M3K2_HUMAN
ID M3K2_HUMAN Reviewed; 619 AA.
AC Q9Y2U5; B9EG87; Q53QL9; Q53S75; Q59GZ6; Q8NC32; Q9NYK3;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 2;
DE EC=2.7.11.25;
DE AltName: Full=MAPK/ERK kinase kinase 2;
DE Short=MEK kinase 2;
DE Short=MEKK 2;
GN Name=MAP3K2; Synonyms=MAPKKK2, MEKK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Su B., Yang J.H., Xia Y., Karin M.;
RT "MEKK2 is involved in transducing T-cell co-stimulatory signals to the JNK
RT cascade.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=T-cell;
RA Wang C., Lo H.;
RT "Cloning of human MEKK2b cDNA.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 180-619.
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP FUNCTION, AND INTERACTION WITH MAP2K7 AND MAPK8.
RX PubMed=10713157; DOI=10.1128/mcb.20.7.2334-2342.2000;
RA Cheng J., Yang J., Xia Y., Karin M., Su B.;
RT "Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK)
RT kinase 2, and JNK1 results in efficient and specific JNK1 activation.";
RL Mol. Cell. Biol. 20:2334-2342(2000).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=15075238; DOI=10.1242/jcs.01040;
RA Raviv Z., Kalie E., Seger R.;
RT "MEK5 and ERK5 are localized in the nuclei of resting as well as stimulated
RT cells, while MEKK2 translocates from the cytosol to the nucleus upon
RT stimulation.";
RL J. Cell Sci. 117:1773-1784(2004).
RN [10]
RP FUNCTION.
RX PubMed=16001074; DOI=10.1038/nature03866;
RA Pelkmans L., Zerial M.;
RT "Kinase-regulated quantal assemblies and kiss-and-run recycling of
RT caveolae.";
RL Nature 436:128-133(2005).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [12]
RP UBIQUITINATION BY XIAP/BIRC4, AND INTERACTION WITH XIAP/BIRC4.
RX PubMed=18761086; DOI=10.1016/j.cellsig.2008.08.004;
RA Winsauer G., Resch U., Hofer-Warbinek R., Schichl Y.M., de Martin R.;
RT "XIAP regulates bi-phasic NF-kappaB induction involving physical
RT interaction and ubiquitination of MEKK2.";
RL Cell. Signal. 20:2107-2112(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-297, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-331 AND SER-344, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [16]
RP INTERACTION WITH STK38, AND SELF-ASSOCIATION.
RX PubMed=17906693; DOI=10.1038/sj.onc.1210828;
RA Enomoto A., Kido N., Ito M., Morita A., Matsumoto Y., Takamatsu N.,
RA Hosoi Y., Miyagawa K.;
RT "Negative regulation of MEKK1/2 signaling by serine-threonine kinase 38
RT (STK38).";
RL Oncogene 27:1930-1938(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-159 AND SER-164, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26; SER-153; SER-331 AND
RP SER-344, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239; SER-331 AND SER-344, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-239; SER-311 AND
RP SER-331, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-331, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP STRUCTURE BY NMR OF 43-132.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PB1 domain of human protein kinase MEKK2B.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [25]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-110; ILE-112 AND GLY-140.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Component of a protein kinase signal transduction cascade.
CC Regulates the JNK and ERK5 pathways by phosphorylating and activating
CC MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-
CC run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157,
CC ECO:0000269|PubMed:16001074}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-524.
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PKN2; the interaction activates PKN2 kinase
CC activity in a MAP3K2-independent kinase activity (By similarity). Self-
CC associates. Binds both upstream activators and downstream substrates in
CC multimolecular complexes. Interacts (via the kinase catalytic domain)
CC with STK38. Interacts with XIAP/BIRC4. {ECO:0000250,
CC ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:17906693,
CC ECO:0000269|PubMed:18761086}.
CC -!- INTERACTION:
CC Q9Y2U5; Q13163: MAP2K5; NbExp=6; IntAct=EBI-357393, EBI-307294;
CC Q9Y2U5; P31947: SFN; NbExp=2; IntAct=EBI-357393, EBI-476295;
CC Q9Y2U5; Q9H7B4-1: SMYD3; NbExp=3; IntAct=EBI-357393, EBI-16204880;
CC Q9Y2U5; Q9UNE7: STUB1; NbExp=9; IntAct=EBI-357393, EBI-357085;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15075238}. Nucleus
CC {ECO:0000269|PubMed:15075238}. Note=Upon EGF stimulation, translocates
CC into the nucleus.
CC -!- PTM: Autophosphorylated. {ECO:0000250}.
CC -!- PTM: Ubiquitination by XIAP/BIRC4 does not lead to proteasomal
CC degradation. {ECO:0000269|PubMed:18761086}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC11348.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF111105; AAD28547.1; -; mRNA.
DR EMBL; AF239798; AAF63496.1; -; mRNA.
DR EMBL; AB208963; BAD92200.1; -; mRNA.
DR EMBL; AC068282; AAY15043.1; -; Genomic_DNA.
DR EMBL; AC110926; AAY15070.1; -; Genomic_DNA.
DR EMBL; CH471103; EAW95315.1; -; Genomic_DNA.
DR EMBL; BC136293; AAI36294.1; -; mRNA.
DR EMBL; AK075004; BAC11348.1; ALT_INIT; mRNA.
DR CCDS; CCDS46404.1; -.
DR RefSeq; NP_006600.3; NM_006609.4.
DR PDB; 2CU1; NMR; -; A=43-132.
DR PDB; 2NPT; X-ray; 1.75 A; B/D=26-123.
DR PDB; 5EX0; X-ray; 2.70 A; D=256-265.
DR PDB; 5HQ8; X-ray; 1.72 A; I/J=250-264.
DR PDB; 6LDV; X-ray; 1.90 A; P=252-265.
DR PDB; 6LDW; X-ray; 1.60 A; C/D=252-265.
DR PDB; 6LDX; X-ray; 1.80 A; B=252-265.
DR PDB; 6LDY; X-ray; 1.77 A; C/M=252-265.
DR PDBsum; 2CU1; -.
DR PDBsum; 2NPT; -.
DR PDBsum; 5EX0; -.
DR PDBsum; 5HQ8; -.
DR PDBsum; 6LDV; -.
DR PDBsum; 6LDW; -.
DR PDBsum; 6LDX; -.
DR PDBsum; 6LDY; -.
DR AlphaFoldDB; Q9Y2U5; -.
DR SMR; Q9Y2U5; -.
DR BioGRID; 115969; 48.
DR CORUM; Q9Y2U5; -.
DR DIP; DIP-39756N; -.
DR IntAct; Q9Y2U5; 35.
DR MINT; Q9Y2U5; -.
DR STRING; 9606.ENSP00000387246; -.
DR BindingDB; Q9Y2U5; -.
DR ChEMBL; CHEMBL5914; -.
DR DrugBank; DB06616; Bosutinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9Y2U5; -.
DR GuidetoPHARMACOLOGY; 2077; -.
DR iPTMnet; Q9Y2U5; -.
DR MetOSite; Q9Y2U5; -.
DR PhosphoSitePlus; Q9Y2U5; -.
DR BioMuta; MAP3K2; -.
DR DMDM; 97536681; -.
DR CPTAC; CPTAC-843; -.
DR CPTAC; CPTAC-844; -.
DR EPD; Q9Y2U5; -.
DR jPOST; Q9Y2U5; -.
DR MassIVE; Q9Y2U5; -.
DR MaxQB; Q9Y2U5; -.
DR PaxDb; Q9Y2U5; -.
DR PeptideAtlas; Q9Y2U5; -.
DR PRIDE; Q9Y2U5; -.
DR ProteomicsDB; 85903; -.
DR ABCD; Q9Y2U5; 4 sequenced antibodies.
DR Antibodypedia; 33427; 277 antibodies from 37 providers.
DR DNASU; 10746; -.
DR Ensembl; ENST00000344908.9; ENSP00000343463.5; ENSG00000169967.17.
DR Ensembl; ENST00000409947.5; ENSP00000387246.1; ENSG00000169967.17.
DR Ensembl; ENST00000682094.1; ENSP00000507315.1; ENSG00000169967.17.
DR GeneID; 10746; -.
DR KEGG; hsa:10746; -.
DR MANE-Select; ENST00000682094.1; ENSP00000507315.1; NM_001371910.2; NP_001358839.1.
DR UCSC; uc002toj.3; human.
DR CTD; 10746; -.
DR DisGeNET; 10746; -.
DR GeneCards; MAP3K2; -.
DR HGNC; HGNC:6854; MAP3K2.
DR HPA; ENSG00000169967; Low tissue specificity.
DR MIM; 609487; gene.
DR neXtProt; NX_Q9Y2U5; -.
DR OpenTargets; ENSG00000169967; -.
DR PharmGKB; PA30598; -.
DR VEuPathDB; HostDB:ENSG00000169967; -.
DR eggNOG; KOG0198; Eukaryota.
DR GeneTree; ENSGT00940000156884; -.
DR HOGENOM; CLU_029447_0_0_1; -.
DR InParanoid; Q9Y2U5; -.
DR OMA; VFTPEYE; -.
DR OrthoDB; 55144at2759; -.
DR PhylomeDB; Q9Y2U5; -.
DR TreeFam; TF105113; -.
DR BRENDA; 2.7.12.2; 2681.
DR PathwayCommons; Q9Y2U5; -.
DR SignaLink; Q9Y2U5; -.
DR SIGNOR; Q9Y2U5; -.
DR BioGRID-ORCS; 10746; 25 hits in 1110 CRISPR screens.
DR ChiTaRS; MAP3K2; human.
DR EvolutionaryTrace; Q9Y2U5; -.
DR GeneWiki; MAP3K2; -.
DR GenomeRNAi; 10746; -.
DR Pharos; Q9Y2U5; Tchem.
DR PRO; PR:Q9Y2U5; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9Y2U5; protein.
DR Bgee; ENSG00000169967; Expressed in jejunal mucosa and 193 other tissues.
DR ExpressionAtlas; Q9Y2U5; baseline and differential.
DR Genevisible; Q9Y2U5; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR CDD; cd06405; PB1_Mekk2_3; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000270; PB1_dom.
DR InterPro; IPR034879; PB1_MEKK2/3.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00564; PB1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51745; PB1; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..619
FT /note="Mitogen-activated protein kinase kinase kinase 2"
FT /id="PRO_0000086243"
FT DOMAIN 43..122
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 357..617
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 25..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 154..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 201..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 201..221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 289..319
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 483
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 362..371
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 385
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 297
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61083"
FT VARIANT 110
FT /note="I -> V (in dbSNP:rs55767983)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040682"
FT VARIANT 112
FT /note="M -> I (in a lung large cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040683"
FT VARIANT 140
FT /note="D -> G (in dbSNP:rs56307783)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040684"
FT CONFLICT 1
FT /note="M -> GTR (in Ref. 3; BAD92200)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="V -> L (in Ref. 1; AAD28547 and 2; AAF63496)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="D -> E (in Ref. 1; AAD28547 and 2; AAF63496)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="D -> G (in Ref. 1; AAD28547)"
FT /evidence="ECO:0000305"
FT CONFLICT 275..277
FT /note="QEY -> KD (in Ref. 1; AAD28547)"
FT /evidence="ECO:0000305"
FT CONFLICT 293..296
FT /note="TSLR -> NQLT (in Ref. 1; AAD28547 and 2; AAF63496)"
FT /evidence="ECO:0000305"
FT CONFLICT 413
FT /note="L -> F (in Ref. 1; AAD28547)"
FT /evidence="ECO:0000305"
FT CONFLICT 459
FT /note="V -> G (in Ref. 1; AAD28547)"
FT /evidence="ECO:0000305"
FT CONFLICT 480
FT /note="V -> L (in Ref. 1; AAD28547)"
FT /evidence="ECO:0000305"
FT CONFLICT 536
FT /note="E -> Q (in Ref. 1; AAD28547 and 2; AAF63496)"
FT /evidence="ECO:0000305"
FT CONFLICT 579
FT /note="N -> S (in Ref. 7; BAC11348)"
FT /evidence="ECO:0000305"
FT STRAND 44..50
FT /evidence="ECO:0007829|PDB:2NPT"
FT STRAND 53..59
FT /evidence="ECO:0007829|PDB:2NPT"
FT HELIX 65..76
FT /evidence="ECO:0007829|PDB:2NPT"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:2NPT"
FT STRAND 89..92
FT /evidence="ECO:0007829|PDB:2NPT"
FT HELIX 96..108
FT /evidence="ECO:0007829|PDB:2NPT"
FT STRAND 114..121
FT /evidence="ECO:0007829|PDB:2NPT"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:5EX0"
SQ SEQUENCE 619 AA; 69741 MW; E034580D349F097F CRC64;
MDDQQALNSI MQDLAVLHKA SRPALSLQET RKAKSSSPKK QNDVRVKFEH RGEKRILQFP
RPVKLEDLRS KAKIAFGQSM DLHYTNNELV IPLTTQDDLD KAVELLDRSI HMKSLKILLV
INGSTQATNL EPLPSLEDLD NTVFGAERKK RLSIIGPTSR DRSSPPPGYI PDELHQVARN
GSFTSINSEG EFIPESMDQM LDPLSLSSPE NSGSGSCPSL DSPLDGESYP KSRMPRAQSY
PDNHQEFSDY DNPIFEKFGK GGTYPRRYHV SYHHQEYNDG RKTFPRARRT QGTSLRSPVS
FSPTDHSLST SSGSSIFTPE YDDSRIRRRG SDIDNPTLTV MDISPPSRSP RAPTNWRLGK
LLGQGAFGRV YLCYDVDTGR ELAVKQVQFD PDSPETSKEV NALECEIQLL KNLLHERIVQ
YYGCLRDPQE KTLSIFMEYM PGGSIKDQLK AYGALTENVT RKYTRQILEG VHYLHSNMIV
HRDIKGANIL RDSTGNVKLG DFGASKRLQT ICLSGTGMKS VTGTPYWMSP EVISGEGYGR
KADIWSVACT VVEMLTEKPP WAEFEAMAAI FKIATQPTNP KLPPHVSDYT RDFLKRIFVE
AKLRPSADEL LRHMFVHYH
