InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAP3K7

Summary

InnateDB Protein

IDBP-94378.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MAP3K7

Protein Name

mitogen-activated protein kinase kinase kinase 7

Synonyms

MEKK7; TAK1; TGF1a;

Species

Homo sapiens

Ensembl Protein

ENSP00000358338

InnateDB Gene

IDBG-94374 (MAP3K7)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10094049, ECO:0000269PubMed:11460167, ECO:0000269PubMed:12589052, ECO:0000269PubMed:16845370, ECO:0000269PubMed:16893890, ECO:0000269PubMed:21512573, ECO:0000269PubMed:8663074, ECO:0000269PubMed:9079627}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:12242293}. Cell membrane {ECO:0000269PubMed:12242293}; Peripheral membrane protein {ECO:0000269PubMed:12242293}; Cytoplasmic side {ECO:0000269PubMed:12242293}. Note=Although the majority of MAP3K7/TAK1 is found in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2, it is also localized at the cell membrane.

Disease Associations

Tissue Specificity

Isoform 1A is the most abundant in ovary, skeletal muscle, spleen and blood mononuclear cells. Isoform 1B is highly expressed in brain, kidney and small intestine. Isoform 1C is the major form in prostate. Isoform 1D is the less abundant form. {ECO:0000269PubMed:11118615}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 231 experimentally validated interaction(s) in this database.
They are also associated with 50 interaction(s) predicted by orthology.

Experimentally validated
Total	231 [view]
Protein-Protein	224 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	50 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004709	MAP kinase kinase kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0097110	scaffold protein binding

Biological Process

GO:0000186	activation of MAPKK activity
GO:0000187	activation of MAPK activity
GO:0002224	toll-like receptor signaling pathway
GO:0002726	positive regulation of T cell cytokine production
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006351	transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007165	signal transduction
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0007250	activation of NF-kappaB-inducing kinase activity
GO:0007252	I-kappaB phosphorylation
GO:0007254	JNK cascade
GO:0032743	positive regulation of interleukin-2 production
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043507	positive regulation of JUN kinase activity
GO:0043966	histone H3 acetylation
GO:0045087	innate immune response (InnateDB)
GO:0050852	T cell receptor signaling pathway
GO:0050870	positive regulation of T cell activation
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051403	stress-activated MAPK cascade
GO:0070423	nucleotide-binding oligomerization domain containing signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005671	Ada2/Gcn5/Ada3 transcription activator complex
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0008385	IkappaB kinase complex
GO:0010008	endosome membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR017421 Mitogen-activated protein (MAP) kinase kinase kinase 7
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

PIRSF038168

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References