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Mitogen-activated protein kinase kinase kinase 7 (EC 2 7 11 25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1)

 M3K7_MOUSE              Reviewed;         579 AA.
Q62073;
01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
17-JUN-2020, entry version 189.
RecName: Full=Mitogen-activated protein kinase kinase kinase 7;
EC=2.7.11.25 {ECO:0000250|UniProtKB:O43318};
AltName: Full=Transforming growth factor-beta-activated kinase 1;
Short=TGF-beta-activated kinase 1;
Name=Map3k7; Synonyms=Tak1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
PubMed=8533096; DOI=10.1126/science.270.5244.2008;
Yamaguchi K., Shirakabe K., Shibuya H., Irie K., Ohishi I., Ueno N.,
Taniguchi T., Nishida E., Matsumoto K.;
"Identification of a member of the MAPKKK family as a potential mediator of
TGF-beta signal transduction.";
Science 270:2008-2011(1995).
[2]
FUNCTION, AND INTERACTION WITH SMAD6.
PubMed=10748100; DOI=10.1074/jbc.m908622199;
Kimura N., Matsuo R., Shibuya H., Nakashima K., Taga T.;
"BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase
pathway that is negatively regulated by Smad6.";
J. Biol. Chem. 275:17647-17652(2000).
[3]
INTERACTION WITH PPM1L.
PubMed=12556533; DOI=10.1074/jbc.m211474200;
Li M.G., Katsura K., Nomiyama H., Komaki K., Ninomiya-Tsuji J.,
Matsumoto K., Kobayashi T., Tamura S.;
"Regulation of the interleukin-1-induced signaling pathways by a novel
member of the protein phosphatase 2C family (PP2Cepsilon).";
J. Biol. Chem. 278:12013-12021(2003).
[4]
FUNCTION, UBIQUITINATION, AND PROTEASOMAL DEGRADATION.
PubMed=16157589; DOI=10.1074/jbc.m505671200;
Kaur S., Wang F., Venkatraman M., Arsura M.;
"X-linked inhibitor of apoptosis (XIAP) inhibits c-Jun N-terminal kinase 1
(JNK1) activation by transforming growth factor beta1 (TGF-beta1) through
ubiquitin-mediated proteosomal degradation of the TGF-beta1-activated
kinase 1 (TAK1).";
J. Biol. Chem. 280:38599-38608(2005).
[5]
UBIQUITINATION, INTERACTION WITH CYLD, AND DEUBIQUITINATION BY CYLD.
PubMed=17548520; DOI=10.1084/jem.20062694;
Reiley W.W., Jin W., Lee A.J., Wright A., Wu X., Tewalt E.F., Leonard T.O.,
Norbury C.C., Fitzpatrick L., Zhang M., Sun S.C.;
"Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent
kinase Tak1 and prevents abnormal T cell responses.";
J. Exp. Med. 204:1475-1485(2007).
[6]
INTERACTION WITH VRK2 AND MAPK8IP1.
PubMed=17709393; DOI=10.1128/mcb.00025-07;
Blanco S., Santos C., Lazo P.A.;
"Vaccinia-related kinase 2 modulates the stress response to hypoxia
mediated by TAK1.";
Mol. Cell. Biol. 27:7273-7283(2007).
[7]
REVIEW ON ACTIVITY REGULATION.
PubMed=17496917; DOI=10.1038/sj.onc.1210413;
Adhikari A., Xu M., Chen Z.J.;
"Ubiquitin-mediated activation of TAK1 and IKK.";
Oncogene 26:3214-3226(2007).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=17242355; DOI=10.1073/pnas.0609836104;
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
"Large-scale phosphorylation analysis of mouse liver.";
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389 AND SER-412, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
Thibault P.;
"The phagosomal proteome in interferon-gamma-activated macrophages.";
Immunity 30:143-154(2009).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389 AND SER-412, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
Spleen, and Testis;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and expression.";
Cell 143:1174-1189(2010).
[11]
REVIEW ON ACTIVITY REGULATION, AND REVIEW ON FUNCTION.
PubMed=20060931; DOI=10.1016/j.biocel.2009.12.023;
Landstrom M.;
"The TAK1-TRAF6 signalling pathway.";
Int. J. Biochem. Cell Biol. 42:585-589(2010).
[12]
IDENTIFICATION IN COMPLEX WITH NDFIP1 AND ITCH, AND UBIQUITINATION BY ITCH.
PubMed=25632008; DOI=10.4049/jimmunol.1402742;
Kathania M., Zeng M., Yadav V.N., Moghaddam S.J., Yang B., Venuprasad K.;
"Ndfip1 regulates itch ligase activity and airway inflammation via UbcH7.";
J. Immunol. 194:2160-2167(2015).
[13]
IDENTIFICATION IN A COMPLEX WITH SH3RF1; RAC2; MAP2K7; MAPK8IP1; MAPK8 AND
MAPK9.
PubMed=27084103; DOI=10.4049/jimmunol.1501728;
Cunningham C.A., Cardwell L.N., Guan Y., Teixeiro E., Daniels M.A.;
"POSH regulates CD4+ T cell differentiation and survival.";
J. Immunol. 196:4003-4013(2016).
[14]
INTERACTION WITH PLEKHM1.
PubMed=27777970; DOI=10.1172/jci.insight.86330;
Fujiwara T., Ye S., Castro-Gomes T., Winchell C.G., Andrews N.W.,
Voth D.E., Varughese K.I., Mackintosh S.G., Feng Y., Pavlos N.,
Nakamura T., Manolagas S.C., Zhao H.;
"PLEKHM1/DEF8/RAB7 complex regulates lysosome positioning and bone
homeostasis.";
JCI Insight 1:E86330-E86330(2016).
[15]
FUNCTION.
PubMed=28842570; DOI=10.1038/s41467-017-00406-w;
Geng J., Ito Y., Shi L., Amin P., Chu J., Ouchida A.T., Mookhtiar A.K.,
Zhao H., Xu D., Shan B., Najafov A., Gao G., Akira S., Yuan J.;
"Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates
apoptosis and necroptosis.";
Nat. Commun. 8:359-359(2017).
[16]
FUNCTION, UBIQUITINATION AT LYS-158 AND LYS-209, DEUBIQUITINATION BY CYLD,
ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-34; LYS-158; LYS-209 AND
LYS-562.
PubMed=29291351; DOI=10.1038/nm.4461;
Ji Y.X., Huang Z., Yang X., Wang X., Zhao L.P., Wang P.X., Zhang X.J.,
Alves-Bezerra M., Cai L., Zhang P., Lu Y.X., Bai L., Gao M.M., Zhao H.,
Tian S., Wang Y., Huang Z.X., Zhu X.Y., Zhang Y., Gong J., She Z.G., Li F.,
Cohen D.E., Li H.;
"The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic
steatohepatitis.";
Nat. Med. 24:213-223(2018).
[17]
INTERACTION WITH RIPK1.
PubMed=31519887; DOI=10.1038/s41467-019-12033-8;
Tang Y., Tu H., Zhang J., Zhao X., Wang Y., Qin J., Lin X.;
"K63-linked ubiquitination regulates RIPK1 kinase activity to prevent cell
death during embryogenesis and inflammation.";
Nat. Commun. 10:4157-4157(2019).
-!- 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)
(PubMed:10748100, PubMed:16157589, PubMed:21183079, PubMed:29291351).
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 (PubMed:16157589, PubMed:8533096, PubMed:29291351). MAP3K7
activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and
mediates BMP2-induced apoptosis (PubMed:10748100). 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). 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 (PubMed:28842570).
{ECO:0000250|UniProtKB:O43318, ECO:0000269|PubMed:10748100,
ECO:0000269|PubMed:16157589, ECO:0000269|PubMed:21183079,
ECO:0000269|PubMed:28842570, ECO:0000269|PubMed:29291351,
ECO:0000269|PubMed:8533096}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.25;
Evidence={ECO:0000250|UniProtKB:O43318};
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
EC=2.7.11.25; Evidence={ECO:0000250|UniProtKB:O43318};
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
-!- ACTIVITY REGULATION: 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. {ECO:0000269|PubMed:29291351}.
-!- SUBUNIT: Can form homodimer (By similarity). Binds both upstream
activators and downstream substrates in multimolecular complexes (By
similarity). Interacts with TAB1/MAP3K7IP1, TAB2/MAP3K7IP2 and
TAB3/MAP3K7IP3 (By similarity). Identified in the TRIKA2 complex
composed of MAP3K7/TAK1, TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 (By
similarity). Interacts with PPM1L and PPM1B/PP2CB (PubMed:12556533).
Interaction with PP2A and PPP6C leads to its repressed activity (By
similarity). Interacts with TRAF6 and TAB1/MAP3K7IP1; during IL-1
signaling (By similarity). Interacts with TAOK1 and TAOK2; interaction
with TAOK2 interferes with MAP3K7 interaction with IKKA, thus
preventing NF-kappa-B activation (By similarity). Interacts with WDR34
(via WD domains) (By similarity). Interacts with CYLD and RBCK1
(PubMed:17548520). Interacts with TGFBR1; induces MAP3K7/TAK1
activation by TRAF6 (By similarity). Interacts with MAPK8IP1 and SMAD6
(PubMed:10748100, PubMed:17709393). Interacts with isoform 1 of VRK2
(PubMed:17709393). Interacts with DAB2; the interaction is induced by
TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation
(By similarity). Interacts with TRIM5 (By similarity). Part of a
complex containing ITCH, NDFIP1 and MAP3K7 (PubMed:25632008). Interacts
with PLEKHM1 (via N- and C-terminus) (PubMed:27777970). Interacts with
TRIM8 (By similarity). Found in a complex with SH3RF1, RAC2,
MAP2K7/MKK7, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2
(PubMed:27084103). Interacts with SASH1 (By similarity). Interacts with
RIPK1 (PubMed:31519887). {ECO:0000250|UniProtKB:O43318,
ECO:0000269|PubMed:10748100, ECO:0000269|PubMed:12556533,
ECO:0000269|PubMed:17548520, ECO:0000269|PubMed:17709393,
ECO:0000269|PubMed:25632008, ECO:0000269|PubMed:27084103,
ECO:0000269|PubMed:27777970, ECO:0000269|PubMed:31519887}.
-!- INTERACTION:
Q62073; Q9WVI9-2: Mapk8ip1; NbExp=4; IntAct=EBI-1775345, EBI-288464;
Q62073; P70340: Smad1; NbExp=3; IntAct=EBI-1775345, EBI-6992047;
Q62073; Q8CF89: Tab1; NbExp=2; IntAct=EBI-1775345, EBI-1778503;
Q62073; Q99K90: Tab2; NbExp=8; IntAct=EBI-1775345, EBI-1775124;
Q62073; P39429: Traf2; NbExp=2; IntAct=EBI-1775345, EBI-520016;
Q62073; Q9NYJ8: TAB2; Xeno; NbExp=2; IntAct=EBI-1775345, EBI-358708;
Q62073; Q8N5C8: TAB3; Xeno; NbExp=2; IntAct=EBI-1775345, EBI-359964;
Q62073; Q86Y07-1: VRK2; Xeno; NbExp=3; IntAct=EBI-1775345, EBI-1207633;
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
{ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
side {ECO:0000250}. 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. {ECO:0000250}.
-!- PTM: Association with TAB1/MAP3K7IP1 promotes autophosphorylation and
subsequent activation. Association with TAB2/MAP3K7IP2, itself
associated with free unanchored Lys-63 polyubiquitin chain, promotes
autophosphorylation and subsequent activation of MAP3K7.
Dephosphorylation at Thr-187 by PP2A and PPP6C leads to inactivation
(By similarity). {ECO:0000250}.
-!- PTM: 'Lys-48'-linked polyubiquitination at Lys-72 is induced by
TNFalpha, and leads to proteasomal degradation (PubMed:16157589).
Undergoes 'Lys-48'-linked polyubiquitination catalyzed by ITCH
(PubMed:25632008). 'Lys-63'-linked polyubiquitination at Lys-158 by
TRIM8 does not lead to proteasomal degradation but contributes to
autophosphorylation and activation. Deubiquitinated by CYLD, a protease
that selectively cleaves 'Lys-63'-linked ubiquitin chains
(PubMed:17548520, PubMed:29291351). {ECO:0000250|UniProtKB:O43318,
ECO:0000269|PubMed:16157589, ECO:0000269|PubMed:17548520,
ECO:0000269|PubMed:25632008, ECO:0000269|PubMed:29291351}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
protein kinase family. MAP kinase kinase kinase subfamily.
{ECO:0000305}.
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EMBL; D76446; BAA11184.1; -; mRNA.
CCDS; CCDS18014.1; -.
RefSeq; NP_766276.1; NM_172688.3.
SMR; Q62073; -.
BioGRID; 204962; 46.
DIP; DIP-40666N; -.
IntAct; Q62073; 21.
MINT; Q62073; -.
STRING; 10090.ENSMUSP00000040307; -.
iPTMnet; Q62073; -.
PhosphoSitePlus; Q62073; -.
EPD; Q62073; -.
jPOST; Q62073; -.
MaxQB; Q62073; -.
PaxDb; Q62073; -.
PRIDE; Q62073; -.
Antibodypedia; 2078; 1137 antibodies.
Ensembl; ENSMUST00000080933; ENSMUSP00000079734; ENSMUSG00000028284.
GeneID; 26409; -.
KEGG; mmu:26409; -.
UCSC; uc008sep.2; mouse.
CTD; 6885; -.
MGI; MGI:1346877; Map3k7.
eggNOG; KOG0192; Eukaryota.
eggNOG; COG0515; LUCA.
GeneTree; ENSGT00940000157785; -.
HOGENOM; CLU_000288_7_41_1; -.
InParanoid; Q62073; -.
KO; K04427; -.
BRENDA; 2.7.11.25; 3474.
Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
Reactome; R-MMU-202424; Downstream TCR signaling.
Reactome; R-MMU-2871837; FCERI mediated NF-kB activation.
Reactome; R-MMU-4086398; Ca2+ pathway.
Reactome; R-MMU-445989; TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
Reactome; R-MMU-450302; activated TAK1 mediates p38 MAPK activation.
Reactome; R-MMU-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
Reactome; R-MMU-5689880; Ub-specific processing proteases.
Reactome; R-MMU-9020702; Interleukin-1 signaling.
Reactome; R-MMU-937042; IRAK2 mediated activation of TAK1 complex.
Reactome; R-MMU-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
Reactome; R-MMU-9645460; Alpha-protein kinase 1 signaling pathway.
Reactome; R-MMU-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
BioGRID-ORCS; 26409; 6 hits in 14 CRISPR screens.
ChiTaRS; Map3k7; mouse.
PRO; PR:Q62073; -.
Proteomes; UP000000589; Chromosome 4.
RNAct; Q62073; protein.
Bgee; ENSMUSG00000028284; Expressed in heart and 291 other tissues.
ExpressionAtlas; Q62073; baseline and differential.
Genevisible; Q62073; MM.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0014069; C:postsynaptic density; IDA:MGI.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
GO; GO:0004708; F:MAP kinase kinase activity; IDA:MGI.
GO; GO:0004709; F:MAP kinase kinase kinase activity; ISS:UniProtKB.
GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:WormBase.
GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:WormBase.
GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
GO; GO:0001525; P:angiogenesis; IMP:MGI.
GO; GO:0043276; P:anoikis; IMP:ParkinsonsUK-UCL.
GO; GO:0007252; P:I-kappaB phosphorylation; IGI:MGI.
GO; GO:0007254; P:JNK cascade; IDA:UniProtKB.
GO; GO:0000165; P:MAPK cascade; IDA:MGI.
GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IMP:MGI.
GO; GO:0060546; P:negative regulation of necroptotic process; IMP:UniProtKB.
GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:UniProtKB.
GO; GO:1902443; P:negative regulation of ripoptosome assembly involved in necroptotic process; IGI:MGI.
GO; GO:0001841; P:neural tube formation; IMP:MGI.
GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:WormBase.
GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IGI:MGI.
GO; GO:0046330; P:positive regulation of JNK cascade; IGI:MGI.
GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:UniProtKB.
GO; GO:0016239; P:positive regulation of macroautophagy; IMP:ParkinsonsUK-UCL.
GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:MGI.
GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:MGI.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR017421; MAPKKK7.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR008271; Ser/Thr_kinase_AS.
PANTHER; PTHR46716; PTHR46716; 2.
Pfam; PF07714; Pkinase_Tyr; 1.
PIRSF; PIRSF038168; MAPKKK7; 1.
PRINTS; PR00109; TYRKINASE.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
1: Evidence at protein level;
Apoptosis; ATP-binding; Cell membrane; Cytoplasm; Isopeptide bond; Kinase;
Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
Reference proteome; Serine/threonine-protein kinase; Stress response;
Transcription; Transcription regulation; Transferase; Ubl conjugation.
CHAIN 1..579
/note="Mitogen-activated protein kinase kinase kinase 7"
/id="PRO_0000086253"
DOMAIN 36..291
/note="Protein kinase"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
NP_BIND 42..50
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
REGION 1..300
/note="Interaction with MAPK8IP1"
/evidence="ECO:0000269|PubMed:17709393"
COMPBIAS 8..16
/note="Poly-Ser"
ACT_SITE 156
/note="Proton acceptor"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000255|PROSITE-ProRule:PRU10027"
BINDING 63
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
MOD_RES 184
/note="Phosphothreonine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O43318"
MOD_RES 187
/note="Phosphothreonine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O43318"
MOD_RES 192
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:O43318"
MOD_RES 367
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:O43318"
MOD_RES 389
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:19144319,
ECO:0000244|PubMed:21183079"
MOD_RES 412
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:17242355,
ECO:0000244|PubMed:19144319, ECO:0000244|PubMed:21183079"
MOD_RES 428
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:O43318"
CROSSLNK 72
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in ubiquitin)"
/evidence="ECO:0000250|UniProtKB:O43318"
CROSSLNK 158
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in ubiquitin)"
/evidence="ECO:0000269|PubMed:29291351"
CROSSLNK 209
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in ubiquitin)"
/evidence="ECO:0000305|PubMed:29291351"
MUTAGEN 34
/note="K->R: No effect on ubiquitination. No effect on
induction of phosphorylation; when associated with R-562."
/evidence="ECO:0000269|PubMed:29291351"
MUTAGEN 158
/note="K->R: Abolishes ubiquitination. Abolishes
ubiquitination and induction of phosphorylation; when
associated with R-209."
/evidence="ECO:0000269|PubMed:29291351"
MUTAGEN 209
/note="K->R: Strongly decreases ubiquitination. Abolishes
ubiquitination and induction of phosphorylation; when
associated with R-158."
/evidence="ECO:0000269|PubMed:29291351"
MUTAGEN 562
/note="K->R: No effect on ubiquitination. No effect on
induction of phosphorylation; when associated with R-34."
/evidence="ECO:0000269|PubMed:29291351"
SEQUENCE 579 AA; 64228 MW; 97C8F6F3C8E283EE CRC64;
MSTASAASSS SSSSASEMIE APSQVLNFEE IDYKEIEVEE VVGRGAFGVV CKAKWRAKDV
AIKQIESESE RKAFIVELRQ LSRVNHPNIV KLYGACLNPV CLVMEYAEGG SLYNVLHGAE
PLPYYTAAHA MSWCLQCSQG VAYLHSMQPK ALIHRDLKPP NLLLVAGGTV LKICDFGTAC
DIQTHMTNNK GSAAWMAPEV FEGSNYSEKC DVFSWGIILW EVITRRKPFD EIGGPAFRIM
WAVHNGTRPP LIKNLPKPIE SLMTRCWSKD PSQRPSMEEI VKIMTHLMRY FPGADEPLQY
PCQYSDEGQS NSATSTGSFM DIASTNTSNK SDTNMEQVPA TNDTIKRLES KLLKNQAKQQ
SESGRLSLGA SRGSSVESLP PTSEGKRMSA DMSEIEARIV ATAGNGQPRR RSIQDLTVTG
TEPGQVSSRS SSPSVRMITT SGPTSEKPAR SHPWTPDDST DTNGSDNSIP MAYLTLDHQL
QPLAPCPNSK ESMAVFEQHC KMAQEYMKVQ TEIALLLQRK QELVAELDQD EKDQQNTSRL
VQEHKKLLDE NKSLSTYYQQ CKKQLEVIRS QQQKRQGTS


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Pathways :
WP32: Translation Factors
WP1493: Carbon assimilation C4 pathway
WP2341: vitamin B1 (thiamin) biosynthesis and salvage pathway
WP1567: Glycolysis and Gluconeogenesis
WP2340: Thiamine (vitamin B1) biosynthesis and salvage
WP1703: Streptomycin biosynthesis
WP1946: Cori Cycle
WP1619: Amino sugar and nucleotide sugar metabolism
WP1844: MAP kinase cascade
WP1681: Pantothenate and CoA biosynthesis
WP1653: Galactose metabolism
WP1701: Starch and sucrose metabolism
WP253: Glycolysis
WP1566: Citrate cycle (TCA cycle)
WP2218: sGC
WP210: Cytoplasmic Ribosomal Proteins
WP1929: Thrombin signalling through proteinase activated receptors (PARs)
WP1835: Interferon alpha/beta signaling
WP448: Mitochondrial LC-Fatty Acid Beta-Oxidation
WP1045: TGF-beta Receptor Signaling Pathway
WP1982: SREBP signalling
WP313: Signaling of Hepatocyte Growth Factor Receptor
WP209: Fatty Acid Beta Oxidation Meta
WP809: TGF-beta Receptor Signaling Pathway
WP1224: EBV LMP1 signaling

Related Genes :
[Map3k7 Tak1] Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1)
[MAP3K7 TAK1] Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1)
[TAB1 MAP3K7IP1] TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 1) (TGF-beta-activated kinase 1-binding protein 1) (TAK1-binding protein 1)
[Tab1 Map3k7ip1] TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 1) (TGF-beta-activated kinase 1-binding protein 1) (TAK1-binding protein 1)
[TAB2 KIAA0733 MAP3K7IP2] TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 2) (TAK1-binding protein 2) (TAB-2) (TGF-beta-activated kinase 1-binding protein 2)
[MAPK11 PRKM11 SAPK2 SAPK2B] Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2)
[TGFBR1 ALK5 SKR4] TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Activin A receptor type II-like protein kinase of 53kD) (Activin receptor-like kinase 5) (ALK-5) (ALK5) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I)
[Tab2 Kiaa0733 Map3k7ip2] TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 2) (TAK1-binding protein 2) (TAB-2) (TGF-beta-activated kinase 1-binding protein 2)
[MAPK14 CSBP CSBP1 CSBP2 CSPB1 MXI2 SAPK2A] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a)
[TAB3 MAP3K7IP3] TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 3) (NF-kappa-B-activating protein 1) (TAK1-binding protein 3) (TAB-3) (TGF-beta-activated kinase 1-binding protein 3)
[Tgfbr1] TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I)
[Mapk14 Crk1 Csbp1 Csbp2] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (CRK1) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha)
[Mapk11 Prkm11] Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38B)
[Map3k1 Mekk Mekk1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[Map3k7] Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25)
[Map3k1 Mekk Mekk1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[MAPK1 ERK2 PRKM1 PRKM2] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Mapk10 Jnk3 Prkm10] Mitogen-activated protein kinase 10 (MAP kinase 10) (MAPK 10) (EC 2.7.11.24) (SAPK-beta) (Stress-activated protein kinase JNK3) (c-Jun N-terminal kinase 3) (p54-beta)
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Mapk14 Csbp1 Csbp2] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (CRK1) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha)
[MAPK9 JNK2 PRKM9 SAPK1A] Mitogen-activated protein kinase 9 (MAP kinase 9) (MAPK 9) (EC 2.7.11.24) (JNK-55) (Stress-activated protein kinase 1a) (SAPK1a) (Stress-activated protein kinase JNK2) (c-Jun N-terminal kinase 2)
[MAPK8 JNK1 PRKM8 SAPK1 SAPK1C] Mitogen-activated protein kinase 8 (MAP kinase 8) (MAPK 8) (EC 2.7.11.24) (JNK-46) (Stress-activated protein kinase 1c) (SAPK1c) (Stress-activated protein kinase JNK1) (c-Jun N-terminal kinase 1)
[MAPK7 BMK1 ERK5 PRKM7] Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5)
[MAPK10 JNK3 JNK3A PRKM10 SAPK1B] Mitogen-activated protein kinase 10 (MAP kinase 10) (MAPK 10) (EC 2.7.11.24) (MAP kinase p49 3F12) (Stress-activated protein kinase 1b) (SAPK1b) (Stress-activated protein kinase JNK3) (c-Jun N-terminal kinase 3)
[MAP3K5 ASK1 MAPKKK5 MEKK5] Mitogen-activated protein kinase kinase kinase 5 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5)
[Mapk7 Bmk1 Erk5] Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5)
[Mapk7 Bmk1 Erk5] Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5)
[KSS1 YGR040W] Mitogen-activated protein kinase KSS1 (MAP kinase KSS1) (EC 2.7.11.24) (Kinase suppressor of SST2)
[MPK4 At4g01370 F2N1.1 F2N1_2-t] Mitogen-activated protein kinase 4 (AtMPK4) (MAP kinase 4) (EC 2.7.11.24)

Bibliography :
[32078472] Transforming Growth Factor Beta-Activated Kinase 1-Dependent Microglial and Macrophage Responses Aggravate Long-Term Outcomes After Ischemic Stroke.
[32071228] Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke.
[31995728] AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System.
[31885808] Myricetin Alleviates Pathological Cardiac Hypertrophy via TRAF6/TAK1/MAPK and Nrf2 Signaling Pathway.
[31825793] MiR-345-3p attenuates apoptosis and inflammation caused by oxidized low-density lipoprotein by targeting TRAF6 via TAK1/p38/NF-kB signaling in endothelial cells.
[31813254] TAK1 deficiency attenuates cisplatin-induced acute kidney injury.
[31668971] TAK1/Map3k7 enhances differentiation of cardiogenic endoderm from mouse embryonic stem cells.
[31665064] BMP3 suppresses colon tumorigenesis via ActRIIB/SMAD2-dependent and TAK1/JNK signaling pathways.
[31658592] Receptor Heterodimerization and Co-Receptor Engagement in TLR2 Activation Induced by MIC1 and MIC4 from .
[31647008] Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis.