M3K1_HUMAN
ID M3K1_HUMAN Reviewed; 1512 AA.
AC Q13233;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 4.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 1;
DE EC=2.7.11.25;
DE AltName: Full=MAPK/ERK kinase kinase 1;
DE Short=MEK kinase 1;
DE Short=MEKK 1;
GN Name=MAP3K1; Synonyms=MAPKKK1, MEKK, MEKK1;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-1512, FUNCTION, AND INTERACTION WITH
RP MAP2K4.
RX PubMed=9808624; DOI=10.1101/gad.12.21.3369;
RA Xia Y., Wu Z., Su B., Murray B., Karin M.;
RT "JNKK1 organizes a MAP kinase module through specific and sequential
RT interactions with upstream and downstream components mediated by its amino-
RT terminal extension.";
RL Genes Dev. 12:3369-3381(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1238-1274.
RC TISSUE=Leukocyte;
RX PubMed=8597633; DOI=10.1007/bf00539003;
RA Vinik B.S., Kay E.S., Fiedorek F.T. Jr.;
RT "Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human
RT chromosome 5.";
RL Mamm. Genome 6:782-783(1995).
RN [4]
RP INTERACTION WITH AXIN1.
RX PubMed=12223491; DOI=10.1074/jbc.m208099200;
RA Rui H.L., Fan E., Zhou H.M., Xu Z., Zhang Y., Lin S.C.;
RT "SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK
RT activation but has no effect on Wnt signaling.";
RL J. Biol. Chem. 277:42981-42986(2002).
RN [5]
RP INTERACTION WITH AXIN1.
RX PubMed=15262978; DOI=10.1074/jbc.m404598200;
RA Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C.;
RT "The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase
RT activation by Axin and dishevelled through distinct mechanisms.";
RL J. Biol. Chem. 279:39366-39373(2004).
RN [6]
RP FUNCTION, AND INTERACTION WITH GRIPAP1.
RX PubMed=17761173; DOI=10.1016/j.febslet.2007.08.008;
RA Ye B., Yu W.P., Thomas G.M., Huganir R.L.;
RT "GRASP-1 is a neuronal scaffold protein for the JNK signaling pathway.";
RL FEBS Lett. 581:4403-4410(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292, 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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154 AND SER-1043, 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 [9]
RP INTERACTION WITH STK38.
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292; SER-297; SER-300;
RP SER-507 AND SER-1018, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275 AND SER-292, 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-21; SER-35; SER-275; THR-285;
RP SER-292; SER-531; SER-923 AND SER-1018, AND IDENTIFICATION BY MASS
RP 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 [14]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-92 AND SER-443.
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).
RN [15]
RP VARIANTS SRXY6 PRO-189; ARG-189; ILE-GLN-211 INS AND ARG-616, AND
RP CHARACTERIZATION OF VARIANTS SRXY6 PRO-189 AND ARG-189.
RX PubMed=21129722; DOI=10.1016/j.ajhg.2010.11.003;
RA Pearlman A., Loke J., Le Caignec C., White S., Chin L., Friedman A.,
RA Warr N., Willan J., Brauer D., Farmer C., Brooks E., Oddoux C., Riley B.,
RA Shajahan S., Camerino G., Homfray T., Crosby A.H., Couper J., David A.,
RA Greenfield A., Sinclair A., Ostrer H.;
RT "Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate
RT a common signal transduction pathway in human testis determination.";
RL Am. J. Hum. Genet. 87:898-904(2010).
CC -!- FUNCTION: Component of a protein kinase signal transduction cascade
CC (PubMed:9808624). Activates the ERK and JNK kinase pathways by
CC phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). May
CC phosphorylate the MAPK8/JNK1 kinase (PubMed:17761173). Activates CHUK
CC and IKBKB, the central protein kinases of the NF-kappa-B pathway
CC (PubMed:9808624). {ECO:0000269|PubMed:17761173,
CC ECO:0000269|PubMed:9808624}.
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 autophosphorylation on Thr-1400 and
CC Thr-1412 following oligomerization.
CC -!- SUBUNIT: Binds both upstream activators and downstream substrates in
CC multimolecular complexes through its N-terminus (PubMed:9808624).
CC Oligomerizes after binding MAP2K4 or TRAF2 (PubMed:9808624). Interacts
CC with AXIN1 (PubMed:12223491, PubMed:15262978). Interacts (via the
CC kinase catalytic domain) with STK38 (PubMed:17906693). Interacts with
CC GRIPAP1 (PubMed:17761173). {ECO:0000269|PubMed:12223491,
CC ECO:0000269|PubMed:15262978, ECO:0000269|PubMed:17761173,
CC ECO:0000269|PubMed:17906693, ECO:0000269|PubMed:9808624}.
CC -!- INTERACTION:
CC Q13233; P15056: BRAF; NbExp=2; IntAct=EBI-49776, EBI-365980;
CC Q13233; P61962: DCAF7; NbExp=7; IntAct=EBI-49776, EBI-359808;
CC Q13233; O75369: FLNB; NbExp=2; IntAct=EBI-49776, EBI-352089;
CC Q13233; P45985: MAP2K4; NbExp=3; IntAct=EBI-49776, EBI-447868;
CC Q13233; Q12851: MAP4K2; NbExp=2; IntAct=EBI-49776, EBI-49783;
CC Q13233; Q93009: USP7; NbExp=2; IntAct=EBI-49776, EBI-302474;
CC -!- PTM: Autophosphorylated. {ECO:0000250}.
CC -!- DISEASE: 46,XY sex reversal 6 (SRXY6) [MIM:613762]: A disorder of sex
CC development. Affected individuals have a 46,XY karyotype but present as
CC phenotypically normal females. {ECO:0000269|PubMed:21129722}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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; AC008937; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF042838; AAC97073.1; -; mRNA.
DR EMBL; U29671; AAB05828.1; -; Genomic_DNA.
DR CCDS; CCDS43318.1; -.
DR PIR; G01887; G01887.
DR RefSeq; NP_005912.1; NM_005921.1.
DR PDB; 6WHB; X-ray; 1.90 A; A=542-888.
DR PDBsum; 6WHB; -.
DR AlphaFoldDB; Q13233; -.
DR SMR; Q13233; -.
DR BioGRID; 110378; 150.
DR DIP; DIP-27520N; -.
DR ELM; Q13233; -.
DR IntAct; Q13233; 42.
DR MINT; Q13233; -.
DR STRING; 9606.ENSP00000382423; -.
DR BindingDB; Q13233; -.
DR ChEMBL; CHEMBL3956; -.
DR DrugBank; DB06061; AZD-8330.
DR DrugBank; DB11967; Binimetinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q13233; -.
DR GuidetoPHARMACOLOGY; 2069; -.
DR GlyGen; Q13233; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13233; -.
DR PhosphoSitePlus; Q13233; -.
DR BioMuta; MAP3K1; -.
DR DMDM; 218512139; -.
DR SWISS-2DPAGE; Q13233; -.
DR CPTAC; CPTAC-1046; -.
DR CPTAC; CPTAC-824; -.
DR CPTAC; CPTAC-825; -.
DR CPTAC; CPTAC-826; -.
DR CPTAC; CPTAC-827; -.
DR CPTAC; CPTAC-829; -.
DR CPTAC; CPTAC-830; -.
DR CPTAC; CPTAC-831; -.
DR CPTAC; CPTAC-832; -.
DR EPD; Q13233; -.
DR jPOST; Q13233; -.
DR MassIVE; Q13233; -.
DR MaxQB; Q13233; -.
DR PaxDb; Q13233; -.
DR PeptideAtlas; Q13233; -.
DR PRIDE; Q13233; -.
DR ProteomicsDB; 59240; -.
DR Antibodypedia; 3855; 460 antibodies from 36 providers.
DR DNASU; 4214; -.
DR Ensembl; ENST00000399503.4; ENSP00000382423.3; ENSG00000095015.6.
DR GeneID; 4214; -.
DR KEGG; hsa:4214; -.
DR MANE-Select; ENST00000399503.4; ENSP00000382423.3; NM_005921.2; NP_005912.1.
DR UCSC; uc003jqw.5; human.
DR CTD; 4214; -.
DR DisGeNET; 4214; -.
DR GeneCards; MAP3K1; -.
DR GeneReviews; MAP3K1; -.
DR HGNC; HGNC:6848; MAP3K1.
DR HPA; ENSG00000095015; Low tissue specificity.
DR MalaCards; MAP3K1; -.
DR MIM; 600982; gene.
DR MIM; 613762; phenotype.
DR neXtProt; NX_Q13233; -.
DR OpenTargets; ENSG00000095015; -.
DR Orphanet; 242; 46,XY complete gonadal dysgenesis.
DR Orphanet; 251510; 46,XY partial gonadal dysgenesis.
DR PharmGKB; PA30592; -.
DR VEuPathDB; HostDB:ENSG00000095015; -.
DR eggNOG; KOG0198; Eukaryota.
DR GeneTree; ENSGT00940000159154; -.
DR HOGENOM; CLU_005805_0_0_1; -.
DR InParanoid; Q13233; -.
DR OMA; CDDNFGC; -.
DR OrthoDB; 797346at2759; -.
DR PhylomeDB; Q13233; -.
DR TreeFam; TF105112; -.
DR BRENDA; 2.7.11.25; 2681.
DR PathwayCommons; Q13233; -.
DR Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-HSA-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
DR Reactome; R-HSA-975871; MyD88 cascade initiated on plasma membrane.
DR SignaLink; Q13233; -.
DR SIGNOR; Q13233; -.
DR BioGRID-ORCS; 4214; 13 hits in 1112 CRISPR screens.
DR ChiTaRS; MAP3K1; human.
DR GeneWiki; MAP3K1; -.
DR GenomeRNAi; 4214; -.
DR Pharos; Q13233; Tchem.
DR PRO; PR:Q13233; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q13233; protein.
DR Bgee; ENSG00000095015; Expressed in buccal mucosa cell and 186 other tissues.
DR Genevisible; Q13233; 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:Reactome.
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; EXP:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0006468; P:protein phosphorylation; NAS:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR007527; Znf_SWIM.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS50966; ZF_SWIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..1512
FT /note="Mitogen-activated protein kinase kinase kinase 1"
FT /id="PRO_0000086240"
FT DOMAIN 1243..1508
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 338..366
FT /note="SWIM-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00325"
FT ZN_FING 443..492
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 67..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 416..436
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 511..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 602..624
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 933..972
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1032..1087
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 82..96
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 164..181
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 243..263
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..432
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 933..955
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1041..1087
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1369
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 1249..1257
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1272
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53349"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 285
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 292
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 297
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 923
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1018
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1043
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 1400
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P53349"
FT MOD_RES 1412
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P53349"
FT VARIANT 92
FT /note="S -> N"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040680"
FT VARIANT 189
FT /note="L -> P (in SRXY6; increases phosphorylation of the
FT downstream target MAPK3/MAPK1 compared to wild-type and
FT enhances binding of RHOA to the mutant MAP3K1 complex;
FT dbSNP:rs387906788)"
FT /evidence="ECO:0000269|PubMed:21129722"
FT /id="VAR_065504"
FT VARIANT 189
FT /note="L -> R (in SRXY6; increases phosphorylation of the
FT downstream targets MAPK14 and MAPK3/MAPK1 compared to wild-
FT type and enhances binding of RHOA to the mutant MAP3K1
FT complex; dbSNP:rs387906788)"
FT /evidence="ECO:0000269|PubMed:21129722"
FT /id="VAR_065505"
FT VARIANT 211
FT /note="V -> VIQ (in SRXY6)"
FT /id="VAR_065506"
FT VARIANT 443
FT /note="C -> S"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040681"
FT VARIANT 616
FT /note="G -> R (in SRXY6; dbSNP:rs143853590)"
FT /evidence="ECO:0000269|PubMed:21129722"
FT /id="VAR_065507"
FT VARIANT 806
FT /note="D -> N (in dbSNP:rs702689)"
FT /id="VAR_051636"
FT VARIANT 906
FT /note="V -> I (in dbSNP:rs832582)"
FT /id="VAR_051637"
FT CONFLICT 20
FT /note="T -> P (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="P -> R (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT CONFLICT 120
FT /note="G -> R (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT CONFLICT 351
FT /note="R -> H (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT CONFLICT 845
FT /note="S -> SV (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT CONFLICT 859
FT /note="I -> Y (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT CONFLICT 878..902
FT /note="DGQQDSFLQASVPNNYLETTENSSP -> QRQQHNSFCRHLFPTTIWKPQRT
FT VPL (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT CONFLICT 933
FT /note="S -> R (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT CONFLICT 1097
FT /note="C -> L (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT CONFLICT 1104..1107
FT /note="AVIP -> CCYT (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT CONFLICT 1200
FT /note="D -> V (in Ref. 2; AAC97073)"
FT /evidence="ECO:0000305"
FT HELIX 551..553
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 554..564
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 566..572
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 577..597
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 629..642
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 648..664
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 670..690
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 696..710
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 711..714
FT /evidence="ECO:0007829|PDB:6WHB"
FT TURN 719..722
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 733..742
FT /evidence="ECO:0007829|PDB:6WHB"
FT TURN 745..747
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 751..767
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 769..772
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 774..776
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 787..790
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 792..802
FT /evidence="ECO:0007829|PDB:6WHB"
FT TURN 803..806
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 810..826
FT /evidence="ECO:0007829|PDB:6WHB"
FT TURN 827..829
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 831..840
FT /evidence="ECO:0007829|PDB:6WHB"
FT HELIX 847..862
FT /evidence="ECO:0007829|PDB:6WHB"
SQ SEQUENCE 1512 AA; 164470 MW; 5CB78242295411D9 CRC64;
MAAAAGNRAS SSGFPGARAT SPEAGGGGGA LKASSAPAAA AGLLREAGSG GRERADWRRR
QLRKVRSVEL DQLPEQPLFL AASPPASSTS PSPEPADAAG SGTGFQPVAV PPPHGAASRG
GAHLTESVAA PDSGASSPAA AEPGEKRAPA AEPSPAAAPA GREMENKETL KGLHKMDDRP
EERMIREKLK ATCMPAWKHE WLERRNRRGP VVVKPIPVKG DGSEMNHLAA ESPGEVQASA
ASPASKGRRS PSPGNSPSGR TVKSESPGVR RKRVSPVPFQ SGRITPPRRA PSPDGFSPYS
PEETNRRVNK VMRARLYLLQ QIGPNSFLIG GDSPDNKYRV FIGPQNCSCA RGTFCIHLLF
VMLRVFQLEP SDPMLWRKTL KNFEVESLFQ KYHSRRSSRI KAPSRNTIQK FVSRMSNSHT
LSSSSTSTSS SENSIKDEEE QMCPICLLGM LDEESLTVCE DGCRNKLHHH CMSIWAEECR
RNREPLICPL CRSKWRSHDF YSHELSSPVD SPSSLRAAQQ QTVQQQPLAG SRRNQESNFN
LTHYGTQQIP PAYKDLAEPW IQVFGMELVG CLFSRNWNVR EMALRRLSHD VSGALLLANG
ESTGNSGGSS GSSPSGGATS GSSQTSISGD VVEACCSVLS MVCADPVYKV YVAALKTLRA
MLVYTPCHSL AERIKLQRLL QPVVDTILVK CADANSRTSQ LSISTLLELC KGQAGELAVG
REILKAGSIG IGGVDYVLNC ILGNQTESNN WQELLGRLCL IDRLLLEFPA EFYPHIVSTD
VSQAEPVEIR YKKLLSLLTF ALQSIDNSHS MVGKLSRRIY LSSARMVTTV PHVFSKLLEM
LSVSSSTHFT RMRRRLMAIA DEVEIAEAIQ LGVEDTLDGQ QDSFLQASVP NNYLETTENS
SPECTVHLEK TGKGLCATKL SASSEDISER LASISVGPSS STTTTTTTTE QPKPMVQTKG
RPHSQCLNSS PLSHHSQLMF PALSTPSSST PSVPAGTATD VSKHRLQGFI PCRIPSASPQ
TQRKFSLQFH RNCPENKDSD KLSPVFTQSR PLPSSNIHRP KPSRPTPGNT SKQGDPSKNS
MTLDLNSSSK CDDSFGCSSN SSNAVIPSDE TVFTPVEEKC RLDVNTELNS SIEDLLEASM
PSSDTTVTFK SEVAVLSPEK AENDDTYKDD VNHNQKCKEK MEAEEEEALA IAMAMSASQD
ALPIVPQLQV ENGEDIIIIQ QDTPETLPGH TKAKQPYRED TEWLKGQQIG LGAFSSCYQA
QDVGTGTLMA VKQVTYVRNT SSEQEEVVEA LREEIRMMSH LNHPNIIRML GATCEKSNYN
LFIEWMAGGS VAHLLSKYGA FKESVVINYT EQLLRGLSYL HENQIIHRDV KGANLLIDST
GQRLRIADFG AAARLASKGT GAGEFQGQLL GTIAFMAPEV LRGQQYGRSC DVWSVGCAII
EMACAKPPWN AEKHSNHLAL IFKIASATTA PSIPSHLSPG LRDVALRCLE LQPQDRPPSR
ELLKHPVFRT TW
