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 27-MAR-2024, entry version 223. 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=3; 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 Q9Y2U5; P62258: YWHAE; NbExp=4; IntAct=EBI-357393, EBI-356498; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 73. DR CORUM; Q9Y2U5; -. DR DIP; DIP-39756N; -. DR IntAct; Q9Y2U5; 37. 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-2983; -. DR CPTAC; CPTAC-843; -. DR CPTAC; CPTAC-844; -. DR EPD; Q9Y2U5; -. DR jPOST; Q9Y2U5; -. DR MassIVE; Q9Y2U5; -. DR MaxQB; Q9Y2U5; -. DR PaxDb; 9606-ENSP00000387246; -. DR PeptideAtlas; Q9Y2U5; -. DR ProteomicsDB; 85903; -. DR Pumba; Q9Y2U5; -. DR ABCD; Q9Y2U5; 4 sequenced antibodies. DR Antibodypedia; 33427; 325 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 AGR; HGNC:6854; -. 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; EYEDSRM; -. DR OrthoDB; 145974at2759; -. 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; 31 hits in 1189 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 195 other cell types or tissues. DR ExpressionAtlas; Q9Y2U5; baseline and differential. 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:0035556; P:intracellular signal transduction; IDA:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR CDD; cd06405; PB1_Mekk2_3; 1. DR CDD; cd06652; STKc_MEKK2; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR48016; MAP KINASE KINASE KINASE SSK2-RELATED-RELATED; 1. DR PANTHER; PTHR48016:SF50; MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 19; 1. DR Pfam; PF00564; PB1; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00666; PB1; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF54277; CAD & PB1 domains; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS51745; PB1; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR Genevisible; Q9Y2U5; HS. 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 //