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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_HUMAN              Reviewed;         606 AA.
O43318; B2RE27; E1P523; O43317; O43319; Q5TDN2; Q5TDN3; Q5TDT7; Q9NTR3;
Q9NZ70;
01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
01-JUN-1998, sequence version 1.
17-JUN-2020, entry version 220.
RecName: Full=Mitogen-activated protein kinase kinase kinase 7;
EC=2.7.11.25 {ECO:0000269|PubMed:10094049, ECO:0000269|PubMed:10838074, ECO:0000269|PubMed:12589052};
AltName: Full=Transforming growth factor-beta-activated kinase 1;
Short=TGF-beta-activated kinase 1;
Name=MAP3K7 {ECO:0000303|PubMed:28397838, ECO:0000312|HGNC:HGNC:6859};
Synonyms=TAK1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A; 1B AND 1C).
TISSUE=Lung;
PubMed=9480845; DOI=10.1006/bbrc.1998.8124;
Sakurai H., Shigemori N., Hasegawa K., Sugita T.;
"TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-
kappa B-inducing kinase-independent mechanism.";
Biochem. Biophys. Res. Commun. 243:545-549(1998).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1D), AND TISSUE SPECIFICITY.
PubMed=11118615; DOI=10.1016/s0167-4781(00)00258-x;
Dempsey C.E., Sakurai H., Sugita T., Guesdon F.;
"Alternative splicing and gene structure of the transforming growth factor
beta-activated kinase 1.";
Biochim. Biophys. Acta 1517:46-52(2000).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
NHLBI resequencing and genotyping service (RS&G);
Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1A).
TISSUE=Trachea;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=14574404; DOI=10.1038/nature02055;
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
Rogers J., Beck S.;
"The DNA sequence and analysis of human chromosome 6.";
Nature 425:805-811(2003).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
Hunkapiller M.W., Myers E.W., Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1A).
TISSUE=Uterus;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project:
the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
FUNCTION IN PHOSPHORYLATION OF MAP2K3/MKK3 AND MAP2K6/MKK6.
PubMed=8663074; DOI=10.1074/jbc.271.23.13675;
Moriguchi T., Kuroyanagi N., Yamaguchi K., Gotoh Y., Irie K., Kano T.,
Shirakabe K., Muro Y., Shibuya H., Matsumoto K., Nishida E., Hagiwara M.;
"A novel kinase cascade mediated by mitogen-activated protein kinase kinase
6 and MKK3.";
J. Biol. Chem. 271:13675-13679(1996).
[9]
INTERACTION WITH TAB1/MAP3K7IP1.
PubMed=8638164; DOI=10.1126/science.272.5265.1179;
Shibuya H., Yamaguchi K., Shirakabe K., Tonegawa A., Gotoh Y., Ueno N.,
Irie K., Nishida E., Matsumoto K.;
"TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction.";
Science 272:1179-1182(1996).
[10]
ACTIVITY REGULATION, AND FUNCTION.
PubMed=9079627; DOI=10.1074/jbc.272.13.8141;
Shirakabe K., Yamaguchi K., Shibuya H., Irie K., Matsuda S., Moriguchi T.,
Gotoh Y., Matsumoto K., Nishida E.;
"TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-
Jun N-terminal kinase.";
J. Biol. Chem. 272:8141-8144(1997).
[11]
INTERACTION WITH TRAF6 AND TAB1/MAP3K7IP1, FUNCTION, AND CATALYTIC
ACTIVITY.
PubMed=10094049; DOI=10.1038/18465;
Ninomiya-Tsuji J., Kishimoto K., Hiyama A., Inoue J., Cao Z., Matsumoto K.;
"The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase
cascade in the IL-1 signalling pathway.";
Nature 398:252-256(1999).
[12]
INTERACTION WITH TAB1, PHOSPHORYLATION AT THR-184; THR-187 AND SER-192,
ACTIVATION, AND CATALYTIC ACTIVITY.
PubMed=10838074; DOI=10.1016/s0014-5793(00)01588-x;
Sakurai H., Miyoshi H., Mizukami J., Sugita T.;
"Phosphorylation-dependent activation of TAK1 mitogen-activated protein
kinase kinase kinase by TAB1.";
FEBS Lett. 474:141-145(2000).
[13]
PHOSPHORYLATION AT SER-192, AND ACTIVITY REGULATION.
PubMed=10702308; DOI=10.1074/jbc.275.10.7359;
Kishimoto K., Matsumoto K., Ninomiya-Tsuji J.;
"TAK1 mitogen-activated protein kinase kinase kinase is activated by
autophosphorylation within its activation loop.";
J. Biol. Chem. 275:7359-7364(2000).
[14]
DEPHOSPHORYLATION BY PPM1B/PP2CB, AND INTERACTION WITH PPM1B/PP2CB.
PubMed=11104763; DOI=10.1074/jbc.m007773200;
Hanada M., Ninomiya-Tsuji J., Komaki K., Ohnishi M., Katsura K.,
Kanamaru R., Matsumoto K., Tamura S.;
"Regulation of the TAK1 signaling pathway by protein phosphatase 2C.";
J. Biol. Chem. 276:5753-5759(2001).
[15]
UBIQUITINATION, FUNCTION, ACTIVITY REGULATION, INTERACTION WITH
TAB1/MAP3K7IP2 AND TAB2/MAP3K7IP2, AND IDENTIFICATION IN THE TRIKA2
COMPLEX.
PubMed=11460167; DOI=10.1038/35085597;
Wang C., Deng L., Hong M., Akkaraju G.R., Inoue J., Chen Z.J.;
"TAK1 is a ubiquitin-dependent kinase of MKK and IKK.";
Nature 412:346-351(2001).
[16]
INTERACTION WITH IRAK; TAB1/MAP3K7IP1; TAB2/MAP3K7IP2 AND TRAF6,
PHOSPHORYLATION, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
PubMed=12242293; DOI=10.1128/mcb.22.20.7158-7167.2002;
Jiang Z., Ninomiya-Tsuji J., Qian Y., Matsumoto K., Li X.;
"Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced
signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and
activate TAK1 in the cytosol.";
Mol. Cell. Biol. 22:7158-7167(2002).
[17]
INTERACTION WITH PELI1 AND PELI2.
PubMed=12804775; DOI=10.1016/s0014-5793(03)00533-7;
Jensen L.E., Whitehead A.S.;
"Pellino2 activates the mitogen activated protein kinase pathway.";
FEBS Lett. 545:199-202(2003).
[18]
INTERACTION WITH PELI3.
PubMed=12874243; DOI=10.4049/jimmunol.171.3.1500;
Jensen L.E., Whitehead A.S.;
"Pellino3, a novel member of the Pellino protein family, promotes
activation of c-Jun and Elk-1 and may act as a scaffolding protein.";
J. Immunol. 171:1500-1506(2003).
[19]
FUNCTION, INTERACTION WITH SMAD7; MAP2K3 AND P38 KINASE, MUTAGENESIS OF
LYS-63, AND CATALYTIC ACTIVITY.
PubMed=12589052; DOI=10.1091/mbc.02-03-0037;
Edlund S., Bu S., Schuster N., Aspenstroem P., Heuchel R., Heldin N.E.,
ten Dijke P., Heldin C.H., Landstrom M.;
"Transforming growth factor-beta1 (TGF-beta)-induced apoptosis of prostate
cancer cells involves Smad7-dependent activation of p38 by TGF-beta-
activated kinase 1 and mitogen-activated protein kinase kinase 3.";
Mol. Biol. Cell 14:529-544(2003).
[20]
INTERACTION WITH TAB3/MAP3K7IP3.
PubMed=14670075; DOI=10.1042/bj20031794;
Cheung P.C., Nebreda A.R., Cohen P.;
"TAB3, a new binding partner of the protein kinase TAK1.";
Biochem. J. 378:27-34(2004).
[21]
INTERACTION WITH DAB2.
PubMed=15894542; DOI=10.1074/jbc.m501150200;
Hocevar B.A., Prunier C., Howe P.H.;
"Disabled-2 (Dab2) mediates transforming growth factor beta (TGFbeta)-
stimulated fibronectin synthesis through TGFbeta-activated kinase 1 and
activation of the JNK pathway.";
J. Biol. Chem. 280:25920-25927(2005).
[22]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling
networks.";
Cell 127:635-648(2006).
[23]
UBIQUITINATION, PHOSPHORYLATION AT THR-187 BY AUTOCATALYSIS, SUBUNIT, AND
FUNCTION.
PubMed=16845370; DOI=10.1038/sj.embor.7400754;
Thiefes A., Wolf A., Doerrie A., Grassl G.A., Matsumoto K., Autenrieth I.,
Bohn E., Sakurai H., Niedenthal R., Resch K., Kracht M.;
"The Yersinia enterocolitica effector YopP inhibits host cell signalling by
inactivating the protein kinase TAK1 in the IL-1 signalling pathway.";
EMBO Rep. 7:838-844(2006).
[24]
FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH TAOK1 AND TAOK2.
PubMed=16893890; DOI=10.1074/jbc.m603627200;
Huangfu W.C., Omori E., Akira S., Matsumoto K., Ninomiya-Tsuji J.;
"Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated
NF-kappaB activation: TAO2 regulates TAK1 pathways.";
J. Biol. Chem. 281:28802-28810(2006).
[25]
INTERACTION WITH PP2A AND PPP6C, AND DEPHOSPHORYLATION AT THR-187 BY PP2A
AND PPP6C.
PubMed=17079228; DOI=10.1074/jbc.m608155200;
Kajino T., Ren H., Iemura S., Natsume T., Stefansson B., Brautigan D.L.,
Matsumoto K., Ninomiya-Tsuji J.;
"Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1
signaling pathway.";
J. Biol. Chem. 281:39891-39896(2006).
[26]
INTERACTION WITH RBCK1.
PubMed=17449468; DOI=10.1074/jbc.m701913200;
Tian Y., Zhang Y., Zhong B., Wang Y.Y., Diao F.C., Wang R.P., Zhang M.,
Chen D.Y., Zhai Z.H., Shu H.B.;
"RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-
triggered NF-kappaB activation by targeting TAB2/3 for degradation.";
J. Biol. Chem. 282:16776-16782(2007).
[27]
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).
[28]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Platelet;
PubMed=18088087; DOI=10.1021/pr0704130;
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
Schuetz C., Walter U., Gambaryan S., Sickmann A.;
"Phosphoproteome of resting human platelets.";
J. Proteome Res. 7:526-534(2008).
[29]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
Greff Z., Keri G., Stemmann O., Mann M.;
"Kinase-selective enrichment enables quantitative phosphoproteomics of the
kinome across the cell cycle.";
Mol. Cell 31:438-448(2008).
[30]
INTERACTION WITH TGFBR1.
PubMed=18758450; DOI=10.1038/ncb1780;
Sorrentino A., Thakur N., Grimsby S., Marcusson A., von Bulow V.,
Schuster N., Zhang S., Heldin C.H., Landstrom M.;
"The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor
kinase-independent manner.";
Nat. Cell Biol. 10:1199-1207(2008).
[31]
INTERACTION WITH VRK2.
PubMed=18286207; DOI=10.1371/journal.pone.0001660;
Blanco S., Sanz-Garcia M., Santos C.R., Lazo P.A.;
"Modulation of interleukin-1 transcriptional response by the interaction
between VRK2 and the JIP1 scaffold protein.";
PLoS ONE 3:E1660-E1660(2008).
[32]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389 AND SER-439, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[33]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19413330; DOI=10.1021/ac9004309;
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
"Lys-N and trypsin cover complementary parts of the phosphoproteome in a
refined SCX-based approach.";
Anal. Chem. 81:4493-4501(2009).
[34]
INTERACTION WITH WDR34.
PubMed=19521662; DOI=10.1007/s00018-009-0059-6;
Gao D., Wang R., Li B., Yang Y., Zhai Z., Chen D.Y.;
"WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced
NF-kappaB activation pathway.";
Cell. Mol. Life Sci. 66:2573-2584(2009).
[35]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389 AND SER-439, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
Mann M., Daub H.;
"Large-scale proteomics analysis of the human kinome.";
Mol. Cell. Proteomics 8:1751-1764(2009).
[36]
INTERACTION WITH TAB2, AND PHOSPHORYLATION AT THR-187.
PubMed=19675569; DOI=10.1038/nature08247;
Xia Z.-P., Sun L., Chen X., Pineda G., Jiang X., Adhikari A., Zeng W.,
Chen Z.J.;
"Direct activation of protein kinases by unanchored polyubiquitin chains.";
Nature 461:114-119(2009).
[37]
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).
[38]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389 AND SER-439, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Leukemic T-cell;
PubMed=19690332; DOI=10.1126/scisignal.2000007;
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
Rodionov V., Han D.K.;
"Quantitative phosphoproteomic analysis of T cell receptor signaling
reveals system-wide modulation of protein-protein interactions.";
Sci. Signal. 2:RA46-RA46(2009).
[39]
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).
[40]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=20068231; DOI=10.1126/scisignal.2000475;
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
"Quantitative phosphoproteomics reveals widespread full phosphorylation
site occupancy during mitosis.";
Sci. Signal. 3:RA3-RA3(2010).
[41]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[42]
INTERACTION WITH TRIM8.
PubMed=22084099; DOI=10.1073/pnas.1110946108;
Li Q., Yan J., Mao A.P., Li C., Ran Y., Shu H.B., Wang Y.Y.;
"Tripartite motif 8 (TRIM8) modulates TNFalpha- and IL-1beta-triggered NF-
kappaB activation by targeting TAK1 for K63-linked polyubiquitination.";
Proc. Natl. Acad. Sci. U.S.A. 108:19341-19346(2011).
[43]
FUNCTION, INTERACTION WITH TRIM5, AND PHOSPHORYLATION AT THR-187.
PubMed=21512573; DOI=10.1038/nature09976;
Pertel T., Hausmann S., Morger D., Zueger S., Guerra J., Lascano J.,
Reinhard C., Santoni F.A., Uchil P.D., Chatel L., Bisiaux A., Albert M.L.,
Strambio-De-Castillia C., Mothes W., Pizzato M., Gruetter M.G., Luban J.;
"TRIM5 is an innate immune sensor for the retrovirus capsid lattice.";
Nature 472:361-365(2011).
[44]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389 AND SER-439, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21406692; DOI=10.1126/scisignal.2001570;
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
"System-wide temporal characterization of the proteome and phosphoproteome
of human embryonic stem cell differentiation.";
Sci. Signal. 4:RS3-RS3(2011).
[45]
UBIQUITINATION AT LYS-72.
PubMed=22406003; DOI=10.1016/j.cellsig.2012.02.017;
Fan Y., Shi Y., Liu S., Mao R., An L., Zhao Y., Zhang H., Zhang F., Xu G.,
Qin J., Yang J.;
"Lys48-linked TAK1 polyubiquitination at lysine-72 downregulates TNFalpha-
induced NF-kappaB activation via mediating TAK1 degradation.";
Cell. Signal. 24:1381-1389(2012).
[46]
INTERACTION WITH SASH1.
PubMed=23776175; DOI=10.4049/jimmunol.1200583;
Dauphinee S.M., Clayton A., Hussainkhel A., Yang C., Park Y.J.,
Fuller M.E., Blonder J., Veenstra T.D., Karsan A.;
"SASH1 is a scaffold molecule in endothelial TLR4 signaling.";
J. Immunol. 191:892-901(2013).
[47]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; SER-389; SER-439 AND
SER-455, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma, and Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[48]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
phosphoproteome.";
J. Proteomics 96:253-262(2014).
[49]
INTERACTION WITH IFIT5.
PubMed=26334375; DOI=10.1016/j.cellsig.2015.08.018;
Zheng C., Zheng Z., Zhang Z., Meng J., Liu Y., Ke X., Hu Q., Wang H.;
"IFIT5 positively regulates NF-kappaB signaling through synergizing the
recruitment of IkappaB kinase (IKK) to TGF-beta-activated kinase 1
(TAK1).";
Cell. Signal. 27:2343-2354(2015).
[50]
INVOLVEMENT IN FMD2, VARIANTS FMD2 GLN-70; GLU-100; ARG-168 AND LEU-512,
CHARACTERIZATION OF VARIANTS FMD2 LEU-512 AND ARG-168, SUBUNIT, AND
MUTAGENESIS OF PRO-512.
PubMed=27426733; DOI=10.1016/j.ajhg.2016.05.024;
Wade E.M., Daniel P.B., Jenkins Z.A., McInerney-Leo A., Leo P., Morgan T.,
Addor M.C., Ades L.C., Bertola D., Bohring A., Carter E., Cho T.J.,
Duba H.C., Fletcher E., Kim C.A., Krakow D., Morava E., Neuhann T.,
Superti-Furga A., Veenstra-Knol I., Wieczorek D., Wilson L.C.,
Hennekam R.C., Sutherland-Smith A.J., Strom T.M., Wilkie A.O., Brown M.A.,
Duncan E.L., Markie D.M., Robertson S.P.;
"Mutations in MAP3K7 that alter the activity of the TAK1 signaling complex
cause frontometaphyseal dysplasia.";
Am. J. Hum. Genet. 99:392-406(2016).
[51]
INVOLVEMENT IN CSCF, AND VARIANTS CSCF VAL-50 DEL; CYS-110 AND ARG-241.
PubMed=27426734; DOI=10.1016/j.ajhg.2016.06.005;
Le Goff C., Rogers C., Le Goff W., Pinto G., Bonnet D., Chrabieh M.,
Alibeu O., Nistchke P., Munnich A., Picard C., Cormier-Daire V.;
"Heterozygous mutations in MAP3K7, encoding TGF-beta-activated kinase 1,
cause cardiospondylocarpofacial syndrome.";
Am. J. Hum. Genet. 99:407-413(2016).
[52]
INTERACTION WITH HHV-2 PROTEIN US2 (MICROBIAL INFECTION).
PubMed=28827540; DOI=10.1038/s41598-017-08856-4;
Lu X., Huang C., Zhang Y., Lin Y., Wang X., Li Q., Liu S., Tang J.,
Zhou L.;
"The Us2 Gene Product of herpes dimplex virus 2 modulates NF-kappaB
activation by targeting TAK1.";
Sci. Rep. 7:8396-8396(2017).
[53]
PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION).
PubMed=28424289; DOI=10.1128/jvi.00546-17;
Rui Y., Su J., Wang H., Chang J., Wang S., Zheng W., Cai Y., Wei W.,
Gordy J.T., Markham R., Kong W., Zhang W., Yu X.F.;
"Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of
Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68.";
J. Virol. 91:0-0(2017).
[54]
ACTIVITY REGULATION.
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).
[55]
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 31-328 IN COMPLEX WITH TAB1 AND
ADENOSINE.
PubMed=16289117; DOI=10.1016/j.jmb.2005.09.098;
Brown K., Vial S.C., Dedi N., Long J.M., Dunster N.J., Cheetham G.M.T.;
"Structural basis for the interaction of TAK1 kinase with its activating
protein TAB1.";
J. Mol. Biol. 354:1013-1020(2005).
[56]
VARIANT GLN-410.
PubMed=28397838; DOI=10.1038/mp.2017.60;
Harripaul R., Vasli N., Mikhailov A., Rafiq M.A., Mittal K.,
Windpassinger C., Sheikh T.I., Noor A., Mahmood H., Downey S., Johnson M.,
Vleuten K., Bell L., Ilyas M., Khan F.S., Khan V., Moradi M., Ayaz M.,
Naeem F., Heidari A., Ahmed I., Ghadami S., Agha Z., Zeinali S., Qamar R.,
Mozhdehipanah H., John P., Mir A., Ansar M., French L., Ayub M.,
Vincent J.B.;
"Mapping autosomal recessive intellectual disability: combined microarray
and exome sequencing identifies 26 novel candidate genes in 192
consanguineous families.";
Mol. Psychiatry 23:973-984(2018).
-!- 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). {ECO:0000250|UniProtKB:Q62073,
ECO:0000269|PubMed:10094049, ECO:0000269|PubMed:11460167,
ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:16845370,
ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:21512573,
ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9079627}.
-!- 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:0000269|PubMed:10094049, ECO:0000269|PubMed:10838074,
ECO:0000269|PubMed:12589052};
-!- 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:0000269|PubMed:10094049,
ECO:0000269|PubMed:10838074, ECO:0000269|PubMed:12589052};
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
-!- 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:10702308,
ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12242293,
ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:29291351,
ECO:0000269|PubMed:9079627}.
-!- SUBUNIT: Can form homodimer (PubMed:27426733). Binds both upstream
activators and downstream substrates in multimolecular complexes.
Interacts with TAB1/MAP3K7IP1, TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3
(PubMed:10838074, PubMed:11460167, PubMed:12242293, PubMed:14670075,
PubMed:16289117, PubMed:19675569, PubMed:8638164). Identified in the
TRIKA2 complex composed of MAP3K7/TAK1, TAB1/MAP3K7IP1 and
TAB2/MAP3K7IP2 (PubMed:11460167). Interacts with PPM1L and PPM1B/PP2CB
(PubMed:11104763). Interaction with PP2A and PPP6C leads to its
repressed activity (PubMed:17079228). Interacts with TRAF6 and
TAB1/MAP3K7IP1; during IL-1 signaling (PubMed:10094049,
PubMed:12242293). Interacts with TAOK1 and TAOK2; interaction with
TAOK2 interferes with MAP3K7 interaction with IKKA, thus preventing NF-
kappa-B activation (PubMed:16893890). Interacts with WDR34 (via WD
domains) (PubMed:19521662). Interacts with CYLD and RBCK1
(PubMed:17449468, PubMed:17548520). Interacts with TGFBR1; induces
MAP3K7/TAK1 activation by TRAF6 (PubMed:18758450). Interacts with
MAPK8IP1 and SMAD6 (By similarity). Interacts with isoform 1 of VRK2
(PubMed:18286207). Interacts with DAB2; the interaction is induced by
TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation
(PubMed:15894542). Interacts with TRIM5 (PubMed:21512573). Part of a
complex containing ITCH, NDFIP1 and MAP3K7 (By similarity). Interacts
with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7
and enhances IKK phosphorylation (PubMed:26334375). Interacts with
PLEKHM1 (via N- and C-terminus) (By similarity). Interacts with TRIM8
(PubMed:22084099). Found in a complex with SH3RF1, RAC2, MAP2K7/MKK7,
MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (By similarity). Interacts
with SASH1 (PubMed:23776175). Interacts with RIPK1 (By similarity).
{ECO:0000250|UniProtKB:Q62073, ECO:0000269|PubMed:10094049,
ECO:0000269|PubMed:10838074, ECO:0000269|PubMed:11104763,
ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12242293,
ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:12804775,
ECO:0000269|PubMed:12874243, ECO:0000269|PubMed:14670075,
ECO:0000269|PubMed:15894542, ECO:0000269|PubMed:16289117,
ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:16893890,
ECO:0000269|PubMed:17079228, ECO:0000269|PubMed:17449468,
ECO:0000269|PubMed:17548520, ECO:0000269|PubMed:18286207,
ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:19521662,
ECO:0000269|PubMed:19675569, ECO:0000269|PubMed:21512573,
ECO:0000269|PubMed:22084099, ECO:0000269|PubMed:23776175,
ECO:0000269|PubMed:26334375, ECO:0000269|PubMed:27426733,
ECO:0000269|PubMed:8638164}.
-!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 2
protein US2; this interaction induces MAP3K7 phosphorylation and
subsequent activation. {ECO:0000269|PubMed:28827540}.
-!- INTERACTION:
O43318; O14733: MAP2K7; NbExp=3; IntAct=EBI-358684, EBI-492605;
O43318; Q9UQF2: MAPK8IP1; NbExp=11; IntAct=EBI-358684, EBI-78404;
O43318; Q9UBE8: NLK; NbExp=3; IntAct=EBI-358684, EBI-366978;
O43318; O00743: PPP6C; NbExp=4; IntAct=EBI-358684, EBI-359751;
O43318; P40763: STAT3; NbExp=4; IntAct=EBI-358684, EBI-518675;
O43318; Q15750: TAB1; NbExp=4; IntAct=EBI-358684, EBI-358643;
O43318; Q9NYJ8: TAB2; NbExp=6; IntAct=EBI-358684, EBI-358708;
O43318; Q8N5C8: TAB3; NbExp=3; IntAct=EBI-358684, EBI-359964;
O43318; Q9UKE5: TNIK; NbExp=3; IntAct=EBI-358684, EBI-1051794;
O43318; Q9Y4K3: TRAF6; NbExp=2; IntAct=EBI-358684, EBI-359276;
O43318; P0CG48: UBC; NbExp=4; IntAct=EBI-358684, EBI-3390054;
O43318; B5Z6S0: cagA; Xeno; NbExp=4; IntAct=EBI-358684, EBI-7287204;
O43318-2; Q16543: CDC37; NbExp=5; IntAct=EBI-358700, EBI-295634;
O43318-2; P07900: HSP90AA1; NbExp=5; IntAct=EBI-358700, EBI-296047;
O43318-2; Q15750: TAB1; NbExp=3; IntAct=EBI-358700, EBI-358643;
O43318-2; Q9NYJ8: TAB2; NbExp=2; IntAct=EBI-358700, EBI-358708;
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12242293}. Cell
membrane {ECO:0000269|PubMed:12242293}; Peripheral membrane protein
{ECO:0000269|PubMed:12242293}; Cytoplasmic side
{ECO:0000269|PubMed: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.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=4;
Name=1B;
IsoId=O43318-1; Sequence=Displayed;
Name=1A;
IsoId=O43318-2; Sequence=VSP_004886;
Name=1C;
IsoId=O43318-3; Sequence=VSP_004887, VSP_004888;
Name=1D;
IsoId=O43318-4; Sequence=VSP_004886, VSP_004887, VSP_004888;
-!- 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:0000269|PubMed:11118615}.
-!- PTM: Association with TAB1/MAP3K7IP1 promotes autophosphorylation at
Ser-192 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 Ser-192 by PPM1B/PP2CB and at Thr-187 by PP2A and
PPP6C leads to inactivation. {ECO:0000269|PubMed:10702308,
ECO:0000269|PubMed:10838074, ECO:0000269|PubMed:16845370,
ECO:0000269|PubMed:17548520, ECO:0000269|PubMed:19675569,
ECO:0000269|PubMed:21512573}.
-!- PTM: 'Lys-48'-linked polyubiquitination at Lys-72 is induced by
TNFalpha, and leads to proteasomal degradation. Undergoes 'Lys-48'-
linked polyubiquitination catalyzed by ITCH (By similarity). Requires
'Lys-63'-linked polyubiquitination for autophosphorylation and
subsequent activation. 'Lys-63'-linked ubiquitination does not lead to
proteasomal degradation. Deubiquitinated by CYLD, a protease that
selectively cleaves 'Lys-63'-linked ubiquitin chains. Deubiquitinated
by Y.enterocolitica YopP. {ECO:0000250|UniProtKB:Q62073,
ECO:0000269|PubMed:17548520, ECO:0000269|PubMed:22406003}.
-!- PTM: (Microbial infection) Cleaved and inactivated by the proteases 3C
of coxsackievirus A16 and human enterovirus D68, allowing the virus to
disrupt TRAF6-triggered NF-kappa-B induction.
{ECO:0000269|PubMed:28424289}.
-!- DISEASE: Frontometaphyseal dysplasia 2 (FMD2) [MIM:617137]: A form of
frontometaphyseal dysplasia, a progressive sclerosing skeletal
dysplasia affecting the long bones and skull. Characteristic features
include supraorbital hyperostosis, cranial hyperostosis, undermodeling
of the small bones, flared metaphyses, and digital anomalies. Extra-
skeletal manifestations include hearing loss, cardiac malformations,
and stenosis, particularly of the upper airway and urinary tract. FMD2
inheritance is autosomal dominant. {ECO:0000269|PubMed:27426733}.
Note=The disease is caused by mutations affecting the gene represented
in this entry.
-!- DISEASE: Cardiospondylocarpofacial syndrome (CSCF) [MIM:157800]: A
syndrome characterized by growth retardation, dysmorphic facial
features, brachydactyly with carpal-tarsal fusion and extensive
posterior cervical vertebral synostosis, cardiac septal defects with
valve dysplasia, and deafness with inner ear malformations. CSCF
transmission pattern is consistent with autosomal dominant inheritance.
{ECO:0000269|PubMed:27426734}. Note=The disease is caused by mutations
affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
protein kinase family. MAP kinase kinase kinase subfamily.
{ECO:0000305}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
Haematology;
URL="http://atlasgeneticsoncology.org/Genes/MAP3K7ID454ch6q15.html";
---------------------------------------------------------------------------
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EMBL; AB009357; BAA25026.1; -; mRNA.
EMBL; AB009356; BAA25025.1; -; mRNA.
EMBL; AB009358; BAA25027.2; -; mRNA.
EMBL; AF218074; AAF27652.1; -; mRNA.
EMBL; DQ314875; ABC40734.1; -; Genomic_DNA.
EMBL; AK315774; BAG38124.1; -; mRNA.
EMBL; AL121964; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AL121837; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471051; EAW48525.1; -; Genomic_DNA.
EMBL; CH471051; EAW48526.1; -; Genomic_DNA.
EMBL; CH471051; EAW48527.1; -; Genomic_DNA.
EMBL; CH471051; EAW48529.1; -; Genomic_DNA.
EMBL; BC017715; AAH17715.1; -; mRNA.
CCDS; CCDS5027.1; -. [O43318-2]
CCDS; CCDS5028.1; -. [O43318-1]
CCDS; CCDS5029.1; -. [O43318-3]
CCDS; CCDS5030.1; -. [O43318-4]
PIR; JC5955; JC5955.
PIR; JC5956; JC5956.
RefSeq; NP_003179.1; NM_003188.3. [O43318-2]
RefSeq; NP_663304.1; NM_145331.2. [O43318-1]
RefSeq; NP_663305.1; NM_145332.2. [O43318-3]
RefSeq; NP_663306.1; NM_145333.2. [O43318-4]
PDB; 2EVA; X-ray; 2.00 A; A=31-303.
PDB; 2YIY; X-ray; 2.49 A; A=31-303.
PDB; 4GS6; X-ray; 2.20 A; A=31-303.
PDB; 4L3P; X-ray; 2.68 A; A=31-303.
PDB; 4L52; X-ray; 2.54 A; A=31-303.
PDB; 4L53; X-ray; 2.55 A; A=31-303.
PDB; 4O91; X-ray; 2.39 A; A=31-303.
PDB; 5E7R; X-ray; 2.11 A; A=31-303.
PDB; 5GJD; X-ray; 2.79 A; A=31-303.
PDB; 5GJF; X-ray; 2.89 A; A=31-303.
PDB; 5GJG; X-ray; 2.61 A; A=31-303.
PDB; 5J7S; X-ray; 2.37 A; A=31-303.
PDB; 5J8I; X-ray; 2.40 A; A=31-303.
PDB; 5J9L; X-ray; 2.75 A; A=31-303.
PDB; 5JGA; X-ray; 2.00 A; A=31-303.
PDB; 5JGB; X-ray; 2.80 A; A=31-303.
PDB; 5JGD; X-ray; 3.10 A; A=31-303.
PDB; 5JH6; X-ray; 2.37 A; A=31-303.
PDB; 5JK3; X-ray; 2.37 A; A=31-303.
PDB; 5V5N; X-ray; 2.01 A; A=31-303.
PDBsum; 2EVA; -.
PDBsum; 2YIY; -.
PDBsum; 4GS6; -.
PDBsum; 4L3P; -.
PDBsum; 4L52; -.
PDBsum; 4L53; -.
PDBsum; 4O91; -.
PDBsum; 5E7R; -.
PDBsum; 5GJD; -.
PDBsum; 5GJF; -.
PDBsum; 5GJG; -.
PDBsum; 5J7S; -.
PDBsum; 5J8I; -.
PDBsum; 5J9L; -.
PDBsum; 5JGA; -.
PDBsum; 5JGB; -.
PDBsum; 5JGD; -.
PDBsum; 5JH6; -.
PDBsum; 5JK3; -.
PDBsum; 5V5N; -.
SMR; O43318; -.
BioGRID; 112748; 181.
CORUM; O43318; -.
DIP; DIP-27523N; -.
IntAct; O43318; 76.
MINT; O43318; -.
STRING; 9606.ENSP00000358335; -.
BindingDB; O43318; -.
ChEMBL; CHEMBL5776; -.
DrugCentral; O43318; -.
GuidetoPHARMACOLOGY; 2082; -.
MoonDB; O43318; Predicted.
iPTMnet; O43318; -.
MetOSite; O43318; -.
PhosphoSitePlus; O43318; -.
BioMuta; MAP3K7; -.
CPTAC; CPTAC-1048; -.
CPTAC; CPTAC-853; -.
CPTAC; CPTAC-854; -.
CPTAC; CPTAC-855; -.
CPTAC; CPTAC-856; -.
EPD; O43318; -.
jPOST; O43318; -.
MassIVE; O43318; -.
MaxQB; O43318; -.
PaxDb; O43318; -.
PeptideAtlas; O43318; -.
PRIDE; O43318; -.
ProteomicsDB; 48898; -. [O43318-1]
ProteomicsDB; 48899; -. [O43318-2]
ProteomicsDB; 48900; -. [O43318-3]
ProteomicsDB; 48901; -. [O43318-4]
Antibodypedia; 2078; 1137 antibodies.
DNASU; 6885; -.
Ensembl; ENST00000369325; ENSP00000358331; ENSG00000135341. [O43318-3]
Ensembl; ENST00000369327; ENSP00000358333; ENSG00000135341. [O43318-4]
Ensembl; ENST00000369329; ENSP00000358335; ENSG00000135341. [O43318-1]
Ensembl; ENST00000369332; ENSP00000358338; ENSG00000135341. [O43318-2]
GeneID; 6885; -.
KEGG; hsa:6885; -.
UCSC; uc003pnz.3; human. [O43318-1]
CTD; 6885; -.
DisGeNET; 6885; -.
EuPathDB; HostDB:ENSG00000135341.17; -.
GeneCards; MAP3K7; -.
HGNC; HGNC:6859; MAP3K7.
HPA; ENSG00000135341; Low tissue specificity.
MalaCards; MAP3K7; -.
MIM; 157800; phenotype.
MIM; 602614; gene.
MIM; 617137; phenotype.
neXtProt; NX_O43318; -.
OpenTargets; ENSG00000135341; -.
Orphanet; 3238; Cardiospondylocarpofacial syndrome.
Orphanet; 1826; Frontometaphyseal dysplasia.
PharmGKB; PA30603; -.
eggNOG; KOG0192; Eukaryota.
eggNOG; COG0515; LUCA.
GeneTree; ENSGT00940000157785; -.
HOGENOM; CLU_000288_7_41_1; -.
InParanoid; O43318; -.
KO; K04427; -.
OMA; FQCSQGV; -.
OrthoDB; 635654at2759; -.
PhylomeDB; O43318; -.
TreeFam; TF105116; -.
Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells.
Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
Reactome; R-HSA-202424; Downstream TCR signaling.
Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
Reactome; R-HSA-4086398; Ca2+ pathway.
Reactome; R-HSA-445989; TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation.
Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
Reactome; R-HSA-5357956; TNFR1-induced NFkappaB signaling pathway.
Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
Reactome; R-HSA-5689880; Ub-specific processing proteases.
Reactome; R-HSA-9014325; TICAM1,TRAF6-dependent induction of TAK1 complex.
Reactome; R-HSA-9020702; Interleukin-1 signaling.
Reactome; R-HSA-937042; IRAK2 mediated activation of TAK1 complex.
Reactome; R-HSA-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
Reactome; R-HSA-9645460; Alpha-protein kinase 1 signaling pathway.
Reactome; R-HSA-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
SignaLink; O43318; -.
SIGNOR; O43318; -.
BioGRID-ORCS; 6885; 100 hits in 818 CRISPR screens.
ChiTaRS; MAP3K7; human.
EvolutionaryTrace; O43318; -.
GeneWiki; MAP3K7; -.
GenomeRNAi; 6885; -.
Pharos; O43318; Tchem.
PRO; PR:O43318; -.
Proteomes; UP000005640; Chromosome 6.
RNAct; O43318; protein.
Bgee; ENSG00000135341; Expressed in tendon and 230 other tissues.
ExpressionAtlas; O43318; baseline and differential.
Genevisible; O43318; HS.
GO; GO:0005671; C:Ada2/Gcn5/Ada3 transcription activator complex; IDA:BHF-UCL.
GO; GO:0005829; C:cytosol; IDA:HPA.
GO; GO:0010008; C:endosome membrane; TAS:Reactome.
GO; GO:0005634; C:nucleus; HDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; IDA:HPA.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:UniProtKB.
GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
GO; GO:0004674; F:protein serine/threonine kinase activity; EXP:Reactome.
GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:WormBase.
GO; GO:0097110; F:scaffold protein binding; IDA:MGI.
GO; GO:0000187; P:activation of MAPK activity; IDA:UniProtKB.
GO; GO:0000186; P:activation of MAPKK activity; IDA:UniProtKB.
GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; IMP:UniProtKB.
GO; GO:0043276; P:anoikis; ISS:BHF-UCL.
GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
GO; GO:0043966; P:histone H3 acetylation; IDA:BHF-UCL.
GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; TAS:Reactome.
GO; GO:0007252; P:I-kappaB phosphorylation; IDA:UniProtKB.
GO; GO:0070498; P:interleukin-1-mediated signaling pathway; TAS:Reactome.
GO; GO:0007254; P:JNK cascade; IDA:UniProtKB.
GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
GO; GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:UniProtKB.
GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:UniProtKB.
GO; GO:0016239; P:positive regulation of macroautophagy; ISS:BHF-UCL.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome.
GO; GO:0002726; P:positive regulation of T cell cytokine production; IMP:UniProtKB.
GO; GO:0016579; P:protein deubiquitination; TAS:Reactome.
GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome.
GO; GO:0051403; P:stress-activated MAPK cascade; IDA:UniProtKB.
GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:ProtInc.
GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
GO; GO:0007223; P:Wnt signaling pathway, calcium modulating pathway; TAS:Reactome.
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; 1.
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;
3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell membrane;
Cytoplasm; Disease mutation; Host-virus interaction; Isopeptide bond;
Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
Phosphoprotein; Polymorphism; Reference proteome;
Serine/threonine-protein kinase; Stress response; Transcription;
Transcription regulation; Transferase; Ubl conjugation.
CHAIN 1..606
/note="Mitogen-activated protein kinase kinase kinase 7"
/id="PRO_0000086252"
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:0000250"
COMPBIAS 8..14
/note="Poly-Ser"
ACT_SITE 156
/note="Proton acceptor"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000255|PROSITE-ProRule:PRU10027"
BINDING 63
/note="ATP"
MOD_RES 184
/note="Phosphothreonine; by autocatalysis"
/evidence="ECO:0000305|PubMed:10838074"
MOD_RES 187
/note="Phosphothreonine; by autocatalysis"
/evidence="ECO:0000269|PubMed:10838074,
ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:19675569,
ECO:0000269|PubMed:21512573"
MOD_RES 192
/note="Phosphoserine; by autocatalysis"
/evidence="ECO:0000269|PubMed:10702308,
ECO:0000269|PubMed:10838074"
MOD_RES 367
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:23186163"
MOD_RES 389
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:19369195, ECO:0000244|PubMed:19690332,
ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:23186163"
MOD_RES 439
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:17081983,
ECO:0000244|PubMed:18088087, ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:18691976, ECO:0000244|PubMed:19369195,
ECO:0000244|PubMed:19690332, ECO:0000244|PubMed:20068231,
ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:23186163,
ECO:0000244|PubMed:24275569"
MOD_RES 455
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:23186163"
CROSSLNK 72
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in ubiquitin)"
/evidence="ECO:0000269|PubMed:22406003"
CROSSLNK 158
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in ubiquitin)"
/evidence="ECO:0000250|UniProtKB:Q62073"
CROSSLNK 209
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in ubiquitin)"
/evidence="ECO:0000250|UniProtKB:Q62073"
VAR_SEQ 404..430
/note="Missing (in isoform 1A and isoform 1D)"
/evidence="ECO:0000303|PubMed:11118615,
ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:9480845"
/id="VSP_004886"
VAR_SEQ 509..518
/note="PLAPCPNSKE -> ARTSCRTGPG (in isoform 1C and isoform
1D)"
/evidence="ECO:0000303|PubMed:11118615,
ECO:0000303|PubMed:9480845"
/id="VSP_004887"
VAR_SEQ 519..606
/note="Missing (in isoform 1C and isoform 1D)"
/evidence="ECO:0000303|PubMed:11118615,
ECO:0000303|PubMed:9480845"
/id="VSP_004888"
VARIANT 50
/note="Missing (in CSCF)"
/evidence="ECO:0000269|PubMed:27426734"
/id="VAR_077341"
VARIANT 70
/note="E -> Q (in FMD2; dbSNP:rs886039231)"
/evidence="ECO:0000269|PubMed:27426733"
/id="VAR_077342"
VARIANT 100
/note="V -> E (in FMD2; dbSNP:rs886039232)"
/evidence="ECO:0000269|PubMed:27426733"
/id="VAR_077343"
VARIANT 110
/note="G -> C (in CSCF; dbSNP:rs886039235)"
/evidence="ECO:0000269|PubMed:27426734"
/id="VAR_077344"
VARIANT 168
/note="G -> R (in FMD2; increases autophosphorylation; no
effect on MAPK signaling; no effect on NF-kappa-B
signaling; dbSNP:rs886039233)"
/evidence="ECO:0000269|PubMed:27426733"
/id="VAR_077345"
VARIANT 241
/note="W -> R (in CSCF; dbSNP:rs886039237)"
/evidence="ECO:0000269|PubMed:27426734"
/id="VAR_077346"
VARIANT 410
/note="R -> Q (found in a consanguineous family with
intellectual disability; unknown pathological significance;
dbSNP:rs201721045)"
/evidence="ECO:0000269|PubMed:28397838"
/id="VAR_080761"
VARIANT 512
/note="P -> L (in FMD2; does not affect interaction with
TAB2; does not affect homodimerization; increases
autophosphorylation; increases MAPK signaling; increases
NF-kappa-B signaling; dbSNP:rs886039230)"
/evidence="ECO:0000269|PubMed:27426733"
/id="VAR_077347"
MUTAGEN 34
/note="K->R: No effect on ubiquitination."
/evidence="ECO:0000269|PubMed:29291351"
MUTAGEN 63
/note="K->W: Loss of kinase activity."
/evidence="ECO:0000269|PubMed:12589052"
MUTAGEN 158
/note="K->R: Abolishes ubiquitination."
/evidence="ECO:0000269|PubMed:29291351"
MUTAGEN 209
/note="K->R: Strongly decreases ubiquitination."
/evidence="ECO:0000269|PubMed:29291351"
MUTAGEN 512
/note="P->R,A: Enhances autophosphorylation; Alters MAPK
signaling."
/evidence="ECO:0000269|PubMed:27426733"
HELIX 33..35
/evidence="ECO:0000244|PDB:2EVA"
STRAND 36..43
/evidence="ECO:0000244|PDB:2EVA"
STRAND 46..55
/evidence="ECO:0000244|PDB:2EVA"
STRAND 58..64
/evidence="ECO:0000244|PDB:2EVA"
HELIX 70..83
/evidence="ECO:0000244|PDB:2EVA"
STRAND 92..95
/evidence="ECO:0000244|PDB:2EVA"
TURN 97..100
/evidence="ECO:0000244|PDB:2EVA"
STRAND 101..105
/evidence="ECO:0000244|PDB:2EVA"
HELIX 112..117
/evidence="ECO:0000244|PDB:2EVA"
STRAND 119..123
/evidence="ECO:0000244|PDB:2EVA"
HELIX 127..145
/evidence="ECO:0000244|PDB:2EVA"
STRAND 148..150
/evidence="ECO:0000244|PDB:2EVA"
HELIX 159..161
/evidence="ECO:0000244|PDB:2EVA"
STRAND 162..165
/evidence="ECO:0000244|PDB:2EVA"
TURN 166..169
/evidence="ECO:0000244|PDB:2EVA"
STRAND 170..173
/evidence="ECO:0000244|PDB:2EVA"
HELIX 182..186
/evidence="ECO:0000244|PDB:5GJF"
HELIX 193..195
/evidence="ECO:0000244|PDB:5JGA"
HELIX 198..201
/evidence="ECO:0000244|PDB:2EVA"
HELIX 209..224
/evidence="ECO:0000244|PDB:2EVA"
TURN 228..232
/evidence="ECO:0000244|PDB:2EVA"
HELIX 236..244
/evidence="ECO:0000244|PDB:2EVA"
HELIX 257..266
/evidence="ECO:0000244|PDB:2EVA"
HELIX 271..273
/evidence="ECO:0000244|PDB:2EVA"
HELIX 277..287
/evidence="ECO:0000244|PDB:2EVA"
HELIX 288..290
/evidence="ECO:0000244|PDB:2EVA"
TURN 292..295
/evidence="ECO:0000244|PDB:5JGA"
STRAND 300..302
/evidence="ECO:0000244|PDB:5JGA"
SEQUENCE 606 AA; 67196 MW; 3D8F8147CD174013 CRC64;
MSTASAASSS SSSSAGEMIE 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 DMSEIEARIA ATTAYSKPKR GHRKTASFGN
ILDVPEIVIS GNGQPRRRSI QDLTVTGTEP GQVSSRSSSP SVRMITTSGP TSEKPTRSHP
WTPDDSTDTN GSDNSIPMAY LTLDHQLQPL APCPNSKESM AVFEQHCKMA QEYMKVQTEI
ALLLQRKQEL VAELDQDEKD QQNTSRLVQE HKKLLDENKS LSTYYQQCKK QLEVIRSQQQ
KRQGTS


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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
WP1681: Pantothenate and CoA biosynthesis
WP1844: MAP kinase cascade
WP1653: Galactose metabolism
WP253: Glycolysis
WP1701: Starch and sucrose metabolism
WP1566: Citrate cycle (TCA cycle)
WP2218: sGC
WP210: Cytoplasmic Ribosomal Proteins
WP1929: Thrombin signalling through proteinase activated receptors (PARs)
WP313: Signaling of Hepatocyte Growth Factor Receptor
WP1835: Interferon alpha/beta signaling
WP448: Mitochondrial LC-Fatty Acid Beta-Oxidation
WP1045: TGF-beta Receptor Signaling Pathway
WP1982: SREBP signalling
WP495: Glucocorticoid & Mineralcorticoid Metabolism
WP209: Fatty Acid Beta Oxidation Meta
WP809: TGF-beta Receptor Signaling Pathway

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)

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