PGFRA_HUMAN
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 03-AUG-2022, entry version 236.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH PDGFA AND
RP PDGFB.
RC TISSUE=Foreskin;
RX 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 growth
RT factor (PDGF) receptor establishes structural similarity to the B-type PDGF
RT 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 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 PDGF
RT receptor genes.";
RL Science 243:800-804(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RX 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 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., 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=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., 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., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., 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., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 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 project:
RT 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 MASS
RP 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 PubMed=7896447; DOI=10.1002/ijc.2910600611;
RA Craven R.J., Xu L.H., Weiner T.M., Fridell Y.-W., Dent G.A., Srivastava S.,
RA 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 CHEMOTAXIS,
RP 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., LaRochelle W.J.,
RA 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 functional
RT coupling with mitogenic and chemotactic signaling 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 PDGFA
RP AND PDGFB, AND AUTOPHOSPHORYLATION.
RX PubMed=1709159; DOI=10.1016/s0021-9258(18)31541-2;
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 subunit
RT 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 AND
RP REGULATION OF PHOSPHATIDYLINOSITOL METABOLISM, INTERACTION WITH PIK3R,
RP PHOSPHORYLATION AT TYR-731 AND TYR-742, AND MUTAGENESIS OF TYR-731 AND
RP TYR-742.
RX PubMed=1646396; DOI=10.1128/mcb.11.7.3780-3785.1991;
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; DOI=10.1016/s0021-9258(18)53739-x;
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 binding
RT 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; DOI=10.1016/s0021-9258(17)36728-5;
RA Vassbotn F.S., Havnen O.K., Heldin C.H., Holmsen H.;
RT "Negative feedback regulation of human platelets via autocrine activation
RT of the platelet-derived growth factor alpha-receptor.";
RL J. Biol. Chem. 269:13874-13879(1994).
RN [15]
RP PHOSPHORYLATION AT TYR-988 AND TYR-1018, AND INTERACTION WITH PLCG1.
RX PubMed=7535778; DOI=10.1074/jbc.270.13.7773;
RA Eriksson A., Naanberg E., Roennstrand L., Engstroem U., Hellman U.,
RA Rupp E., Carpenter G., Heldin C.H., Claesson-Welsh L.;
RT "Demonstration of functionally different interactions between phospholipase
RT C-gamma and the two types of platelet-derived growth factor receptors.";
RL J. Biol. Chem. 270:7773-7781(1995).
RN [16]
RP FUNCTION IN PROMOTING CHEMOTAXIS.
RX PubMed=8760137; DOI=10.1152/ajplung.1996.271.1.l93;
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 receptor-
RT alpha.";
RL Am. J. Physiol. 271:L93-L99(1996).
RN [17]
RP PHOSPHORYLATION AT TYR-768.
RX PubMed=8617789; DOI=10.1074/jbc.271.9.5101;
RA Yokote K., Mori S., Siegbahn A., Ronnstrand L., Wernstedt C., Heldin C.H.,
RA Claesson-Welsh L.;
RT "Structural determinants in the platelet-derived growth factor alpha-
RT receptor implicated in modulation of chemotaxis.";
RL J. Biol. Chem. 271:5101-5111(1996).
RN [18]
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 factor
RT alpha- and beta-receptors.";
RL J. Biol. Chem. 271:30942-30949(1996).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF PTPN11; ACTIVATION OF HRAS AND REGULATION OF
RP CELL PROLIFERATION, PHOSPHORYLATION AT TYR-720, INTERACTION WITH GRB2;
RP PTPN11; PLCG1 AND PIK3R1, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF TYR-720.
RX PubMed=8943348; DOI=10.1128/mcb.16.12.6926;
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 [20]
RP INTERACTION WITH CRK, PHOSPHORYLATION AT TYR-762, AND MUTAGENESIS OF
RP TYR-762.
RX PubMed=10733900; DOI=10.1006/bbrc.2000.2374;
RA Matsumoto T., Yokote K., Take A., Takemoto M., Asaumi S., Hashimoto Y.,
RA Matsuda M., Saito Y., Mori S.;
RT "Differential interaction of CrkII adaptor protein with platelet-derived
RT growth factor alpha- and beta-receptors is determined by its internal
RT tyrosine phosphorylation.";
RL Biochem. Biophys. Res. Commun. 270:28-33(2000).
RN [21]
RP INTERACTION WITH SHF, AND PHOSPHORYLATION AT TYR-720.
RX 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 [22]
RP FUNCTION IN PLATELET ACTIVATION.
RX PubMed=10947961; DOI=10.1042/bj3500469;
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 activation.";
RL Biochem. J. 350:469-475(2000).
RN [23]
RP FUNCTION IN ACTIVATION OF MAPK1/ERK2 AND/OR MAPK3/ERK1, DEGRADATION,
RP PHOSPHORYLATION AT TYR-572 AND TYR-574, AND MUTAGENESIS OF TYR-572 AND
RP 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., Band H.,
RA 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 [24]
RP FUNCTION AS A RECEPTOR FOR PDGFC, AND INTERACTION WITH PDGFC.
RX 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 [25]
RP SUBCELLULAR LOCATION, INTERACTION WITH SRC, AND MUTAGENESIS OF TYR-572 AND
RP 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 [26]
RP INVOLVEMENT IN HES.
RX PubMed=12660384; DOI=10.1056/nejmoa025217;
RA Cools J., DeAngelo D.J., Gotlib J., Stover E.H., Legare R.D., Cortes J.,
RA Kutok J., Clark J., Galinsky I., Griffin J.D., Cross N.C., Tefferi A.,
RA Malone J., Alam R., Schrier S.L., Schmid J., Rose M., Vandenberghe P.,
RA Verhoef G., Boogaerts M., Wlodarska I., Kantarjian H., Marynen P.,
RA Coutre S.E., Stone R., Gilliland D.G.;
RT "A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a
RT therapeutic target of imatinib in idiopathic hypereosinophilic syndrome.";
RL N. Engl. J. Med. 348:1201-1214(2003).
RN [27]
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 AND
RP 845-HIS--PRO-448 DEL, AND CHARACTERIZATION OF VARIANTS ASP-561; VAL-842;
RP 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 [28]
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, CHARACTERIZATION OF
RP VARIANTS ASP-561; LYS-659; TYR-842; VAL-842; 842-ASP--HIS-845 DEL
RP 845-HIS--PRO-448 DEL AND CYS-849, AND ACTIVITY REGULATION.
RX PubMed=15928335; DOI=10.1200/jco.2005.14.068;
RA Corless C.L., Schroeder A., Griffith D., Town A., McGreevey L., Harrell P.,
RA Shiraga S., Bainbridge T., Morich J., Heinrich M.C.;
RT "PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum
RT and in vitro sensitivity to imatinib.";
RL J. Clin. Oncol. 23:5357-5364(2005).
RN [29]
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 [30]
RP PHOSPHORYLATION AT TYR-754.
RX PubMed=17604334; DOI=10.1158/1535-7163.mct-06-0720;
RA Stock P., Monga D., Tan X., Micsenyi A., Loizos N., Monga S.P.;
RT "Platelet-derived growth factor receptor-alpha: a novel therapeutic target
RT in human hepatocellular cancer.";
RL Mol. Cancer Ther. 6:1932-1941(2007).
RN [31]
RP INTERACTION WITH HHV-5 GB (MICROBIAL INFECTION).
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 [32]
RP FUNCTION IN PHOSPHORYLATION OF STAT 5A AND/OR STAT5B, ROLE IN
RP HYPEREOSINOPHILIC SYNDROME, VARIANTS GLY-481; PRO-507; MET-562; ARG-570;
RP GLN-650; SER-659; PRO-705; GLY-748 AND SER-849, CHARACTERIZATION OF
RP VARIANTS GLY-481; PRO-507; MET-562; ARG-570; GLN-650; SER-659; PRO-705;
RP GLY-748 AND SER-849, AND ACTIVITY REGULATION.
RX PubMed=21224473; DOI=10.1182/blood-2010-05-286757;
RA Elling C., Erben P., Walz C., Frickenhaus M., Schemionek M., Stehling M.,
RA Serve H., Cross N.C., Hochhaus A., Hofmann W.K., Berdel W.E.,
RA Muller-Tidow C., Reiter A., Koschmieder S.;
RT "Novel imatinib-sensitive PDGFRA-activating point mutations in
RT hypereosinophilic syndrome induce growth factor independence and leukemia-
RT like disease.";
RL Blood 117:2935-2943(2011).
RN [33]
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 decreased
RT Cbl-mediated platelet-derived growth factor receptor alpha and fibroblast
RT growth factor receptor 2 ubiquitination.";
RL J. Biol. Chem. 286:24443-24450(2011).
RN [34]
RP ROLE IN DISEASE, CHARACTERIZATION OF VARIANT VAL-842, AND ACTIVITY
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 myeloid
RT neoplasms with abnormalities of PDGFRA might be related to the limited
RT repertoire of possible PDGFRA kinase domain mutations in vitro.";
RL Oncogene 30:933-943(2011).
RN [35]
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 [36]
RP REVIEW ON ROLE IN DISEASE AND ACTIVITY 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 tumor
RT vasculature and stroma.";
RL Cytokine Growth Factor Rev. 15:275-286(2004).
RN [37]
RP REVIEW ON ROLE IN DISEASE AND ACTIVITY 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 [38]
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 [39]
RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEINS GH; GL AND GO (MICROBIAL
RP INFECTION).
RX PubMed=28403202; DOI=10.1371/journal.ppat.1006281;
RA Wu Y., Prager A., Boos S., Resch M., Brizic I., Mach M., Wildner S.,
RA Scrivano L., Adler B.;
RT "Human cytomegalovirus glycoprotein complex gH/gL/gO uses PDGFR-alpha as a
RT key for entry.";
RL PLoS Pathog. 13:E1006281-E1006281(2017).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1185-1189 IN COMPLEX WITH SLC9A3R1
RP AND PDGFRB.
RX 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 factor
RT receptors.";
RL J. Biol. Chem. 277:18973-18978(2002).
RN [41]
RP INVOLVEMENT IN GISTPS, AND VARIANT GISTPS TYR-846.
RX PubMed=14699510; DOI=10.1053/j.gastro.2003.10.079;
RA Chompret A., Kannengiesser C., Barrois M., Terrier P., Dahan P., Tursz T.,
RA Lenoir G.M., Bressac-De Paillerets B.;
RT "PDGFRA germline mutation in a family with multiple cases of
RT gastrointestinal stromal tumor.";
RL Gastroenterology 126:318-321(2004).
RN [42]
RP VARIANT GISTPS CYS-555, CHARACTERIZATION OF VARIANT GISTPS CYS-555, AND
RP FUNCTION.
RX PubMed=17087943; DOI=10.1053/j.gastro.2006.07.002;
RA de Raedt T., Cools J., Debiec-Rychter M., Brems H., Mentens N., Sciot R.,
RA Himpens J., de Wever I., Schoeffski P., Marynen P., Legius E.;
RT "Intestinal neurofibromatosis is a subtype of familial GIST and results
RT from a dominant activating mutation in PDGFRA.";
RL Gastroenterology 131:1907-1912(2006).
RN [43]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-79; ASP-426; PRO-478; CYS-764; ARG-829;
RP LYS-996 AND ASN-1071.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [44]
RP VARIANT GISTPS LEU-653.
RX PubMed=25975287; DOI=10.1038/modpathol.2015.56;
RA Ricci R., Martini M., Cenci T., Carbone A., Lanza P., Biondi A., Rindi G.,
RA Cassano A., Larghi A., Persiani R., Larocca L.M.;
RT "PDGFRA-mutant syndrome.";
RL Mod. Pathol. 28:954-964(2015).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor
CC for PDGFA, PDGFB and PDGFC and plays an essential role in the
CC regulation of embryonic development, cell proliferation, survival and
CC chemotaxis. Depending on the context, promotes or inhibits cell
CC proliferation and cell migration. Plays an important role in the
CC differentiation of bone marrow-derived mesenchymal stem cells. Required
CC for normal skeleton development and cephalic closure during embryonic
CC development. Required for normal development of the mucosa lining the
CC gastrointestinal tract, and for recruitment of mesenchymal cells and
CC normal development of intestinal villi. Plays a role in cell migration
CC and chemotaxis in wound healing. Plays a role in platelet activation,
CC secretion of agonists from platelet granules, and in thrombin-induced
CC platelet aggregation. Binding of its cognate ligands - homodimeric
CC PDGFA, 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 and is
CC modulated by the formation of heterodimers between PDGFRA and PDGFRB.
CC Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to
CC the production of the cellular signaling molecules diacylglycerol and
CC inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the
CC activation of protein kinase C. Phosphorylates PIK3R1, the regulatory
CC subunit of phosphatidylinositol 3-kinase, and thereby mediates
CC activation of the AKT1 signaling pathway. Mediates activation of HRAS
CC and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes
CC activation of STAT family members STAT1, STAT3 and STAT5A and/or
CC STAT5B. Receptor signaling is down-regulated by protein phosphatases
CC that dephosphorylate the receptor and its down-stream effectors, and by
CC rapid internalization of the activated receptor.
CC {ECO:0000269|PubMed:10734113, ECO:0000269|PubMed:10947961,
CC ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:12522257,
CC ECO:0000269|PubMed:1646396, ECO:0000269|PubMed:17087943,
CC ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:17141222,
CC ECO:0000269|PubMed:20972453, ECO:0000269|PubMed:21224473,
CC ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:2554309,
CC ECO:0000269|PubMed:8188664, ECO:0000269|PubMed:8760137,
CC ECO:0000269|PubMed:8943348}.
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=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. Binding of PDGFA and/or PDGFB leads to dimerization
CC and activation by autophosphorylation on tyrosine residues. Inhibited
CC by imatinib, nilotinib and sorafenib. {ECO:0000269|PubMed:15928335,
CC ECO:0000269|PubMed:20972453, ECO:0000269|PubMed:21224473}.
CC -!- SUBUNIT: Interacts with homodimeric PDGFA, PDGFB and PDGFC, and with
CC heterodimers formed by PDGFA and PDGFB. Monomer in the absence of bound
CC ligand. Interaction with dimeric PDGFA, PDGFB and/or PDGFC leads to
CC receptor dimerization, where both PDGFRA homodimers and heterodimers
CC with PDGFRB are observed. Interacts (tyrosine phosphorylated) with SHB
CC (via SH2 domain) (By similarity). Interacts (tyrosine phosphorylated)
CC with SHF (via SH2 domain). Interacts (tyrosine phosphorylated) with SRC
CC (via SH2 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 {ECO:0000250, ECO:0000269|PubMed:10733900, ECO:0000269|PubMed:11095946,
CC ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:11882663,
CC ECO:0000269|PubMed:14644164, ECO:0000269|PubMed:1646396,
CC ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:2173144,
CC ECO:0000269|PubMed:2536956, ECO:0000269|PubMed:2544881,
CC ECO:0000269|PubMed:7535778, ECO:0000269|PubMed:7679113,
CC ECO:0000269|PubMed:8940081, ECO:0000269|PubMed:8943348}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human
CC cytomegalovirus/HHV-5 envelope glycoprotein B/gB. Interacts also with
CC the trimeric complex gH-gL-gO. {ECO:0000269|PubMed:20660204,
CC ECO:0000269|PubMed:28403202}.
CC -!- INTERACTION:
CC P16234; P46108: CRK; NbExp=4; IntAct=EBI-2861522, EBI-886;
CC P16234; P46109: CRKL; NbExp=3; IntAct=EBI-2861522, EBI-910;
CC P16234; P00533: EGFR; NbExp=4; IntAct=EBI-2861522, EBI-297353;
CC P16234; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-2861522, EBI-749265;
CC P16234; P04085: PDGFA; NbExp=6; IntAct=EBI-2861522, EBI-2881386;
CC P16234; P01127: PDGFB; NbExp=11; IntAct=EBI-2861522, EBI-1554925;
CC P16234; Q9NRA1: PDGFC; NbExp=2; IntAct=EBI-2861522, EBI-8833587;
CC P16234-1; Q9NRA1-1: PDGFC; NbExp=2; IntAct=EBI-15499330, EBI-15499301;
CC P16234-1; A8T7D5: UL55; Xeno; NbExp=2; IntAct=EBI-15499330, EBI-15722055;
CC P16234-2; P05067: APP; NbExp=3; IntAct=EBI-13380852, EBI-77613;
CC P16234-2; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-13380852, EBI-11721828;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14644164,
CC ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:8188664}; Single-pass
CC type I membrane protein {ECO:0000269|PubMed:14644164,
CC ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:8188664}. Cell
CC projection, cilium {ECO:0000250|UniProtKB:P26618}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P26618}.
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 Name=3;
CC IsoId=P16234-3; Sequence=VSP_042015, VSP_042016;
CC -!- TISSUE SPECIFICITY: Detected in platelets (at protein level). Widely
CC expressed. Detected in brain, fibroblasts, smooth muscle, heart, and
CC embryo. Expressed in primary and metastatic colon tumors and in normal
CC colon tissue. {ECO:0000269|PubMed:2536956, ECO:0000269|PubMed:7896447,
CC ECO:0000269|PubMed:8188664}.
CC -!- PTM: N-glycosylated.
CC -!- PTM: Ubiquitinated, leading to its internalization and degradation.
CC {ECO:0000305|PubMed:21596750}.
CC -!- PTM: Autophosphorylated on tyrosine residues upon ligand binding.
CC Autophosphorylation occurs in trans, i.e. one subunit of the dimeric
CC receptor phosphorylates tyrosine residues on the other subunit.
CC Phosphorylation at Tyr-731 and Tyr-742 is important for interaction
CC with PIK3R1. Phosphorylation at Tyr-720 and Tyr-754 is important for
CC interaction with PTPN11. Phosphorylation at Tyr-762 is important for
CC interaction with CRK. Phosphorylation at Tyr-572 and Tyr-574 is
CC important for interaction with SRC and SRC family members.
CC Phosphorylation at Tyr-988 and Tyr-1018 is important for interaction
CC with PLCG1. {ECO:0000269|PubMed:10733900, ECO:0000269|PubMed:10734113,
CC ECO:0000269|PubMed:11095946, ECO:0000269|PubMed:1646396,
CC ECO:0000269|PubMed:7535778, ECO:0000269|PubMed:8943348}.
CC -!- DISEASE: Note=A chromosomal aberration involving PDGFRA is found in
CC some cases of hypereosinophilic syndrome. Interstitial chromosomal
CC deletion del(4)(q12q12) causes the fusion of FIP1L1 and PDGFRA (FIP1L1-
CC PDGFRA). Mutations that cause overexpression and/or constitutive
CC activation of PDGFRA may be a cause of hypereosinophilic syndrome.
CC {ECO:0000269|PubMed:12808148}.
CC -!- DISEASE: Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common
CC mesenchymal neoplasms arising in the gastrointestinal tract, most often
CC in the stomach. They are histologically, immunohistochemically, and
CC genetically different from typical leiomyomas, leiomyosarcomas, and
CC schwannomas. Most GISTs are composed of a fairly uniform population of
CC spindle-shaped cells. Some tumors are dominated by epithelioid cells or
CC contain a mixture of spindle and epithelioid morphologies. Primary
CC GISTs in the gastrointestinal tract commonly metastasize in the omentum
CC and mesenteries, often as multiple nodules. However, primary tumors may
CC also occur outside of the gastrointestinal tract, in other intra-
CC abdominal locations, especially in the omentum and mesentery.
CC {ECO:0000269|PubMed:12522257, ECO:0000269|PubMed:15928335}. Note=The
CC gene represented in this entry may be involved in disease pathogenesis.
CC Mutations causing PDGFRA constitutive activation have been found in
CC gastrointestinal stromal tumors lacking KIT mutations
CC (PubMed:12522257). {ECO:0000269|PubMed:12522257}.
CC -!- DISEASE: GIST-plus syndrome (GISTPS) [MIM:175510]: A disorder
CC characterized by multiple mesenchymal tumors of the gastrointestinal
CC tract, including gastrointestinal stromal tumor, inflammatory fibroid
CC polyps, and fibroid tumors. Additional features are coarse facies and
CC skin, broad hands and feet, and premature tooth loss. GISTPS is an
CC autosomal dominant disease with incomplete penetrance. Gastrointestinal
CC stromal tumor and inflammatory fibroid polyps may also occur in
CC isolation. {ECO:0000269|PubMed:14699510, ECO:0000269|PubMed:17087943,
CC ECO:0000269|PubMed:25975287}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP69563.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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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 CCDS; CCDS3495.1; -. [P16234-1]
DR PIR; A40162; PFHUGA.
DR RefSeq; NP_001334758.1; NM_001347829.1. [P16234-1]
DR RefSeq; NP_006197.1; NM_006206.5. [P16234-1]
DR RefSeq; XP_005265800.1; XM_005265743.1. [P16234-1]
DR PDB; 1GQ5; X-ray; 2.20 A; -.
DR PDB; 5GRN; X-ray; 1.77 A; A=550-973.
DR PDB; 5K5X; X-ray; 2.17 A; A=550-973.
DR PDB; 6A32; X-ray; 1.87 A; A=550-973.
DR PDB; 6JOI; X-ray; 3.10 A; A=550-973.
DR PDB; 6JOJ; X-ray; 2.60 A; A=550-973.
DR PDB; 6JOK; X-ray; 3.80 A; A=550-973.
DR PDB; 6JOL; X-ray; 1.90 A; A=550-973.
DR PDB; 7LBF; EM; 2.80 A; D=1-524.
DR PDBsum; 1GQ5; -.
DR PDBsum; 5GRN; -.
DR PDBsum; 5K5X; -.
DR PDBsum; 6A32; -.
DR PDBsum; 6JOI; -.
DR PDBsum; 6JOJ; -.
DR PDBsum; 6JOK; -.
DR PDBsum; 6JOL; -.
DR PDBsum; 7LBF; -.
DR AlphaFoldDB; P16234; -.
DR SMR; P16234; -.
DR BioGRID; 111182; 324.
DR ComplexPortal; CPX-2881; PDGF receptor alpha - PDGF-AA complex.
DR ComplexPortal; CPX-2883; PDGF receptor alpha-beta - PDGF-BB complex.
DR ComplexPortal; CPX-2884; PDGF receptor alpha - PDGF-BB complex.
DR ComplexPortal; CPX-2885; PDGF receptor alpha - PDGF-AB complex.
DR ComplexPortal; CPX-2887; PDGF receptor alpha - PDGF-CC complex.
DR ComplexPortal; CPX-2888; PDGF receptor alpha-beta - PDGF-CC complex.
DR ComplexPortal; CPX-2890; PDGF receptor alpha-beta - PDGF-DD complex.
DR ComplexPortal; CPX-2892; PDGF receptor alpha-beta - PDGF-AB complex.
DR CORUM; P16234; -.
DR DIP; DIP-5736N; -.
DR IntAct; P16234; 60.
DR MINT; P16234; -.
DR STRING; 9606.ENSP00000257290; -.
DR BindingDB; P16234; -.
DR ChEMBL; CHEMBL2007; -.
DR DrugBank; DB12742; Amuvatinib.
DR DrugBank; DB00102; Becaplermin.
DR DrugBank; DB12147; Erdafitinib.
DR DrugBank; DB10772; Foreskin keratinocyte (neonatal).
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB09078; Lenvatinib.
DR DrugBank; DB06595; Midostaurin.
DR DrugBank; DB09079; Nintedanib.
DR DrugBank; DB06043; Olaratumab.
DR DrugBank; DB06589; Pazopanib.
DR DrugBank; DB08901; Ponatinib.
DR DrugBank; DB08896; Regorafenib.
DR DrugBank; DB14840; Ripretinib.
DR DrugBank; DB01268; Sunitinib.
DR DrugBank; DB11800; Tivozanib.
DR DrugBank; DB05146; XL820.
DR DrugCentral; P16234; -.
DR GuidetoPHARMACOLOGY; 1803; -.
DR GlyGen; P16234; 8 sites.
DR iPTMnet; P16234; -.
DR PhosphoSitePlus; P16234; -.
DR BioMuta; PDGFRA; -.
DR DMDM; 129892; -.
DR CPTAC; CPTAC-1767; -.
DR jPOST; P16234; -.
DR MassIVE; P16234; -.
DR MaxQB; P16234; -.
DR PaxDb; P16234; -.
DR PeptideAtlas; P16234; -.
DR PRIDE; P16234; -.
DR ProteomicsDB; 53328; -. [P16234-1]
DR ProteomicsDB; 53329; -. [P16234-2]
DR ProteomicsDB; 53330; -. [P16234-3]
DR ABCD; P16234; 32 sequenced antibodies.
DR Antibodypedia; 1381; 2189 antibodies from 46 providers.
DR DNASU; 5156; -.
DR Ensembl; ENST00000257290.10; ENSP00000257290.5; ENSG00000134853.12. [P16234-1]
DR Ensembl; ENST00000508170.5; ENSP00000425648.1; ENSG00000134853.12. [P16234-2]
DR Ensembl; ENST00000509490.5; ENSP00000424218.1; ENSG00000134853.12. [P16234-3]
DR GeneID; 5156; -.
DR KEGG; hsa:5156; -.
DR MANE-Select; ENST00000257290.10; ENSP00000257290.5; NM_006206.6; NP_006197.1.
DR UCSC; uc003hal.4; human. [P16234-1]
DR CTD; 5156; -.
DR DisGeNET; 5156; -.
DR GeneCards; PDGFRA; -.
DR HGNC; HGNC:8803; PDGFRA.
DR HPA; ENSG00000134853; Tissue enhanced (ovary).
DR MalaCards; PDGFRA; -.
DR MIM; 173490; gene.
DR MIM; 175510; phenotype.
DR MIM; 606764; phenotype.
DR MIM; 607685; phenotype.
DR neXtProt; NX_P16234; -.
DR OpenTargets; ENSG00000134853; -.
DR Orphanet; 585877; B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality.
DR Orphanet; 168940; Chronic eosinophilic leukemia.
DR Orphanet; 44890; Gastrointestinal stromal tumor.
DR Orphanet; 168947; Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement.
DR Orphanet; 314950; Primary hypereosinophilic syndrome.
DR PharmGKB; PA33147; -.
DR VEuPathDB; HostDB:ENSG00000134853; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000156021; -.
DR HOGENOM; CLU_000288_49_0_1; -.
DR InParanoid; P16234; -.
DR OMA; CFLTGPF; -.
DR OrthoDB; 236292at2759; -.
DR PhylomeDB; P16234; -.
DR TreeFam; TF325768; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P16234; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-186763; Downstream signal transduction.
DR Reactome; R-HSA-186797; Signaling by PDGF.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-9673767; Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants.
DR Reactome; R-HSA-9673770; Signaling by PDGFRA extracellular domain mutants.
DR Reactome; R-HSA-9674396; Imatinib-resistant PDGFR mutants.
DR Reactome; R-HSA-9674401; Sunitinib-resistant PDGFR mutants.
DR Reactome; R-HSA-9674403; Regorafenib-resistant PDGFR mutants.
DR Reactome; R-HSA-9674404; Sorafenib-resistant PDGFR mutants.
DR Reactome; R-HSA-9674428; PDGFR mutants bind TKIs.
DR SignaLink; P16234; -.
DR SIGNOR; P16234; -.
DR BioGRID-ORCS; 5156; 37 hits in 1100 CRISPR screens.
DR ChiTaRS; PDGFRA; human.
DR EvolutionaryTrace; P16234; -.
DR GeneWiki; PDGFRA; -.
DR GenomeRNAi; 5156; -.
DR Pharos; P16234; Tclin.
DR PRO; PR:P16234; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P16234; protein.
DR Bgee; ENSG00000134853; Expressed in tibia and 205 other tissues.
DR ExpressionAtlas; P16234; baseline and differential.
DR Genevisible; P16234; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0062063; F:BBSome binding; IEA:Ensembl.
DR GO; GO:0019838; F:growth factor binding; IBA:GO_Central.
DR GO; GO:0005018; F:platelet-derived growth factor alpha-receptor activity; IDA:UniProtKB.
DR GO; GO:0048407; F:platelet-derived growth factor binding; IDA:UniProtKB.
DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0038085; F:vascular endothelial growth factor binding; IPI:BHF-UCL.
DR GO; GO:0005021; F:vascular endothelial growth factor receptor activity; IDA:BHF-UCL.
DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
DR GO; GO:0055003; P:cardiac myofibril assembly; ISS:UniProtKB.
DR GO; GO:0001775; P:cell activation; TAS:BHF-UCL.
DR GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:MGI.
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:0048704; P:embryonic skeletal system morphogenesis; ISS:UniProtKB.
DR GO; GO:0008210; P:estrogen metabolic process; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0060325; P:face morphogenesis; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0033327; P:Leydig cell differentiation; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0001553; P:luteinization; ISS:UniProtKB.
DR GO; GO:0030539; P:male genitalia development; IEA:Ensembl.
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:Ensembl.
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:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0035790; P:platelet-derived growth factor receptor-alpha signaling pathway; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
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:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:UniProtKB.
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:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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 signaling; 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:0061298; P:retina vasculature development in camera-type eye; ISS:UniProtKB.
DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0050872; P:white fat cell differentiation; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
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_sf.
DR InterPro; IPR027290; PDGFRA.
DR InterPro; IPR000719; Prot_kinase_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; IPR001824; Tyr_kinase_rcpt_3_CS.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF500950; Alpha-PDGF_receptor; 1.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 4.
DR SUPFAM; SSF56112; SSF56112; 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 Cell projection; Chemotaxis; Developmental protein; Disease variant;
KW Disulfide bond; Glycoprotein; Golgi apparatus; Host-virus interaction;
KW Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Proto-oncogene; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..23
FT CHAIN 24..1089
FT /note="Platelet-derived growth factor receptor alpha"
FT /id="PRO_0000016760"
FT TOPO_DOM 24..528
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 529..549
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550..1089
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..113
FT /note="Ig-like C2-type 1"
FT DOMAIN 117..201
FT /note="Ig-like C2-type 2"
FT DOMAIN 202..306
FT /note="Ig-like C2-type 3"
FT DOMAIN 319..410
FT /note="Ig-like C2-type 4"
FT DOMAIN 414..517
FT /note="Ig-like C2-type 5"
FT DOMAIN 593..954
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1018..1089
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1029..1044
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1045..1060
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 818
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 599..607
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 627
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 578..579
FT /note="Breakpoint for interstitial deletion to form the
FT FIP1L1-PDGFRA fusion protein"
FT MOD_RES 572
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10734113"
FT MOD_RES 574
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10734113"
FT MOD_RES 720
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11095946,
FT ECO:0000269|PubMed:8943348"
FT MOD_RES 731
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:1646396"
FT MOD_RES 742
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:1646396"
FT MOD_RES 754
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17604334"
FT MOD_RES 762
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10733900"
FT MOD_RES 768
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8617789"
FT MOD_RES 849
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 988
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:7535778"
FT MOD_RES 1018
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:7535778"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 359
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 458
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 468
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 150..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 235..290
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 435..501
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 210..218
FT /note="ATSELDLEM -> GTCIISFLL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007833"
FT VAR_SEQ 219..1089
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007834"
FT VAR_SEQ 720..743
FT /note="YVILSFENNGDYMDMKQADTTQYV -> SGQGCLSSGTLQELSVDLQARGPC
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042015"
FT VAR_SEQ 744..1089
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042016"
FT VARIANT 79
FT /note="G -> D (in dbSNP:rs36035373)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042032"
FT VARIANT 426
FT /note="G -> D (in dbSNP:rs55865821)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042033"
FT VARIANT 478
FT /note="S -> P (in dbSNP:rs35597368)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17344846"
FT /id="VAR_034378"
FT VARIANT 481
FT /note="R -> G (in a hypereosinophilic syndrome sample; does
FT not lead to constitutive kinase activation)"
FT /evidence="ECO:0000269|PubMed:21224473"
FT /id="VAR_066460"
FT VARIANT 507
FT /note="L -> P (in a hypereosinophilic syndrome sample; does
FT not lead to constitutive kinase activation)"
FT /evidence="ECO:0000269|PubMed:21224473"
FT /id="VAR_066461"
FT VARIANT 555
FT /note="Y -> C (in GISTPS; increased platelet-derived growth
FT factor alpha-receptor activity; constitutively activated
FT kinase; dbSNP:rs121908589)"
FT /evidence="ECO:0000269|PubMed:17087943"
FT /id="VAR_083158"
FT VARIANT 561
FT /note="V -> D (in a GIST sample; constitutively activated
FT kinase; dbSNP:rs121908586)"
FT /evidence="ECO:0000269|PubMed:12522257,
FT ECO:0000269|PubMed:15928335"
FT /id="VAR_066462"
FT VARIANT 562
FT /note="I -> M (in a hypereosinophilic syndrome sample; does
FT not lead to constitutive kinase activation)"
FT /evidence="ECO:0000269|PubMed:21224473"
FT /id="VAR_066463"
FT VARIANT 570
FT /note="H -> R (in a hypereosinophilic syndrome sample; does
FT not lead to constitutive kinase activation)"
FT /evidence="ECO:0000269|PubMed:21224473"
FT /id="VAR_066464"
FT VARIANT 650
FT /note="H -> Q (in a hypereosinophilic syndrome sample;
FT constitutively activated kinase)"
FT /evidence="ECO:0000269|PubMed:21224473"
FT /id="VAR_066465"
FT VARIANT 653
FT /note="P -> L (in GISTPS; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:25975287"
FT /id="VAR_083159"
FT VARIANT 659
FT /note="N -> K (in GIST sample; constitutively activated
FT kinase; dbSNP:rs1057519700)"
FT /evidence="ECO:0000269|PubMed:15928335"
FT /id="VAR_066466"
FT VARIANT 659
FT /note="N -> S (in a hypereosinophilic syndrome sample;
FT constitutively activated kinase)"
FT /evidence="ECO:0000269|PubMed:21224473"
FT /id="VAR_066467"
FT VARIANT 705
FT /note="L -> P (in a hypereosinophilic syndrome sample; does
FT not lead to constitutive kinase activation)"
FT /evidence="ECO:0000269|PubMed:21224473"
FT /id="VAR_066468"
FT VARIANT 748
FT /note="R -> G (in a hypereosinophilic syndrome sample;
FT constitutively activated kinase)"
FT /evidence="ECO:0000269|PubMed:21224473"
FT /id="VAR_066469"
FT VARIANT 764
FT /note="R -> C (in dbSNP:rs34392012)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042034"
FT VARIANT 829
FT /note="G -> R (in a glioblastoma multiforme sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042035"
FT VARIANT 842..845
FT /note="Missing (in a GIST sample; constitutively activated
FT kinase)"
FT /evidence="ECO:0000269|PubMed:12522257,
FT ECO:0000269|PubMed:15928335"
FT /id="VAR_066470"
FT VARIANT 842
FT /note="D -> V (in a GIST sample; imatinib resistant,
FT constitutively activated kinase; dbSNP:rs121908585)"
FT /evidence="ECO:0000269|PubMed:12522257,
FT ECO:0000269|PubMed:15928335, ECO:0000269|PubMed:20972453"
FT /id="VAR_066471"
FT VARIANT 842
FT /note="D -> Y (in a GIST sample; imatinib sensitive,
FT constitutively activated kinase; dbSNP:rs121913265)"
FT /evidence="ECO:0000269|PubMed:15928335"
FT /id="VAR_066472"
FT VARIANT 845..848
FT /note="Missing (in a GIST sample; constitutively activated
FT kinase)"
FT /evidence="ECO:0000269|PubMed:12522257,
FT ECO:0000269|PubMed:15928335"
FT /id="VAR_066473"
FT VARIANT 846
FT /note="D -> Y (in GISTPS; unknown pathological
FT significance; dbSNP:rs121908588)"
FT /evidence="ECO:0000269|PubMed:14699510"
FT /id="VAR_083160"
FT VARIANT 849
FT /note="Y -> C (in GIST)"
FT /evidence="ECO:0000269|PubMed:15928335"
FT /id="VAR_066474"
FT VARIANT 849
FT /note="Y -> S (in a hypereosinophilic syndrome sample;
FT constitutively activated kinase)"
FT /evidence="ECO:0000269|PubMed:21224473"
FT /id="VAR_066475"
FT VARIANT 996
FT /note="E -> K (in a metastatic melanoma sample; somatic
FT mutation; dbSNP:rs779173667)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042036"
FT VARIANT 1071
FT /note="D -> N (in a lung neuroendocrine carcinoma sample;
FT somatic mutation; dbSNP:rs376544204)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042037"
FT MUTAGEN 572
FT /note="Y->F: Abolishes interaction with SRC-family members
FT and impairs internalization of the activated receptor; when
FT associated with F-574."
FT /evidence="ECO:0000269|PubMed:10734113,
FT ECO:0000269|PubMed:14644164"
FT MUTAGEN 574
FT /note="Y->F: Abolishes interaction with SRC-family members
FT and impairs internalization of the activated receptor; when
FT associated with F-572."
FT /evidence="ECO:0000269|PubMed:10734113,
FT ECO:0000269|PubMed:14644164"
FT MUTAGEN 720
FT /note="Y->F: Strongly reduced interaction with PTPN11 and
FT GRB2."
FT /evidence="ECO:0000269|PubMed:8943348"
FT MUTAGEN 731
FT /note="Y->F: No effect on autophosphorylation and
FT phosphorylation of PLCG1. Abolishes activation of
FT phosphatidylinositol 3-kinase."
FT /evidence="ECO:0000269|PubMed:1646396"
FT MUTAGEN 742
FT /note="Y->F: No effect on autophosphorylation and
FT phosphorylation of PLCG1. Abolishes activation of
FT phosphatidylinositol 3-kinase."
FT /evidence="ECO:0000269|PubMed:1646396"
FT MUTAGEN 762
FT /note="Y->F: Abolishes interaction with CRK."
FT /evidence="ECO:0000269|PubMed:10733900"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 46..53
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:7LBF"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:7LBF"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 107..111
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 114..120
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 133..141
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 159..167
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:7LBF"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 177..181
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 184..192
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 203..208
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 216..219
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 231..237
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:7LBF"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 258..264
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 270..279
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 286..292
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 301..306
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:7LBF"
FT STRAND 560..565
FT /evidence="ECO:0007829|PDB:6A32"
FT STRAND 567..570
FT /evidence="ECO:0007829|PDB:6A32"
FT STRAND 572..574
FT /evidence="ECO:0007829|PDB:6A32"
FT HELIX 577..579
FT /evidence="ECO:0007829|PDB:6A32"
FT HELIX 584..586
FT /evidence="ECO:0007829|PDB:6JOL"
FT HELIX 590..592
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 593..601
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 603..614
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 616..618
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 620..629
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 635..651
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 660..664
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 666..669
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 671..675
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 678..681
FT /evidence="ECO:0007829|PDB:6JOJ"
FT HELIX 682..688
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 690..696
FT /evidence="ECO:0007829|PDB:6A32"
FT HELIX 769..774
FT /evidence="ECO:0007829|PDB:6A32"
FT HELIX 778..781
FT /evidence="ECO:0007829|PDB:5K5X"
FT HELIX 792..811
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 821..823
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 824..827
FT /evidence="ECO:0007829|PDB:5GRN"
FT TURN 828..830
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 831..834
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 838..840
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 843..845
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 849..851
FT /evidence="ECO:0007829|PDB:5GRN"
FT STRAND 853..857
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 859..861
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 864..869
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 874..889
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 903..910
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 923..932
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 937..939
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 943..953
FT /evidence="ECO:0007829|PDB:5GRN"
FT HELIX 956..971
FT /evidence="ECO:0007829|PDB:6A32"
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
