ID M3K15_HUMAN Reviewed; 1313 AA. AC Q6ZN16; A2AI49; A2AI50; A6NJ61; Q5JPR4; Q6ZMV3; DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 160. DE RecName: Full=Mitogen-activated protein kinase kinase kinase 15; DE EC=2.7.11.25 {ECO:0000269|PubMed:20362554, ECO:0000269|PubMed:26732173}; DE AltName: Full=Apoptosis signal-regulating kinase 3; DE AltName: Full=MAPK/ERK kinase kinase 15; DE Short=MEK kinase 15; DE Short=MEKK 15; GN Name=MAP3K15; Synonyms=ASK3; 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 MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Teratocarcinoma, and Testis; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [3] 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 [4] RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY. RX PubMed=20362554; DOI=10.1016/j.bbrc.2010.03.164; RA Kaji T., Yoshida S., Kawai K., Fuchigami Y., Watanabe W., Kubodera H., RA Kishimoto T.; RT "ASK3, a novel member of the apoptosis signal-regulating kinase family, is RT essential for stress-induced cell death in HeLa cells."; RL Biochem. Biophys. Res. Commun. 395:213-218(2010). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-994, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; 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 [6] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-681. RX PubMed=26732173; DOI=10.1038/srep18710; RA Maruyama J., Kobayashi Y., Umeda T., Vandewalle A., Takeda K., Ichijo H., RA Naguro I.; RT "Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK- RT MK pathway."; RL Sci. Rep. 6:18710-18710(2016). RN [7] RP VARIANTS [LARGE SCALE ANALYSIS] THR-192; ASN-199; HIS-226; SER-255; RP GLY-456; CYS-494; LEU-562; GLN-677; SER-838; LEU-993; HIS-1029; ARG-1247 RP AND GLU-1251. 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 a component of the MAP CC kinase signal transduction pathway (PubMed:20362554, PubMed:26732173). CC Once activated, acts as an upstream activator of the p38 MAPK signal CC transduction cascade through the phosphorylation and activation of CC several MAP kinase kinases (PubMed:20362554, PubMed:26732173). May CC function in a signal transduction pathway that is activated by various CC cell stresses and leads to apoptosis (PubMed:20362554). Involved in CC phosphorylation of WNK4 in response to osmotic stress or hypotonic low- CC chloride stimulation via the p38 MAPK signal transduction cascade CC (PubMed:26732173). {ECO:0000269|PubMed:20362554, CC ECO:0000269|PubMed:26732173}. 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:0000269|PubMed:20362554, ECO:0000269|PubMed:26732173}; 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:0000269|PubMed:20362554}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:Q99683}; CC -!- ACTIVITY REGULATION: Contains an N-terminal autoinhibitory domain. CC Activated by phosphorylation at Thr-812, inhibited by phosphorylation CC at Ser-924 and Ser-994 (By similarity). {ECO:0000250|UniProtKB:Q99683}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q6ZN16-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6ZN16-2; Sequence=VSP_021038; CC Name=3; CC IsoId=Q6ZN16-3; Sequence=VSP_021039, VSP_021040; CC -!- TISSUE SPECIFICITY: Isoform 2 and isoform 3 are widely expressed. CC Isoform 2 highest levels are observed in fetal brain, and isoform 3 CC highest levels in pancreas, peripheral blood leukocytes, fetal brain CC and spleen. {ECO:0000269|PubMed:20362554}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr CC protein kinase family. MAP kinase kinase kinase subfamily. CC {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; AK131412; BAD18559.1; -; mRNA. DR EMBL; AK131477; BAD18622.1; -; mRNA. DR EMBL; AL732326; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL732423; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS35212.2; -. [Q6ZN16-1] DR RefSeq; NP_001001671.3; NM_001001671.3. [Q6ZN16-1] DR RefSeq; XP_011543813.1; XM_011545511.2. [Q6ZN16-2] DR PDB; 6V0M; X-ray; 1.80 A; A/B/C=1241-1308. DR PDBsum; 6V0M; -. DR AlphaFoldDB; Q6ZN16; -. DR SMR; Q6ZN16; -. DR BioGRID; 133293; 21. DR IntAct; Q6ZN16; 8. DR STRING; 9606.ENSP00000345629; -. DR BindingDB; Q6ZN16; -. DR ChEMBL; CHEMBL1163127; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; Q6ZN16; -. DR iPTMnet; Q6ZN16; -. DR PhosphoSitePlus; Q6ZN16; -. DR BioMuta; MAP3K15; -. DR DMDM; 116248533; -. DR CPTAC; CPTAC-841; -. DR CPTAC; CPTAC-842; -. DR jPOST; Q6ZN16; -. DR MassIVE; Q6ZN16; -. DR PaxDb; 9606-ENSP00000345629; -. DR PeptideAtlas; Q6ZN16; -. DR ProteomicsDB; 67956; -. [Q6ZN16-1] DR ProteomicsDB; 67957; -. [Q6ZN16-2] DR ProteomicsDB; 67958; -. [Q6ZN16-3] DR Antibodypedia; 571; 172 antibodies from 27 providers. DR DNASU; 389840; -. DR Ensembl; ENST00000338883.9; ENSP00000345629.4; ENSG00000180815.15. [Q6ZN16-1] DR GeneID; 389840; -. DR KEGG; hsa:389840; -. DR MANE-Select; ENST00000338883.9; ENSP00000345629.4; NM_001001671.4; NP_001001671.3. DR UCSC; uc004czj.3; human. [Q6ZN16-1] DR AGR; HGNC:31689; -. DR CTD; 389840; -. DR DisGeNET; 389840; -. DR GeneCards; MAP3K15; -. DR HGNC; HGNC:31689; MAP3K15. DR HPA; ENSG00000180815; Group enriched (adrenal gland, choroid plexus). DR MIM; 300820; gene. DR neXtProt; NX_Q6ZN16; -. DR OpenTargets; ENSG00000180815; -. DR PharmGKB; PA134935369; -. DR VEuPathDB; HostDB:ENSG00000180815; -. DR eggNOG; KOG4279; Eukaryota. DR GeneTree; ENSGT00940000159562; -. DR HOGENOM; CLU_048342_0_0_1; -. DR InParanoid; Q6ZN16; -. DR OMA; MQPNWDS; -. DR OrthoDB; 5388799at2759; -. DR PhylomeDB; Q6ZN16; -. DR TreeFam; TF105115; -. DR PathwayCommons; Q6ZN16; -. DR SignaLink; Q6ZN16; -. DR BioGRID-ORCS; 389840; 3 hits in 297 CRISPR screens. DR ChiTaRS; MAP3K15; human. DR GenomeRNAi; 389840; -. DR Pharos; Q6ZN16; Tchem. DR PRO; PR:Q6ZN16; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q6ZN16; Protein. DR Bgee; ENSG00000180815; Expressed in adrenal tissue and 80 other cell types or tissues. DR ExpressionAtlas; Q6ZN16; baseline and differential. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR CDD; cd06624; STKc_ASK; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR046872; DRHyd-ASK. DR InterPro; IPR046873; HisK-N-like. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR043969; MAP3K_PH. DR InterPro; IPR025136; MAP3K_TRAF-bd. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR013761; SAM/pointed_sf. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR11584:SF363; MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 15; 1. DR PANTHER; PTHR11584; SERINE/THREONINE PROTEIN KINASE; 1. DR Pfam; PF19039; ASK_PH; 1. DR Pfam; PF20309; DRHyd-ASK; 1. DR Pfam; PF20302; HisK-N-like; 1. DR Pfam; PF13281; MAP3K_TRAF_bd; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF47769; SAM/Pointed domain; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 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; Coiled coil; Kinase; KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transferase. FT CHAIN 1..1313 FT /note="Mitogen-activated protein kinase kinase kinase 15" FT /id="PRO_0000253481" FT DOMAIN 652..908 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..58 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 939..958 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 1179..1225 FT /evidence="ECO:0000255" FT COMPBIAS 939..953 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 773 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 658..666 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 681 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 994 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..565 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_021038" FT VAR_SEQ 1..525 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_021039" FT VAR_SEQ 526..582 FT /note="GLRFPVLVIEPTKVYQPSYVSINNEAEERTVSLWHVSPTEMKQMHEWNFTAS FT SIKGI -> MACLTHRNETDARMEFYSLFHKGNKAGVQWHDLGSLQPLPPRFKRFSCLS FT LQSSWDY (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_021040" FT VARIANT 192 FT /note="A -> T (in dbSNP:rs5909299)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040716" FT VARIANT 199 FT /note="S -> N (in dbSNP:rs55916006)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040717" FT VARIANT 226 FT /note="D -> H (in dbSNP:rs56338727)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040718" FT VARIANT 255 FT /note="R -> S (in a lung squamous cell carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040719" FT VARIANT 456 FT /note="S -> G (in dbSNP:rs56212339)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040720" FT VARIANT 494 FT /note="R -> C (in dbSNP:rs41305349)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040721" FT VARIANT 562 FT /note="S -> L (in a lung adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040722" FT VARIANT 677 FT /note="R -> Q (in a metastatic melanoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040723" FT VARIANT 838 FT /note="G -> S (in dbSNP:rs56381411)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040724" FT VARIANT 993 FT /note="S -> L (in dbSNP:rs56233219)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040725" FT VARIANT 1029 FT /note="N -> H (in dbSNP:rs55787622)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040726" FT VARIANT 1247 FT /note="W -> R (in a colorectal adenocarcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040727" FT VARIANT 1251 FT /note="Q -> E (in dbSNP:rs15943)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040728" FT MUTAGEN 681 FT /note="K->M: Abolished protein kinase activity." FT /evidence="ECO:0000269|PubMed:26732173" FT CONFLICT 793 FT /note="F -> L (in Ref. 1; BAD18622)" FT /evidence="ECO:0000305" FT HELIX 1241..1250 FT /evidence="ECO:0007829|PDB:6V0M" FT HELIX 1255..1263 FT /evidence="ECO:0007829|PDB:6V0M" FT HELIX 1268..1273 FT /evidence="ECO:0007829|PDB:6V0M" FT HELIX 1277..1282 FT /evidence="ECO:0007829|PDB:6V0M" FT HELIX 1287..1307 FT /evidence="ECO:0007829|PDB:6V0M" SQ SEQUENCE 1313 AA; 147437 MW; 60751706D6AEE3E9 CRC64; MESGGGNAPA GALGAASESP QCPPPPGVEG AAGPAEPDGA AEGAAGGSGE GESGGGPRRA LRAVYVRSES SQGGAAGGPE AGARQCLLRA CEAEGAHLTS VPFGELDFGE TAVLDAFYDA DVAVVDMSDV SRQPSLFYHL GVRESFDMAN NVILYHDTDA DTALSLKDMV TQKNTASSGN YYFIPYIVTP CADYFCCESD AQRRASEYMQ PNWDNILGPL CMPLVDRFIS LLKDIHVTSC VYYKETLLND IRKAREKYQG EELAKELARI KLRMDNTEVL TSDIIINLLL SYRDIQDYDA MVKLVETLEM LPTCDLADQH NIKFHYAFAL NRRNSTGDRE KALQIMLQVL QSCDHPGPDM FCLCGRIYKD IFLDSDCKDD TSRDSAIEWY RKGFELQSSL YSGINLAVLL IVAGQQFETS LELRKIGVRL NSLLGRKGSL EKMNNYWDVG QFFSVSMLAH DVGKAVQAAE RLFKLKPPVW YLRSLVQNLL LIRRFKKTII EHSPRQERLN FWLDIIFEAT NEVTNGLRFP VLVIEPTKVY QPSYVSINNE AEERTVSLWH VSPTEMKQMH EWNFTASSIK GISLSKFDER CCFLYVHDNS DDFQIYFSTE EQCSRFFSLV KEMITNTAGS TVELEGETDG DTLEYEYDHD ANGERVVLGK GTYGIVYAGR DLSNQVRIAI KEIPERDSRY SQPLHEEIAL HKYLKHRNIV QYLGSVSENG YIKIFMEQVP GGSLSALLRS KWGPMKEPTI KFYTKQILEG LKYLHENQIV HRDIKGDNVL VNTYSGVVKI SDFGTSKRLA GVNPCTETFT GTLQYMAPEI IDQGPRGYGA PADIWSLGCT IIEMATSKPP FHELGEPQAA MFKVGMFKIH PEIPEALSAE ARAFILSCFE PDPHKRATTA ELLREGFLRQ VNKGKKNRIA FKPSEGPRGV VLALPTQGEP MATSSSEHGS VSPDSDAQPD ALFERTRAPR HHLGHLLSVP DESSALEDRG LASSPEDRDQ GLFLLRKDSE RRAILYKILW EEQNQVASNL QECVAQSSEE LHLSVGHIKQ IIGILRDFIR SPEHRVMATT ISKLKVDLDF DSSSISQIHL VLFGFQDAVN KILRNHLIRP HWMFAMDNII RRAVQAAVTI LIPELRAHFE PTCETEGVDK DMDEAEEGYP PATGPGQEAQ PHQQHLSLQL GELRQETNRL LEHLVEKERE YQNLLRQTLE QKTQELYHLQ LKLKSNCITE NPAGPYGQRT DKELIDWLRL QGADAKTIEK IVEEGYTLSD ILNEITKEDL RYLRLRGGLL CRLWSAVSQY RRAQEASETK DKA //