M3K3_HUMAN
ID M3K3_HUMAN Reviewed; 626 AA.
AC Q99759; B2RCW2; D3DU15; Q5BKZ6; Q8N3I9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 3;
DE EC=2.7.11.25;
DE AltName: Full=MAPK/ERK kinase kinase 3;
DE Short=MEK kinase 3;
DE Short=MEKK 3;
GN Name=MAP3K3; Synonyms=MAPKKK3, MEKK3;
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] (ISOFORM 1), AND FUNCTION.
RX PubMed=9006902; DOI=10.1074/jbc.272.5.2668;
RA Ellinger-Ziegelbauer H.C., Brown K., Kelly K., Siebenlist U.;
RT "Direct activation of the stress-activated protein kinase (SAPK) and
RT extracellular signal-regulated protein kinase (ERK) pathways by an
RT inducible mitogen-activated protein kinase/ERK kinase kinase 3 (MEKK)
RT derivative.";
RL J. Biol. Chem. 272:2668-2674(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and PNS;
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 PHOSPHORYLATION AT SER-166 AND SER-337 BY SGK1.
RX PubMed=12761204; DOI=10.1093/jb/mvg010;
RA Chun J., Kwon T., Kim D.J., Park I., Chung G., Lee E.J., Hong S.K.,
RA Chang S.I., Kim H.Y., Kang S.S.;
RT "Inhibition of mitogen-activated kinase kinase kinase 3 activity through
RT phosphorylation by the serum- and glucocorticoid-induced kinase 1.";
RL J. Biochem. 133:103-108(2003).
RN [8]
RP FUNCTION, AND INTERACTION WITH MAP2K5.
RX PubMed=12912994; DOI=10.1074/jbc.c300313200;
RA Nakamura K., Johnson G.L.;
RT "PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for
RT activation of the ERK5 pathway.";
RL J. Biol. Chem. 278:36989-36992(2003).
RN [9]
RP FUNCTION, AND INTERACTION WITH TRAF6.
RX PubMed=14661019; DOI=10.1038/ni1014;
RA Huang Q., Yang J., Lin Y., Walker C., Cheng J., Liu Z.G., Su B.;
RT "Differential regulation of interleukin 1 receptor and Toll-like receptor
RT signaling by MEKK3.";
RL Nat. Immunol. 5:98-103(2004).
RN [10]
RP FUNCTION, AND INTERACTION WITH TRAF7.
RX PubMed=14743216; DOI=10.1038/ncb1086;
RA Bouwmeester T., Bauch A., Ruffner H., Angrand P.-O., Bergamini G.,
RA Croughton K., Cruciat C., Eberhard D., Gagneur J., Ghidelli S., Hopf C.,
RA Huhse B., Mangano R., Michon A.-M., Schirle M., Schlegl J., Schwab M.,
RA Stein M.A., Bauer A., Casari G., Drewes G., Gavin A.-C., Jackson D.B.,
RA Joberty G., Neubauer G., Rick J., Kuster B., Superti-Furga G.;
RT "A physical and functional map of the human TNF-alpha/NF-kappa B signal
RT transduction pathway.";
RL Nat. Cell Biol. 6:97-105(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250; SER-337 AND SER-340, 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250; SER-337 AND SER-340, AND
RP 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337 AND SER-340, 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166; SER-250; SER-312;
RP SER-337 AND SER-340, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [15]
RP VARIANT [LARGE SCALE ANALYSIS] MET-281.
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 Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional
CC regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019,
CC ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:9006902}.
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-530.
CC {ECO:0000250}.
CC -!- SUBUNIT: Binds both upstream activators and downstream substrates in
CC multimolecular complexes. Part of a complex with MAP2K3, RAC1 and CCM2.
CC Interacts with MAP2K5 and SPAG9. {ECO:0000269|PubMed:12912994,
CC ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216}.
CC -!- INTERACTION:
CC Q99759; Q9BSQ5-1: CCM2; NbExp=6; IntAct=EBI-307281, EBI-16157769;
CC Q99759; Q13163: MAP2K5; NbExp=4; IntAct=EBI-307281, EBI-307294;
CC Q99759; Q6Q0C0: TRAF7; NbExp=3; IntAct=EBI-307281, EBI-307556;
CC Q99759; P31946: YWHAB; NbExp=2; IntAct=EBI-307281, EBI-359815;
CC Q99759; P62258: YWHAE; NbExp=3; IntAct=EBI-307281, EBI-356498;
CC Q99759; P61981: YWHAG; NbExp=3; IntAct=EBI-307281, EBI-359832;
CC Q99759; Q04917: YWHAH; NbExp=3; IntAct=EBI-307281, EBI-306940;
CC Q99759; P27348: YWHAQ; NbExp=2; IntAct=EBI-307281, EBI-359854;
CC Q99759; P63104: YWHAZ; NbExp=2; IntAct=EBI-307281, EBI-347088;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99759-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99759-2; Sequence=VSP_035967;
CC -!- PTM: Phosphorylation at Ser-166 and Ser-337 by SGK1 inhibits its
CC activity. {ECO:0000269|PubMed:12761204}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
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DR EMBL; U78876; AAB41729.1; -; mRNA.
DR EMBL; AK315305; BAG37709.1; -; mRNA.
DR EMBL; AL834303; CAD38973.1; -; mRNA.
DR EMBL; AC046185; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471109; EAW94297.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94298.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94299.1; -; Genomic_DNA.
DR EMBL; BC090859; AAH90859.1; -; mRNA.
DR EMBL; BC093672; AAH93672.1; -; mRNA.
DR EMBL; BC093674; AAH93674.1; -; mRNA.
DR CCDS; CCDS32701.1; -. [Q99759-2]
DR CCDS; CCDS32702.1; -. [Q99759-1]
DR RefSeq; NP_002392.2; NM_002401.3. [Q99759-1]
DR RefSeq; NP_976226.1; NM_203351.1. [Q99759-2]
DR PDB; 2C60; X-ray; 1.25 A; A=37-124.
DR PDB; 2JRH; NMR; -; A=42-126.
DR PDB; 2O2V; X-ray; 1.83 A; B=37-124.
DR PDB; 2PPH; NMR; -; A=42-126.
DR PDB; 4Y5O; X-ray; 2.35 A; B=1-124.
DR PDB; 4YL6; X-ray; 2.10 A; B=1-22.
DR PDBsum; 2C60; -.
DR PDBsum; 2JRH; -.
DR PDBsum; 2O2V; -.
DR PDBsum; 2PPH; -.
DR PDBsum; 4Y5O; -.
DR PDBsum; 4YL6; -.
DR AlphaFoldDB; Q99759; -.
DR BMRB; Q99759; -.
DR SMR; Q99759; -.
DR BioGRID; 110379; 69.
DR CORUM; Q99759; -.
DR DIP; DIP-27521N; -.
DR IntAct; Q99759; 40.
DR MINT; Q99759; -.
DR STRING; 9606.ENSP00000354927; -.
DR BindingDB; Q99759; -.
DR ChEMBL; CHEMBL5970; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q99759; -.
DR iPTMnet; Q99759; -.
DR PhosphoSitePlus; Q99759; -.
DR BioMuta; MAP3K3; -.
DR DMDM; 160332306; -.
DR CPTAC; CPTAC-845; -.
DR CPTAC; CPTAC-846; -.
DR EPD; Q99759; -.
DR jPOST; Q99759; -.
DR MassIVE; Q99759; -.
DR MaxQB; Q99759; -.
DR PaxDb; Q99759; -.
DR PeptideAtlas; Q99759; -.
DR PRIDE; Q99759; -.
DR ProteomicsDB; 78464; -. [Q99759-1]
DR ProteomicsDB; 78465; -. [Q99759-2]
DR Antibodypedia; 31306; 246 antibodies from 39 providers.
DR DNASU; 4215; -.
DR Ensembl; ENST00000361357.7; ENSP00000354927.3; ENSG00000198909.8. [Q99759-2]
DR Ensembl; ENST00000361733.8; ENSP00000354485.4; ENSG00000198909.8. [Q99759-1]
DR Ensembl; ENST00000579585.5; ENSP00000461988.1; ENSG00000198909.8. [Q99759-2]
DR GeneID; 4215; -.
DR KEGG; hsa:4215; -.
DR MANE-Select; ENST00000361733.8; ENSP00000354485.4; NM_002401.5; NP_002392.2.
DR UCSC; uc002jbe.4; human. [Q99759-1]
DR CTD; 4215; -.
DR DisGeNET; 4215; -.
DR GeneCards; MAP3K3; -.
DR HGNC; HGNC:6855; MAP3K3.
DR HPA; ENSG00000198909; Low tissue specificity.
DR MIM; 602539; gene.
DR neXtProt; NX_Q99759; -.
DR OpenTargets; ENSG00000198909; -.
DR PharmGKB; PA30599; -.
DR VEuPathDB; HostDB:ENSG00000198909; -.
DR eggNOG; KOG0198; Eukaryota.
DR GeneTree; ENSGT00940000158767; -.
DR InParanoid; Q99759; -.
DR OMA; DNRKECS; -.
DR OrthoDB; 55144at2759; -.
DR PhylomeDB; Q99759; -.
DR TreeFam; TF105113; -.
DR BRENDA; 2.7.11.25; 2681.
DR BRENDA; 2.7.12.2; 2681.
DR PathwayCommons; Q99759; -.
DR Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR SignaLink; Q99759; -.
DR SIGNOR; Q99759; -.
DR BioGRID-ORCS; 4215; 13 hits in 1111 CRISPR screens.
DR ChiTaRS; MAP3K3; human.
DR EvolutionaryTrace; Q99759; -.
DR GeneWiki; MAP3K3; -.
DR GenomeRNAi; 4215; -.
DR Pharos; Q99759; Tchem.
DR PRO; PR:Q99759; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q99759; protein.
DR Bgee; ENSG00000198909; Expressed in monocyte and 177 other tissues.
DR ExpressionAtlas; Q99759; baseline and differential.
DR Genevisible; Q99759; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; TAS:ProtInc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
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:0001568; P:blood vessel development; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR GO; GO:0000165; P:MAPK cascade; TAS:ProtInc.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IMP:BHF-UCL.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; IGI:BHF-UCL.
DR GO; GO:0071864; P:positive regulation of cell proliferation in bone marrow; IMP:BHF-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
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 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; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..626
FT /note="Mitogen-activated protein kinase kinase kinase 3"
FT /id="PRO_0000086245"
FT DOMAIN 44..123
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 362..622
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 146..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 218..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..253
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 489
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 368..376
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 391
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61084"
FT MOD_RES 166
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000269|PubMed:12761204,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 337
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000269|PubMed:12761204,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 42
FT /note="Q -> QKKHNSSSSALLNSPTVTTSSCAGASEKKKFL (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_035967"
FT VARIANT 281
FT /note="V -> M (in dbSNP:rs36109904)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040685"
FT VARIANT 325
FT /note="A -> G (in dbSNP:rs34042309)"
FT /id="VAR_037275"
FT VARIANT 435
FT /note="A -> G (in dbSNP:rs9910858)"
FT /id="VAR_037276"
FT CONFLICT 135
FT /note="G -> E (in Ref. 1; AAB41729)"
FT /evidence="ECO:0000305"
FT HELIX 3..18
FT /evidence="ECO:0007829|PDB:4YL6"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:2C60"
FT STRAND 45..51
FT /evidence="ECO:0007829|PDB:2C60"
FT STRAND 54..60
FT /evidence="ECO:0007829|PDB:2C60"
FT HELIX 66..77
FT /evidence="ECO:0007829|PDB:2C60"
FT STRAND 82..86
FT /evidence="ECO:0007829|PDB:2C60"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:4Y5O"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:2C60"
FT HELIX 97..109
FT /evidence="ECO:0007829|PDB:2C60"
FT TURN 111..114
FT /evidence="ECO:0007829|PDB:2JRH"
FT STRAND 115..121
FT /evidence="ECO:0007829|PDB:2C60"
SQ SEQUENCE 626 AA; 70898 MW; 28129168A57571DD CRC64;
MDEQEALNSI MNDLVALQMN RRHRMPGYET MKNKDTGHSN RQSDVRIKFE HNGERRIIAF
SRPVKYEDVE HKVTTVFGQP LDLHYMNNEL SILLKNQDDL DKAIDILDRS SSMKSLRILL
LSQDRNHNSS SPHSGVSRQV RIKASQSAGD INTIYQPPEP RSRHLSVSSQ NPGRSSPPPG
YVPERQQHIA RQGSYTSINS EGEFIPETSE QCMLDPLSSA ENSLSGSCQS LDRSADSPSF
RKSRMSRAQS FPDNRQEYSD RETQLYDKGV KGGTYPRRYH VSVHHKDYSD GRRTFPRIRR
HQGNLFTLVP SSRSLSTNGE NMGLAVQYLD PRGRLRSADS ENALSVQERN VPTKSPSAPI
NWRRGKLLGQ GAFGRVYLCY DVDTGRELAS KQVQFDPDSP ETSKEVSALE CEIQLLKNLQ
HERIVQYYGC LRDRAEKTLT IFMEYMPGGS VKDQLKAYGA LTESVTRKYT RQILEGMSYL
HSNMIVHRDI KGANILRDSA GNVKLGDFGA SKRLQTICMS GTGMRSVTGT PYWMSPEVIS
GEGYGRKADV WSLGCTVVEM LTEKPPWAEY EAMAAIFKIA TQPTNPQLPS HISEHGRDFL
RRIFVEARQR PSAEELLTHH FAQLMY
