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 27-MAR-2024, entry version 238. 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}. 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; 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 PDB; 7T1K; X-ray; 1.25 A; A=453-551. DR PDB; 7T1L; X-ray; 1.35 A; A/B=453-550. 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 PDBsum; 7T1K; -. DR PDBsum; 7T1L; -. DR AlphaFoldDB; P07332; -. DR BMRB; P07332; -. DR SMR; P07332; -. DR BioGRID; 108533; 36. 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; 9606-ENSP00000331504; -. DR PeptideAtlas; P07332; -. DR ProteomicsDB; 51989; -. [P07332-1] DR ProteomicsDB; 51990; -. [P07332-2] DR ProteomicsDB; 51991; -. [P07332-3] DR ProteomicsDB; 51992; -. [P07332-4] DR Antibodypedia; 734; 504 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 AGR; HGNC:3657; -. 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; QNTENMY; -. DR OrthoDB; 2903566at2759; -. 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 1175 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 102 other cell types or tissues. DR ExpressionAtlas; P07332; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; TAS:Reactome. 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:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; 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:0001578; P:microtubule bundle formation; IEA:Ensembl. DR GO; GO:0051450; P:myoblast proliferation; IEA:Ensembl. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA: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 CDD; cd07685; F-BAR_Fes; 1. DR CDD; cd05084; PTKc_Fes; 1. DR CDD; cd10361; SH2_Fps_family; 1. DR Gene3D; 1.20.1270.60; Arfaptin homology (AH) domain/BAR domain; 1. DR Gene3D; 1.10.287.160; HR1 repeat; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF197; TYROSINE-PROTEIN KINASE FES_FPS; 1. 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; BAR/IMD domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 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. DR Genevisible; P07332; HS. 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; FT AAS82866/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:7T1K" FT STRAND 461..464 FT /evidence="ECO:0007829|PDB:1WQU" FT HELIX 467..473 FT /evidence="ECO:0007829|PDB:7T1K" FT STRAND 479..483 FT /evidence="ECO:0007829|PDB:7T1K" FT STRAND 486..490 FT /evidence="ECO:0007829|PDB:7T1K" FT STRAND 492..497 FT /evidence="ECO:0007829|PDB:7T1K" FT STRAND 500..505 FT /evidence="ECO:0007829|PDB:7T1K" FT STRAND 507..509 FT /evidence="ECO:0007829|PDB:7T1K" FT STRAND 512..517 FT /evidence="ECO:0007829|PDB:7T1K" FT STRAND 520..522 FT /evidence="ECO:0007829|PDB:7T1K" FT HELIX 523..533 FT /evidence="ECO:0007829|PDB:7T1K" FT TURN 539..541 FT /evidence="ECO:0007829|PDB:7T1K" 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 //