokine Signaling in Immune system | IEA |
| R-MMU-1280218 | Adaptive Immune System | IEA |
| R-MMU-162582 | Signal Transduction | IEA |
| R-MMU-166016 | Toll Like Receptor 4 (TLR4) Cascade | IEA |
| R-MMU-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | IEA |
| R-MMU-166166 | MyD88-independent TLR4 cascade | IEA |
| R-MMU-168138 | Toll Like Receptor 9 (TLR9) Cascade | IEA |
| R-MMU-168142 | Toll Like Receptor 10 (TLR10) Cascade | IEA |
| R-MMU-168164 | Toll Like Receptor 3 (TLR3) Cascade | IEA |
| R-MMU-168176 | Toll Like Receptor 5 (TLR5) Cascade | IEA |
| R-MMU-168179 | Toll Like Receptor TLR1:TLR2 Cascade | IEA |
| R-MMU-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | IEA |
| R-MMU-168188 | Toll Like Receptor TLR6:TLR2 Cascade | IEA |
| R-MMU-168249 | Innate Immune System | IEA |
| R-MMU-168256 | Immune System | IEA |
| R-MMU-168638 | NOD1/2 Signaling Pathway | IEA |
| R-MMU-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways | IEA |
| R-MMU-168898 | Toll-like Receptor Cascades | IEA |
| R-MMU-181438 | Toll Like Receptor 2 (TLR2) Cascade | IEA |
| R-MMU-195721 | Signaling by WNT | IEA |
| R-MMU-202403 | TCR signaling | IEA |
| R-MMU-202424 | Downstream TCR signaling | IEA |
| R-MMU-2454202 | Fc epsilon receptor (FCERI) signaling | IEA |
| R-MMU-2871837 | FCERI mediated NF-kB activation | IEA |
| R-MMU-3858494 | Beta-catenin independent WNT signaling | IEA |
| R-MMU-392499 | Metabolism of proteins | IEA |
| R-MMU-4086398 | Ca2+ pathway | IEA |
| R-MMU-445989 | TAK1 activates NFkB by phosphorylation and activation of IKKs complex | IEA |
| R-MMU-446652 | Interleukin-1 family signaling | IEA |
| R-MMU-448424 | Interleukin-17 signaling | IEA |
| R-MMU-449147 | Signaling by Interleukins | IEA |
| R-MMU-450294 | MAP kinase activation | IEA |
| R-MMU-450302 | activated TAK1 mediates p38 MAPK activation | IEA |
| R-MMU-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 | IEA |
| R-MMU-5357956 | TNFR1-induced NFkappaB signaling pathway | IEA |
| R-MMU-5607764 | CLEC7A (Dectin-1) signaling | IEA |
| R-MMU-5621481 | C-type lectin receptors (CLRs) | IEA |
| R-MMU-5688426 | Deubiquitination | IEA |
| R-MMU-5689880 | Ub-specific processing proteases | IEA |
| R-MMU-597592 | Post-translational protein modification | IEA |
| R-MMU-73887 | Death Receptor Signalling | IEA |
| R-MMU-75893 | TNF signaling | IEA |
| R-MMU-9020702 | Interleukin-1 signaling | IEA |
| R-MMU-937042 | IRAK2 mediated activation of TAK1 complex | IEA |
| R-MMU-937061 | TRIF(TICAM1)-mediated TLR4 signaling | IEA |
| R-MMU-937072 | TRAF6-mediated induction of TAK1 complex within TLR4 complex | IEA |
| R-MMU-9645460 | Alpha-protein kinase 1 signaling pathway | IEA |
| R-MMU-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | IEA |
| R-MMU-975155 | MyD88 dependent cascade initiated on endosome | IEA |
| R-MMU-975163 | IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation | IEA |
| R-MMU-975871 | MyD88 cascade initiated on plasma membrane | IEA |
| Keyword ID | Keyword Term |
|---|---|
| KW-0053 | Apoptosis |
| KW-0067 | ATP-binding |
| KW-1003 | Cell membrane |
| KW-0963 | Cytoplasm |
| KW-1017 | Isopeptide bond |
| KW-0418 | Kinase |
| KW-0460 | Magnesium |
| KW-0472 | Membrane |
| KW-0479 | Metal-binding |
| KW-0547 | Nucleotide-binding |
| KW-0597 | Phosphoprotein |
| KW-1185 | Reference proteome |
| KW-0723 | Serine/threonine-protein kinase |
| KW-0346 | Stress response |
| KW-0804 | Transcription |
| KW-0805 | Transcription regulation |
| KW-0808 | Transferase |
| KW-0832 | Ubl conjugation |
| Pfam ID | Pfam Term |
|---|---|
| PF07714 | Pkinase_Tyr |