dbPAF Protein Information

Tag Content
dbPAF ID dbPAF-0001516
Uniprot Accession O43318; M3K7_HUMAN; B2RE27; E1P523; O43317; O43319; Q5TDN2; Q5TDN3; Q5TDT7; Q9NTR3; Q9NZ70;
Genbank Protein ID NP_003179.1; NP_663304.1; NP_663305.1; NP_663306.1;
Genbank Nucleotide ID NM_003188.3; NM_145331.2; NM_145332.2; NM_145333.2;
Protein Name Mitogen-activated protein kinase kinase kinase 7
Protein Synonyms/Alias Transforming growth factor-beta-activated kinase 1;TGF-beta-activated kinase 1;
Gene Name MAP3K7
Gene Synonyms/Alias TAK1;
Organism Homo sapiens(Human)
NCBI Taxa ID 9606
Functional Description
(View all)		 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.
Phosphorylation Sites
 dbPAF PTMs: 32 (View all)
PositionPeptidesSourceReferences ( PMIDs )
69IKQIESESERKAFIVdbPTM 3.0;HPRD 9;curated20068231; 16381945; 23193290; 18988627; 22817900
178LKICDFGTACDIQTHdbPTM 3.0;PhosphoSitePlus;curated18617512; 20538596; 16381945; 23193290; 22135298; 22817900
184GTACDIQTHMTNNKGdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;curated10838074; 16381945; 23193290; 17379600; 18617512; 20538596;
187CDIQTHMTNNKGSAAdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;curated10838074; 16845370; 17079228; 16381945; 23193290; 15590691;
192HMTNNKGSAAWMAPEdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoPep 2.0;PhosphoSitePlus;curated10702308; 10838074; 16381945; 23193290; 15590691; 20538596;
331STNTSNKSDTNMEQVcurated25627689; 22199227; 22817900; 25849741
333NTSNKSDTNMEQVPAdbPTM 3.0;PhosphoSitePlus;curated21406692; 16381945; 23193290; 22135298; 25627689; 22817900;
363QAKQQSESGRLSLGAcurated25627689
367QSESGRLSLGASRGSPhosphoSitePlus;curated22135298; 25627689; 23917254; 24961811
374SLGASRGSSVESLPPcurated25627689; 23090842
375LGASRGSSVESLPPTcurated25627689; 23917254
378SRGSSVESLPPTSEGcurated23090842
389TSEGKRMSADMSEIEdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;SysPTM 2.0;UniProt;curated18669648; 19369195; 19690332; 16381945; 23193290; 20363803;
393KRMSADMSEIEARIAPhosphoSitePlus;curated22135298; 20071362
403EARIAATTAYSKPKRdbPTM 3.0;HPRD 9;curated20068231; 16381945; 23193290; 18988627
405RIAATTAYSKPKRGHPhosphoSitePlus22135298
406IAATTAYSKPKRGHRdbPTM 3.0;HPRD 9;PhosphoSitePlus;curated20068231; 16381945; 23193290; 18988627; 22135298
415PKRGHRKTASFGNILPhosphoSitePlus;curated22135298; 23090842; 25852190; 19690332; 22817900; 25849741
417RGHRKTASFGNILDVPhosphoSitePlus;curated22135298; 23090842; 19690332; 22817900; 25849741
439NGQPRRRSIQDLTVTdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;SysPTM 2.0;UniProt;curated17081983; 18088087; 18669648; 18691976; 19369195; 19413330;
Sequence
(Fasta)		MSTASAASSS SSSSAGEMIE 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 DMSEIEARIA ATTAYSKPKR GHRKTASFGN 420
ILDVPEIVIS GNGQPRRRSI QDLTVTGTEP GQVSSRSSSP SVRMITTSGP TSEKPTRSHP 480
WTPDDSTDTN GSDNSIPMAY LTLDHQLQPL APCPNSKESM AVFEQHCKMA QEYMKVQTEI 540
ALLLQRKQEL VAELDQDEKD QQNTSRLVQE HKKLLDENKS LSTYYQQCKK QLEVIRSQQQ 600
KRQGTS 607
Keyword

KW-0002--3D-structure
KW-0025--Alternative splicing
KW-0053--Apoptosis
KW-0067--ATP-binding
KW-1003--Cell membrane
KW-0181--Complete proteome
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
Interpro

IPR011009--Kinase-like_dom
IPR017421--MAPKKK7
IPR000719--Prot_kinase_dom
IPR017441--Protein_kinase_ATP_BS
IPR001245--Ser-Thr/Tyr_kinase_cat_dom
IPR008271--Ser/Thr_kinase_AS
PROSITE

PS00107--PROTEIN_KINASE_ATP
PS50011--PROTEIN_KINASE_DOM
PS00108--PROTEIN_KINASE_ST
Pfam

PF07714--Pkinase_Tyr
Gene Ontology

GO:0005671--C:Ada2/Gcn5/Ada3 transcription activator complex
GO:0005737--C:cytoplasm
GO:0005829--C:cytosol
GO:0010008--C:endosome membrane
GO:0097481--C:neuronal postsynaptic density
GO:0005634--C:nucleus
GO:0005886--C:plasma membrane
GO:0005524--F:ATP binding
GO:0000287--F:magnesium ion binding
GO:0004708--F:MAP kinase kinase activity
GO:0004709--F:MAP kinase kinase kinase activity
GO:0004672--F:protein kinase activity
GO:0004674--F:protein serine/threonine kinase activity
GO:0097110--F:scaffold protein binding
GO:0000187--P:activation of MAPK activity
GO:0000186--P:activation of MAPKK activity
GO:0007250--P:activation of NF-kappaB-inducing kinase activity
GO:0001525--P:angiogenesis
GO:0006915--P:apoptotic process
GO:0007166--P:cell surface receptor signaling pathway
GO:0038095--P:Fc-epsilon receptor signaling pathway
GO:0043966--P:histone H3 acetylation
GO:0007249--P:I-kappaB kinase/NF-kappaB signaling
GO:0007252--P:I-kappaB phosphorylation
GO:0045087--P:innate immune response
GO:0007254--P:JNK cascade
GO:0002755--P:MyD88-dependent toll-like receptor signaling pathway
GO:0002756--P:MyD88-independent toll-like receptor signaling pathway
GO:2001234--P:negative regulation of apoptotic signaling pathway
GO:1902443--P:negative regulation of ripoptosome assembly involved in necroptotic process
GO:0001841--P:neural tube formation
GO:0035872--P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0070423--P:nucleotide-binding oligomerization domain containing signaling pathway
GO:0043123--P:positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0032743--P:positive regulation of interleukin-2 production
GO:0043507--P:positive regulation of JUN kinase activity
GO:0051092--P:positive regulation of NF-kappaB transcription factor activity
GO:0050870--P:positive regulation of T cell activation
GO:0002726--P:positive regulation of T cell cytokine production
GO:2000377--P:regulation of reactive oxygen species metabolic process
GO:0002223--P:stimulatory C-type lectin receptor signaling pathway
GO:0051403--P:stress-activated MAPK cascade
GO:0050852--P:T cell receptor signaling pathway
GO:0034166--P:toll-like receptor 10 signaling pathway
GO:0034134--P:toll-like receptor 2 signaling pathway
GO:0034138--P:toll-like receptor 3 signaling pathway
GO:0034142--P:toll-like receptor 4 signaling pathway
GO:0034146--P:toll-like receptor 5 signaling pathway
GO:0034162--P:toll-like receptor 9 signaling pathway
GO:0002224--P:toll-like receptor signaling pathway
GO:0038123--P:toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124--P:toll-like receptor TLR6:TLR2 signaling pathway
GO:0006351--P:transcription, DNA-templated
GO:0007179--P:transforming growth factor beta receptor signaling pathway
GO:0035666--P:TRIF-dependent toll-like receptor signaling pathway
GO:0033209--P:tumor necrosis factor-mediated signaling pathway