CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-014395
UniProt Accession
Genbank Protein ID
 D76446 
Genbank Nucleotide ID
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 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
563TYYQQCKKQLEVIRSubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
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). 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 (By similarity). 
Sequence Annotation
 DOMAIN 36 291 Protein kinase.
 NP_BIND 42 50 ATP (By similarity).
 REGION 1 300 Interaction with MAPK8IP1.
 ACT_SITE 156 156 Proton acceptor (By similarity).
 BINDING 63 63 ATP (By similarity).
 MOD_RES 184 184 Phosphothreonine; by autocatalysis (By
 MOD_RES 187 187 Phosphothreonine; by autocatalysis (By
 MOD_RES 192 192 Phosphoserine; by autocatalysis (By
 MOD_RES 389 389 Phosphoserine.
 MOD_RES 412 412 Phosphoserine.  
Keyword
 Apoptosis; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Stress response; Transcription; Transcription regulation; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 579 AA 
Protein 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 
Gene Ontology
 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0000287; F:magnesium ion binding; IEA:InterPro.
 GO:0004708; F:MAP kinase kinase activity; IDA:MGI.
 GO:0004709; F:MAP kinase kinase kinase activity; ISS:UniProtKB.
 GO:0001525; P:angiogenesis; IMP:MGI.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0007252; P:I-kappaB phosphorylation; ISS:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
 GO:0060546; P:negative regulation of necroptosis; IMP:UniProtKB.
 GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:UniProtKB.
 GO:0001841; P:neural tube formation; IMP:MGI.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IGI:MGI.
 GO:0046330; P:positive regulation of JNK cascade; IGI:MGI.
 GO:0043507; P:positive regulation of JUN kinase activity; ISS:UniProtKB.
 GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0006950; P:response to stress; IEA:UniProtKB-KW.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:MGI. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR017421; MAPKKK7.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF07714; Pkinase_Tyr 
SMART
  
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS
 PR00109; TYRKINASE.