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}.
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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
//
