M4K1_HUMAN
ID M4K1_HUMAN Reviewed; 833 AA.
AC Q92918;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase kinase 1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:8824585};
DE AltName: Full=Hematopoietic progenitor kinase;
DE AltName: Full=MAPK/ERK kinase kinase kinase 1;
DE Short=MEK kinase kinase 1;
DE Short=MEKKK 1;
GN Name=MAP4K1; Synonyms=HPK1;
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 {ECO:0000312|EMBL:AAB97983.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP TISSUE SPECIFICITY, AND INTERACTION WITH MAP3K1.
RC TISSUE=Fetal liver;
RX PubMed=8824585; DOI=10.1101/gad.10.18.2251;
RA Hu M.C.-T., Qiu W.R., Wang X., Meyer C.F., Tan T.-H.;
RT "Human HPK1, a novel human hematopoietic progenitor kinase that activates
RT the JNK/SAPK kinase cascade.";
RL Genes Dev. 10:2251-2264(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421 AND SER-586, 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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405; SER-407; SER-413 AND
RP SER-421, AND 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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-312; SER-351; LEU-361 AND PHE-737.
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 [7]
RP FUNCTION, PHOSPHORYLATION AT THR-165; SER-171; THR-175 AND THR-355,
RP UBIQUITINATION, MUTAGENESIS OF THR-355, AND INTERACTION WITH FBXW8.
RX PubMed=24362026; DOI=10.1074/jbc.m113.520106;
RA Wang H., Chen Y., Lin P., Li L., Zhou G., Liu G., Logsdon C., Jin J.,
RA Abbruzzese J.L., Tan T.H., Wang H.;
RT "The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin
RT ligase promotes degradation of hematopoietic progenitor kinase 1.";
RL J. Biol. Chem. 289:4009-4017(2014).
CC -!- FUNCTION: Serine/threonine-protein kinase, which may play a role in the
CC response to environmental stress (PubMed:24362026). Appears to act
CC upstream of the JUN N-terminal pathway (PubMed:8824585). May play a
CC role in hematopoietic lineage decisions and growth regulation
CC (PubMed:8824585, PubMed:24362026). Able to autophosphorylate
CC (PubMed:8824585). Together with CLNK, it enhances CD3-triggered
CC activation of T-cells and subsequent IL2 production (By similarity).
CC {ECO:0000250|UniProtKB:P70218, ECO:0000269|PubMed:24362026,
CC ECO:0000269|PubMed:8824585}.
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=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:8824585};
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=2.7.11.1; Evidence={ECO:0000269|PubMed:8824585};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:8824585};
CC -!- SUBUNIT: Interacts with MAP3K1 (PubMed:8824585). Interacts with FBXW8
CC (PubMed:24362026). Interacts with CLNK (via its SH2 domain) (By
CC similarity). {ECO:0000250|UniProtKB:P70218,
CC ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:8824585}.
CC -!- INTERACTION:
CC Q92918; P00519: ABL1; NbExp=3; IntAct=EBI-881, EBI-375543;
CC Q92918; P46108: CRK; NbExp=4; IntAct=EBI-881, EBI-886;
CC Q92918; P46109: CRKL; NbExp=5; IntAct=EBI-881, EBI-910;
CC Q92918; P06241: FYN; NbExp=2; IntAct=EBI-881, EBI-515315;
CC Q92918; P62993: GRB2; NbExp=9; IntAct=EBI-881, EBI-401755;
CC Q92918; P08238: HSP90AB1; NbExp=4; IntAct=EBI-881, EBI-352572;
CC Q92918; P16333: NCK1; NbExp=4; IntAct=EBI-881, EBI-389883;
CC Q92918; P27986: PIK3R1; NbExp=2; IntAct=EBI-881, EBI-79464;
CC Q92918; P19174: PLCG1; NbExp=6; IntAct=EBI-881, EBI-79387;
CC Q92918; Q13291: SLAMF1; NbExp=3; IntAct=EBI-881, EBI-4315002;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92918-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92918-2; Sequence=VSP_040340;
CC -!- TISSUE SPECIFICITY: Expressed primarily in hematopoietic organs,
CC including bone marrow, spleen and thymus. Also expressed at very low
CC levels in lung, kidney, mammary glands and small intestine.
CC {ECO:0000269|PubMed:8824585}.
CC -!- PTM: Autophosphorylates: phosphorylation promotes ubiquitination by the
CC Cul7-RING(FBXW8) ubiquitin-protein ligase complex, leading to its
CC degradation by the proteasome. {ECO:0000269|PubMed:24362026}.
CC -!- PTM: Tyrosine-phosphorylated after activation of hemopoietic cells.
CC {ECO:0000250|UniProtKB:P70218}.
CC -!- PTM: Ubiquitinated by the Cul7-RING(FBXW8) ubiquitin-protein ligase
CC complex following autophosphorylation, leading to its degradation by
CC the proteasome. {ECO:0000269|PubMed:24362026}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; U66464; AAB97983.1; -; mRNA.
DR EMBL; AC005933; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC008649; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS42564.1; -. [Q92918-2]
DR CCDS; CCDS59385.1; -. [Q92918-1]
DR RefSeq; NP_001036065.1; NM_001042600.2. [Q92918-2]
DR RefSeq; NP_009112.1; NM_007181.5. [Q92918-1]
DR PDB; 6CQD; X-ray; 2.12 A; A/B=2-293.
DR PDB; 6CQE; X-ray; 1.89 A; A/B=2-293.
DR PDB; 6CQF; X-ray; 2.25 A; A=2-293.
DR PDB; 6NFY; X-ray; 2.17 A; A/B=10-307.
DR PDB; 6NFZ; X-ray; 2.97 A; A/B=1-307.
DR PDB; 6NG0; X-ray; 2.05 A; A/B=1-307.
DR PDB; 7KAC; X-ray; 1.85 A; A/B=1-319.
DR PDB; 7L24; X-ray; 2.68 A; A/B/C/D=7-294.
DR PDB; 7L25; X-ray; 1.85 A; A/B=6-294.
DR PDB; 7L26; X-ray; 2.30 A; A/B/C/D=8-294.
DR PDB; 7M0K; X-ray; 2.01 A; A/B/C/D=6-294.
DR PDB; 7M0L; X-ray; 2.43 A; A/B/C/D=5-294.
DR PDB; 7M0M; X-ray; 1.93 A; A/B=2-294.
DR PDB; 7R9L; X-ray; 2.33 A; A=2-293.
DR PDB; 7R9N; X-ray; 1.50 A; A/B=2-293.
DR PDB; 7R9P; X-ray; 2.27 A; A/B=2-293.
DR PDB; 7R9T; X-ray; 2.00 A; A/B=2-293.
DR PDB; 7SIU; X-ray; 1.79 A; A/B=2-295.
DR PDBsum; 6CQD; -.
DR PDBsum; 6CQE; -.
DR PDBsum; 6CQF; -.
DR PDBsum; 6NFY; -.
DR PDBsum; 6NFZ; -.
DR PDBsum; 6NG0; -.
DR PDBsum; 7KAC; -.
DR PDBsum; 7L24; -.
DR PDBsum; 7L25; -.
DR PDBsum; 7L26; -.
DR PDBsum; 7M0K; -.
DR PDBsum; 7M0L; -.
DR PDBsum; 7M0M; -.
DR PDBsum; 7R9L; -.
DR PDBsum; 7R9N; -.
DR PDBsum; 7R9P; -.
DR PDBsum; 7R9T; -.
DR PDBsum; 7SIU; -.
DR AlphaFoldDB; Q92918; -.
DR SMR; Q92918; -.
DR BioGRID; 116354; 79.
DR DIP; DIP-31019N; -.
DR IntAct; Q92918; 68.
DR MINT; Q92918; -.
DR STRING; 9606.ENSP00000465039; -.
DR BindingDB; Q92918; -.
DR ChEMBL; CHEMBL5749; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q92918; -.
DR iPTMnet; Q92918; -.
DR PhosphoSitePlus; Q92918; -.
DR BioMuta; MAP4K1; -.
DR DMDM; 29427916; -.
DR EPD; Q92918; -.
DR jPOST; Q92918; -.
DR MassIVE; Q92918; -.
DR MaxQB; Q92918; -.
DR PaxDb; Q92918; -.
DR PeptideAtlas; Q92918; -.
DR PRIDE; Q92918; -.
DR ProteomicsDB; 75603; -. [Q92918-1]
DR ProteomicsDB; 75604; -. [Q92918-2]
DR Antibodypedia; 2067; 582 antibodies from 40 providers.
DR DNASU; 11184; -.
DR Ensembl; ENST00000396857.7; ENSP00000380066.1; ENSG00000104814.13. [Q92918-2]
DR Ensembl; ENST00000591517.5; ENSP00000465039.1; ENSG00000104814.13. [Q92918-1]
DR Ensembl; ENST00000634395.1; ENSP00000489001.1; ENSG00000282928.2. [Q92918-1]
DR Ensembl; ENST00000634494.2; ENSP00000489158.1; ENSG00000282928.2. [Q92918-2]
DR GeneID; 11184; -.
DR KEGG; hsa:11184; -.
DR MANE-Select; ENST00000396857.7; ENSP00000380066.1; NM_001042600.3; NP_001036065.1. [Q92918-2]
DR UCSC; uc002oix.3; human. [Q92918-1]
DR CTD; 11184; -.
DR DisGeNET; 11184; -.
DR GeneCards; MAP4K1; -.
DR HGNC; HGNC:6863; MAP4K1.
DR HPA; ENSG00000104814; Tissue enhanced (intestine, lymphoid tissue).
DR MIM; 601983; gene.
DR neXtProt; NX_Q92918; -.
DR OpenTargets; ENSG00000104814; -.
DR PharmGKB; PA30609; -.
DR VEuPathDB; HostDB:ENSG00000104814; -.
DR eggNOG; KOG0576; Eukaryota.
DR GeneTree; ENSGT00940000160308; -.
DR InParanoid; Q92918; -.
DR OMA; FLCCALD; -.
DR OrthoDB; 996262at2759; -.
DR PhylomeDB; Q92918; -.
DR TreeFam; TF105121; -.
DR PathwayCommons; Q92918; -.
DR SignaLink; Q92918; -.
DR SIGNOR; Q92918; -.
DR BioGRID-ORCS; 11184; 14 hits in 1105 CRISPR screens.
DR ChiTaRS; MAP4K1; human.
DR GeneWiki; MAP4K1; -.
DR GenomeRNAi; 11184; -.
DR Pharos; Q92918; Tchem.
DR PRO; PR:Q92918; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q92918; protein.
DR Bgee; ENSG00000104814; Expressed in granulocyte and 99 other tissues.
DR ExpressionAtlas; Q92918; baseline and differential.
DR Genevisible; Q92918; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0008349; F:MAP kinase kinase kinase kinase activity; IDA: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:0008283; P:cell population proliferation; IMP:UniProtKB.
DR GO; GO:1904628; P:cellular response to phorbol 13-acetate 12-myristate; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007254; P:JNK cascade; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR InterPro; IPR001180; CNH_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR021160; MAPKKKK.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00780; CNH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF038172; MAPKKKK; 1.
DR SMART; SM00036; CNH; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50219; CNH; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..833
FT /note="Mitogen-activated protein kinase kinase kinase
FT kinase 1"
FT /id="PRO_0000086273"
FT DOMAIN 17..274
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 495..800
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT REGION 296..478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..313
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 333..347
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 389..405
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 432..446
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 137
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 23..31
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 46
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 165
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:24362026"
FT MOD_RES 171
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:24362026"
FT MOD_RES 175
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:24362026"
FT MOD_RES 355
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:24362026"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70218"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70218"
FT MOD_RES 405
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 407
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 421
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 586
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT VAR_SEQ 800..833
FT /note="LECSGTISPHCNLLLPGSSNSPASASRVAGITGL -> PVVVETRPVDDPTA
FT PSNLYIQE (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_040340"
FT VARIANT 312
FT /note="P -> T (in dbSNP:rs55924696)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040739"
FT VARIANT 351
FT /note="P -> S (in dbSNP:rs34591617)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040740"
FT VARIANT 361
FT /note="P -> L (in dbSNP:rs56060067)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040741"
FT VARIANT 737
FT /note="S -> F (in a metastatic melanoma sample; somatic
FT mutation; dbSNP:rs1238066548)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040742"
FT VARIANT 811
FT /note="N -> S (in dbSNP:rs12975825)"
FT /id="VAR_051643"
FT MUTAGEN 355
FT /note="T->A: Retains kinase activity. Not degraded by the
FT Cul7-RING ubiquitin-protein ligase complex containing
FT FBXW8."
FT /evidence="ECO:0000269|PubMed:24362026"
FT STRAND 8..11
FT /evidence="ECO:0007829|PDB:7L25"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:7R9N"
FT STRAND 17..26
FT /evidence="ECO:0007829|PDB:7R9N"
FT STRAND 29..36
FT /evidence="ECO:0007829|PDB:7R9N"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:7R9N"
FT STRAND 42..49
FT /evidence="ECO:0007829|PDB:7R9N"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:7L24"
FT HELIX 57..67
FT /evidence="ECO:0007829|PDB:7R9N"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:7R9N"
FT STRAND 86..92
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 99..106
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 111..130
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:7R9N"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:7R9N"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 157..171
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:6CQD"
FT HELIX 181..189
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 196..210
FT /evidence="ECO:0007829|PDB:7R9N"
FT TURN 214..217
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 220..227
FT /evidence="ECO:0007829|PDB:7R9N"
FT TURN 240..242
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 245..254
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 265..268
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 272..275
FT /evidence="ECO:0007829|PDB:7R9N"
FT HELIX 282..292
FT /evidence="ECO:0007829|PDB:7R9N"
SQ SEQUENCE 833 AA; 91296 MW; 3C98CF01BE42E151 CRC64;
MDVVDPDIFN RDPRDHYDLL QRLGGGTYGE VFKARDKVSG DLVALKMVKM EPDDDVSTLQ
KEILILKTCR HANIVAYHGS YLWLQKLWIC MEFCGAGSLQ DIYQVTGSLS ELQISYVCRE
VLQGLAYLHS QKKIHRDIKG ANILINDAGE VRLADFGISA QIGATLARRL SFIGTPYWMA
PEVAAVALKG GYNELCDIWS LGITAIELAE LQPPLFDVHP LRVLFLMTKS GYQPPRLKEK
GKWSAAFHNF IKVTLTKSPK KRPSATKMLS HQLVSQPGLN RGLILDLLDK LKNPGKGPSI
GDIEDEEPEL PPAIPRRIRS THRSSSLGIP DADCCRRHME FRKLRGMETR PPANTARLQP
PRDLRSSSPR KQLSESSDDD YDDVDIPTPA EDTPPPLPPK PKFRSPSDEG PGSMGDDGQL
SPGVLVRCAS GPPPNSPRPG PPPSTSSPHL TAHSEPSLWN PPSRELDKPP LLPPKKEKMK
RKGCALLVKL FNGCPLRIHS TAAWTHPSTK DQHLLLGAEE GIFILNRNDQ EATLEMLFPS
RTTWVYSINN VLMSLSGKTP HLYSHSILGL LERKETRAGN PIAHISPHRL LARKNMVSTK
IQDTKGCRAC CVAEGASSGG PFLCGALETS VVLLQWYQPM NKFLLVRQVL FPLPTPLSVF
ALLTGPGSEL PAVCIGVSPG RPGKSVLFHT VRFGALSCWL GEMSTEHRGP VQVTQVEEDM
VMVLMDGSVK LVTPEGSPVR GLRTPEIPMT EAVEAVAMVG GQLQAFWKHG VQVWALGSDQ
LLQELRDPTL TFRLLGSPRL ECSGTISPHC NLLLPGSSNS PASASRVAGI TGL
