M3K9_HUMAN
ID M3K9_HUMAN Reviewed; 1104 AA.
AC P80192; A3KN85; Q0D2G7; Q6EH31; Q9H2N5;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 9;
DE EC=2.7.11.25;
DE AltName: Full=Mixed lineage kinase 1;
GN Name=MAP3K9; Synonyms=MLK1, PRKE1;
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), FUNCTION, ACTIVITY REGULATION,
RP PHOSPHORYLATION AT THR-304; THR-305; SER-308 AND THR-312, AND MUTAGENESIS
RP OF LYS-171; THR-304; THR-305; SER-308 AND THR-312.
RX PubMed=15610029; DOI=10.1021/bi049866y;
RA Durkin J.T., Holskin B.P., Kopec K.K., Reed M.S., Spais C.M., Steffy B.M.,
RA Gessner G., Angeles T.S., Pohl J., Ator M.A., Meyer S.L.;
RT "Phosphoregulation of mixed-lineage kinase 1 activity by multiple
RT phosphorylation in the activation loop.";
RL Biochemistry 43:16348-16355(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 53-1104 (ISOFORM 2).
RA McNee J.J., Dower S.K., Guesdon F.;
RT "cDNA sequence and gene organisation of mixed lineage kinase 1.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 142-535, AND TISSUE SPECIFICITY.
RC TISSUE=Colon epithelium;
RX PubMed=8477742; DOI=10.1111/j.1432-1033.1993.tb17810.x;
RA Dorow D.S., Devereux L., Dietzsch E., de Kretser T.;
RT "Identification of a new family of human epithelial protein kinases
RT containing two leucine/isoleucine-zipper domains.";
RL Eur. J. Biochem. 213:701-710(1993).
RN [5]
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND PHOSPHORYLATION OF
RP MAP2K4/MKK4.
RX PubMed=11325962; DOI=10.1074/jbc.m011601200;
RA Maroney A.C., Finn J.P., Connors T.J., Durkin J.T., Angeles T., Gessner G.,
RA Xu Z., Meyer S.L., Savage M.J., Greene L.A., Scott R.W., Vaught J.L.;
RT "Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase
RT family.";
RL J. Biol. Chem. 276:25302-25308(2001).
RN [6]
RP FUNCTION IN THE APOPTOSIS PATHWAY.
RX PubMed=11416147; DOI=10.1128/mcb.21.14.4713-4724.2001;
RA Xu Z., Maroney A.C., Dobrzanski P., Kukekov N.V., Greene L.A.;
RT "The MLK family mediates c-Jun N-terminal kinase activation in neuronal
RT apoptosis.";
RL Mol. Cell. Biol. 21:4713-4724(2001).
RN [7]
RP ACTIVITY REGULATION.
RX PubMed=11755341; DOI=10.1016/s0960-894x(01)00690-4;
RA Murakata C., Kaneko M., Gessner G., Angeles T.S., Ator M.A., O'Kane T.M.,
RA McKenna B.A., Thomas B.A., Mathiasen J.R., Saporito M.S.,
RA Bozyczko-Coyne D., Hudkins R.L.;
RT "Mixed lineage kinase activity of indolocarbazole analogues.";
RL Bioorg. Med. Chem. Lett. 12:147-150(2002).
RN [8]
RP POSSIBLE ROLE IN ESOPHAGEAL CANCER.
RX PubMed=18241037; DOI=10.1002/ijc.23397;
RA Chen J., Guo L., Peiffer D.A., Zhou L., Chan O.T., Bibikova M.,
RA Wickham-Garcia E., Lu S.H., Zhan Q., Wang-Rodriguez J., Jiang W., Fan J.B.;
RT "Genomic profiling of 766 cancer-related genes in archived esophageal
RT normal and carcinoma tissues.";
RL Int. J. Cancer 122:2249-2254(2008).
RN [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-533, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [11]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 136-406.
RX PubMed=18714982; DOI=10.1021/jm8005838;
RA Hudkins R.L., Diebold J.L., Tao M., Josef K.A., Park C.H., Angeles T.S.,
RA Aimone L.D., Husten J., Ator M.A., Meyer S.L., Holskin B.P., Durkin J.T.,
RA Fedorov A.A., Fedorov E.V., Almo S.C., Mathiasen J.R., Bozyczko-Coyne D.,
RA Saporito M.S., Scott R.W., Mallamo J.P.;
RT "Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective
RT dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-
RT lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-
RT phenyltetrahydropyridine models.";
RL J. Med. Chem. 51:5680-5689(2008).
RN [12]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-246; CYS-467; GLN-497 AND CYS-646.
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: Serine/threonine kinase which acts as an essential component
CC of the MAP kinase signal transduction pathway. Plays an important role
CC in the cascades of cellular responses evoked by changes in the
CC environment. Once activated, acts as an upstream activator of the
CC MKK/JNK signal transduction cascade through the phosphorylation of
CC MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The
CC MKK/JNK signaling pathway regulates stress response via activator
CC protein-1 (JUN) and GATA4 transcription factors. Also plays a role in
CC mitochondrial death signaling pathway, including the release cytochrome
CC c, leading to apoptosis. {ECO:0000269|PubMed:11416147,
CC ECO:0000269|PubMed:15610029}.
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: Homodimerization via the leucine zipper domains is
CC required for autophosphorylation of multiple sites in the activation
CC loop and subsequent activation. Autophosphorylation at Thr-312 is the
CC key step in activation of MAP3K9/MLK1 and is required for full
CC phosphorylation. Autophosphorylation at Thr-304 and Ser-308 have been
CC shown to be of secondary importance in the activation of MAP3K9/MLK1.
CC CEP-1347 and many indolocarbazole analogs have been shown to act as
CC inhibitors of MAP3K9/MLK1 activity. {ECO:0000269|PubMed:11325962,
CC ECO:0000269|PubMed:11755341, ECO:0000269|PubMed:15610029}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=62 uM for ATP {ECO:0000269|PubMed:11325962};
CC KM=7 uM for myelin basic protein (MBP) as substrate
CC {ECO:0000269|PubMed:11325962};
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- INTERACTION:
CC P80192; P08238: HSP90AB1; NbExp=2; IntAct=EBI-3951604, EBI-352572;
CC P80192; Q92993: KAT5; NbExp=3; IntAct=EBI-3951604, EBI-399080;
CC P80192; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-3951604, EBI-11742507;
CC P80192; P17252: PRKCA; NbExp=3; IntAct=EBI-3951604, EBI-1383528;
CC P80192; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-3951604, EBI-9090795;
CC P80192; P61981: YWHAG; NbExp=3; IntAct=EBI-3951604, EBI-359832;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P80192-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P80192-4; Sequence=VSP_013765;
CC -!- TISSUE SPECIFICITY: Expressed in epithelial tumor cell lines of
CC colonic, breast and esophageal origin. {ECO:0000269|PubMed:8477742}.
CC -!- PTM: Autophosphorylation on serine and threonine residues within the
CC activation loop plays a role in enzyme activation. Thr-312 is likely to
CC be the main autophosphorylation site. Autophosphorylation also occurs
CC on Thr-304 and Ser-308. {ECO:0000269|PubMed:11325962,
CC ECO:0000269|PubMed:15610029}.
CC -!- DISEASE: Note=May play a role in esophageal cancer susceptibility
CC and/or development.
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=AAI11408.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY327900; AAQ23054.1; -; mRNA.
DR EMBL; BC111407; AAI11408.1; ALT_INIT; mRNA.
DR EMBL; BC133706; AAI33707.1; -; mRNA.
DR EMBL; AF251442; AAG44591.1; -; mRNA.
DR CCDS; CCDS32112.1; -. [P80192-4]
DR CCDS; CCDS61488.1; -. [P80192-1]
DR PIR; S32467; JU0229.
DR RefSeq; NP_001271159.1; NM_001284230.1. [P80192-1]
DR RefSeq; NP_149132.2; NM_033141.3. [P80192-4]
DR PDB; 3DTC; X-ray; 2.60 A; A=136-406.
DR PDB; 4UY9; X-ray; 2.81 A; A/B=135-456.
DR PDBsum; 3DTC; -.
DR PDBsum; 4UY9; -.
DR AlphaFoldDB; P80192; -.
DR SMR; P80192; -.
DR BioGRID; 110439; 10.
DR IntAct; P80192; 24.
DR STRING; 9606.ENSP00000451263; -.
DR BindingDB; P80192; -.
DR ChEMBL; CHEMBL2872; -.
DR DrugBank; DB08703; 12-(2-hydroxyethyl)-2-(1-methylethoxy)-13,14-dihydronaphtho[2,1-a]pyrrolo[3,4-c]carbazol-5(12H)-one.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P80192; -.
DR GuidetoPHARMACOLOGY; 2084; -.
DR iPTMnet; P80192; -.
DR PhosphoSitePlus; P80192; -.
DR BioMuta; MAP3K9; -.
DR DMDM; 116242625; -.
DR CPTAC; CPTAC-860; -.
DR CPTAC; CPTAC-861; -.
DR EPD; P80192; -.
DR jPOST; P80192; -.
DR MassIVE; P80192; -.
DR PaxDb; P80192; -.
DR PeptideAtlas; P80192; -.
DR PRIDE; P80192; -.
DR ProteomicsDB; 57671; -. [P80192-1]
DR ProteomicsDB; 57672; -. [P80192-4]
DR Antibodypedia; 75; 369 antibodies from 33 providers.
DR DNASU; 4293; -.
DR Ensembl; ENST00000554752.7; ENSP00000451612.2; ENSG00000006432.16. [P80192-1]
DR Ensembl; ENST00000555993.6; ENSP00000451263.2; ENSG00000006432.16. [P80192-4]
DR GeneID; 4293; -.
DR KEGG; hsa:4293; -.
DR MANE-Select; ENST00000554752.7; ENSP00000451612.2; NM_001284230.2; NP_001271159.1.
DR UCSC; uc001xml.5; human. [P80192-1]
DR CTD; 4293; -.
DR DisGeNET; 4293; -.
DR GeneCards; MAP3K9; -.
DR HGNC; HGNC:6861; MAP3K9.
DR HPA; ENSG00000006432; Tissue enhanced (brain, retina).
DR MIM; 600136; gene.
DR neXtProt; NX_P80192; -.
DR OpenTargets; ENSG00000006432; -.
DR PharmGKB; PA30607; -.
DR VEuPathDB; HostDB:ENSG00000006432; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000158243; -.
DR InParanoid; P80192; -.
DR OMA; DSECLNG; -.
DR OrthoDB; 115270at2759; -.
DR PhylomeDB; P80192; -.
DR TreeFam; TF105118; -.
DR PathwayCommons; P80192; -.
DR SABIO-RK; P80192; -.
DR SignaLink; P80192; -.
DR SIGNOR; P80192; -.
DR BioGRID-ORCS; 4293; 8 hits in 1101 CRISPR screens.
DR ChiTaRS; MAP3K9; human.
DR EvolutionaryTrace; P80192; -.
DR GeneWiki; MAP3K9; -.
DR GenomeRNAi; 4293; -.
DR Pharos; P80192; Tchem.
DR PRO; PR:P80192; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P80192; protein.
DR Bgee; ENSG00000006432; Expressed in buccal mucosa cell and 160 other tissues.
DR ExpressionAtlas; P80192; baseline and differential.
DR Genevisible; P80192; HS.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; ISS:UniProtKB.
DR GO; GO:0004708; F:MAP kinase kinase activity; NAS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR CDD; cd12059; SH3_MLK1-3; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR035779; MLK1-3_SH3.
DR InterPro; IPR016231; MLK1-4.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PIRSF; PIRSF000556; MAPKKK9_11; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 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; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; SH3 domain; Stress response;
KW Transcription; Transcription regulation; Transferase.
FT CHAIN 1..1104
FT /note="Mitogen-activated protein kinase kinase kinase 9"
FT /id="PRO_0000086258"
FT DOMAIN 52..116
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 144..412
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 12..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 430..451
FT /note="Leucine-zipper 1"
FT REGION 465..486
FT /note="Leucine-zipper 2"
FT REGION 532..636
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 675..742
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 781..819
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 890..1038
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..41
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 532..552
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 578..595
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 719..739
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 783..801
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 894..915
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 927..941
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 955..969
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 971..985
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1012..1038
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 268
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 150..158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 171
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 304
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15610029"
FT MOD_RES 305
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15610029"
FT MOD_RES 308
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15610029"
FT MOD_RES 312
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15610029"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 675
FT /note="M -> MALLAASWVVPIDIE (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_013765"
FT VARIANT 246
FT /note="A -> V (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040698"
FT VARIANT 467
FT /note="R -> C (in a gastric adenocarcinoma sample; somatic
FT mutation; dbSNP:rs773256562)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040699"
FT VARIANT 497
FT /note="R -> Q (in dbSNP:rs56196343)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040700"
FT VARIANT 646
FT /note="Y -> C (in dbSNP:rs34322726)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040701"
FT MUTAGEN 171
FT /note="K->A: Loss of kinase activity and threonine
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:15610029"
FT MUTAGEN 304
FT /note="T->A: Reduces threonine phosphorylation. Impairs JNK
FT activation."
FT /evidence="ECO:0000269|PubMed:15610029"
FT MUTAGEN 305
FT /note="T->A: Little effect on threonine phosphorylation.
FT Mildly impairs JNK activation."
FT /evidence="ECO:0000269|PubMed:15610029"
FT MUTAGEN 308
FT /note="S->A: Impairs JNK activation."
FT /evidence="ECO:0000269|PubMed:15610029"
FT MUTAGEN 312
FT /note="T->A: Loss of threonine phosphorylation. Strongly
FT impairs JNK activation."
FT /evidence="ECO:0000269|PubMed:15610029"
FT CONFLICT 356
FT /note="A -> R (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 433
FT /note="M -> T (in Ref. 1; AAQ23054)"
FT /evidence="ECO:0000305"
FT CONFLICT 511..535
FT /note="KLKDGNRISLPSDFQHKFTVQASPT -> AQPVLPFPHGHSRCPGGTGSSWG
FT GQ (in Ref. 4)"
FT /evidence="ECO:0000305"
FT STRAND 143..153
FT /evidence="ECO:0007829|PDB:3DTC"
FT STRAND 156..163
FT /evidence="ECO:0007829|PDB:3DTC"
FT STRAND 166..172
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 185..197
FT /evidence="ECO:0007829|PDB:3DTC"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:3DTC"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 228..232
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 239..258
FT /evidence="ECO:0007829|PDB:3DTC"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:3DTC"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:3DTC"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:3DTC"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 299..301
FT /evidence="ECO:0007829|PDB:4UY9"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 318..323
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 328..344
FT /evidence="ECO:0007829|PDB:3DTC"
FT TURN 348..351
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 354..362
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 376..385
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 396..404
FT /evidence="ECO:0007829|PDB:3DTC"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:4UY9"
FT HELIX 418..439
FT /evidence="ECO:0007829|PDB:4UY9"
FT HELIX 441..444
FT /evidence="ECO:0007829|PDB:4UY9"
SQ SEQUENCE 1104 AA; 121895 MW; 0F059C867FCE7276 CRC64;
MEPSRALLGC LASAAAAAPP GEDGAGAGAE EEEEEEEEAA AAVGPGELGC DAPLPYWTAV
FEYEAAGEDE LTLRLGDVVE VLSKDSQVSG DEGWWTGQLN QRVGIFPSNY VTPRSAFSSR
CQPGGEDPSC YPPIQLLEID FAELTLEEII GIGGFGKVYR AFWIGDEVAV KAARHDPDED
ISQTIENVRQ EAKLFAMLKH PNIIALRGVC LKEPNLCLVM EFARGGPLNR VLSGKRIPPD
ILVNWAVQIA RGMNYLHDEA IVPIIHRDLK SSNILILQKV ENGDLSNKIL KITDFGLARE
WHRTTKMSAA GTYAWMAPEV IRASMFSKGS DVWSYGVLLW ELLTGEVPFR GIDGLAVAYG
VAMNKLALPI PSTCPEPFAK LMEDCWNPDP HSRPSFTNIL DQLTTIEESG FFEMPKDSFH
CLQDNWKHEI QEMFDQLRAK EKELRTWEEE LTRAALQQKN QEELLRRREQ ELAEREIDIL
ERELNIIIHQ LCQEKPRVKK RKGKFRKSRL KLKDGNRISL PSDFQHKFTV QASPTMDKRK
SLINSRSSPP ASPTIIPRLR AIQLTPGESS KTWGRSSVVP KEEGEEEEKR APKKKGRTWG
PGTLGQKELA SGDEGSPQRR EKANGLSTPS ESPHFHLGLK SLVDGYKQWS SSAPNLVKGP
RSSPALPGFT SLMEMEDEDS EGPGSGESRL QHSPSQSYLC IPFPRGEDGD GPSSDGIHEE
PTPVNSATST PQLTPTNSLK RGGAHHRRCE VALLGCGAVL AATGLGFDLL EAGKCQLLPL
EEPEPPAREE KKRREGLFQR SSRPRRSTSP PSRKLFKKEE PMLLLGDPSA SLTLLSLSSI
SECNSTRSLL RSDSDEIVVY EMPVSPVEAP PLSPCTHNPL VNVRVERFKR DPNQSLTPTH
VTLTTPSQPS SHRRTPSDGA LKPETLLASR SPSSNGLSPS PGAGMLKTPS PSRDPGEFPR
LPDPNVVFPP TPRRWNTQQD STLERPKTLE FLPRPRPSAN RQRLDPWWFV SPSHARSTSP
ANSSSTETPS NLDSCFASSS STVEERPGLP ALLPFQAGPL PPTERTLLDL DAEGQSQDST
VPLCRAELNT HRPAPYEIQQ EFWS
