M3K7_MOUSE
ID M3K7_MOUSE Reviewed; 579 AA.
AC Q62073;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 7;
DE EC=2.7.11.25 {ECO:0000250|UniProtKB:O43318};
DE AltName: Full=Transforming growth factor-beta-activated kinase 1;
DE Short=TGF-beta-activated kinase 1;
GN Name=Map3k7; Synonyms=Tak1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8533096; DOI=10.1126/science.270.5244.2008;
RA Yamaguchi K., Shirakabe K., Shibuya H., Irie K., Ohishi I., Ueno N.,
RA Taniguchi T., Nishida E., Matsumoto K.;
RT "Identification of a member of the MAPKKK family as a potential mediator of
RT TGF-beta signal transduction.";
RL Science 270:2008-2011(1995).
RN [2]
RP FUNCTION, AND INTERACTION WITH SMAD6.
RX PubMed=10748100; DOI=10.1074/jbc.m908622199;
RA Kimura N., Matsuo R., Shibuya H., Nakashima K., Taga T.;
RT "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase
RT pathway that is negatively regulated by Smad6.";
RL J. Biol. Chem. 275:17647-17652(2000).
RN [3]
RP INTERACTION WITH PPM1L.
RX PubMed=12556533; DOI=10.1074/jbc.m211474200;
RA Li M.G., Katsura K., Nomiyama H., Komaki K., Ninomiya-Tsuji J.,
RA Matsumoto K., Kobayashi T., Tamura S.;
RT "Regulation of the interleukin-1-induced signaling pathways by a novel
RT member of the protein phosphatase 2C family (PP2Cepsilon).";
RL J. Biol. Chem. 278:12013-12021(2003).
RN [4]
RP FUNCTION, UBIQUITINATION, AND PROTEASOMAL DEGRADATION.
RX PubMed=16157589; DOI=10.1074/jbc.m505671200;
RA Kaur S., Wang F., Venkatraman M., Arsura M.;
RT "X-linked inhibitor of apoptosis (XIAP) inhibits c-Jun N-terminal kinase 1
RT (JNK1) activation by transforming growth factor beta1 (TGF-beta1) through
RT ubiquitin-mediated proteosomal degradation of the TGF-beta1-activated
RT kinase 1 (TAK1).";
RL J. Biol. Chem. 280:38599-38608(2005).
RN [5]
RP UBIQUITINATION, INTERACTION WITH CYLD, AND DEUBIQUITINATION BY CYLD.
RX PubMed=17548520; DOI=10.1084/jem.20062694;
RA Reiley W.W., Jin W., Lee A.J., Wright A., Wu X., Tewalt E.F., Leonard T.O.,
RA Norbury C.C., Fitzpatrick L., Zhang M., Sun S.C.;
RT "Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent
RT kinase Tak1 and prevents abnormal T cell responses.";
RL J. Exp. Med. 204:1475-1485(2007).
RN [6]
RP INTERACTION WITH VRK2 AND MAPK8IP1.
RX PubMed=17709393; DOI=10.1128/mcb.00025-07;
RA Blanco S., Santos C., Lazo P.A.;
RT "Vaccinia-related kinase 2 modulates the stress response to hypoxia
RT mediated by TAK1.";
RL Mol. Cell. Biol. 27:7273-7283(2007).
RN [7]
RP REVIEW ON ACTIVITY REGULATION.
RX PubMed=17496917; DOI=10.1038/sj.onc.1210413;
RA Adhikari A., Xu M., Chen Z.J.;
RT "Ubiquitin-mediated activation of TAK1 and IKK.";
RL Oncogene 26:3214-3226(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389 AND SER-412, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389 AND SER-412, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP REVIEW ON ACTIVITY REGULATION, AND REVIEW ON FUNCTION.
RX PubMed=20060931; DOI=10.1016/j.biocel.2009.12.023;
RA Landstrom M.;
RT "The TAK1-TRAF6 signalling pathway.";
RL Int. J. Biochem. Cell Biol. 42:585-589(2010).
RN [12]
RP IDENTIFICATION IN COMPLEX WITH NDFIP1 AND ITCH, AND UBIQUITINATION BY ITCH.
RX PubMed=25632008; DOI=10.4049/jimmunol.1402742;
RA Kathania M., Zeng M., Yadav V.N., Moghaddam S.J., Yang B., Venuprasad K.;
RT "Ndfip1 regulates itch ligase activity and airway inflammation via UbcH7.";
RL J. Immunol. 194:2160-2167(2015).
RN [13]
RP IDENTIFICATION IN A COMPLEX WITH SH3RF1; RAC2; MAP2K7; MAPK8IP1; MAPK8 AND
RP MAPK9.
RX PubMed=27084103; DOI=10.4049/jimmunol.1501728;
RA Cunningham C.A., Cardwell L.N., Guan Y., Teixeiro E., Daniels M.A.;
RT "POSH regulates CD4+ T cell differentiation and survival.";
RL J. Immunol. 196:4003-4013(2016).
RN [14]
RP INTERACTION WITH PLEKHM1.
RX PubMed=27777970; DOI=10.1172/jci.insight.86330;
RA Fujiwara T., Ye S., Castro-Gomes T., Winchell C.G., Andrews N.W.,
RA Voth D.E., Varughese K.I., Mackintosh S.G., Feng Y., Pavlos N.,
RA Nakamura T., Manolagas S.C., Zhao H.;
RT "PLEKHM1/DEF8/RAB7 complex regulates lysosome positioning and bone
RT homeostasis.";
RL JCI Insight 1:E86330-E86330(2016).
RN [15]
RP FUNCTION.
RX PubMed=28842570; DOI=10.1038/s41467-017-00406-w;
RA Geng J., Ito Y., Shi L., Amin P., Chu J., Ouchida A.T., Mookhtiar A.K.,
RA Zhao H., Xu D., Shan B., Najafov A., Gao G., Akira S., Yuan J.;
RT "Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates
RT apoptosis and necroptosis.";
RL Nat. Commun. 8:359-359(2017).
RN [16]
RP FUNCTION, UBIQUITINATION AT LYS-158 AND LYS-209, DEUBIQUITINATION BY CYLD,
RP ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-34; LYS-158; LYS-209 AND
RP LYS-562.
RX PubMed=29291351; DOI=10.1038/nm.4461;
RA Ji Y.X., Huang Z., Yang X., Wang X., Zhao L.P., Wang P.X., Zhang X.J.,
RA Alves-Bezerra M., Cai L., Zhang P., Lu Y.X., Bai L., Gao M.M., Zhao H.,
RA Tian S., Wang Y., Huang Z.X., Zhu X.Y., Zhang Y., Gong J., She Z.G., Li F.,
RA Cohen D.E., Li H.;
RT "The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic
RT steatohepatitis.";
RL Nat. Med. 24:213-223(2018).
RN [17]
RP INTERACTION WITH RIPK1.
RX PubMed=31519887; DOI=10.1038/s41467-019-12033-8;
RA Tang Y., Tu H., Zhang J., Zhao X., Wang Y., Qin J., Lin X.;
RT "K63-linked ubiquitination regulates RIPK1 kinase activity to prevent cell
RT death during embryogenesis and inflammation.";
RL Nat. Commun. 10:4157-4157(2019).
CC -!- FUNCTION: Serine/threonine kinase which acts as an essential component
CC of the MAP kinase signal transduction pathway. Plays an important role
CC in the cascades of cellular responses evoked by changes in the
CC environment. Mediates signal transduction of TRAF6, various cytokines
CC including interleukin-1 (IL-1), transforming growth factor-beta (TGFB),
CC TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR),
CC tumor necrosis factor receptor CD40 and B-cell receptor (BCR)
CC (PubMed:10748100, PubMed:16157589, PubMed:21183079, PubMed:29291351).
CC Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts
CC as an upstream activator of the MKK/JNK signal transduction cascade and
CC the p38 MAPK signal transduction cascade through the phosphorylation
CC and activation of several MAP kinase kinases like MAP2K1/MEK1,
CC MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate
CC p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex
CC (IKK). Both p38 MAPK and JNK pathways control the transcription factors
CC activator protein-1 (AP-1), while nuclear factor-kappa B is activated
CC by IKK (PubMed:16157589, PubMed:8533096, PubMed:29291351). MAP3K7
CC activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and
CC mediates BMP2-induced apoptosis (PubMed:10748100). In osmotic stress
CC signaling, plays a major role in the activation of MAPK8/JNK1, but not
CC that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity
CC (By similarity). Phosphorylates RIPK1 at 'Ser-321' which positively
CC regulates RIPK1 interaction with RIPK3 to promote necroptosis but
CC negatively regulates RIPK1 kinase activity and its interaction with
CC FADD to mediate apoptosis (PubMed:28842570).
CC {ECO:0000250|UniProtKB:O43318, ECO:0000269|PubMed:10748100,
CC ECO:0000269|PubMed:16157589, ECO:0000269|PubMed:21183079,
CC ECO:0000269|PubMed:28842570, ECO:0000269|PubMed:29291351,
CC ECO:0000269|PubMed:8533096}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.25;
CC Evidence={ECO:0000250|UniProtKB:O43318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.25; Evidence={ECO:0000250|UniProtKB:O43318};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by pro-inflammatory cytokines and in
CC response to physical and chemical stresses, including osmotic stress,
CC oxidative stress, arsenic and ultraviolet light irradiation. Activated
CC by 'Lys-63'-linked polyubiquitination and by autophosphorylation.
CC Association with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 promotes activation
CC through autophosphorylation, whereas PPM1B/PP2CB, PP2A and PPP6C
CC dephosphorylation leads to inactivation. {ECO:0000269|PubMed:29291351}.
CC -!- SUBUNIT: Can form homodimer (By similarity). Binds both upstream
CC activators and downstream substrates in multimolecular complexes (By
CC similarity). Interacts with TAB1/MAP3K7IP1, TAB2/MAP3K7IP2 and
CC TAB3/MAP3K7IP3 (By similarity). Identified in the TRIKA2 complex
CC composed of MAP3K7/TAK1, TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 (By
CC similarity). Interacts with PPM1L and PPM1B/PP2CB (PubMed:12556533).
CC Interaction with PP2A and PPP6C leads to its repressed activity (By
CC similarity). Interacts with TRAF6 and TAB1/MAP3K7IP1; during IL-1
CC signaling (By similarity). Interacts with TAOK1 and TAOK2; interaction
CC with TAOK2 interferes with MAP3K7 interaction with IKKA, thus
CC preventing NF-kappa-B activation (By similarity). Interacts with
CC DYNC2I2 (via WD domains) (By similarity). Interacts with CYLD and RBCK1
CC (PubMed:17548520). Interacts with TGFBR1; induces MAP3K7/TAK1
CC activation by TRAF6 (By similarity). Interacts with MAPK8IP1 and SMAD6
CC (PubMed:10748100, PubMed:17709393). Interacts with isoform 1 of VRK2
CC (PubMed:17709393). Interacts with DAB2; the interaction is induced by
CC TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation
CC (By similarity). Interacts with TRIM5 (By similarity). Part of a
CC complex containing ITCH, NDFIP1 and MAP3K7 (PubMed:25632008). Interacts
CC with PLEKHM1 (via N- and C-terminus) (PubMed:27777970). Interacts with
CC TRIM8 (By similarity). Found in a complex with SH3RF1, RAC2,
CC MAP2K7/MKK7, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2
CC (PubMed:27084103). Interacts with SASH1 (By similarity). Interacts with
CC RIPK1 (PubMed:31519887). {ECO:0000250|UniProtKB:O43318,
CC ECO:0000269|PubMed:10748100, ECO:0000269|PubMed:12556533,
CC ECO:0000269|PubMed:17548520, ECO:0000269|PubMed:17709393,
CC ECO:0000269|PubMed:25632008, ECO:0000269|PubMed:27084103,
CC ECO:0000269|PubMed:27777970, ECO:0000269|PubMed:31519887}.
CC -!- INTERACTION:
CC Q62073; Q9WVI9-2: Mapk8ip1; NbExp=4; IntAct=EBI-1775345, EBI-288464;
CC Q62073; P70340: Smad1; NbExp=3; IntAct=EBI-1775345, EBI-6992047;
CC Q62073; Q8CF89: Tab1; NbExp=2; IntAct=EBI-1775345, EBI-1778503;
CC Q62073; Q99K90: Tab2; NbExp=8; IntAct=EBI-1775345, EBI-1775124;
CC Q62073; P39429: Traf2; NbExp=2; IntAct=EBI-1775345, EBI-520016;
CC Q62073; Q9NYJ8: TAB2; Xeno; NbExp=2; IntAct=EBI-1775345, EBI-358708;
CC Q62073; Q8N5C8: TAB3; Xeno; NbExp=2; IntAct=EBI-1775345, EBI-359964;
CC Q62073; Q86Y07-1: VRK2; Xeno; NbExp=3; IntAct=EBI-1775345, EBI-1207633;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
CC side {ECO:0000250}. Note=Although the majority of MAP3K7/TAK1 is found
CC in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2,
CC it is also localized at the cell membrane. {ECO:0000250}.
CC -!- PTM: Association with TAB1/MAP3K7IP1 promotes autophosphorylation and
CC subsequent activation. Association with TAB2/MAP3K7IP2, itself
CC associated with free unanchored Lys-63 polyubiquitin chain, promotes
CC autophosphorylation and subsequent activation of MAP3K7.
CC Dephosphorylation at Thr-187 by PP2A and PPP6C leads to inactivation
CC (By similarity). {ECO:0000250}.
CC -!- PTM: 'Lys-48'-linked polyubiquitination at Lys-72 is induced by
CC TNFalpha, and leads to proteasomal degradation (PubMed:16157589).
CC Undergoes 'Lys-48'-linked polyubiquitination catalyzed by ITCH
CC (PubMed:25632008). 'Lys-63'-linked polyubiquitination at Lys-158 by
CC TRIM8 does not lead to proteasomal degradation but contributes to
CC autophosphorylation and activation. Deubiquitinated by CYLD, a protease
CC that selectively cleaves 'Lys-63'-linked ubiquitin chains
CC (PubMed:17548520, PubMed:29291351). {ECO:0000250|UniProtKB:O43318,
CC ECO:0000269|PubMed:16157589, ECO:0000269|PubMed:17548520,
CC ECO:0000269|PubMed:25632008, ECO:0000269|PubMed:29291351}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
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DR EMBL; D76446; BAA11184.1; -; mRNA.
DR CCDS; CCDS18014.1; -.
DR RefSeq; NP_766276.1; NM_172688.3.
DR AlphaFoldDB; Q62073; -.
DR SMR; Q62073; -.
DR BioGRID; 204962; 48.
DR DIP; DIP-40666N; -.
DR IntAct; Q62073; 21.
DR MINT; Q62073; -.
DR STRING; 10090.ENSMUSP00000040307; -.
DR iPTMnet; Q62073; -.
DR PhosphoSitePlus; Q62073; -.
DR EPD; Q62073; -.
DR jPOST; Q62073; -.
DR MaxQB; Q62073; -.
DR PaxDb; Q62073; -.
DR PRIDE; Q62073; -.
DR ProteomicsDB; 292068; -.
DR Antibodypedia; 2078; 1240 antibodies from 45 providers.
DR DNASU; 26409; -.
DR Ensembl; ENSMUST00000080933; ENSMUSP00000079734; ENSMUSG00000028284.
DR GeneID; 26409; -.
DR KEGG; mmu:26409; -.
DR UCSC; uc008sep.2; mouse.
DR CTD; 6885; -.
DR MGI; MGI:1346877; Map3k7.
DR VEuPathDB; HostDB:ENSMUSG00000028284; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000157785; -.
DR HOGENOM; CLU_000288_7_41_1; -.
DR InParanoid; Q62073; -.
DR OMA; PARTQCF; -.
DR BRENDA; 2.7.11.25; 3474.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-MMU-4086398; Ca2+ pathway.
DR Reactome; R-MMU-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-MMU-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR Reactome; R-MMU-937042; IRAK2 mediated activation of TAK1 complex.
DR Reactome; R-MMU-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
DR Reactome; R-MMU-9645460; Alpha-protein kinase 1 signaling pathway.
DR Reactome; R-MMU-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
DR BioGRID-ORCS; 26409; 26 hits in 77 CRISPR screens.
DR ChiTaRS; Map3k7; mouse.
DR PRO; PR:Q62073; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q62073; protein.
DR Bgee; ENSMUSG00000028284; Expressed in undifferentiated genital tubercle and 263 other tissues.
DR ExpressionAtlas; Q62073; baseline and differential.
DR Genevisible; Q62073; MM.
DR GO; GO:0140672; C:ATAC complex; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0008385; C:IkappaB kinase complex; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0004707; F:MAP kinase activity; ISO:MGI.
DR GO; GO:0004708; F:MAP kinase kinase activity; IDA:MGI.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; ISS:UniProtKB.
DR GO; GO:0008349; F:MAP kinase kinase kinase kinase activity; IMP:MGI.
DR GO; GO:0019211; F:phosphatase activator activity; IMP:MGI.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IMP:MGI.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:WormBase.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:WormBase.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0043276; P:anoikis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0097190; P:apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0060348; P:bone development; IMP:MGI.
DR GO; GO:0043966; P:histone H3 acetylation; ISO:MGI.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IGI:MGI.
DR GO; GO:0007252; P:I-kappaB phosphorylation; IGI:MGI.
DR GO; GO:0007254; P:JNK cascade; IDA:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IDA:MGI.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0060546; P:negative regulation of necroptotic process; IMP:UniProtKB.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:UniProtKB.
DR GO; GO:1902443; P:negative regulation of ripoptosome assembly involved in necroptotic process; IGI:MGI.
DR GO; GO:0001841; P:neural tube formation; IMP:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IMP:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:WormBase.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IGI:MGI.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISO:MGI.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IGI:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0002726; P:positive regulation of T cell cytokine production; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:MGI.
DR GO; GO:0051403; P:stress-activated MAPK cascade; ISO:MGI.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:MGI.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017421; MAPKKK7.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR46716; PTHR46716; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF038168; MAPKKK7; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Apoptosis; ATP-binding; Cell membrane; Cytoplasm; Isopeptide bond; Kinase;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Stress response;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation.
FT CHAIN 1..579
FT /note="Mitogen-activated protein kinase kinase kinase 7"
FT /id="PRO_0000086253"
FT DOMAIN 36..291
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..300
FT /note="Interaction with MAPK8IP1"
FT /evidence="ECO:0000269|PubMed:17709393"
FT REGION 301..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 354..391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 416..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..338
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..448
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 156
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 42..50
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 184
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT MOD_RES 187
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT MOD_RES 192
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT MOD_RES 367
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT CROSSLNK 72
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O43318"
FT CROSSLNK 158
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:29291351"
FT CROSSLNK 209
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:29291351"
FT MUTAGEN 34
FT /note="K->R: No effect on ubiquitination. No effect on
FT induction of phosphorylation; when associated with R-562."
FT /evidence="ECO:0000269|PubMed:29291351"
FT MUTAGEN 158
FT /note="K->R: Abolishes ubiquitination. Abolishes
FT ubiquitination and induction of phosphorylation; when
FT associated with R-209."
FT /evidence="ECO:0000269|PubMed:29291351"
FT MUTAGEN 209
FT /note="K->R: Strongly decreases ubiquitination. Abolishes
FT ubiquitination and induction of phosphorylation; when
FT associated with R-158."
FT /evidence="ECO:0000269|PubMed:29291351"
FT MUTAGEN 562
FT /note="K->R: No effect on ubiquitination. No effect on
FT induction of phosphorylation; when associated with R-34."
FT /evidence="ECO:0000269|PubMed:29291351"
SQ 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
