FES_HUMAN
ID FES_HUMAN Reviewed; 822 AA.
AC P07332; B2R6E6; B4DUD0; E9PC94; E9PC95; Q2VXS7; Q2VXS8; Q2VXT0; Q6GTU5;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Tyrosine-protein kinase Fes/Fps;
DE EC=2.7.10.2;
DE AltName: Full=Feline sarcoma/Fujinami avian sarcoma oncogene homolog;
DE AltName: Full=Proto-oncogene c-Fes;
DE AltName: Full=Proto-oncogene c-Fps;
DE AltName: Full=p93c-fes;
GN Name=FES; Synonyms=FPS;
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).
RX PubMed=2179816;
RA Alcalay M., Antolini F., van de Ven W.J.M., Lanfrancone L., Grignani F.,
RA Pelicci P.G.;
RT "Characterization of human and mouse c-fes cDNA clones and identification
RT of the 5' end of the gene.";
RL Oncogene 5:267-275(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=4065096; DOI=10.1002/j.1460-2075.1985.tb04020.x;
RA Roebroek A.J.M., Schalken J.A., Verbeek J.S., van den Ouweland A.M.W.,
RA Onnekink C., Bloemers H.P.J., van de Ven W.J.M.;
RT "The structure of the human c-fes/fps proto-oncogene.";
RL EMBO J. 4:2897-2903(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
RA Lefebvre J.-C.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Tongue;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [8]
RP FUNCTION IN CELL DIFFERENTIATION AND AS TUMOR SUPPRESSOR, AND CATALYTIC
RP ACTIVITY.
RX PubMed=2656706; DOI=10.1016/s0021-9258(18)81796-3;
RA Yu G., Smithgall T.E., Glazer R.I.;
RT "K562 leukemia cells transfected with the human c-fes gene acquire the
RT ability to undergo myeloid differentiation.";
RL J. Biol. Chem. 264:10276-10281(1989).
RN [9]
RP PHOSPHORYLATION AT TYR-713, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-713.
RX PubMed=7687763;
RA Hjermstad S.J., Peters K.L., Briggs S.D., Glazer R.I., Smithgall T.E.;
RT "Regulation of the human c-fes protein tyrosine kinase (p93c-fes) by its
RT src homology 2 domain and major autophosphorylation site (Tyr-713).";
RL Oncogene 8:2283-2292(1993).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF BCR, AUTOPHOSPHORYLATION, AND ACTIVITY
RP REGULATION.
RX PubMed=8955135; DOI=10.1074/jbc.271.51.32930;
RA Li J., Smithgall T.E.;
RT "Co-expression with BCR induces activation of the FES tyrosine kinase and
RT phosphorylation of specific N-terminal BCR tyrosine residues.";
RL J. Biol. Chem. 271:32930-32936(1996).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=11339827; DOI=10.1006/excr.2001.5217;
RA Zirngibl R., Schulze D., Mirski S.E., Cole S.P., Greer P.A.;
RT "Subcellular localization analysis of the closely related Fps/Fes and Fer
RT protein-tyrosine kinases suggests a distinct role for Fps/Fes in vesicular
RT trafficking.";
RL Exp. Cell Res. 266:87-94(2001).
RN [12]
RP FUNCTION IN CELL PROLIFERATION AND CELL SPREADING, CATALYTIC ACTIVITY,
RP AUTOPHOSPHORYLATION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF LEU-145 AND
RP LEU-334.
RX PubMed=11509660; DOI=10.1128/mcb.21.18.6170-6180.2001;
RA Cheng H.Y., Schiavone A.P., Smithgall T.E.;
RT "A point mutation in the N-terminal coiled-coil domain releases c-Fes
RT tyrosine kinase activity and survival signaling in myeloid leukemia
RT cells.";
RL Mol. Cell. Biol. 21:6170-6180(2001).
RN [13]
RP REVIEW.
RX PubMed=11994747; DOI=10.1038/nrm783;
RA Greer P.;
RT "Closing in on the biological functions of Fps/Fes and Fer.";
RL Nat. Rev. Mol. Cell Biol. 3:278-289(2002).
RN [14]
RP FUNCTION IN REORGANIZATION OF THE ACTIN CYTOSKELETON AND CELL
RP DIFFERENTIATION, AND INTERACTION WITH BCR.
RX PubMed=15302586; DOI=10.1016/j.yexcr.2004.05.010;
RA Laurent C.E., Smithgall T.E.;
RT "The c-Fes tyrosine kinase cooperates with the breakpoint cluster region
RT protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent
RT manner.";
RL Exp. Cell Res. 299:188-198(2004).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TUBULIN AND MICROTUBULES,
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-713, PHOSPHORYLATION BY HCK,
RP AND MUTAGENESIS OF LEU-145; ARG-483 AND LYS-590.
RX PubMed=15485904; DOI=10.1128/mcb.24.21.9351-9358.2004;
RA Laurent C.E., Delfino F.J., Cheng H.Y., Smithgall T.E.;
RT "The human c-Fes tyrosine kinase binds tubulin and microtubules through
RT separate domains and promotes microtubule assembly.";
RL Mol. Cell. Biol. 24:9351-9358(2004).
RN [16]
RP CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF MET-704;
RP ARG-706; VAL-743 AND SER-759.
RX PubMed=15867340; DOI=10.1158/0008-5472.can-04-3468;
RA Sangrar W., Zirgnibl R.A., Gao Y., Muller W.J., Jia Z., Greer P.A.;
RT "An identity crisis for fps/fes: oncogene or tumor suppressor?";
RL Cancer Res. 65:3518-3522(2005).
RN [17]
RP ALTERNATIVE SPLICING.
RX PubMed=15869408; DOI=10.1089/dna.2005.24.311;
RA Carlson A., Berkowitz J.M., Browning D., Slamon D.J., Gasson J.C.,
RA Yates K.E.;
RT "Expression of c-Fes protein isoforms correlates with differentiation in
RT myeloid leukemias.";
RL DNA Cell Biol. 24:311-316(2005).
RN [18]
RP INTERACTION WITH TRIM28.
RX PubMed=16792528; DOI=10.1042/bj20060194;
RA Delfino F.J., Shaffer J.M., Smithgall T.E.;
RT "The KRAB-associated co-repressor KAP-1 is a coiled-coil binding partner,
RT substrate and activator of the c-Fes protein tyrosine kinase.";
RL Biochem. J. 399:141-150(2006).
RN [19]
RP FUNCTION IN STAT3 PHOSPHORYLATION, ROLE AS PUTATIVE TUMOR SUPPRESSOR IN
RP COLON CANCER, MUTAGENESIS OF MET-704; ARG-706; VAL-743 AND SER-759,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16455651; DOI=10.1074/jbc.m507331200;
RA Delfino F.J., Stevenson H., Smithgall T.E.;
RT "A growth-suppressive function for the c-fes protein-tyrosine kinase in
RT colorectal cancer.";
RL J. Biol. Chem. 281:8829-8835(2006).
RN [20]
RP FUNCTION IN KIT SIGNALING, AND POSSIBLE ROLE IN CANCER CELL PROLIFERATION.
RX PubMed=17595334; DOI=10.1182/blood-2007-02-076471;
RA Voisset E., Lopez S., Dubreuil P., De Sepulveda P.;
RT "The tyrosine kinase FES is an essential effector of KITD816V proliferation
RT signal.";
RL Blood 110:2593-2599(2007).
RN [21]
RP FUNCTION IN CYTOSKELETON REORGANIZATION, INTERACTION WITH EZR,
RP PHOSPHORYLATION AT TYR-713, AND SUBCELLULAR LOCATION.
RX PubMed=18046454; DOI=10.1038/sj.emboj.7601943;
RA Naba A., Reverdy C., Louvard D., Arpin M.;
RT "Spatial recruitment and activation of the Fes kinase by ezrin promotes
RT HGF-induced cell scattering.";
RL EMBO J. 27:38-50(2008).
RN [22]
RP SUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-713, PHOSPHORYLATION
RP BY HCK, AND DOMAIN.
RX PubMed=19382747; DOI=10.1021/bi900238f;
RA Shaffer J.M., Hellwig S., Smithgall T.E.;
RT "Bimolecular fluorescence complementation demonstrates that the c-Fes
RT protein-tyrosine kinase forms constitutive oligomers in living cells.";
RL Biochemistry 48:4780-4788(2009).
RN [23]
RP FUNCTION, TISSUE SPECIFICITY, AND ROLE AS PUTATIVE TUMOR SUPPRESSOR IN
RP COLON CANCER.
RX PubMed=19051325; DOI=10.1002/gcc.20638;
RA Shaffer J.M., Smithgall T.E.;
RT "Promoter methylation blocks FES protein-tyrosine kinase gene expression in
RT colorectal cancer.";
RL Genes Chromosomes Cancer 48:272-284(2009).
RN [24]
RP PUTATIVE ROLE IN RENAL CARCINOMA.
RX PubMed=19082481;
RA Kanda S., Miyata Y., Kanetake H., Smithgall T.E.;
RT "Downregulation of the c-Fes protein-tyrosine kinase inhibits the
RT proliferation of human renal carcinoma cells.";
RL Int. J. Oncol. 34:89-96(2009).
RN [25]
RP FUNCTION, INTERACTION WITH MS4A2/FCER1B AND HCLS1/HS1, SUBCELLULAR
RP LOCATION, PHOSPHORYLATION, INTERACTION WITH PHOSPHOINOSITIDE-CONTAINING
RP MEMBRANES, AND MUTAGENESIS OF 113-ARG-LYS-114.
RX PubMed=19001085; DOI=10.1128/mcb.00904-08;
RA McPherson V.A., Everingham S., Karisch R., Smith J.A., Udell C.M.,
RA Zheng J., Jia Z., Craig A.W.;
RT "Contributions of F-BAR and SH2 domains of Fes protein tyrosine kinase for
RT coupling to the FcepsilonRI pathway in mast cells.";
RL Mol. Cell. Biol. 29:389-401(2009).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; SER-67; TYR-261; TYR-713
RP AND SER-716, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [27]
RP FUNCTION, PHOSPHORYLATION AT THR-421, AND INTERACTION WITH FLT3.
RX PubMed=20111072; DOI=10.1038/leu.2009.301;
RA Voisset E., Lopez S., Chaix A., Georges C., Hanssens K., Prebet T.,
RA Dubreuil P., De Sepulveda P.;
RT "FES kinases are required for oncogenic FLT3 signaling.";
RL Leukemia 24:721-728(2010).
RN [28]
RP REVIEW.
RX PubMed=21622225; DOI=10.2741/3902;
RA Hellwig S., Smithgall T.E.;
RT "Structure and regulation of the c-Fes protein-tyrosine kinase.";
RL Front. Biosci. 16:3146-3155(2011).
RN [29]
RP POSSIBLE ROLE IN PROSTATE CANCER.
RX PubMed=21563194; DOI=10.1002/pros.21422;
RA Miyata Y., Watanabe S.I., Matsuo T., Hayashi T., Sakai H., Xuan J.W.,
RA Greer P.A., Kanda S.;
RT "Pathological significance and predictive value for biochemical recurrence
RT of c-Fes expression in prostate cancer.";
RL Prostate 72:201-208(2012).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-408 AND SER-411, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [31]
RP TISSUE SPECIFICITY, ROLE AS TUMOR SUPPRESSOR IN MELANOMA, AND MUTAGENESIS
RP OF LYS-590.
RX PubMed=28463229; DOI=10.1172/jci91291;
RA Olvedy M., Tisserand J.C., Luciani F., Boeckx B., Wouters J., Lopez S.,
RA Rambow F., Aibar S., Thienpont B., Barra J., Koehler C., Radaelli E.,
RA Tartare-Deckert S., Aerts S., Dubreuil P., van den Oord J.J.,
RA Lambrechts D., De Sepulveda P., Marine J.C.;
RT "Comparative oncogenomics identifies tyrosine kinase FES as a tumor
RT suppressor in melanoma.";
RL J. Clin. Invest. 127:2310-2325(2017).
RN [32]
RP STRUCTURE BY NMR OF 450-550.
RX PubMed=15929003; DOI=10.1007/s10858-005-0946-6;
RA Scott A., Pantoja-Uceda D., Koshiba S., Inoue M., Kigawa T., Terada T.,
RA Shirouzu M., Tanaka A., Sugano S., Yokoyama S., Guentert P.;
RT "Solution structure of the Src homology 2 domain from the human feline
RT sarcoma oncogene Fes.";
RL J. Biomol. NMR 31:357-361(2005).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF 448-822 OF UNPHOSPHORYLATED
RP APOPROTEIN AND IN COMPLEX WITH STAUROSPORINE AND A SUBSTRATE PEPTIDE,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, PHOSPHORYLATION AT TYR-713, NMR
RP SPECTROSCOPY, AND MUTAGENESIS OF GLY-463 AND ARG-483.
RX PubMed=18775312; DOI=10.1016/j.cell.2008.07.047;
RA Filippakopoulos P., Kofler M., Hantschel O., Gish G.D., Grebien F.,
RA Salah E., Neudecker P., Kay L.E., Turk B.E., Superti-Furga G., Pawson T.,
RA Knapp S.;
RT "Structural coupling of SH2-kinase domains links Fes and Abl substrate
RT recognition and kinase activation.";
RL Cell 134:793-803(2008).
RN [34]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-85; GLN-246 AND VAL-323.
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: Tyrosine-protein kinase that acts downstream of cell surface
CC receptors and plays a role in the regulation of the actin cytoskeleton,
CC microtubule assembly, cell attachment and cell spreading. Plays a role
CC in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated
CC signaling in mast cells. Acts down-stream of the activated FCER1
CC receptor and the mast/stem cell growth factor receptor KIT. Plays a
CC role in the regulation of mast cell degranulation. Plays a role in the
CC regulation of cell differentiation and promotes neurite outgrowth in
CC response to NGF signaling. Plays a role in cell scattering and cell
CC migration in response to HGF-induced activation of EZR. Phosphorylates
CC BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1,
CC PECAM1, STAT3 and TRIM28. {ECO:0000269|PubMed:11509660,
CC ECO:0000269|PubMed:15302586, ECO:0000269|PubMed:15485904,
CC ECO:0000269|PubMed:16455651, ECO:0000269|PubMed:17595334,
CC ECO:0000269|PubMed:18046454, ECO:0000269|PubMed:19001085,
CC ECO:0000269|PubMed:19051325, ECO:0000269|PubMed:20111072,
CC ECO:0000269|PubMed:2656706, ECO:0000269|PubMed:8955135}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:11509660, ECO:0000269|PubMed:15485904,
CC ECO:0000269|PubMed:15867340, ECO:0000269|PubMed:18775312,
CC ECO:0000269|PubMed:2656706, ECO:0000269|PubMed:7687763};
CC -!- ACTIVITY REGULATION: Kinase activity is tightly regulated. Activated in
CC response to signaling from a cell surface receptor. Activation probably
CC requires binding of a substrate via the SH2 domain, plus
CC autophosphorylation at Tyr-713. Present in an inactive form in the
CC absence of activating stimuli. {ECO:0000269|PubMed:18775312,
CC ECO:0000269|PubMed:8955135}.
CC -!- SUBUNIT: Homooligomer. Interacts with BCR. Interacts (when activated,
CC via coiled coil domain) with TRIM28. Interacts (via SH2 domain) with
CC phosphorylated EZR, MS4A2/FCER1B and HCLS1/HS1. Interacts with
CC phosphorylated KIT. Interacts with FLT3. Interacts (via F-BAR domain)
CC with soluble tubulin. Interacts (via SH2 domain) with microtubules.
CC {ECO:0000269|PubMed:11509660, ECO:0000269|PubMed:15302586,
CC ECO:0000269|PubMed:15485904, ECO:0000269|PubMed:16792528,
CC ECO:0000269|PubMed:18046454, ECO:0000269|PubMed:18775312,
CC ECO:0000269|PubMed:19001085, ECO:0000269|PubMed:19382747,
CC ECO:0000269|PubMed:20111072}.
CC -!- INTERACTION:
CC P07332; P10275: AR; NbExp=3; IntAct=EBI-1055635, EBI-608057;
CC P07332; P15924: DSP; NbExp=2; IntAct=EBI-1055635, EBI-355041;
CC P07332; P15311: EZR; NbExp=8; IntAct=EBI-1055635, EBI-1056902;
CC P07332; Q13480: GAB1; NbExp=2; IntAct=EBI-1055635, EBI-517684;
CC P07332; P10721: KIT; NbExp=2; IntAct=EBI-1055635, EBI-1379503;
CC P07332; P54274: TERF1; NbExp=2; IntAct=EBI-1055635, EBI-710997;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cytoplasm, cytoskeleton. Cell
CC membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmic
CC vesicle. Golgi apparatus. Cell junction, focal adhesion.
CC Note=Distributed throughout the cytosol when the kinase is not
CC activated. Association with microtubules requires activation of the
CC kinase activity. Shuttles between focal adhesions and cell-cell
CC contacts in epithelial cells. Recruited to the lateral cell membrane in
CC polarized epithelial cells by interaction with phosphorylated EZR.
CC Detected at tubular membrane structures in the cytoplasm and at the
CC cell periphery.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P07332-1; Sequence=Displayed;
CC Name=2; Synonyms=Variant 1;
CC IsoId=P07332-2; Sequence=VSP_041748, VSP_041749;
CC Name=3; Synonyms=Variant 3;
CC IsoId=P07332-3; Sequence=VSP_041748;
CC Name=4; Synonyms=Variant 4;
CC IsoId=P07332-4; Sequence=VSP_041749;
CC -!- TISSUE SPECIFICITY: Widely expressed. Detected in adult colon
CC epithelium (at protein level) (PubMed:16455651, PubMed:19051325).
CC Expressed in melanocytes (at protein level) (PubMed:28463229).
CC {ECO:0000269|PubMed:16455651, ECO:0000269|PubMed:19051325,
CC ECO:0000269|PubMed:28463229}.
CC -!- DOMAIN: The coiled coil domains are important for regulating the kinase
CC activity. They mediate homooligomerization and probably also
CC interaction with other proteins.
CC -!- DOMAIN: The N-terminal region including the first coiled coil domain
CC mediates interaction with phosphoinositide-containing membranes.
CC -!- PTM: Autophosphorylated on Tyr-713. Phosphorylated by LYN in response
CC to FCER1 activation. Phosphorylated by HCK.
CC {ECO:0000269|PubMed:15485904, ECO:0000269|PubMed:18046454,
CC ECO:0000269|PubMed:18775312, ECO:0000269|PubMed:19001085,
CC ECO:0000269|PubMed:19382747, ECO:0000269|PubMed:20111072,
CC ECO:0000269|PubMed:7687763}.
CC -!- DISEASE: Note=Has been shown to act as proto-oncogene in some types of
CC cancer, possibly due to abnormal activation of the kinase. Has been
CC shown to act as tumor suppressor in other types of cancer. Expressed
CC and present as activated kinase in a subset of acute myeloid leukemia
CC patients; promotes survival of leukemia cells (PubMed:20111072).
CC Expression is absent in K562 leukemia cells; ectopic expression of
CC FSP/FES restores myeloid differentiation (PubMed:2656706). May function
CC as tumor suppressor in colorectal cancer; expression is reduced or
CC absent in samples from some colon cancer patients (PubMed:16455651).
CC May function as tumor suppressor in melanoma by preventing melanoma
CC cell proliferation; expression is reduced or absent in samples from
CC some melanoma patients (PubMed:28463229). Ectopic expression of FSP/FES
CC suppresses anchorage-independent growth in colon cancer cell lines
CC (PubMed:16455651). Up-regulated in prostate cancer, and might be a
CC predictor of recurrence after radical surgery (PubMed:16455651). May
CC promote growth of renal carcinoma cells (PubMed:19082481).
CC {ECO:0000269|PubMed:16455651, ECO:0000269|PubMed:19082481,
CC ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:2656706,
CC ECO:0000269|PubMed:28463229}.
CC -!- MISCELLANEOUS: Cellular homolog of retroviral oncogenes. In contrast to
CC the viral oncoproteins, the kinase activity of cellular FSP/FES is
CC tightly regulated, and the kinase is inactive in normal cells in the
CC absence of activating stimuli (PubMed:15485904).
CC {ECO:0000305|PubMed:15485904}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Fes/fps subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; X52192; CAA36438.1; -; mRNA.
DR EMBL; X06292; CAA29619.1; -; Genomic_DNA.
DR EMBL; AY513654; AAS82866.1; -; mRNA.
DR EMBL; AY513656; AAS82868.1; -; mRNA.
DR EMBL; AY513657; AAS82869.1; -; mRNA.
DR EMBL; AK300595; BAG62292.1; -; mRNA.
DR EMBL; AK312545; BAG35443.1; -; mRNA.
DR EMBL; AC124248; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471101; EAX02114.1; -; Genomic_DNA.
DR EMBL; BC035357; AAH35357.1; -; mRNA.
DR CCDS; CCDS10365.1; -. [P07332-1]
DR CCDS; CCDS45349.1; -. [P07332-4]
DR CCDS; CCDS45350.1; -. [P07332-3]
DR CCDS; CCDS45351.1; -. [P07332-2]
DR PIR; A24673; TVHUFF.
DR RefSeq; NP_001137255.1; NM_001143783.1. [P07332-3]
DR RefSeq; NP_001137256.1; NM_001143784.1. [P07332-4]
DR RefSeq; NP_001137257.1; NM_001143785.1. [P07332-2]
DR RefSeq; NP_001996.1; NM_002005.3. [P07332-1]
DR RefSeq; XP_005254937.1; XM_005254880.1. [P07332-3]
DR RefSeq; XP_005254939.1; XM_005254882.1. [P07332-4]
DR RefSeq; XP_016877494.1; XM_017022005.1. [P07332-1]
DR RefSeq; XP_016877495.1; XM_017022006.1. [P07332-3]
DR RefSeq; XP_016877496.1; XM_017022007.1. [P07332-4]
DR RefSeq; XP_016877497.1; XM_017022008.1. [P07332-2]
DR RefSeq; XP_016877498.1; XM_017022009.1. [P07332-1]
DR RefSeq; XP_016877499.1; XM_017022010.1. [P07332-3]
DR PDB; 1WQU; NMR; -; A=450-550.
DR PDB; 2DCR; NMR; -; A=450-550.
DR PDB; 3BKB; X-ray; 1.78 A; A=448-822.
DR PDB; 3CBL; X-ray; 1.75 A; A=448-822.
DR PDB; 3CD3; X-ray; 1.98 A; A=448-822.
DR PDB; 4DYL; X-ray; 2.18 A; A=1-405.
DR PDB; 4E93; X-ray; 1.84 A; A=448-822.
DR PDB; 6JMF; X-ray; 2.00 A; A=449-822.
DR PDBsum; 1WQU; -.
DR PDBsum; 2DCR; -.
DR PDBsum; 3BKB; -.
DR PDBsum; 3CBL; -.
DR PDBsum; 3CD3; -.
DR PDBsum; 4DYL; -.
DR PDBsum; 4E93; -.
DR PDBsum; 6JMF; -.
DR AlphaFoldDB; P07332; -.
DR BMRB; P07332; -.
DR SMR; P07332; -.
DR BioGRID; 108533; 32.
DR IntAct; P07332; 36.
DR MINT; P07332; -.
DR STRING; 9606.ENSP00000331504; -.
DR BindingDB; P07332; -.
DR ChEMBL; CHEMBL5455; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P07332; -.
DR GuidetoPHARMACOLOGY; 2023; -.
DR iPTMnet; P07332; -.
DR PhosphoSitePlus; P07332; -.
DR BioMuta; FES; -.
DR DMDM; 115502390; -.
DR CPTAC; CPTAC-1778; -.
DR EPD; P07332; -.
DR jPOST; P07332; -.
DR MassIVE; P07332; -.
DR MaxQB; P07332; -.
DR PaxDb; P07332; -.
DR PeptideAtlas; P07332; -.
DR PRIDE; P07332; -.
DR ProteomicsDB; 51989; -. [P07332-1]
DR ProteomicsDB; 51990; -. [P07332-2]
DR ProteomicsDB; 51991; -. [P07332-3]
DR ProteomicsDB; 51992; -. [P07332-4]
DR Antibodypedia; 734; 468 antibodies from 35 providers.
DR DNASU; 2242; -.
DR Ensembl; ENST00000328850.8; ENSP00000331504.3; ENSG00000182511.12. [P07332-1]
DR Ensembl; ENST00000394300.7; ENSP00000377837.3; ENSG00000182511.12. [P07332-3]
DR Ensembl; ENST00000414248.6; ENSP00000414629.2; ENSG00000182511.12. [P07332-2]
DR Ensembl; ENST00000444422.2; ENSP00000400868.2; ENSG00000182511.12. [P07332-4]
DR GeneID; 2242; -.
DR KEGG; hsa:2242; -.
DR MANE-Select; ENST00000328850.8; ENSP00000331504.3; NM_002005.4; NP_001996.1.
DR UCSC; uc002bpv.4; human. [P07332-1]
DR CTD; 2242; -.
DR DisGeNET; 2242; -.
DR GeneCards; FES; -.
DR HGNC; HGNC:3657; FES.
DR HPA; ENSG00000182511; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 190030; gene.
DR neXtProt; NX_P07332; -.
DR OpenTargets; ENSG00000182511; -.
DR PharmGKB; PA28098; -.
DR VEuPathDB; HostDB:ENSG00000182511; -.
DR eggNOG; KOG0194; Eukaryota.
DR GeneTree; ENSGT00940000158881; -.
DR HOGENOM; CLU_005265_0_1_1; -.
DR InParanoid; P07332; -.
DR OMA; RAKDKYV; -.
DR PhylomeDB; P07332; -.
DR TreeFam; TF315363; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P07332; -.
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT.
DR Reactome; R-HSA-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-HSA-399955; SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
DR Reactome; R-HSA-399956; CRMPs in Sema3A signaling.
DR SignaLink; P07332; -.
DR SIGNOR; P07332; -.
DR BioGRID-ORCS; 2242; 15 hits in 1099 CRISPR screens.
DR ChiTaRS; FES; human.
DR EvolutionaryTrace; P07332; -.
DR GeneWiki; Feline_sarcoma_oncogene; -.
DR GenomeRNAi; 2242; -.
DR Pharos; P07332; Tclin.
DR PRO; PR:P07332; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P07332; protein.
DR Bgee; ENSG00000182511; Expressed in monocyte and 100 other tissues.
DR ExpressionAtlas; P07332; baseline and differential.
DR Genevisible; P07332; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0034987; F:immunoglobulin receptor binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IEA:Ensembl.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071305; P:cellular response to vitamin D; IMP:ARUK-UCL.
DR GO; GO:0007098; P:centrosome cycle; IEA:Ensembl.
DR GO; GO:0006935; P:chemotaxis; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0001578; P:microtubule bundle formation; IEA:Ensembl.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IMP:UniProtKB.
DR GO; GO:0045657; P:positive regulation of monocyte differentiation; IMP:ARUK-UCL.
DR GO; GO:0045639; P:positive regulation of myeloid cell differentiation; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; IMP:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; IMP:UniProtKB.
DR GO; GO:2000145; P:regulation of cell motility; IMP:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0043304; P:regulation of mast cell degranulation; IMP:UniProtKB.
DR GO; GO:0060627; P:regulation of vesicle-mediated transport; TAS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10361; SH2_Fps_family; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR031160; F_BAR.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR035849; Fes/Fps/Fer_SH2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR016250; Tyr-prot_kinase_Fes/Fps.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF00611; FCH; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR PIRSF; PIRSF000632; TyrPK_fps; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51741; F_BAR; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell junction;
KW Cell membrane; Coiled coil; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Golgi apparatus; Kinase; Lipid-binding; Membrane; Nucleotide-binding;
KW Phosphoprotein; Proto-oncogene; Reference proteome; SH2 domain;
KW Transferase; Tumor suppressor; Tyrosine-protein kinase.
FT CHAIN 1..822
FT /note="Tyrosine-protein kinase Fes/Fps"
FT /id="PRO_0000088088"
FT DOMAIN 1..260
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 460..549
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 561..822
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..300
FT /note="Important for interaction with membranes containing
FT phosphoinositides"
FT REGION 394..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 125..169
FT /evidence="ECO:0000255"
FT COILED 324..368
FT /evidence="ECO:0000255"
FT ACT_SITE 683
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 567..575
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 590
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 261
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 421
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:20111072"
FT MOD_RES 713
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15485904,
FT ECO:0000269|PubMed:18046454, ECO:0000269|PubMed:18775312,
FT ECO:0000269|PubMed:19382747, ECO:0000269|PubMed:7687763,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 716
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT VAR_SEQ 72..129
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_041748"
FT VAR_SEQ 441..510
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_041749"
FT VARIANT 85
FT /note="R -> C (in dbSNP:rs56041861)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041697"
FT VARIANT 246
FT /note="R -> Q (in dbSNP:rs34573430)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041698"
FT VARIANT 323
FT /note="M -> V (in dbSNP:rs56296062)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041699"
FT MUTAGEN 113..114
FT /note="RK->EE: Reduced binding to membranes containing
FT phosphoinositides."
FT /evidence="ECO:0000269|PubMed:19001085"
FT MUTAGEN 113..114
FT /note="RK->QQ: Reduced binding to membranes containing
FT phosphoinositides."
FT /evidence="ECO:0000269|PubMed:19001085"
FT MUTAGEN 145
FT /note="L->P: Constitutively activated kinase that can act
FT as oncogene. Promotes myeloid cell survival and
FT proliferation."
FT /evidence="ECO:0000269|PubMed:11509660,
FT ECO:0000269|PubMed:15485904"
FT MUTAGEN 334
FT /note="L->P: Abolishes autophosphorylation."
FT /evidence="ECO:0000269|PubMed:11509660"
FT MUTAGEN 463
FT /note="G->V: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:18775312"
FT MUTAGEN 483
FT /note="R->M: Abolishes pTyr binding. Abolishes association
FT with microtubules. Abolishes autophosphorylation. Reduced
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:15485904,
FT ECO:0000269|PubMed:18775312"
FT MUTAGEN 590
FT /note="K->E: Abolishes kinase activity. Fails to inhibit
FT proliferation of melanoma cells."
FT /evidence="ECO:0000269|PubMed:15485904,
FT ECO:0000269|PubMed:28463229"
FT MUTAGEN 704
FT /note="M->V: Reduced autophosphorylation and strongly
FT reduced kinase activity."
FT /evidence="ECO:0000269|PubMed:15867340,
FT ECO:0000269|PubMed:16455651"
FT MUTAGEN 706
FT /note="R->Q: Negligible effect on autophosphorylation and
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:15867340,
FT ECO:0000269|PubMed:16455651"
FT MUTAGEN 713
FT /note="Y->F: Reduces kinase activity by over 90%."
FT /evidence="ECO:0000269|PubMed:7687763"
FT MUTAGEN 743
FT /note="V->M: Strongly reduced autophosphorylation and
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:15867340,
FT ECO:0000269|PubMed:16455651"
FT MUTAGEN 759
FT /note="S->F: Reduced autophosphorylation and strongly
FT reduced kinase activity."
FT /evidence="ECO:0000269|PubMed:15867340,
FT ECO:0000269|PubMed:16455651"
FT CONFLICT 719
FT /note="L -> S (in Ref. 1; CAA36438 and 3; AAS82866/
FT AAS82869/AAS82868)"
FT /evidence="ECO:0000305"
FT HELIX 3..6
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 10..51
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 68..96
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 98..131
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 133..154
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 167..202
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 204..234
FT /evidence="ECO:0007829|PDB:4DYL"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 239..254
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 262..268
FT /evidence="ECO:0007829|PDB:4DYL"
FT TURN 300..302
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 303..344
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 350..353
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 354..389
FT /evidence="ECO:0007829|PDB:4DYL"
FT TURN 390..393
FT /evidence="ECO:0007829|PDB:4DYL"
FT HELIX 450..452
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 455..457
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 461..464
FT /evidence="ECO:0007829|PDB:1WQU"
FT HELIX 467..473
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 479..484
FT /evidence="ECO:0007829|PDB:3CBL"
FT TURN 486..489
FT /evidence="ECO:0007829|PDB:3BKB"
FT STRAND 491..494
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 503..506
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 507..509
FT /evidence="ECO:0007829|PDB:3BKB"
FT STRAND 512..517
FT /evidence="ECO:0007829|PDB:3BKB"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:3BKB"
FT HELIX 523..533
FT /evidence="ECO:0007829|PDB:3CBL"
FT TURN 539..541
FT /evidence="ECO:0007829|PDB:3BKB"
FT HELIX 558..560
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 561..570
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 573..580
FT /evidence="ECO:0007829|PDB:3CBL"
FT TURN 581..583
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 586..591
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 598..601
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 602..605
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 606..611
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 622..626
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 628..631
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 633..637
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 644..651
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 652..654
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 657..676
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 686..688
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 689..691
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 697..699
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 702..704
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 711..714
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 720..723
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 724..726
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 729..734
FT /evidence="ECO:0007829|PDB:3CBL"
FT STRAND 736..738
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 739..754
FT /evidence="ECO:0007829|PDB:3CBL"
FT TURN 755..757
FT /evidence="ECO:0007829|PDB:4E93"
FT HELIX 766..774
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 787..796
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 801..803
FT /evidence="ECO:0007829|PDB:3CBL"
FT HELIX 807..820
FT /evidence="ECO:0007829|PDB:3CBL"
SQ SEQUENCE 822 AA; 93497 MW; 4C2A90555857F045 CRC64;
MGFSSELCSP QGHGVLQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDSGGQS
RAISPDSPIS QSWAEITSQT EGLSRLLRQH AEDLNSGPLS KLSLLIRERQ QLRKTYSEQW
QQLQQELTKT HSQDIEKLKS QYRALARDSA QAKRKYQEAS KDKDRDKAKD KYVRSLWKLF
AHHNRYVLGV RAAQLHHQHH HQLLLPGLLR SLQDLHEEMA CILKEILQEY LEISSLVQDE
VVAIHREMAA AAARIQPEAE YQGFLRQYGS APDVPPCVTF DESLLEEGEP LEPGELQLNE
LTVESVQHTL TSVTDELAVA TEMVFRRQEM VTQLQQELRN EEENTHPRER VQLLGKRQVL
QEALQGLQVA LCSQAKLQAQ QELLQTKLEH LGPGEPPPVL LLQDDRHSTS SSEQEREGGR
TPTLEILKSH ISGIFRPKFS LPPPLQLIPE VQKPLHEQLW YHGAIPRAEV AELLVHSGDF
LVRESQGKQE YVLSVLWDGL PRHFIIQSLD NLYRLEGEGF PSIPLLIDHL LSTQQPLTKK
SGVVLHRAVP KDKWVLNHED LVLGEQIGRG NFGEVFSGRL RADNTLVAVK SCRETLPPDL
KAKFLQEARI LKQYSHPNIV RLIGVCTQKQ PIYIVMELVQ GGDFLTFLRT EGARLRVKTL
LQMVGDAAAG MEYLESKCCI HRDLAARNCL VTEKNVLKIS DFGMSREEAD GVYAASGGLR
QVPVKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGASP YPNLSNQQTR EFVEKGGRLP
CPELCPDAVF RLMEQCWAYE PGQRPSFSTI YQELQSIRKR HR
