Protein: O43318

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
O43318 (Uniprot) M3K7_HUMAN MAP3K7 Mitogen-activated protein kinase kinase kinase 7 human No
Uniprot: 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). 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. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. 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. more..
MoonDB Dissimilar Functions
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0007165 signal transduction 308 GO:0034641 cellular nitrogen compound metabolic process 595 4.22e-144 6.90e-18
Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
106 GO:0006464 cellular protein modification process
106 GO:0031325 positive regulation of cellular metabolic process
106 GO:0010604 positive regulation of macromolecule metabolic process
106 GO:0051173 positive regulation of nitrogen compound metabolic process
106 GO:0009966 regulation of signal transduction
106 GO:0006355 regulation of transcription, DNA-templated
308 GO:0007166 cell surface receptor signaling pathway
308 GO:0071310 cellular response to organic substance
308 GO:0035556 intracellular signal transduction
308 GO:0043085 positive regulation of catalytic activity
308 GO:0031328 positive regulation of cellular biosynthetic process
308 GO:0010604 positive regulation of macromolecule metabolic process
308 GO:0045935 positive regulation of nucleobase-containing compound metabolic process
308 GO:0009967 positive regulation of signal transduction
308 GO:0006468 protein phosphorylation
308 GO:0031399 regulation of protein modification process
308 GO:0006355 regulation of transcription, DNA-templated
544 GO:0016070 RNA metabolic process
544 GO:0006464 cellular protein modification process
544 GO:0006796 phosphate-containing compound metabolic process
544 GO:0031325 positive regulation of cellular metabolic process
544 GO:0010604 positive regulation of macromolecule metabolic process
544 GO:0051173 positive regulation of nitrogen compound metabolic process
544 GO:0032268 regulation of cellular protein metabolic process
544 GO:0010468 regulation of gene expression
544 GO:0023051 regulation of signaling
544 GO:0007165 signal transduction
549 GO:0008219 cell death
549 GO:0070887 cellular response to chemical stimulus
549 GO:0033554 cellular response to stress
549 GO:0035556 intracellular signal transduction
549 GO:0031325 positive regulation of cellular metabolic process
549 GO:0010604 positive regulation of macromolecule metabolic process
549 GO:0051173 positive regulation of nitrogen compound metabolic process
549 GO:0048584 positive regulation of response to stimulus
549 GO:0006468 protein phosphorylation
549 GO:0051252 regulation of RNA metabolic process
549 GO:2000112 regulation of cellular macromolecule biosynthetic process
549 GO:0032268 regulation of cellular protein metabolic process
549 GO:0010468 regulation of gene expression
549 GO:0009966 regulation of signal transduction
549 GO:0006351 transcription, DNA-templated
595 GO:0044271 cellular nitrogen compound biosynthetic process
595 GO:0006464 cellular protein modification process
595 GO:0035556 intracellular signal transduction
595 GO:0006139 nucleobase-containing compound metabolic process
595 GO:0031325 positive regulation of cellular metabolic process
595 GO:0010604 positive regulation of macromolecule metabolic process
595 GO:0051173 positive regulation of nitrogen compound metabolic process
595 GO:0031326 regulation of cellular biosynthetic process
595 GO:0010468 regulation of gene expression
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
106 GO:0005829 cytosol
106 GO:0005654 nucleoplasm
308 GO:0005829 cytosol
308 GO:0070013 intracellular organelle lumen
308 GO:0044428 nuclear part
308 GO:0005886 plasma membrane
544 GO:0005829 cytosol
544 GO:0005634 nucleus
549 GO:0005829 cytosol
549 GO:0005634 nucleus
595 GO:0005654 nucleoplasm
671 GO:0005829 cytosol
671 GO:0070013 intracellular organelle lumen
671 GO:0005634 nucleus
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0000186 activation of MAPKK activity IDA
GO:0000187 activation of MAPK activity TAS
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0002726 positive regulation of T cell cytokine production IMP
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS
GO:0006351 transcription, DNA-templated IEA
GO:0007179 transforming growth factor beta receptor signaling pathway TAS
GO:0007223 Wnt signaling pathway, calcium modulating pathway TAS
GO:0007249 I-kappaB kinase/NF-kappaB signaling TAS
GO:0007250 activation of NF-kappaB-inducing kinase activity IMP
GO:0007252 I-kappaB phosphorylation IDA
GO:0007254 JNK cascade TAS
GO:0016239 positive regulation of macroautophagy ISS
GO:0016579 protein deubiquitination TAS
GO:0032743 positive regulation of interleukin-2 production IMP
GO:0038095 Fc-epsilon receptor signaling pathway TAS
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling IMP
GO:0043276 anoikis ISS
GO:0043507 positive regulation of JUN kinase activity IDA
GO:0043966 histone H3 acetylation IDA
GO:0050852 T cell receptor signaling pathway TAS
GO:0050870 positive regulation of T cell activation IC
GO:0051092 positive regulation of NF-kappaB transcription factor activity TAS
GO:0051403 stress-activated MAPK cascade IDA
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway TAS
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0005634 nucleus IDA
GO:0005671 Ada2/Gcn5/Ada3 transcription activator complex IDA
GO:0005829 cytosol TAS
GO:0005886 plasma membrane IEA
GO:0008385 IkappaB kinase complex IPI
GO:0010008 endosome membrane TAS
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0005634 nucleus GO:0005886 plasma membrane 5.35e-300 7.52e-165
GO:0005634 nucleus GO:0010008 endosome membrane 1.38e-08 8.40e-30
PMID Article Title
8638164 TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction.
8663074 A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3.
9079627 TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase.
9480845 TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism.
10094049 The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway.
10702308 TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop.
10838074 Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1.
11104763 Regulation of the TAK1 signaling pathway by protein phosphatase 2C.
11118615 Alternative splicing and gene structure of the transforming growth factor beta-activated kinase 1.
11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK.
12242293 Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol.
12589052 Transforming growth factor-beta1 (TGF-beta)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-beta-activated kinase 1 and mitogen-activated protein kinase kinase 3.
12804775 Pellino2 activates the mitogen activated protein kinase pathway.
12874243 Pellino3, a novel member of the Pellino protein family, promotes activation of c-Jun and Elk-1 and may act as a scaffolding protein.
14574404 The DNA sequence and analysis of human chromosome 6.
14670075 TAB3, a new binding partner of the protein kinase TAK1.
14702039 Complete sequencing and characterization of 21,243 full-length human cDNAs.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15894542 Disabled-2 (Dab2) mediates transforming growth factor beta (TGFbeta)-stimulated fibronectin synthesis through TGFbeta-activated kinase 1 and activation of the JNK pathway.
16289117 Structural basis for the interaction of TAK1 kinase with its activating protein TAB1.
16845370 The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway.
16893890 Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated NF-kappaB activation: TAO2 regulates TAK1 pathways.
17079228 Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway.
17081983 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
17449468 RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation.
17496917 Ubiquitin-mediated activation of TAK1 and IKK.
17548520 Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses.
18088087 Phosphoproteome of resting human platelets.
18286207 Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein.
18669648 A quantitative atlas of mitotic phosphorylation.
18691976 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18758450 The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner.
19369195 Large-scale proteomics analysis of the human kinome.
19413330 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19521662 WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway.
19675569 Direct activation of protein kinases by unanchored polyubiquitin chains.
19690332 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
20060931 The TAK1-TRAF6 signalling pathway.
20068231 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
21269460 Initial characterization of the human central proteome.
21406692 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21512573 TRIM5 is an innate immune sensor for the retrovirus capsid lattice.
22406003 Lys48-linked TAK1 polyubiquitination at lysine-72 downregulates TNFalpha-induced NF-kappaB activation via mediating TAK1 degradation.
23186163 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
26334375 IFIT5 positively regulates NF-kappaB signaling through synergizing the recruitment of IkappaB kinase (IKK) to TGF-beta-activated kinase 1 (TAK1).
27426733 Mutations in MAP3K7 that alter the activity of the TAK1 signaling complex cause frontometaphyseal dysplasia.
27426734 Heterozygous mutations in MAP3K7, encoding TGF-beta-activated kinase 1, cause cardiospondylocarpofacial syndrome.
28827540 The Us2 Gene Product of herpes dimplex virus 2 modulates NF-kappaB activation by targeting TAK1.
OMIM ID Disease Name
157800 Cardiospondylocarpofacial syndrome
617137 Frontometaphyseal dysplasia 2
Domain Name Domain ID Source
Prot_kinase_dom IPR000719 InterPro
Ser-Thr/Tyr_kinase_cat_dom IPR001245 InterPro
Ser/Thr_kinase_AS IPR008271 InterPro
Kinase-like_dom_sf IPR011009 InterPro
MAPKKK7 IPR017421 InterPro
Protein_kinase_ATP_BS IPR017441 InterPro
JC5955 JC5955 PIR
JC5956 JC5956 PIR
Pkinase_Tyr PF07714 Pfam
MAPKKK7 PIRSF038168 PIRSF
TYRKINASE PR00109 PRINTS
PROTEIN_KINASE_ATP PS00107 PROSITE
PROTEIN_KINASE_ST PS00108 PROSITE
PROTEIN_KINASE_DOM PS50011 PROSITE
PTHR26392:SF74 PTHR26392:SF74 PANTHER
S_TKc SM00220 SMART
SSF56112 SSF56112 SUPFAM