ID PGFRA_HUMAN Reviewed; 1089 AA. AC P16234; B2RE69; E9PBH0; Q6P4H5; Q96KZ7; Q9UD28; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 05-SEP-2012, entry version 146. DE RecName: Full=Platelet-derived growth factor receptor alpha; DE Short=PDGF-R-alpha; DE Short=PDGFR-alpha; DE EC=2.7.10.1; DE AltName: Full=Alpha platelet-derived growth factor receptor; DE AltName: Full=Alpha-type platelet-derived growth factor receptor; DE AltName: Full=CD140 antigen-like family member A; DE AltName: Full=CD140a antigen; DE AltName: Full=Platelet-derived growth factor alpha receptor; DE AltName: Full=Platelet-derived growth factor receptor 2; DE Short=PDGFR-2; DE AltName: CD_antigen=CD140a; DE Flags: Precursor; GN Name=PDGFRA; Synonyms=PDGFR2, RHEPDGFRA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH PDGFA AND RP PDGFB. RC TISSUE=Foreskin; RX MEDLINE=89296915; PubMed=2544881; DOI=10.1073/pnas.86.13.4917; RA Claesson-Welsh L., Eriksson A., Westermark B., Heldin C.H.; RT "cDNA cloning and expression of the human A-type platelet-derived RT growth factor (PDGF) receptor establishes structural similarity to the RT B-type PDGF receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 86:4917-4921(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AUTOPHOSPHORYLATION, TISSUE RP SPECIFICITY, AND INTERACTION WITH PDGFA AND PDGFB. RC TISSUE=Brain; RX MEDLINE=89130149; PubMed=2536956; DOI=10.1126/science.2536956; RA Matsui T., Heidaran M., Miki T., Popescu N., la Rochelle W., Kraus M., RA Pierce J., Aaronson S.; RT "Isolation of a novel receptor cDNA establishes the existence of two RT PDGF receptor genes."; RL Science 243:800-804(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Blood; RX MEDLINE=96163874; PubMed=8586421; DOI=10.1006/geno.1995.9883; RA Kawagishi J., Ku T.; RT "Structure, organization, and transcription units of the human alpha- RT platelet-derived growth factor receptor gene, PDGFRA."; RL Genomics 30:224-232(1995). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP PRO-478. RC TISSUE=Lung, and Trachea; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT RP PRO-478. RC TISSUE=Placenta; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 579-1089, DISEASE, AND IDENTIFICATION BY RP MASS SPECTROMETRY OF FIP1L1-PDGFRA FUSION PROTEIN. RC TISSUE=Eosinophil; RX PubMed=12808148; DOI=10.1073/pnas.0932698100; RA Griffin J.H., Leung J., Bruner R.J., Caligiuri M.A., Briesewitz R.; RT "Discovery of a fusion kinase in EOL-1 cells and idiopathic RT hypereosinophilic syndrome."; RL Proc. Natl. Acad. Sci. U.S.A. 100:7830-7835(2003). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 823-876, AND TISSUE SPECIFICITY. RC TISSUE=Colon tumor; RX MEDLINE=95204052; PubMed=7896447; DOI=10.1002/ijc.2910600611; RA Craven R.J., Xu L.H., Weiner T.M., Fridell Y.-W., Dent G.A., RA Srivastava S., Varnum B., Liu E.T., Cance W.G.; RT "Receptor tyrosine kinases expressed in metastatic colon cancer."; RL Int. J. Cancer 60:791-797(1995). RN [9] RP FUNCTION AS PDGFA AND PDGFB RECEPTOR IN CELL PROLIFERATION AND RP CHEMOTAXIS, AND SUBCELLULAR LOCATION. RX PubMed=2554309; DOI=10.1073/pnas.86.21.8314; RA Matsui T., Pierce J.H., Fleming T.P., Greenberger J.S., RA LaRochelle W.J., Ruggiero M., Aaronson S.A.; RT "Independent expression of human alpha or beta platelet-derived growth RT factor receptor cDNAs in a naive hematopoietic cell leads to RT functional coupling with mitogenic and chemotactic signaling RT pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 86:8314-8318(1989). RN [10] RP INTERACTION WITH PLCG1 AND SRC. RX PubMed=2173144; DOI=10.1126/science.2173144; RA Anderson D., Koch C.A., Grey L., Ellis C., Moran M.F., Pawson T.; RT "Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to RT activated growth factor receptors."; RL Science 250:979-982(1990). RN [11] RP INTERACTION WITH PDGFRA; PDGFA AND PDGFB, FUNCTION AS RECEPTOR FOR RP PDGFA AND PDGFB, AND AUTOPHOSPHORYLATION. RX PubMed=1709159; RA Kelly J.D., Haldeman B.A., Grant F.J., Murray M.J., Seifert R.A., RA Bowen-Pope D.F., Cooper J.A., Kazlauskas A.; RT "Platelet-derived growth factor (PDGF) stimulates PDGF receptor RT subunit dimerization and intersubunit trans-phosphorylation."; RL J. Biol. Chem. 266:8987-8992(1991). RN [12] RP FUNCTION AS PDGFB RECEPTOR IN CHEMOTAXIS; CELL PROLIFERATION; RP PHOSPHORYLATION OF PLCG1; ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE RP AND REGULATION OF PHOSPHATIDYLINOSITOL METABOLISM, INTERACTION WITH RP PIK3R, AND MUTAGENESIS OF TYR-731 AND TYR-742. RX PubMed=1646396; RA Yu J.C., Heidaran M.A., Pierce J.H., Gutkind J.S., Lombardi D., RA Ruggiero M., Aaronson S.A.; RT "Tyrosine mutations within the alpha platelet-derived growth factor RT receptor kinase insert domain abrogate receptor-associated RT phosphatidylinositol-3 kinase activity without affecting mitogenic or RT chemotactic signal transduction."; RL Mol. Cell. Biol. 11:3780-3785(1991). RN [13] RP INTERACTION WITH PDGFA AND PDGFB. RX PubMed=7679113; RA Fretto L.J., Snape A.J., Tomlinson J.E., Seroogy J.J., Wolf D.L., RA LaRochelle W.J., Giese N.A.; RT "Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB RT binding to alpha and beta PDGF receptor."; RL J. Biol. Chem. 268:3625-3631(1993). RN [14] RP FUNCTION AS PDGFA RECEPTOR IN REGULATION OF PLATELET ACTIVATION, RP SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, AND TISSUE SPECIFICITY. RX PubMed=8188664; RA Vassbotn F.S., Havnen O.K., Heldin C.H., Holmsen H.; RT "Negative feedback regulation of human platelets via autocrine RT activation of the platelet-derived growth factor alpha-receptor."; RL J. Biol. Chem. 269:13874-13879(1994). RN [15] RP FUNCTION IN PROMOTING CHEMOTAXIS. RX PubMed=8760137; RA Osornio-Vargas A.R., Lindroos P.M., Coin P.G., Badgett A., RA Hernandez-Rodriguez N.A., Bonner J.C.; RT "Maximal PDGF-induced lung fibroblast chemotaxis requires PDGF RT receptor-alpha."; RL Am. J. Physiol. 271:L93-L99(1996). RN [16] RP INTERACTION WITH GRB7 AND PIK3R1. RX PubMed=8940081; DOI=10.1074/jbc.271.48.30942; RA Yokote K., Margolis B., Heldin C.H., Claesson-Welsh L.; RT "Grb7 is a downstream signaling component of platelet-derived growth RT factor alpha- and beta-receptors."; RL J. Biol. Chem. 271:30942-30949(1996). RN [17] RP FUNCTION IN PHOSPHORYLATION OF PTPN11; ACTIVATION OF HRAS AND RP REGULATION OF CELL PROLIFERATION, PHOSPHORYLATION AT TYR-720, RP INTERACTION WITH GRB2; PTPN11; PLCG1 AND PIK3R1, AUTOPHOSPHORYLATION, RP AND MUTAGENESIS OF TYR-720. RX PubMed=8943348; RA Bazenet C.E., Gelderloos J.A., Kazlauskas A.; RT "Phosphorylation of tyrosine 720 in the platelet-derived growth factor RT alpha receptor is required for binding of Grb2 and SHP-2 but not for RT activation of Ras or cell proliferation."; RL Mol. Cell. Biol. 16:6926-6936(1996). RN [18] RP INTERACTION WITH CRK, AND MUTAGENESIS OF TYR-762. RX PubMed=10733900; DOI=10.1006/bbrc.2000.2374; RA Matsumoto T., Yokote K., Take A., Takemoto M., Asaumi S., RA Hashimoto Y., Matsuda M., Saito Y., Mori S.; RT "Differential interaction of CrkII adaptor protein with platelet- RT derived growth factor alpha- and beta-receptors is determined by its RT internal tyrosine phosphorylation."; RL Biochem. Biophys. Res. Commun. 270:28-33(2000). RN [19] RP INTERACTION WITH SHF, AND PROBABLE PHOSPHORYLATION AT TYR-720. RX MEDLINE=20548990; PubMed=11095946; DOI=10.1006/bbrc.2000.3847; RA Lindholm C.K., Frantz J.D., Shoelson S.E., Welsh M.; RT "Shf, a Shb-like adapter protein, is involved in PDGF-alpha-receptor RT regulation of apoptosis."; RL Biochem. Biophys. Res. Commun. 278:537-543(2000). RN [20] RP FUNCTION IN PLATELET ACTIVATION. RX PubMed=10947961; DOI=10.1042/0264-6021:3500469; RA Selheim F., Fukami M.H., Holmsen H., Vassbotn F.S.; RT "Platelet-derived-growth-factor-induced signalling in human platelets: RT phosphoinositide-3-kinase-dependent inhibition of platelet RT activation."; RL Biochem. J. 350:469-475(2000). RN [21] RP FUNCTION IN ACTIVATION OF MAPK1/ERK2 AND/OR MAPK3/ERK1, DEGRADATION, RP AND MUTAGENESIS OF TYR-572 AND TYR-574. RX PubMed=10734113; DOI=10.1074/jbc.275.13.9620; RA Rosenkranz S., Ikuno Y., Leong F.L., Klinghoffer R.A., Miyake S., RA Band H., Kazlauskas A.; RT "Src family kinases negatively regulate platelet-derived growth factor RT alpha receptor-dependent signaling and disease progression."; RL J. Biol. Chem. 275:9620-9627(2000). RN [22] RP FUNCTION AS A RECEPTOR FOR PDGFC, AND INTERACTION WITH PDGFC. RX MEDLINE=21347863; PubMed=11297552; DOI=10.1074/jbc.M101056200; RA Gilbertson D.G., Duff M.E., West J.W., Kelly J.D., Sheppard P.O., RA Hofstrand P.D., Gao Z., Shoemaker K., Bukowski T.R., Moore M., RA Feldhaus A.L., Humes J.M., Palmer T.E., Hart C.E.; RT "Platelet-derived growth factor C (PDGF-C), a novel growth factor that RT binds to PDGF alpha and beta receptor."; RL J. Biol. Chem. 276:27406-27414(2001). RN [23] RP SUBCELLULAR LOCATION, INTERACTION WITH SRC, AND MUTAGENESIS OF TYR-572 RP AND TYR-574. RX PubMed=14644164; DOI=10.1016/j.yexcr.2003.08.001; RA Avrov K., Kazlauskas A.; RT "The role of c-Src in platelet-derived growth factor alpha receptor RT internalization."; RL Exp. Cell Res. 291:426-434(2003). RN [24] RP INVOLVEMENT IN HES. RX MEDLINE=22547205; PubMed=12660384; DOI=10.1056/NEJMoa025217; RA Cools J., DeAngelo D.J., Gotlib J., Stover E.H., Legare R.D., RA Cortes J., Kutok J., Clark J., Galinsky I., Griffin J.D., Cross N.C., RA Tefferi A., Malone J., Alam R., Schrier S.L., Schmid J., Rose M., RA Vandenberghe P., Verhoef G., Boogaerts M., Wlodarska I., RA Kantarjian H., Marynen P., Coutre S.E., Stone R., Gilliland D.G.; RT "A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as RT a therapeutic target of imatinib in idiopathic hypereosinophilic RT syndrome."; RL N. Engl. J. Med. 348:1201-1214(2003). RN [25] RP FUNCTION IN PHOSPHORYLATION OF AKT1; MAP KINASES; STAT1 AND STAT3, RP INVOLVEMENT IN GIST, VARIANTS ASP-561; VAL-842; 842-ASP--HIS-845 DEL RP AND 845-HIS--PRO-448 DEL, AND CHARACTERIZATION OF VARIANTS ASP-561; RP VAL-842; 842-ASP--HIS-845 DEL AND 845-HIS--PRO-448 DEL. RX PubMed=12522257; DOI=10.1126/science.1079666; RA Heinrich M.C., Corless C.L., Duensing A., McGreevey L., Chen C.J., RA Joseph N., Singer S., Griffith D.J., Haley A., Town A., Demetri G.D., RA Fletcher C.D., Fletcher J.A.; RT "PDGFRA activating mutations in gastrointestinal stromal tumors."; RL Science 299:708-710(2003). RN [26] RP INVOLVEMENT IN GIST, VARIANTS ASP-561; LYS-659; TYR-842; VAL-842; RP 842-ASP--HIS-845 DEL 845-HIS--PRO-448 DEL AND CYS-849, RP CHARACTERIZATION OF VARIANTS ASP-561; LYS-659; TYR-842; VAL-842; RP 842-ASP--HIS-845 DEL 845-HIS--PRO-448 DEL AND CYS-849, AND ENZYME RP REGULATION. RX PubMed=15928335; DOI=10.1200/JCO.2005.14.068; RA Corless C.L., Schroeder A., Griffith D., Town A., McGreevey L., RA Harrell P., Shiraga S., Bainbridge T., Morich J., Heinrich M.C.; RT "PDGFRA mutations in gastrointestinal stromal tumors: frequency, RT spectrum and in vitro sensitivity to imatinib."; RL J. Clin. Oncol. 23:5357-5364(2005). RN [27] RP FUNCTION IN CELL SURVIVAL. RX PubMed=17141222; DOI=10.1016/j.febslet.2006.11.034; RA Vantler M., Huntgeburth M., Caglayan E., Ten Freyhaus H., Schnabel P., RA Rosenkranz S.; RT "PI3-kinase/Akt-dependent antiapoptotic signaling by the PDGF alpha RT receptor is negatively regulated by Src family kinases."; RL FEBS Lett. 580:6769-6776(2006). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-762; TYR-768; TYR-849 RP AND TYR-1018, AND MASS SPECTROMETRY. RC TISSUE=Lung carcinoma; RX PubMed=18083107; DOI=10.1016/j.cell.2007.11.025; RA Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., RA Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., RA Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., RA Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., RA Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; RT "Global survey of phosphotyrosine signaling identifies oncogenic RT kinases in lung cancer."; RL Cell 131:1190-1203(2007). RN [29] RP INTERACTION WITH HHV-5 GB. RX PubMed=20660204; DOI=10.1128/JVI.00710-10; RA Feire A.L., Roy R.M., Manley K., Compton T.; RT "The glycoprotein B disintegrin-like domain binds beta 1 integrin to RT mediate cytomegalovirus entry."; RL J. Virol. 84:10026-10037(2010). RN [30] RP FUNCTION IN PHOSPHORYLATION OF STAT 5A AND/OR STAT5B, ROLE IN RP HYPEREOSINOPHILIC SYNDROME, VARIANTS GLY-481; PRO-507; MET-562; RP ARG-570; GLN-650; SER-659; PRO-705; GLY-748 AND SER-849, RP CHARACTERIZATION OF VARIANTS GLY-481; PRO-507; MET-562; ARG-570; RP GLN-650; SER-659; PRO-705; GLY-748 AND SER-849, AND ENZYME REGULATION. RX PubMed=21224473; DOI=10.1182/blood-2010-05-286757; RA Elling C., Erben P., Walz C., Frickenhaus M., Schemionek M., RA Stehling M., Serve H., Cross N.C., Hochhaus A., Hofmann W.K., RA Berdel W.E., Muller-Tidow C., Reiter A., Koschmieder S.; RT "Novel imatinib-sensitive PDGFRA-activating point mutations in RT hypereosinophilic syndrome induce growth factor independence and RT leukemia-like disease."; RL Blood 117:2935-2943(2011). RN [31] RP FUNCTION IN CELL DIFFERENTIATION, AND UBIQUITINATION. RX PubMed=21596750; DOI=10.1074/jbc.M110.197525; RA Severe N., Miraoui H., Marie P.J.; RT "The Casitas B lineage lymphoma (Cbl) mutant G306E enhances osteogenic RT differentiation in human mesenchymal stromal cells in part by RT decreased Cbl-mediated platelet-derived growth factor receptor alpha RT and fibroblast growth factor receptor 2 ubiquitination."; RL J. Biol. Chem. 286:24443-24450(2011). RN [32] RP ROLE IN DISEASE, CHARACTERIZATION OF VARIANT VAL-842, AND ENZYME RP REGULATION. RX PubMed=20972453; DOI=10.1038/onc.2010.476; RA von Bubnoff N., Gorantla S.P., Engh R.A., Oliveira T.M., Thone S., RA Aberg E., Peschel C., Duyster J.; RT "The low frequency of clinical resistance to PDGFR inhibitors in RT myeloid neoplasms with abnormalities of PDGFRA might be related to the RT limited repertoire of possible PDGFRA kinase domain mutations in RT vitro."; RL Oncogene 30:933-943(2011). RN [33] RP REVIEW ON SIGNALING AND AUTOPHOSPHORYLATION. RX PubMed=9739761; DOI=10.1016/S0304-419X(98)00015-8; RA Heldin C.H., Ostman A., Ronnstrand L.; RT "Signal transduction via platelet-derived growth factor receptors."; RL Biochim. Biophys. Acta 1378:F79-113(1998). RN [34] RP REVIEW ON ROLE IN DISEASE AND ENZYME REGULATION. RX PubMed=15207817; DOI=10.1016/j.cytogfr.2004.03.002; RA Ostman A.; RT "PDGF receptors-mediators of autocrine tumor growth and regulators of RT tumor vasculature and stroma."; RL Cytokine Growth Factor Rev. 15:275-286(2004). RN [35] RP REVIEW ON ROLE IN DISEASE AND ENZYME REGULATION. RX PubMed=17419949; DOI=10.1016/S0065-230X(06)97011-0; RA Ostman A., Heldin C.H.; RT "PDGF receptors as targets in tumor treatment."; RL Adv. Cancer Res. 97:247-274(2007). RN [36] RP REVIEW ON FUNCTION IN DEVELOPMENT AND DISEASE; LIGANDS AND SIGNALING RP PATHWAYS. RX PubMed=18483217; DOI=10.1101/gad.1653708; RA Andrae J., Gallini R., Betsholtz C.; RT "Role of platelet-derived growth factors in physiology and medicine."; RL Genes Dev. 22:1276-1312(2008). RN [37] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1185-1189 IN COMPLEX WITH RP SLC9A3R1 AND PDGFRB. RX MEDLINE=22013966; PubMed=11882663; DOI=10.1074/jbc.M201507200; RA Karthikeyan S., Leung T., Ladias J.A.A.; RT "Structural determinants of the Na+/H+ exchanger regulatory factor RT interaction with the beta 2 adrenergic and platelet-derived growth RT factor receptors."; RL J. Biol. Chem. 277:18973-18978(2002). RN [38] RP VARIANTS [LARGE SCALE ANALYSIS] ASP-79; ASP-426; PRO-478; CYS-764; RP ARG-829; LYS-996 AND ASN-1071. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., 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 as a cell-surface CC receptor for PDGFA, PDGFB and PDGFC and plays an essential role in CC the regulation of embryonic development, cell proliferation, CC survival and chemotaxis. Depending on the context, promotes or CC inhibits cell proliferation and cell migration. Plays an important CC role in the differentiation of bone marrow-derived mesenchymal CC stem cells. Required for normal skeleton development and cephalic CC closure during embryonic development. Required for normal CC development of the mucosa lining the gastrointestinal tract, and CC for recruitment of mesenchymal cells and normal development of CC intestinal villi. Plays a role in cell migration and chemotaxis in CC wound healing. Plays a role in platelet activation, secretion of CC agonists from platelet granules, and in thrombin-induced platelet CC aggregation. Binding of its cognate ligands - homodimeric PDGFA, CC homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or CC homodimeric PDGFC -leads to the activation of several signaling CC cascades; the response depends on the nature of the bound ligand CC and is modulated by the formation of heterodimers between PDGFRA CC and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation CC of PLCG1 leads to the production of the cellular signaling CC molecules diacylglycerol and inositol 1,4,5-trisphosphate, CC mobilization of cytosolic Ca(2+) and the activation of protein CC kinase C. Phosphorylates PIK3R1, the regulatory subunit of CC phosphatidylinositol 3-kinase, and thereby mediates activation of CC the AKT1 signaling pathway. Mediates activation of HRAS and of the CC MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of CC STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. CC Receptor signaling is down-regulated by protein phosphatases that CC dephosphorylate the receptor and its down-stream effectors, and by CC rapid internalization of the activated receptor. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- ENZYME REGULATION: Present in an inactive conformation in the CC absence of bound ligand. Binding of PDGFA and/or PDGFB leads to CC dimerization and activation by autophosphorylation on tyrosine CC residues. Inhibited by imatinib, nilotinib and sorafenib. CC -!- SUBUNIT: Interacts with homodimeric PDGFA, PDGFB and PDGFC, and CC with heterodimers formed by PDGFA and PDGFB. Monomer in the CC absence of bound ligand. Interaction with dimeric PDGFA, PDGFB CC and/or PDGFC leads to receptor dimerization, where both PDGFRA CC homodimers and heterodimers with PDGFRB are observed. Interacts CC (tyrosine phosphorylated) with SHB (via SH2 domain) (By CC similarity). Interacts (tyrosine phosphorylated) with SHF (via SH2 CC domain). Interacts (tyrosine phosphorylated) with SRC (via SH2 CC domain). Interacts (tyrosine phosphorylated) with PIK3R1. CC Interacts (tyrosine phosphorylated) with PLCG1 (via SH2 domain). CC Interacts (tyrosine phosphorylated) with CRK, GRB2 and GRB7. CC Interacts with human cytomegalovirus/HHV-5 envelop glycoprotein CC B/gB. CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein. Note=The activated receptor is rapidly internalized and CC degraded. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P16234-1; Sequence=Displayed; CC Name=2; CC IsoId=P16234-2; Sequence=VSP_007833, VSP_007834; CC Note=No experimental confirmation available; CC Name=3; CC IsoId=P16234-3; Sequence=VSP_042015, VSP_042016; CC -!- TISSUE SPECIFICITY: Detected in platelets (at protein level). CC Widely expressed. Detected in brain, fibroblasts, smooth muscle, CC heart, and embryo. Expressed in primary and metastatic colon CC tumors and in normal colon tissue. CC -!- PTM: N-glycosylated. CC -!- PTM: Ubiquitinated, leading to its degradation (Probable). CC -!- PTM: Autophosphorylated on tyrosine residues upon ligand binding. CC Autophosphorylation occurs in trans, i.e. one subunit of the CC dimeric receptor phosphorylates tyrosine residues on the other CC subunit. Phosphorylation at Tyr-731 and Tyr-742 is important for CC interaction with PIK3R1. Phosphorylation at Tyr-720 and Tyr-754 is CC important for interaction with PTPN11. Phosphorylation at Tyr-762 CC is important for interaction with CRK. Phosphorylation at Tyr-572 CC and Tyr-574 is important for interaction with SRC and SRC family CC members. Phosphorylation at Tyr-988 and Tyr-1018 is important for CC interaction with PLCG1. CC -!- DISEASE: Note=A chromosomal aberration involving PDGFRA is found CC in some cases of hypereosinophilic syndrome. Interstitial CC chromosomal deletion del(4)(q12q12) causes the fusion of FIP1L1 CC and PDGFRA (FIP1L1-PDGFRA). Mutations that cause overexpression CC and/or constitutive activation of PDGFRA may be a cause of CC hypereosinophilic syndrome. CC -!- DISEASE: Defects in PDGFRA are a cause of gastrointestinal stromal CC tumor (GIST) [MIM:606764]. Note=Mutations that cause constitutive CC activation of PDGFRA may be a cause of gastrointestinal stromal CC tumor (GIST). CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. CSF-1/PDGF receptor subfamily. CC -!- SIMILARITY: Contains 5 Ig-like C2-type (immunoglobulin-like) CC domains. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SEQUENCE CAUTION: CC Sequence=AAP69563.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; 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; M22734; AAA60048.1; -; mRNA. DR EMBL; M21574; AAA96715.1; -; mRNA. DR EMBL; D50017; BAA08742.1; -; Genomic_DNA. DR EMBL; AK316578; BAG38166.1; -; mRNA. DR EMBL; AC098587; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC138779; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC015186; AAH15186.1; -; mRNA. DR EMBL; BC063414; AAH63414.1; -; mRNA. DR EMBL; AY229892; AAP69563.1; ALT_INIT; mRNA. DR IPI; IPI00027721; -. DR IPI; IPI00336178; -. DR PIR; A40162; PFHUGA. DR RefSeq; NP_006197.1; NM_006206.4. DR UniGene; Hs.74615; -. DR PDB; 1GQ5; X-ray; 2.20 A; -. DR PDBsum; 1GQ5; -. DR ProteinModelPortal; P16234; -. DR SMR; P16234; 24-516, 546-956. DR DIP; DIP-5736N; -. DR IntAct; P16234; 3. DR STRING; P16234; -. DR PhosphoSite; P16234; -. DR DMDM; 129892; -. DR PRIDE; P16234; -. DR DNASU; 5156; -. DR Ensembl; ENST00000257290; ENSP00000257290; ENSG00000134853. DR Ensembl; ENST00000508170; ENSP00000425648; ENSG00000134853. DR Ensembl; ENST00000509490; ENSP00000424218; ENSG00000134853. DR GeneID; 5156; -. DR KEGG; hsa:5156; -. DR UCSC; uc003hal.3; human. DR UCSC; uc003han.4; human. DR CTD; 5156; -. DR GeneCards; GC04P055095; -. DR HGNC; HGNC:8803; PDGFRA. DR HPA; CAB018143; -. DR MIM; 173490; gene. DR MIM; 606764; phenotype. DR MIM; 607685; phenotype. DR neXtProt; NX_P16234; -. DR Orphanet; 44890; Gastrointestinal stromal tumor. DR Orphanet; 3260; Idiopathic hypereosinophilic syndrome. DR Orphanet; 168947; Myeloid neoplasm associated with PDGFRA rearrangement. DR Orphanet; 99860; Precursor B-cell acute lymphoblastic leukemia. DR PharmGKB; PA33147; -. DR eggNOG; COG0515; -. DR GeneTree; ENSGT00660000095142; -. DR HOGENOM; HOG000112009; -. DR HOVERGEN; HBG004335; -. DR InParanoid; P16234; -. DR KO; K04363; -. DR OMA; HEKGFIE; -. DR OrthoDB; EOG4XWFX0; -. DR PhylomeDB; P16234; -. DR BRENDA; 2.7.10.1; 2681. DR Pathway_Interaction_DB; pdgfrapathway; PDGFR-alpha signaling pathway. DR Reactome; REACT_111102; Signal Transduction. DR DrugBank; DB00102; Becaplermin. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB01268; Sunitinib. DR EvolutionaryTrace; P16234; -. DR GenomeRNAi; 5156; -. DR NextBio; 19946; -. DR ArrayExpress; P16234; -. DR Bgee; E9PBH0; -. DR CleanEx; HS_PDGFRA; -. DR Genevestigator; P16234; -. DR GermOnline; ENSG00000134853; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005887; C:integral to plasma membrane; IDA:BHF-UCL. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005018; F:platelet-derived growth factor alpha-receptor activity; IDA:UniProtKB. DR GO; GO:0005021; F:vascular endothelial growth factor-activated receptor activity; IDA:BHF-UCL. DR GO; GO:0030325; P:adrenal gland development; IEA:Compara. DR GO; GO:0055003; P:cardiac myofibril assembly; ISS:UniProtKB. DR GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Compara. DR GO; GO:0007204; P:elevation of cytosolic calcium ion concentration; IMP:UniProtKB. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISS:UniProtKB. DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; ISS:UniProtKB. DR GO; GO:0008210; P:estrogen metabolic process; IEA:Compara. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Compara. DR GO; GO:0060325; P:face morphogenesis; IEA:Compara. DR GO; GO:0042063; P:gliogenesis; IEA:Compara. DR GO; GO:0001701; P:in utero embryonic development; IEA:Compara. DR GO; GO:0048839; P:inner ear development; IEA:Compara. DR GO; GO:0044419; P:interspecies interaction between organisms; IEA:UniProtKB-KW. DR GO; GO:0033327; P:Leydig cell differentiation; IEA:Compara. DR GO; GO:0030324; P:lung development; IEA:Compara. DR GO; GO:0001553; P:luteinization; ISS:UniProtKB. DR GO; GO:0030539; P:male genitalia development; IEA:Compara. DR GO; GO:0072277; P:metanephric glomerular capillary formation; ISS:UniProtKB. DR GO; GO:0010544; P:negative regulation of platelet activation; IDA:UniProtKB. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Compara. DR GO; GO:0060021; P:palate development; IEA:Compara. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IMP:UniProtKB. DR GO; GO:0070527; P:platelet aggregation; IMP:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB. DR GO; GO:0038091; P:positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0045740; P:positive regulation of DNA replication; IDA:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:BHF-UCL. DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IMP:UniProtKB. DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; TAS:UniProtKB. DR GO; GO:0010863; P:positive regulation of phospholipase C activity; IMP:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; TAS:UniProtKB. DR GO; GO:0050920; P:regulation of chemotaxis; IMP:UniProtKB. DR GO; GO:2000739; P:regulation of mesenchymal stem cell differentiation; IMP:UniProtKB. DR GO; GO:0034097; P:response to cytokine stimulus; IEA:Compara. DR GO; GO:0032355; P:response to estradiol stimulus; IEA:Compara. DR GO; GO:0055093; P:response to hyperoxia; IEA:Compara. DR GO; GO:0010035; P:response to inorganic substance; IEA:Compara. DR GO; GO:0061298; P:retina vasculature development in camera-type eye; ISS:UniProtKB. DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Compara. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IEA:InterPro. DR Gene3D; G3DSA:2.60.40.10; Ig-like_fold; 5. DR InterPro; IPR007110; Ig-like. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016243; Tyr_kinase_CSF1/PDGF_rcpt. DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS. DR InterPro; IPR009134; Tyr_kinase_VEGFR_rcpt_N. DR Pfam; PF07679; I-set; 2. DR Pfam; PF07714; Pkinase_Tyr; 1. DR PIRSF; PIRSF000615; TyrPK_CSF1-R; 1. DR PRINTS; PR01832; VEGFRECEPTOR. DR SMART; SM00409; IG; 2. DR SMART; SM00408; IGc2; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF56112; Kinase_like; 1. DR PROSITE; PS50835; IG_LIKE; 2. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Chemotaxis; Complete proteome; Developmental protein; Disulfide bond; KW Glycoprotein; Host-virus interaction; Immunoglobulin domain; Kinase; KW Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; KW Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; KW Transferase; Transmembrane; Transmembrane helix; KW Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1 23 FT CHAIN 24 1089 Platelet-derived growth factor receptor FT alpha. FT /FTId=PRO_0000016760. FT TOPO_DOM 24 528 Extracellular (Potential). FT TRANSMEM 529 549 Helical; (Potential). FT TOPO_DOM 550 1089 Cytoplasmic (Potential). FT DOMAIN 24 113 Ig-like C2-type 1. FT DOMAIN 117 201 Ig-like C2-type 2. FT DOMAIN 202 306 Ig-like C2-type 3. FT DOMAIN 319 410 Ig-like C2-type 4. FT DOMAIN 414 517 Ig-like C2-type 5. FT DOMAIN 593 954 Protein kinase. FT NP_BIND 599 607 ATP (By similarity). FT COMPBIAS 1041 1087 Ser-rich. FT ACT_SITE 818 818 Proton acceptor (By similarity). FT BINDING 627 627 ATP (By similarity). FT SITE 578 579 Breakpoint for interstitial deletion to FT form the FIP1L1-PDGFRA fusion protein. FT MOD_RES 555 555 Phosphotyrosine. FT MOD_RES 572 572 Phosphotyrosine; by autocatalysis. FT MOD_RES 574 574 Phosphotyrosine; by autocatalysis. FT MOD_RES 582 582 Phosphotyrosine. FT MOD_RES 720 720 Phosphotyrosine; by autocatalysis. FT MOD_RES 731 731 Phosphotyrosine; by autocatalysis. FT MOD_RES 742 742 Phosphotyrosine; by autocatalysis. FT MOD_RES 754 754 Phosphotyrosine; by autocatalysis. FT MOD_RES 762 762 Phosphotyrosine; by autocatalysis. FT MOD_RES 768 768 Phosphotyrosine; by autocatalysis. FT MOD_RES 849 849 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 944 944 Phosphotyrosine. FT MOD_RES 958 958 Phosphotyrosine. FT MOD_RES 962 962 Phosphotyrosine. FT MOD_RES 988 988 Phosphotyrosine; by autocatalysis. FT MOD_RES 993 993 Phosphotyrosine. FT MOD_RES 1018 1018 Phosphotyrosine; by autocatalysis. FT CARBOHYD 42 42 N-linked (GlcNAc...) (Potential). FT CARBOHYD 76 76 N-linked (GlcNAc...) (Potential). FT CARBOHYD 103 103 N-linked (GlcNAc...) (Potential). FT CARBOHYD 179 179 N-linked (GlcNAc...) (Potential). FT CARBOHYD 353 353 N-linked (GlcNAc...) (Potential). FT CARBOHYD 359 359 N-linked (GlcNAc...) (Potential). FT CARBOHYD 458 458 N-linked (GlcNAc...) (Potential). FT CARBOHYD 468 468 N-linked (GlcNAc...) (Potential). FT DISULFID 49 100 By similarity. FT DISULFID 150 189 By similarity. FT DISULFID 235 290 By similarity. FT DISULFID 435 501 By similarity. FT VAR_SEQ 210 218 ATSELDLEM -> GTCIISFLL (in isoform 2). FT /FTId=VSP_007833. FT VAR_SEQ 219 1089 Missing (in isoform 2). FT /FTId=VSP_007834. FT VAR_SEQ 720 743 YVILSFENNGDYMDMKQADTTQYV -> SGQGCLSSGTLQE FT LSVDLQARGPC (in isoform 3). FT /FTId=VSP_042015. FT VAR_SEQ 744 1089 Missing (in isoform 3). FT /FTId=VSP_042016. FT VARIANT 79 79 G -> D (in dbSNP:rs36035373). FT /FTId=VAR_042032. FT VARIANT 426 426 G -> D (in dbSNP:rs55865821). FT /FTId=VAR_042033. FT VARIANT 478 478 S -> P (in dbSNP:rs35597368). FT /FTId=VAR_034378. FT VARIANT 481 481 R -> G (in a hypereosinophilic syndrome FT sample; does not lead to constitutive FT kinase activation). FT /FTId=VAR_066460. FT VARIANT 507 507 L -> P (in a hypereosinophilic syndrome FT sample; does not lead to constitutive FT kinase activation). FT /FTId=VAR_066461. FT VARIANT 561 561 V -> D (in a GIST sample; constitutively FT activated kinase). FT /FTId=VAR_066462. FT VARIANT 562 562 I -> M (in a hypereosinophilic syndrome FT sample; does not lead to constitutive FT kinase activation). FT /FTId=VAR_066463. FT VARIANT 570 570 H -> R (in a hypereosinophilic syndrome FT sample; does not lead to constitutive FT kinase activation). FT /FTId=VAR_066464. FT VARIANT 650 650 H -> Q (in a hypereosinophilic syndrome FT sample; constitutively activated kinase). FT /FTId=VAR_066465. FT VARIANT 659 659 N -> K (in GIST sample; constitutively FT activated kinase). FT /FTId=VAR_066466. FT VARIANT 659 659 N -> S (in a hypereosinophilic syndrome FT sample; constitutively activated kinase). FT /FTId=VAR_066467. FT VARIANT 705 705 L -> P (in a hypereosinophilic syndrome FT sample; does not lead to constitutive FT kinase activation). FT /FTId=VAR_066468. FT VARIANT 748 748 R -> G (in a hypereosinophilic syndrome FT sample; constitutively activated kinase). FT /FTId=VAR_066469. FT VARIANT 764 764 R -> C (in dbSNP:rs34392012). FT /FTId=VAR_042034. FT VARIANT 829 829 G -> R (in a glioblastoma multiforme FT sample; somatic mutation). FT /FTId=VAR_042035. FT VARIANT 842 845 Missing (in a GIST sample; constitutively FT activated kinase). FT /FTId=VAR_066470. FT VARIANT 842 842 D -> V (in a GIST sample; imatinib FT resistant, constitutively activated FT kinase). FT /FTId=VAR_066471. FT VARIANT 842 842 D -> Y (in a GIST sample; imatinib FT sensitive, constitutively activated FT kinase). FT /FTId=VAR_066472. FT VARIANT 845 848 Missing (in a GIST sample; constitutively FT activated kinase). FT /FTId=VAR_066473. FT VARIANT 849 849 Y -> C (in GIST). FT /FTId=VAR_066474. FT VARIANT 849 849 Y -> S (in a hypereosinophilic syndrome FT sample; constitutively activated kinase). FT /FTId=VAR_066475. FT VARIANT 996 996 E -> K (in a metastatic melanoma sample; FT somatic mutation). FT /FTId=VAR_042036. FT VARIANT 1071 1071 D -> N (in a lung neuroendocrine FT carcinoma sample; somatic mutation). FT /FTId=VAR_042037. FT MUTAGEN 572 572 Y->F: Abolishes interaction with SRC- FT family members and impairs FT internalization of the activated FT receptor; when associated with F-574. FT MUTAGEN 574 574 Y->F: Abolishes interaction with SRC- FT family members and impairs FT internalization of the activated FT receptor; when associated with F-572. FT MUTAGEN 720 720 Y->F: Strongly reduced interaction with FT PTPN11 and GRB2. FT MUTAGEN 731 731 Y->F: No effect on autophosphorylation FT and phosphorylation of PLCG1. Abolishes FT activation of phosphatidylinositol 3- FT kinase. FT MUTAGEN 742 742 Y->F: No effect on autophosphorylation FT and phosphorylation of PLCG1. Abolishes FT activation of phosphatidylinositol 3- FT kinase. FT MUTAGEN 762 762 Y->F: Abolishes interaction with CRK. SQ SEQUENCE 1089 AA; 122670 MW; 5E3FB9940ACD1BE8 CRC64; MGTSHPAFLV LGCLLTGLSL ILCQLSLPSI LPNENEKVVQ LNSSFSLRCF GESEVSWQYP MSEEESSDVE IRNEENNSGL FVTVLEVSSA SAAHTGLYTC YYNHTQTEEN ELEGRHIYIY VPDPDVAFVP LGMTDYLVIV EDDDSAIIPC RTTDPETPVT LHNSEGVVPA SYDSRQGFNG TFTVGPYICE ATVKGKKFQT IPFNVYALKA TSELDLEMEA LKTVYKSGET IVVTCAVFNN EVVDLQWTYP GEVKGKGITM LEEIKVPSIK LVYTLTVPEA TVKDSGDYEC AARQATREVK EMKKVTISVH EKGFIEIKPT FSQLEAVNLH EVKHFVVEVR AYPPPRISWL KNNLTLIENL TEITTDVEKI QEIRYRSKLK LIRAKEEDSG HYTIVAQNED AVKSYTFELL TQVPSSILDL VDDHHGSTGG QTVRCTAEGT PLPDIEWMIC KDIKKCNNET SWTILANNVS NIITEIHSRD RSTVEGRVTF AKVEETIAVR CLAKNLLGAE NRELKLVAPT LRSELTVAAA VLVLLVIVII SLIVLVVIWK QKPRYEIRWR VIESISPDGH EYIYVDPMQL PYDSRWEFPR DGLVLGRVLG SGAFGKVVEG TAYGLSRSQP VMKVAVKMLK PTARSSEKQA LMSELKIMTH LGPHLNIVNL LGACTKSGPI YIITEYCFYG DLVNYLHKNR DSFLSHHPEK PKKELDIFGL NPADESTRSY VILSFENNGD YMDMKQADTT QYVPMLERKE VSKYSDIQRS LYDRPASYKK KSMLDSEVKN LLSDDNSEGL TLLDLLSFTY QVARGMEFLA SKNCVHRDLA ARNVLLAQGK IVKICDFGLA RDIMHDSNYV SKGSTFLPVK WMAPESIFDN LYTTLSDVWS YGILLWEIFS LGGTPYPGMM VDSTFYNKIK SGYRMAKPDH ATSEVYEIMV KCWNSEPEKR PSFYHLSEIV ENLLPGQYKK SYEKIHLDFL KSDHPAVARM RVDSDNAYIG VTYKNEEDKL KDWEGGLDEQ RLSADSGYII PLPDIDPVPE EEDLGKRNRH SSQTSEESAI ETGSSSSTFI KREDETIEDI DMMDDIGIDS SDLVEDSFL //