MAP3K7 (mitogen-activated protein kinase kinase kinase 7)

Gene

• Entrez ID: 6885
• Gene name: Mitogen-activated protein kinase kinase kinase 7
• Gene symbol: MAP3K7
• Synonyms: CSCF, FMD2, MEKK7, TAK1, TGF1a
• Chromosome: 6
• Chromosome location: 6q15
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs886039230	G>A,C,T	Pathogenic	Coding sequence variant, intron variant, missense variant
rs886039231	C>G	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs886039232	A>T	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs886039233	C>G	Pathogenic	Coding sequence variant, missense variant
rs886039234	TCTTCC>-	Pathogenic	5 prime UTR variant, inframe deletion, coding sequence variant
rs886039235	C>A	Pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs886039236	AAC>-	Pathogenic	5 prime UTR variant, inframe deletion, coding sequence variant
rs886039237	A>C,T	Pathogenic	Coding sequence variant, missense variant
rs1057517758	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1064795771	C>T	Likely-pathogenic	Coding sequence variant, 5 prime UTR variant, missense variant
rs1180249151	C>A,T	Likely-pathogenic	Splice acceptor variant
rs1554184177	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1582233787	AAC>-	Likely-pathogenic	Coding sequence variant, 5 prime UTR variant, inframe deletion

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005509	hsa-miR-10a-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot, Reporter assay;Other	20624982
MIRT025316	hsa-miR-34a-5p	Sequencing	20371350
MIRT027011	hsa-miR-103a-3p	Sequencing, PAR-CLIP	20371350
MIRT027011	hsa-miR-103a-3p	PAR-CLIP	23446348
MIRT036539	hsa-miR-1226-5p	CLASH	23622248
MIRT051235	hsa-miR-16-5p	CLASH	23622248
MIRT051235	hsa-miR-16-5p	PAR-CLIP	20371350
MIRT053639	hsa-miR-143-3p	Microarray	22942087
MIRT445925	hsa-miR-4635	PAR-CLIP	22100165
MIRT445926	hsa-miR-4709-3p	PAR-CLIP	22100165
MIRT449701	hsa-miR-3914	PAR-CLIP	22100165
MIRT512935	hsa-miR-548au-3p	PAR-CLIP	23446348
MIRT512935	hsa-miR-548au-3p	PAR-CLIP	20371350
MIRT512936	hsa-miR-107	PAR-CLIP	23446348
MIRT512936	hsa-miR-107	PAR-CLIP	20371350
MIRT512937	hsa-miR-545-3p	PAR-CLIP	23446348
MIRT512937	hsa-miR-545-3p	PAR-CLIP	20371350
MIRT512938	hsa-miR-1295b-3p	PAR-CLIP	23446348
MIRT512938	hsa-miR-1295b-3p	PAR-CLIP	20371350
MIRT512939	hsa-miR-449c-5p	PAR-CLIP	23446348
MIRT512939	hsa-miR-449c-5p	PAR-CLIP	20371350
MIRT512940	hsa-miR-34b-5p	PAR-CLIP	23446348
MIRT512940	hsa-miR-34b-5p	PAR-CLIP	20371350
MIRT512941	hsa-miR-2682-5p	PAR-CLIP	23446348
MIRT512941	hsa-miR-2682-5p	PAR-CLIP	20371350
MIRT512942	hsa-miR-940	PAR-CLIP	23446348
MIRT512942	hsa-miR-940	PAR-CLIP	20371350
MIRT512943	hsa-miR-6893-5p	PAR-CLIP	23446348
MIRT512943	hsa-miR-6893-5p	PAR-CLIP	20371350
MIRT512944	hsa-miR-6808-5p	PAR-CLIP	23446348
MIRT512944	hsa-miR-6808-5p	PAR-CLIP	20371350
MIRT512945	hsa-miR-6511a-5p	PAR-CLIP	23446348
MIRT512945	hsa-miR-6511a-5p	PAR-CLIP	20371350
MIRT512946	hsa-miR-1910-3p	PAR-CLIP	23446348
MIRT512946	hsa-miR-1910-3p	PAR-CLIP	20371350
MIRT566822	hsa-miR-599	PAR-CLIP	20371350
MIRT566823	hsa-miR-4524b-5p	PAR-CLIP	20371350
MIRT566824	hsa-miR-4524a-5p	PAR-CLIP	20371350
MIRT566825	hsa-miR-5589-3p	PAR-CLIP	20371350
MIRT566826	hsa-miR-875-5p	PAR-CLIP	20371350
MIRT566827	hsa-miR-646	PAR-CLIP	20371350
MIRT566828	hsa-miR-503-5p	PAR-CLIP	20371350
MIRT566829	hsa-miR-6838-5p	PAR-CLIP	20371350
MIRT566830	hsa-miR-497-5p	PAR-CLIP	20371350
MIRT566831	hsa-miR-424-5p	PAR-CLIP	20371350
MIRT566832	hsa-miR-195-5p	PAR-CLIP	20371350
MIRT566833	hsa-miR-15b-5p	PAR-CLIP	20371350
MIRT566834	hsa-miR-15a-5p	PAR-CLIP	20371350
MIRT616953	hsa-miR-335-3p	HITS-CLIP	23824327
MIRT616954	hsa-miR-1305	HITS-CLIP	23824327
MIRT616955	hsa-miR-607	HITS-CLIP	23824327
MIRT616956	hsa-miR-664b-3p	HITS-CLIP	23824327
MIRT616957	hsa-miR-579-3p	HITS-CLIP	23824327
MIRT616958	hsa-miR-5696	HITS-CLIP	23824327
MIRT616959	hsa-miR-3671	HITS-CLIP	23824327
MIRT616960	hsa-miR-153-5p	HITS-CLIP	23824327
MIRT616961	hsa-miR-1250-3p	HITS-CLIP	23824327
MIRT733454	hsa-miR-892b	Immunoprecipitaion, Luciferase reporter assay, qRT-PCR, Western blot	26747895

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000186	Process	Activation of MAPKK activity	IDA	8663074, 9079627
GO:0000187	Process	Activation of MAPK activity	IDA	9079627
GO:0000187	Process	Activation of MAPK activity	TAS
GO:0000287	Function	Magnesium ion binding	IEA
GO:0002223	Process	Stimulatory C-type lectin receptor signaling pathway	TAS
GO:0002726	Process	Positive regulation of T cell cytokine production	IMP	15125833
GO:0002755	Process	MyD88-dependent toll-like receptor signaling pathway	TAS
GO:0004672	Function	Protein kinase activity	IDA	10094049
GO:0004674	Function	Protein serine/threonine kinase activity	EXP	10702308, 11460167, 20538596
GO:0004674	Function	Protein serine/threonine kinase activity	TAS
GO:0004709	Function	MAP kinase kinase kinase activity	EXP	11460167
GO:0004709	Function	MAP kinase kinase kinase activity	IBA	21873635
GO:0004709	Function	MAP kinase kinase kinase activity	IDA	11460167
GO:0005515	Function	Protein binding	IPI	10094049, 11460167, 12496252, 15075345, 15764709, 16840345, 16845370, 17079228, 17110930, 17158449, 17449468, 17709393, 18286207, 18591963, 18758450, 19820695, 21512573, 21903422, 22081109, 22158122, 22904686, 25241761, 26334375, 27426733
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005671	Component	Ada2/Gcn5/Ada3 transcription activator complex	IDA	18838386
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	TAS	9466656
GO:0007223	Process	Wnt signaling pathway, calcium modulating pathway	TAS
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	TAS
GO:0007250	Process	Activation of NF-kappaB-inducing kinase activity	IMP	10094049, 15125833
GO:0007252	Process	I-kappaB phosphorylation	IDA	11460167
GO:0007254	Process	JNK cascade	IBA	21873635
GO:0007254	Process	JNK cascade	IDA	9079627
GO:0007254	Process	JNK cascade	TAS
GO:0008385	Component	IkappaB kinase complex	IPI	10094049
GO:0010008	Component	Endosome membrane	TAS
GO:0016032	Process	Viral process	IEA
GO:0016239	Process	Positive regulation of macroautophagy	ISS
GO:0016579	Process	Protein deubiquitination	TAS
GO:0030971	Function	Receptor tyrosine kinase binding	IPI	18762249
GO:0032743	Process	Positive regulation of interleukin-2 production	IMP	15125833
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0042802	Function	Identical protein binding	IPI	27426733
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP	14982987
GO:0043276	Process	Anoikis	ISS
GO:0043507	Process	Positive regulation of JUN kinase activity	IDA	11460167
GO:0043507	Process	Positive regulation of JUN kinase activity	IMP	10094049
GO:0043966	Process	Histone H3 acetylation	IDA	18838386
GO:0050852	Process	T cell receptor signaling pathway	NAS	15125833
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	TAS
GO:0051403	Process	Stress-activated MAPK cascade	IDA	9079627
GO:0070423	Process	Nucleotide-binding oligomerization domain containing signaling pathway	TAS
GO:0070498	Process	Interleukin-1-mediated signaling pathway	TAS
GO:0097110	Function	Scaffold protein binding	IDA	23776175

Other IDs

• MIM: 602614
• HGNC: 6859
• e!Ensembl: ENSG00000135341

Protein

• UniProt ID: O43318
• Protein name: Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1)
• Protein function: 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. 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).
• PDB: 2EVA, 2YIY, 4GS6, 4L3P, 4L52, 4L53, 4O91, 5E7R, 5GJD, 5GJF, 5GJG, 5J7S, 5J8I, 5J9L, 5JGA, 5JGB, 5JGD, 5JH6, 5JK3, 5V5N
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07714	PK_Tyr_Ser-Thr	36 → 284	Protein tyrosine and serine/threonine kinase	Domain

• Sequence:

  MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDV
  AIKQIESESERKAFIVELRQLSRVNHPNIVKLYGACLNPVCLVMEYAEGGSLYNVLHGAE
  PLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTAC
  DIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIM
  WAVHNGTRPPLIKNLPKPIESLMTRCWSKDPSQRPSMEEIVKIMTHLMRYFPGADEPLQY
  PCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQ
  SESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTAYSKPKRGHRKTASFGN
  ILDVPEIVISGNGQPRRRSIQDLTVTGTEPGQVSSRSSSPSVRMITTSGPTSEKPTRSHP
  WTPDDSTDTNGSDNSIPMAYLTLDHQLQPLAPCPNSKESMAVFEQHCKMAQEYMKVQTEI
  ALLLQRKQELVAELDQDEKDQQNTSRLVQEHKKLLDENKSLSTYYQQCKKQLEVIRSQQQ
  KRQGTS

• Sequence length: 606