MAP3K7 - Mitogen-activated protein kinase kinase kinase 7 - human protein (Function)
 
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MAP3K7 »  Mitogen-activated protein kinase kinase kinase 7   [ EC 2.7.11.25 ]
 
Protein also known as:  Transforming growth factor-beta-activated kinase 1 (TGF-beta-activated kinase 1).
Gene name:  MAP3K7
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 184 4
GENE REF ISO

Function

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Overview 
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.  
9
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Magnesium ion bindingdefinition[GO:0000287] silver  
1
  • InterPro 2 GO
MAP kinase kinase activitydefinition[GO:0004708] silver  
1
  • Ortholog Compara
MAP kinase kinase kinase activitydefinition[GO:0004709]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
22
  • IntAct
  • UniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • UniProtKB
Scaffold protein bindingdefinition[GO:0097110]  
1
  • MGI
GO biological process 
Activation of MAPK activitydefinition[GO:0000187]  
1
  • UniProtKB
Activation of MAPKK activitydefinition[GO:0000186]  
2
  • UniProtKB
Activation of NF-kappaB-inducing kinase activitydefinition[GO:0007250]  
2
  • UniProtKB
Angiogenesisdefinition[GO:0001525] silver  
1
  • Ortholog Compara
Apoptotic processdefinition[GO:0006915]  
1
  • UniProtKB KW
Histone H3 acetylationdefinition[GO:0043966]  
1
  • BHF-UCL
I-kappaB phosphorylationdefinition[GO:0007252]  
1
  • UniProtKB
JNK cascadedefinition[GO:0007254]  
1
  • UniProtKB
Negative regulation of apoptotic signaling pathwaydefinition[GO:2001234] silver  
1
  • Ortholog Compara
Negative regulation of ripoptosome assembly involved in necroptotic processdefinition[GO:1902443] silver  
1
  • Ortholog Compara
Neural tube formationdefinition[GO:0001841] silver  
1
  • Ortholog Compara
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
1
  • UniProtKB
Positive regulation of interleukin-2 productiondefinition[GO:0032743]  
1
  • UniProtKB
Positive regulation of JUN kinase activitydefinition[GO:0043507]  
2
  • UniProtKB
Positive regulation of T cell activationdefinition[GO:0050870]  
1
  • UniProtKB
Positive regulation of T cell cytokine productiondefinition[GO:0002726]  
1
  • UniProtKB
Regulation of reactive oxygen species metabolic processdefinition[GO:2000377] silver  
1
  • Ortholog Compara
Stress-activated MAPK cascadedefinition[GO:0051403]  
1
  • UniProtKB
T cell receptor signaling pathwaydefinition[GO:0050852]  
1
  • UniProtKB
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • UniProtKB KW
Transforming growth factor beta receptor signaling pathwaydefinition[GO:0007179] silver  
1
  • Ortholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.25: ATP + a protein ADP + a phosphoprotein.  
1
  • UniProtKB
It requires the following cofactor
 Mg(2+)  
1
  • UniProtKB
It is regulated in the following manner
Activated by proinflammatory cytokines and in response to physical and chemical stresses, including osmotic stress, oxidative stress, arsenic and ultraviolet light irradiation. Activated by 'Lys-63'-linked polyubiquitination and by autophosphorylation. Association with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 promotes activation through autophosphorylation, whereas PPM1B/PP2CB, PP2A and PPP6C dephosphorylation leads to inactivation.  
6
  • UniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Adherens junction  hsa04520+6885  
Herpes simplex infection  hsa05168+6885  
Leishmaniasis  hsa05140+6885  
MAPK signaling pathway  hsa04010+6885  
Measles  hsa05162+6885  
NOD-like receptor signaling pathway  hsa04621+6885  
Osteoclast differentiation  hsa04380+6885  
RIG-I-like receptor signaling pathway  hsa04622+6885  
T cell receptor signaling pathway  hsa04660+6885  
Toll-like receptor signaling pathway  hsa04620+6885  
Toxoplasmosis  hsa05145+6885  
Wnt signaling pathway  hsa04310+6885  
According to Reactome, this protein belongs to the following pathways:
activated TAK1 mediates p38 MAPK activation  REACT_21399  
Activation of NF-kappaB in B cells  REACT_118656  
Ca2+ pathway  REACT_263982  
Downstream TCR signaling  REACT_12555  
FCERI mediated NF-kB activation  REACT_163994  
Interleukin-1 signaling  REACT_22442  
IRAK2 mediated activation of TAK1 complex  REACT_25380  
IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation  REACT_25018  
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1  REACT_21368  
NOD1/2 Signaling Pathway  REACT_75776  
TAK1 activates NFkB by phosphorylation and activation of IKKs complex  REACT_21281  
TRAF6 mediated induction of TAK1 complex  REACT_25351  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Stress response  definition   [KW-0346]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MAP3K7
GenomeRNAi: 6885
PRO: PR:O43318
Chemistry
GuidetoPHARMACOLOGY: 2082