M3K12_HUMAN
ID M3K12_HUMAN Reviewed; 859 AA.
AC Q12852; B3KSS9; G3V1Y2; Q86VQ5; Q8WY25;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 12;
DE EC=2.7.11.25 {ECO:0000250|UniProtKB:Q60700};
DE AltName: Full=Dual leucine zipper bearing kinase;
DE Short=DLK;
DE AltName: Full=Leucine-zipper protein kinase;
DE Short=ZPK;
DE AltName: Full=MAPK-upstream kinase;
DE Short=MUK;
DE AltName: Full=Mixed lineage kinase;
GN Name=MAP3K12; Synonyms=ZPK;
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 TISSUE SPECIFICITY.
RC TISSUE=Teratocarcinoma;
RX PubMed=8037767; DOI=10.1006/bbrc.1994.1972;
RA Reddy U.R., Pleasure D.;
RT "Cloning of a novel putative protein kinase having a leucine zipper domain
RT from human brain.";
RL Biochem. Biophys. Res. Commun. 202:613-620(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=14697235; DOI=10.1016/j.bbrc.2003.11.152;
RA Itoh A., Wang Z., Ito Y., Reddy U.R., Itoh T.;
RT "SP3 acts as a positive regulator on the core promoter of human ZPK gene.";
RL Biochem. Biophys. Res. Commun. 313:612-618(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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] (ISOFORM 1).
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 INTERACTION WITH MBIP, AND DOMAIN.
RX PubMed=10801814; DOI=10.1074/jbc.m001488200;
RA Fukuyama K., Yoshida M., Yamashita A., Deyama T., Baba M., Suzuki A.,
RA Mohri H., Ikezawa Z., Nakajima H., Hirai S., Ohno S.;
RT "MAPK upstream kinase (MUK)-binding inhibitory protein, a negative
RT regulator of MUK/Dual leucine zipper-bearing kinase/leucine zipper protein
RT kinase.";
RL J. Biol. Chem. 275:21247-21254(2000).
RN [8]
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 [9]
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 [10]
RP FUNCTION, AND PTM.
RX PubMed=28111074; DOI=10.1016/j.cell.2016.12.044;
RA Huang Y.A., Zhou B., Wernig M., Suedhof T.C.;
RT "ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and
RT Abeta Secretion.";
RL Cell 168:427-441(2017).
RN [11]
RP VARIANTS [LARGE SCALE ANALYSIS] LYS-409; ARG-628 AND SER-640.
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: Part of a non-canonical MAPK signaling pathway
CC (PubMed:28111074). Activated by APOE, enhances the AP-1-mediated
CC transcription of APP, via a MAP kinase signal transduction pathway
CC composed of MAP2K7 and MAPK1/ERK2 and MAPK3/ERK1 (PubMed:28111074). May
CC be an activator of the JNK/SAPK pathway. {ECO:0000269|PubMed:28111074}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.25;
CC Evidence={ECO:0000250|UniProtKB:Q60700};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.25; Evidence={ECO:0000250|UniProtKB:Q60700};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with MBIP
CC (PubMed:10801814). {ECO:0000250|UniProtKB:Q60700,
CC ECO:0000269|PubMed:10801814}.
CC -!- INTERACTION:
CC Q12852; P00533: EGFR; NbExp=3; IntAct=EBI-710223, EBI-297353;
CC Q12852; Q70Z53: FRA10AC1; NbExp=2; IntAct=EBI-710223, EBI-710176;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q60700}. Cell
CC membrane {ECO:0000250|UniProtKB:Q60700}. Note=Behaves essentially as an
CC integral membrane protein. {ECO:0000250|UniProtKB:Q60700}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q12852-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q12852-2; Sequence=VSP_044646;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and kidney.
CC {ECO:0000269|PubMed:8037767}.
CC -!- DOMAIN: Interacts with MBIP through the leucine-zipper motif.
CC {ECO:0000269|PubMed:10801814}.
CC -!- PTM: Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under
CC basal conditions and dephosphorylated when membrane-associated (By
CC similarity). {ECO:0000250|UniProtKB:Q60700}.
CC -!- PTM: The activity of MAP3K12 can be regulated through its proteasomal
CC degradation. APOE, through a receptor-mediated mechanism, activates
CC MAP3K12 by preventing its proteasomal degradation.
CC {ECO:0000269|PubMed:28111074}.
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; U07358; AAA67343.1; -; mRNA.
DR EMBL; AF283475; AAL67158.1; -; Genomic_DNA.
DR EMBL; AK094195; BAG52841.1; -; mRNA.
DR EMBL; AC023509; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW96715.1; -; Genomic_DNA.
DR EMBL; BC050050; AAH50050.1; ALT_SEQ; mRNA.
DR CCDS; CCDS55831.1; -. [Q12852-2]
DR CCDS; CCDS8860.1; -. [Q12852-1]
DR PIR; JC2363; JC2363.
DR RefSeq; NP_001180440.1; NM_001193511.1. [Q12852-2]
DR RefSeq; NP_006292.3; NM_006301.3. [Q12852-1]
DR RefSeq; XP_005269195.1; XM_005269138.3. [Q12852-2]
DR RefSeq; XP_006719651.1; XM_006719588.3. [Q12852-2]
DR RefSeq; XP_011537027.1; XM_011538725.2. [Q12852-2]
DR RefSeq; XP_016875445.1; XM_017019956.1. [Q12852-1]
DR PDB; 5CEN; X-ray; 1.70 A; A=115-402.
DR PDB; 5CEO; X-ray; 2.28 A; A=115-402.
DR PDB; 5CEP; X-ray; 1.99 A; A=115-402.
DR PDB; 5CEQ; X-ray; 1.91 A; A=115-402.
DR PDB; 5VO1; X-ray; 2.45 A; A=115-402.
DR PDB; 5VO2; X-ray; 2.96 A; A=115-402.
DR PDBsum; 5CEN; -.
DR PDBsum; 5CEO; -.
DR PDBsum; 5CEP; -.
DR PDBsum; 5CEQ; -.
DR PDBsum; 5VO1; -.
DR PDBsum; 5VO2; -.
DR AlphaFoldDB; Q12852; -.
DR SMR; Q12852; -.
DR BioGRID; 113566; 16.
DR IntAct; Q12852; 9.
DR MINT; Q12852; -.
DR STRING; 9606.ENSP00000448689; -.
DR BindingDB; Q12852; -.
DR ChEMBL; CHEMBL1908389; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q12852; -.
DR GuidetoPHARMACOLOGY; 2072; -.
DR iPTMnet; Q12852; -.
DR PhosphoSitePlus; Q12852; -.
DR SwissPalm; Q12852; -.
DR BioMuta; MAP3K12; -.
DR DMDM; 116242624; -.
DR jPOST; Q12852; -.
DR MassIVE; Q12852; -.
DR PaxDb; Q12852; -.
DR PeptideAtlas; Q12852; -.
DR PRIDE; Q12852; -.
DR ProteomicsDB; 32474; -.
DR ProteomicsDB; 58985; -. [Q12852-1]
DR Antibodypedia; 27132; 230 antibodies from 31 providers.
DR DNASU; 7786; -.
DR Ensembl; ENST00000267079.6; ENSP00000267079.2; ENSG00000139625.13. [Q12852-1]
DR Ensembl; ENST00000547035.5; ENSP00000448689.1; ENSG00000139625.13. [Q12852-2]
DR Ensembl; ENST00000547488.6; ENSP00000449038.1; ENSG00000139625.13. [Q12852-2]
DR GeneID; 7786; -.
DR KEGG; hsa:7786; -.
DR MANE-Select; ENST00000547488.6; ENSP00000449038.1; NM_001193511.2; NP_001180440.1. [Q12852-2]
DR UCSC; uc001sdm.3; human. [Q12852-1]
DR CTD; 7786; -.
DR DisGeNET; 7786; -.
DR GeneCards; MAP3K12; -.
DR HGNC; HGNC:6851; MAP3K12.
DR HPA; ENSG00000139625; Low tissue specificity.
DR MIM; 600447; gene.
DR neXtProt; NX_Q12852; -.
DR OpenTargets; ENSG00000139625; -.
DR PharmGKB; PA30595; -.
DR VEuPathDB; HostDB:ENSG00000139625; -.
DR eggNOG; KOG4721; Eukaryota.
DR GeneTree; ENSGT00940000159006; -.
DR HOGENOM; CLU_009311_2_1_1; -.
DR InParanoid; Q12852; -.
DR OMA; PSAWEVC; -.
DR OrthoDB; 938929at2759; -.
DR PhylomeDB; Q12852; -.
DR PathwayCommons; Q12852; -.
DR SignaLink; Q12852; -.
DR SIGNOR; Q12852; -.
DR BioGRID-ORCS; 7786; 13 hits in 1103 CRISPR screens.
DR ChiTaRS; MAP3K12; human.
DR GeneWiki; MAP3K12; -.
DR GenomeRNAi; 7786; -.
DR Pharos; Q12852; Tchem.
DR PRO; PR:Q12852; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q12852; protein.
DR Bgee; ENSG00000139625; Expressed in right hemisphere of cerebellum and 186 other tissues.
DR ExpressionAtlas; Q12852; baseline and differential.
DR Genevisible; Q12852; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISS:ARUK-UCL.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:0007254; P:JNK cascade; ISS:UniProtKB.
DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:ARUK-UCL.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:ARUK-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017419; MAP3K12_MAP3K13.
DR InterPro; IPR027257; MAPKKK12.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF500741; MAPKKK12; 1.
DR PIRSF; PIRSF038165; MAPKKK12_MAPKKK13; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm;
KW Kinase; Magnesium; Membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..859
FT /note="Mitogen-activated protein kinase kinase kinase 12"
FT /id="PRO_0000086261"
FT DOMAIN 125..366
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 51..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..411
FT /note="Leucine-zipper 1"
FT REGION 443..464
FT /note="Leucine-zipper 2"
FT REGION 524..587
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 613..859
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 731..778
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 802..816
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 236
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 131..139
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 152
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 37
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60700"
FT MOD_RES 43
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60700"
FT MOD_RES 607
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60700"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60700"
FT VAR_SEQ 46
FT /note="H -> QCVLRDVVPLGGQGGGGPSPSPGGEPPPEPFANS (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044646"
FT VARIANT 409
FT /note="E -> K (in a breast pleomorphic lobular carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040705"
FT VARIANT 628
FT /note="G -> R (in dbSNP:rs34366500)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040706"
FT VARIANT 640
FT /note="G -> S (in dbSNP:rs55794887)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040707"
FT CONFLICT 355
FT /note="P -> S (in Ref. 3; BAG52841)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="K -> N (in Ref. 1; AAA67343)"
FT /evidence="ECO:0000305"
FT CONFLICT 504
FT /note="K -> Q (in Ref. 1; AAA67343)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="T -> A (in Ref. 1; AAA67343)"
FT /evidence="ECO:0000305"
FT CONFLICT 533
FT /note="G -> A (in Ref. 1; AAA67343)"
FT /evidence="ECO:0000305"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:5CEN"
FT STRAND 126..134
FT /evidence="ECO:0007829|PDB:5CEN"
FT STRAND 137..144
FT /evidence="ECO:0007829|PDB:5CEN"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 157..160
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:5CEN"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:5CEN"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 198..203
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 210..229
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:5CEN"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:5CEN"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 264..271
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 272..276
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 279..282
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 290..305
FT /evidence="ECO:0007829|PDB:5CEN"
FT TURN 309..312
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 315..323
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 337..346
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 351..353
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 357..372
FT /evidence="ECO:0007829|PDB:5CEN"
FT HELIX 376..396
FT /evidence="ECO:0007829|PDB:5CEN"
SQ SEQUENCE 859 AA; 93219 MW; 1E1BCAD2F6DFCFE8 CRC64;
MACLHETRTP SPSFGGFVST LSEASMRKLD PDTSDCTPEK DLTPTHVLQL HEQDAGGPGG
AAGSPESRAS RVRADEVRLQ CQSGSGFLEG LFGCLRPVWT MIGKAYSTEH KQQQEDLWEV
PFEEILDLQW VGSGAQGAVF LGRFHGEEVA VKKVRDLKET DIKHLRKLKH PNIITFKGVC
TQAPCYCILM EFCAQGQLYE VLRAGRPVTP SLLVDWSMGI AGGMNYLHLH KIIHRDLKSP
NMLITYDDVV KISDFGTSKE LSDKSTKMSF AGTVAWMAPE VIRNEPVSEK VDIWSFGVVL
WELLTGEIPY KDVDSSAIIW GVGSNSLHLP VPSSCPDGFK ILLRQCWNSK PRNRPSFRQI
LLHLDIASAD VLSTPQETYF KSQAEWREEV KLHFEKIKSE GTCLHRLEEE LVMRRREELR
HALDIREHYE RKLERANNLY MELNALMLQL ELKERELLRR EQALERRCPG LLKPHPSRGL
LHGNTMEKLI KKRNVPQKLS PHSKRPDILK TESLLPKLDA ALSGVGLPGC PKGPPSPGRS
RRGKTRHRKA SAKGSCGDLP GLRTAVPPHE PGGPGSPGGL GGGPSAWEAC PPALRGLHHD
LLLRKMSSSS PDLLSAALGS RGRGATGGAG DPGSPPPARG DTPPSEGSAP GSTSPDSPGG
AKGEPPPPVG PGEGVGLLGT GREGTSGRGG SRAGSQHLTP AALLYRAAVT RSQKRGISSE
EEEGEVDSEV ELTSSQRWPQ SLNMRQSLST FSSENPSDGE EGTASEPSPS GTPEVGSTNT
DERPDERSDD MCSQGSEIPL DPPPSEVIPG PEPSSLPIPH QELLRERGPP NSEDSDCDST
ELDNSNSVDA LRPPASLPP
