FGFR1_HUMAN
ID FGFR1_HUMAN Reviewed; 822 AA.
AC P11362; A8K6T9; A8K8V5; C1KBH8; P17049; Q02063; Q02065; Q14306; Q14307;
AC Q53H63; Q59H40; Q5BJG2; Q8N685; Q9UD50; Q9UDF0; Q9UDF1; Q9UDF2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 3.
DT 03-AUG-2022, entry version 270.
DE RecName: Full=Fibroblast growth factor receptor 1;
DE Short=FGFR-1;
DE EC=2.7.10.1 {ECO:0000269|PubMed:1379697, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:19665973, ECO:0000269|PubMed:20133753, ECO:0000269|PubMed:8622701};
DE AltName: Full=Basic fibroblast growth factor receptor 1;
DE Short=BFGFR;
DE Short=bFGF-R-1;
DE AltName: Full=Fms-like tyrosine kinase 2;
DE Short=FLT-2;
DE AltName: Full=N-sam;
DE AltName: Full=Proto-oncogene c-Fgr;
DE AltName: CD_antigen=CD331;
DE Flags: Precursor;
GN Name=FGFR1; Synonyms=BFGFR, CEK, FGFBR, FLG, FLT2, HBGFR;
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 15).
RC TISSUE=Placenta;
RX PubMed=2162671; DOI=10.1016/0006-291x(90)90384-y;
RA Itoh N., Terachi T., Ohta M., Seo M.K.;
RT "The complete amino acid sequence of the shorter form of human basic
RT fibroblast growth factor receptor deduced from its cDNA.";
RL Biochem. Biophys. Res. Commun. 169:680-685(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH FGF1 AND FGF2.
RC TISSUE=Neonatal brain stem;
RX PubMed=1697263; DOI=10.1002/j.1460-2075.1990.tb07454.x;
RA Dionne C.A., Crumley G.R., Bellot F., Kaplow J.M., Searfoss G., Ruta M.,
RA Burgess W.H., Jaye M., Schlessinger J.;
RT "Cloning and expression of two distinct high-affinity receptors cross-
RT reacting with acidic and basic fibroblast growth factors.";
RL EMBO J. 9:2685-2692(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 6; 15; 17 AND 18).
RX PubMed=2167437; DOI=10.1128/mcb.10.9.4728-4736.1990;
RA Johnson D.E., Lee P.L., Lu J., Williams L.T.;
RT "Diverse forms of a receptor for acidic and basic fibroblast growth
RT factors.";
RL Mol. Cell. Biol. 10:4728-4736(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=2159626; DOI=10.1093/nar/18.7.1906;
RA Isacchi A., Bergonzoni L., Sarmientos P.;
RT "Complete sequence of a human receptor for acidic and basic fibroblast
RT growth factors.";
RL Nucleic Acids Res. 18:1906-1906(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 14), AND INTERACTION WITH FGF1 AND
RP FGF2.
RC TISSUE=Teratocarcinoma;
RX PubMed=1722683; DOI=10.3109/08977199109104816;
RA Wennstroem S., Sandstroem C., Claesson-Welsh L.;
RT "cDNA cloning and expression of a human FGF receptor which binds acidic and
RT basic FGF.";
RL Growth Factors 4:197-208(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 14).
RX PubMed=1662973; DOI=10.3109/08977199109000276;
RA Kiefer M.C., Baird A., George-Nascimento C., Nguyen T., Mason O.B.,
RA Boley L.J., Valenzuela P., Barr P.J.;
RT "Molecular cloning of a human basic fibroblast growth factor receptor cDNA
RT and expression of a biologically active extracellular domain in a
RT baculovirus system.";
RL Growth Factors 5:115-127(1991).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 6; 14; 15 AND 16).
RC TISSUE=Lung;
RX PubMed=1650441;
RA Eisemann A., Ahn J.A., Graziani G., Tronick S.R., Ron D.;
RT "Alternative splicing generates at least five different isoforms of the
RT human basic-FGF receptor.";
RL Oncogene 6:1195-1202(1991).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12
RP AND 13).
RC TISSUE=Liver;
RX PubMed=1846977; DOI=10.1126/science.1846977;
RA Hou J., Kan M., McKeehan K., McBride G., Adams P., McKeehan W.L.;
RT "Fibroblast growth factor receptors from liver vary in three structural
RT domains.";
RL Science 251:665-668(1991).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1317750;
RA Hattori Y., Odagiri H., Katoh O., Sakamoto H., Morita T., Shimotohno K.,
RA Tobinai K., Sugimura T., Terada M.;
RT "K-sam-related gene, N-sam, encodes fibroblast growth factor receptor and
RT is expressed in T-lymphocytic tumors.";
RL Cancer Res. 52:3367-3371(1992).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 19), AND ROLE IN DISEASE.
RX PubMed=20139426; DOI=10.1093/humrep/deq006;
RA Miura K., Miura S., Yoshiura K., Seminara S., Hamaguchi D., Niikawa N.,
RA Masuzaki H.;
RT "A case of Kallmann syndrome carrying a missense mutation in alternatively
RT spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast
RT growth factor receptor 1.";
RL Hum. Reprod. 25:1076-1080(2010).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 6; 14 AND 21).
RC TISSUE=Placenta, and Testis;
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 [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 14 AND 20).
RC TISSUE=Brain, and Colon;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-22; ARG-818 AND
RP CYS-822.
RG NIEHS SNPs program;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [15]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4; 14 AND 15), AND VARIANT
RP GLY-213.
RC TISSUE=Pancreas, Testis, and Uterus;
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 [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-370 (ISOFORM 15), AND PROTEIN SEQUENCE OF
RP 22-129 (ISOFORM 15).
RX PubMed=7520751; DOI=10.1021/bi00200a003;
RA Pantoliano M.W., Horlick R.A., Springer B.A., Van Dyk D.E., Tobery T.,
RA Wetmore D.R., Lear J.D., Nahapetian A.T., Bradley J.D., Sisk W.P.;
RT "Multivalent ligand-receptor binding interactions in the fibroblast growth
RT factor system produce a cooperative growth factor and heparin mechanism for
RT receptor dimerization.";
RL Biochemistry 33:10229-10248(1994).
RN [17]
RP PROTEIN SEQUENCE OF 81-100 (ISOFORMS 1/2/4/5/14/16).
RX PubMed=8074689; DOI=10.1006/bbrc.1994.2203;
RA Rusnati M., Coltrini D., Caccia P., Dell'Era P., Zoppetti G., Oreste P.,
RA Valsasina B., Presta M.;
RT "Distinct role of 2-O-, N-, and 6-O-sulfate groups of heparin in the
RT formation of the ternary complex with basic fibroblast growth factor and
RT soluble FGF receptor-1.";
RL Biochem. Biophys. Res. Commun. 203:450-458(1994).
RN [18]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 201-822 (ISOFORMS 1/6/10/14/15).
RA Ruta M., Howk R., Ricca G., Drohan W., Zabelshansky M., Laureys G.,
RA Barton D.E., Francke U., Schlessinger J., Givol D.;
RT "A novel protein tyrosine kinase gene whose expression is modulated during
RT endothelial cell differentiation.";
RL Oncogene 3:9-15(1988).
RN [19]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 313-391 (ISOFORMS 17/18), NUCLEOTIDE
RP SEQUENCE [GENOMIC DNA] OF 313-360 (ISOFORMS
RP 1/2/4/5/6/7/8/9/10/11/12/13/14/15), NUCLEOTIDE SEQUENCE [GENOMIC DNA /
RP MRNA] OF 313-360 (ISOFORM 19), AND TISSUE SPECIFICITY.
RC TISSUE=Foreskin fibroblast, and Umbilical vein;
RX PubMed=1652059; DOI=10.1128/mcb.11.9.4627-4634.1991;
RA Johnson D.E., Lu J., Chen H., Werner S., Williams L.T.;
RT "The human fibroblast growth factor receptor genes: a common structural
RT arrangement underlies the mechanisms for generating receptor forms that
RT differ in their third immunoglobulin domain.";
RL Mol. Cell. Biol. 11:4627-4634(1991).
RN [20]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1847500; DOI=10.1128/mcb.11.3.1500-1507.1991;
RA Gutkind S.J., Link D.C., Katamine S., Lacal P., Miki T., Ley T.J.,
RA Robbins K.C.;
RT "A novel c-fgr exon utilized in Epstein-Barr virus-infected B lymphocytes
RT but not in normal monocytes.";
RL Mol. Cell. Biol. 11:1500-1507(1991).
RN [21]
RP INTERACTION WITH PLCG1.
RX PubMed=1656221; DOI=10.1128/mcb.11.10.5068-5078.1991;
RA Mohammadi M., Honegger A.M., Rotin D., Fischer R., Bellot F., Li W.,
RA Dionne C.A., Jaye M., Rubinstein M., Schlessinger J.;
RT "A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast
RT growth factor receptor (Flg) is a binding site for the SH2 domain of
RT phospholipase C-gamma 1.";
RL Mol. Cell. Biol. 11:5068-5078(1991).
RN [22]
RP MUTAGENESIS OF TYR-766, FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION,
RP AND INTERACTION WITH PLCG1.
RX PubMed=1379697; DOI=10.1038/358678a0;
RA Peters K.G., Marie J., Wilson E., Ives H.E., Escobedo J., del Rosario M.,
RA Mirda D., Williams L.T.;
RT "Point mutation of an FGF receptor abolishes phosphatidylinositol turnover
RT and Ca2+ flux but not mitogenesis.";
RL Nature 358:678-681(1992).
RN [23]
RP MUTAGENESIS OF TYR-766, AND FUNCTION IN CELL PROLIFERATION.
RX PubMed=1379698; DOI=10.1038/358681a0;
RA Mohammadi M., Dionne C.A., Li W., Lin N., Spivak T., Honegger A.M.,
RA Jaye M., Schlessinger J.;
RT "Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis
RT without affecting mitogenesis.";
RL Nature 358:681-684(1992).
RN [24]
RP MUTAGENESIS OF TYR-766, AND SUBCELLULAR LOCATION.
RX PubMed=7516330; DOI=10.1016/s0021-9258(17)32519-x;
RA Sorokin A., Mohammadi M., Huang J., Schlessinger J.;
RT "Internalization of fibroblast growth factor receptor is inhibited by a
RT point mutation at tyrosine 766.";
RL J. Biol. Chem. 269:17056-17061(1994).
RN [25]
RP PHOSPHORYLATION AT TYR-463; TYR-583; TYR-585; TYR-653; TYR-654 AND TYR-730,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, FUNCTION IN PHOSPHORYLATION OF
RP PLCG1 AND SHC1; ACTIVATION OF MAP KINASES AND REGULATION OF CELL
RP PROLIFERATION AND DIFFERENTIATION, AND MUTAGENESIS OF TYR-653 AND TYR-654.
RX PubMed=8622701; DOI=10.1128/mcb.16.3.977;
RA Mohammadi M., Dikic I., Sorokin A., Burgess W.H., Jaye M., Schlessinger J.;
RT "Identification of six novel autophosphorylation sites on fibroblast growth
RT factor receptor 1 and elucidation of their importance in receptor
RT activation and signal transduction.";
RL Mol. Cell. Biol. 16:977-989(1996).
RN [26]
RP INTERACTION WITH FGF1; FGF2; FGF4; FGF5; FGF6, AND FUNCTION IN CELL
RP PROLIFERATION.
RX PubMed=8663044; DOI=10.1074/jbc.271.25.15292;
RA Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A., Coulier F.,
RA Gao G., Goldfarb M.;
RT "Receptor specificity of the fibroblast growth factor family.";
RL J. Biol. Chem. 271:15292-15297(1996).
RN [27]
RP CHROMOSOMAL TRANSLOCATION WITH ZMYM2.
RX PubMed=9716603;
RA Reiter A., Sohal J., Kulkarni S., Chase A., Macdonald D.H.C.,
RA Aguiar R.C.T., Goncalves C., Hernandez J.M., Jennings B.A., Goldman J.M.,
RA Cross N.C.P.;
RT "Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in
RT the t(8;13)(p11;q12) myeloproliferative syndrome.";
RL Blood 92:1735-1742(1998).
RN [28]
RP INTERACTION WITH FGF1, AND PHOSPHORYLATION.
RX PubMed=9655399; DOI=10.1038/31741;
RA DiGabriele A.D., Lax I., Chen D.I., Svahn C.M., Jaye M., Schlessinger J.,
RA Hendrickson W.A.;
RT "Structure of a heparin-linked biologically active dimer of fibroblast
RT growth factor.";
RL Nature 393:812-817(1998).
RN [29]
RP CHROMOSOMAL TRANSLOCATION WITH CEP43.
RX PubMed=9949182;
RA Popovici C., Zhang B., Gregoire M.-J., Jonveaux P., Lafage-Pochitaloff M.,
RA Birnbaum D., Pebusque M.-J.;
RT "The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative
RT disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1.";
RL Blood 93:1381-1389(1999).
RN [30]
RP INTERACTION WITH GRB10.
RX PubMed=10454568; DOI=10.1128/mcb.19.9.6217;
RA Wang J., Dai H., Yousaf N., Moussaif M., Deng Y., Boufelliga A.,
RA Swamy O.R., Leone M.E., Riedel H.;
RT "Grb10, a positive, stimulatory signaling adapter in platelet-derived
RT growth factor BB-, insulin-like growth factor I-, and insulin-mediated
RT mitogenesis.";
RL Mol. Cell. Biol. 19:6217-6228(1999).
RN [31]
RP INVOLVEMENT IN JWS, AND VARIANT JWS ARG-252.
RX PubMed=10861678;
RX DOI=10.1002/1096-8628(20000703)93:1<22::aid-ajmg5>3.0.co;2-u;
RA Roscioli T., Flanagan S., Kumar P., Masel J., Gattas M., Hyland V.J.,
RA Glass I.A.;
RT "Clinical findings in a patient with FGFR1 P252R mutation and comparison
RT with the literature.";
RL Am. J. Med. Genet. 93:22-28(2000).
RN [32]
RP CHROMOSOMAL TRANSLOCATION WITH CNTRL.
RX PubMed=10688839;
RA Guasch G., Mack G.J., Popovici C., Dastugue N., Birnbaum D., Rattner J.B.,
RA Pebusque M.-J.;
RT "FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12
RT stem cell myeloproliferative disorder with t(8;9)(p12;q33).";
RL Blood 95:1788-1796(2000).
RN [33]
RP FUNCTION IN PHOSPHORYLATION OF FRS2 AND GAB1 AND IN ACTIVATION OF PIK3R1.
RX PubMed=11353842; DOI=10.1073/pnas.111114298;
RA Ong S.H., Hadari Y.R., Gotoh N., Guy G.R., Schlessinger J., Lax I.;
RT "Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor
RT receptors is mediated by coordinated recruitment of multiple docking
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:6074-6079(2001).
RN [34]
RP FUNCTION IN ACTIVATION OF SIGNALING VIA RAS AND MAP KINASES AND CELL
RP PROLIFERATION, FUNCTION IN PHOSPHORYLATION OF FRS2; SHB AND PTPN11/SHP2,
RP INTERACTION WITH SHB AND FGF2, AND MUTAGENESIS OF TYR-766.
RX PubMed=12181353; DOI=10.1091/mbc.e02-02-0103;
RA Cross M.J., Lu L., Magnusson P., Nyqvist D., Holmqvist K., Welsh M.,
RA Claesson-Welsh L.;
RT "The Shb adaptor protein binds to tyrosine 766 in the FGFR-1 and regulates
RT the Ras/MEK/MAPK pathway via FRS2 phosphorylation in endothelial cells.";
RL Mol. Biol. Cell 13:2881-2893(2002).
RN [35]
RP CHROMOSOMAL TRANSLOCATION WITH FGFR1OP2.
RX PubMed=15034873; DOI=10.1002/gcc.20023;
RA Grand E.K., Grand F.H., Chase A.J., Ross F.M., Corcoran M.M., Oscier D.G.,
RA Cross N.C.P.;
RT "Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11
RT myeloproliferative syndrome.";
RL Genes Chromosomes Cancer 40:78-83(2004).
RN [36]
RP FUNCTION IN ACTIVATION OF RPS6KA1 AND CREB1, CATALYTIC ACTIVITY,
RP INTERACTION WITH RPS6KA1, MUTAGENESIS OF LYS-514, AND SUBCELLULAR LOCATION.
RX PubMed=15117958; DOI=10.1074/jbc.m311144200;
RA Hu Y., Fang X., Dunham S.M., Prada C., Stachowiak E.K., Stachowiak M.K.;
RT "90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast
RT growth factor receptor 1 (FGFR1): role in FGFR1 signaling.";
RL J. Biol. Chem. 279:29325-29335(2004).
RN [37]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-296.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [38]
RP CHROMOSOMAL TRANSLOCATION WITH FGFR1OP2.
RX PubMed=16946300; DOI=10.1182/blood-2006-06-026666;
RA Gu T.-L., Goss V.L., Reeves C., Popova L., Nardone J., Macneill J.,
RA Walters D.K., Wang Y., Rush J., Comb M.J., Druker B.J., Polakiewicz R.D.;
RT "Phosphotyrosine profiling identifies the KG-1 cell line as a model for the
RT study of FGFR1 fusions in acute myeloid leukemia.";
RL Blood 108:4202-4204(2006).
RN [39]
RP INTERACTION WITH FGF1; FGF8; FGF10; FGF19; FGF21; FGF22 AND FGF23, AND
RP FUNCTION IN STIMULATION OF CELL PROLIFERATION.
RX PubMed=16597617; DOI=10.1074/jbc.m601252200;
RA Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M.;
RT "Receptor specificity of the fibroblast growth factor family. The complete
RT mammalian FGF family.";
RL J. Biol. Chem. 281:15694-15700(2006).
RN [40]
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=16481405; DOI=10.1091/mbc.e05-08-0749;
RA Dunham-Ems S.M., Pudavar H.E., Myers J.M., Maher P.A., Prasad P.N.,
RA Stachowiak M.K.;
RT "Factors controlling fibroblast growth factor receptor-1's cytoplasmic
RT trafficking and its regulation as revealed by FRAP analysis.";
RL Mol. Biol. Cell 17:2223-2235(2006).
RN [41]
RP PHOSPHORYLATION AT TYR-463; TYR-653; TYR-654; TYR-583 AND TYR-585, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16507368; DOI=10.1016/j.molcel.2006.01.022;
RA Furdui C.M., Lew E.D., Schlessinger J., Anderson K.S.;
RT "Autophosphorylation of FGFR1 kinase is mediated by a sequential and
RT precisely ordered reaction.";
RL Mol. Cell 21:711-717(2006).
RN [42]
RP CHROMOSOMAL TRANSLOCATION WITH FGFR1OP2.
RX PubMed=17389761; DOI=10.1182/blood-2006-12-065615;
RA Dong S., Kang S., Gu T., Kardar S., Fu H., Lonial S., Khoury H.J.,
RA Khuri F., Chen J.;
RT "14-3-3 integrates pro-survival signals mediated by the AKT and MAPK
RT pathways in ZNF198-FGFR1 transformed hematopoietic cells.";
RL Blood 110:360-369(2007).
RN [43]
RP INTERACTION WITH FGF19; FGF21 AND KLB, AND FUNCTION IN REGULATION OF
RP GLUCOSE UPTAKE IN ADIPOCYTES.
RX PubMed=17623664; DOI=10.1074/jbc.m704165200;
RA Kurosu H., Choi M., Ogawa Y., Dickson A.S., Goetz R., Eliseenkova A.V.,
RA Mohammadi M., Rosenblatt K.P., Kliewer S.A., Kuro-o M.;
RT "Tissue-specific expression of betaKlotho and fibroblast growth factor
RT (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21.";
RL J. Biol. Chem. 282:26687-26695(2007).
RN [44]
RP FUNCTION IN STAT1 PHOSPHORYLATION, GLYCOSYLATION, AND PHOSPHORYLATION.
RX PubMed=17311277; DOI=10.1002/jcp.21014;
RA Citores L., Bai L., Sorensen V., Olsnes S.;
RT "Fibroblast growth factor receptor-induced phosphorylation of STAT1 at the
RT Golgi apparatus without translocation to the nucleus.";
RL J. Cell. Physiol. 212:148-156(2007).
RN [45]
RP BINDING TO FGF1, AND IDENTIFICATION IN A COMPLEX WITH INTEGRIN AND FGF1.
RX PubMed=18441324; DOI=10.1074/jbc.m801213200;
RA Mori S., Wu C.Y., Yamaji S., Saegusa J., Shi B., Ma Z., Kuwabara Y.,
RA Lam K.S., Isseroff R.R., Takada Y.K., Takada Y.;
RT "Direct binding of integrin alphavbeta3 to FGF1 plays a role in FGF1
RT signaling.";
RL J. Biol. Chem. 283:18066-18075(2008).
RN [46]
RP UBIQUITINATION, CATALYTIC ACTIVITY, FUNCTION AS FGF1 RECEPTOR AND IN
RP ACTIVATION OF PLCG1; FRS2; MAPK1/ERK2 AND MAPK3/ERK1, ACTIVITY REGULATION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=18480409; DOI=10.1091/mbc.e07-12-1219;
RA Haugsten E.M., Malecki J., Bjorklund S.M., Olsnes S., Wesche J.;
RT "Ubiquitination of fibroblast growth factor receptor 1 is required for its
RT intracellular sorting but not for its endocytosis.";
RL Mol. Biol. Cell 19:3390-3403(2008).
RN [47]
RP INTERACTION WITH ANOS1.
RX PubMed=19696444; DOI=10.1074/jbc.m109.049155;
RA Hu Y., Guimond S.E., Travers P., Cadman S., Hohenester E., Turnbull J.E.,
RA Kim S.H., Bouloux P.M.;
RT "Novel mechanisms of fibroblast growth factor receptor 1 regulation by
RT extracellular matrix protein anosmin-1.";
RL J. Biol. Chem. 284:29905-29920(2009).
RN [48]
RP FUNCTION IN CHROMATIN BINDING AND TRANSCRIPTION REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19261810; DOI=10.1091/mbc.e08-06-0600;
RA Dunham-Ems S.M., Lee Y.W., Stachowiak E.K., Pudavar H., Claus P.,
RA Prasad P.N., Stachowiak M.K.;
RT "Fibroblast growth factor receptor-1 (FGFR1) nuclear dynamics reveal a
RT novel mechanism in transcription control.";
RL Mol. Biol. Cell 20:2401-2412(2009).
RN [49]
RP FUNCTION AS PROTO-ONCOGENE, ACTIVE SITE, MUTAGENESIS OF ASP-623, CATALYTIC
RP ACTIVITY, PHOSPHORYLATION AT TYR-463; TYR-653; TYR-654; TYR-583; TYR-585
RP AND TYR-730, CHARACTERIZATION OF VARIANT ECCL LYS-546, IDENTIFICATION BY
RP MASS SPECTROMETRY, AND ACTIVITY REGULATION.
RX PubMed=19224897; DOI=10.1126/scisignal.2000021;
RA Lew E.D., Furdui C.M., Anderson K.S., Schlessinger J.;
RT "The precise sequence of FGF receptor autophosphorylation is kinetically
RT driven and is disrupted by oncogenic mutations.";
RL Sci. Signal. 2:RA6-RA6(2009).
RN [50]
RP BINDING TO FGF1, AND IDENTIFICATION IN A COMPLEX WITH INTEGRIN AND FGF1.
RX PubMed=20422052; DOI=10.1371/journal.pone.0010273;
RA Yamaji S., Saegusa J., Ieguchi K., Fujita M., Mori S., Takada Y.K.,
RA Takada Y.;
RT "A novel fibroblast growth factor-1 (FGF1) mutant that acts as an FGF
RT antagonist.";
RL PLoS ONE 5:E10273-E10273(2010).
RN [51]
RP INTERACTION WITH FGF23 AND KLB.
RX PubMed=19966287; DOI=10.1073/pnas.0902006107;
RA Goetz R., Nakada Y., Hu M.C., Kurosu H., Wang L., Nakatani T., Shi M.,
RA Eliseenkova A.V., Razzaque M.S., Moe O.W., Kuro-o M., Mohammadi M.;
RT "Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by
RT inhibiting FGF23-FGFR-Klotho complex formation.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:407-412(2010).
RN [52]
RP FUNCTION IN ACTIVATION OF AKT1; PLCG1; MAPK1/ERK2, MAPK3/ERK1 AND MAP
RP KINASE SIGNALING, FUNCTION IN REGULATION OF NEURONAL DIFFERENTIATION AND
RP EMBRYONIC DEVELOPMENT, SUBCELLULAR LOCATION, INTERACTION WITH NEDD4; PLCG1
RP AND FRS2, UBIQUITINATION, AND DEGRADATION.
RX PubMed=21765395; DOI=10.1038/emboj.2011.234;
RA Persaud A., Alberts P., Hayes M., Guettler S., Clarke I., Sicheri F.,
RA Dirks P., Ciruna B., Rotin D.;
RT "Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis
RT and function.";
RL EMBO J. 30:3259-3273(2011).
RN [53]
RP REVIEW ON ALTERNATIVE SPLICE FORMS; LIGANDS; SIGNALING PATHWAYS AND
RP SUBCELLULAR LOCATION.
RX PubMed=12141425;
RA Groth C., Lardelli M.;
RT "The structure and function of vertebrate fibroblast growth factor receptor
RT 1.";
RL Int. J. Dev. Biol. 46:393-400(2002).
RN [54]
RP REVIEW ON FUNCTION; ROLE IN DISEASE; SIGNALING PATHWAYS; SUBUNIT; DOMAIN
RP STRUCTURE; LIGAND SELECTIVITY AND ACTIVITY REGULATION.
RX PubMed=15863030; DOI=10.1016/j.cytogfr.2005.01.001;
RA Eswarakumar V.P., Lax I., Schlessinger J.;
RT "Cellular signaling by fibroblast growth factor receptors.";
RL Cytokine Growth Factor Rev. 16:139-149(2005).
RN [55]
RP REVIEW ON FUNCTION IN FGF SIGNALING.
RX PubMed=20094046; DOI=10.1038/nrc2780;
RA Turner N., Grose R.;
RT "Fibroblast growth factor signalling: from development to cancer.";
RL Nat. Rev. Cancer 10:116-129(2010).
RN [56]
RP REVIEW ON SIGNALING AND ROLE IN KALLMAN SYNDROME.
RX PubMed=20117945; DOI=10.1016/j.tem.2010.01.004;
RA Hu Y., Bouloux P.M.;
RT "Novel insights in FGFR1 regulation: lessons from Kallmann syndrome.";
RL Trends Endocrinol. Metab. 21:385-393(2010).
RN [57]
RP INVOLVEMENT IN ECCL, VARIANTS ECCL LYS-546 AND GLU-656, AND VARIANT
RP MET-561.
RX PubMed=26942290; DOI=10.1016/j.ajhg.2016.02.006;
RG University of Washington Center for Mendelian Genomics;
RG Care4Rare Canada Consortium;
RA Bennett J.T., Tan T.Y., Alcantara D., Tetrault M., Timms A.E., Jensen D.,
RA Collins S., Nowaczyk M.J., Lindhurst M.J., Christensen K.M., Braddock S.R.,
RA Brandling-Bennett H., Hennekam R.C., Chung B., Lehman A., Su J., Ng S.,
RA Amor D.J., Majewski J., Biesecker L.G., Boycott K.M., Dobyns W.B.,
RA O'Driscoll M., Moog U., McDonell L.M.;
RT "Mosaic activating mutations in FGFR1 cause encephalocraniocutaneous
RT lipomatosis.";
RL Am. J. Hum. Genet. 98:579-587(2016).
RN [58]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 464-762.
RX PubMed=8752212; DOI=10.1016/s0092-8674(00)80131-2;
RA Mohammadi M., Schlessinger J., Hubbard S.R.;
RT "Structure of the FGF receptor tyrosine kinase domain reveals a novel
RT autoinhibitory mechanism.";
RL Cell 86:577-587(1996).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 464-762 IN COMPLEX WITH SU4984.
RX PubMed=9139660; DOI=10.1126/science.276.5314.955;
RA Mohammadi M., McMahon G., Sun L., Tang C., Hirth P., Yeh B.K.,
RA Hubbard S.R., Schlessinger J.;
RT "Structures of the tyrosine kinase domain of fibroblast growth factor
RT receptor in complex with inhibitors.";
RL Science 276:955-960(1997).
RN [60]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 141-365 IN COMPLEX WITH FGF1,
RP FUNCTION, AND DISULFIDE BONDS.
RX PubMed=10830168; DOI=10.1016/s0092-8674(00)80851-x;
RA Plotnikov A.N., Hubbard S.R., Schlessinger J., Mohammadi M.;
RT "Crystal structures of two FGF-FGFR complexes reveal the determinants of
RT ligand-receptor specificity.";
RL Cell 101:413-424(2000).
RN [61]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 143-364 IN COMPLEX WITH FGF2 AND
RP HEPARIN, AND DISULFIDE BONDS.
RX PubMed=11030354; DOI=10.1016/s1097-2765(00)00073-3;
RA Schlessinger J., Plotnikov A.N., Ibrahimi O.A., Eliseenkova A.V., Yeh B.K.,
RA Yayon A., Linhardt R.J., Mohammadi M.;
RT "Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual
RT role for heparin in FGFR binding and dimerization.";
RL Mol. Cell 6:743-750(2000).
RN [62]
RP STRUCTURE BY NMR OF 38-124.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first Ig-like domain of human fibroblast growth
RT factor receptor 1.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [63]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 458-774 IN COMPLEX WITH PLCG1 AND
RP ATP ANALOG, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AUTOPHOSPHORYLATION, AND
RP PHOSPHORYLATION AT TYR-653; TYR-654 AND TYR-766.
RX PubMed=19665973; DOI=10.1016/j.cell.2009.05.028;
RA Bae J.H., Lew E.D., Yuzawa S., Tome F., Lax I., Schlessinger J.;
RT "The selectivity of receptor tyrosine kinase signaling is controlled by a
RT secondary SH2 domain binding site.";
RL Cell 138:514-524(2009).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 458-765 OF MUTANT GLU-577,
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF ARG-577.
RX PubMed=20133753; DOI=10.1073/pnas.0914157107;
RA Bae J.H., Boggon T.J., Tome F., Mandiyan V., Lax I., Schlessinger J.;
RT "Asymmetric receptor contact is required for tyrosine autophosphorylation
RT of fibroblast growth factor receptor in living cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2866-2871(2010).
RN [65]
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 461-765 IN COMPLEX WITH ARQ 069,
RP AND ACTIVITY REGULATION.
RX PubMed=21454610; DOI=10.1074/jbc.m110.213736;
RA Eathiraj S., Palma R., Hirschi M., Volckova E., Nakuci E., Castro J.,
RA Chen C.R., Chan T.C., France D.S., Ashwell M.A.;
RT "A novel mode of protein kinase inhibition exploiting hydrophobic motifs of
RT autoinhibited kinases: discovery of ATP-independent inhibitors of
RT fibroblast growth factor receptor.";
RL J. Biol. Chem. 286:20677-20687(2011).
RN [66]
RP VARIANT PS ARG-252.
RX PubMed=7874169; DOI=10.1038/ng1194-269;
RA Muenke M., Schell U., Hehr A., Robin N.H., Losken H.W., Schinzel A.,
RA Pulleyn L.J., Rutland P., Reardon W., Malcolm S., Winter R.M.;
RT "A common mutation in the fibroblast growth factor receptor 1 gene in
RT Pfeiffer syndrome.";
RL Nat. Genet. 8:269-274(1994).
RN [67]
RP VARIANT TRIGNO1 THR-300.
RX PubMed=11173846; DOI=10.1159/000056834;
RA Kress W., Petersen B., Collmann H., Grimm T.;
RT "An unusual FGFR1 mutation (fibroblast growth factor receptor 1 mutation)
RT in a girl with non-syndromic trigonocephaly.";
RL Cytogenet. Cell Genet. 91:138-140(2000).
RN [68]
RP VARIANTS HH2 ASP-97; CYS-99; SER-167; TYR-277; MET-607; 622-ARG--ARG-822
RP DEL; ARG-666 AND ARG-719, AND VARIANT SER-772.
RX PubMed=12627230; DOI=10.1038/ng1122;
RA Dode C., Levilliers J., Dupont J.-M., De Paepe A., Le Du N.,
RA Soussi-Yanicostas N., Coimbra R.S., Delmaghani S., Compain-Nouaille S.,
RA Baverel F., Pecheux C., Le Tessier D., Cruaud C., Delpech M., Speleman F.,
RA Vermeulen S., Amalfitano A., Bachelot Y., Bouchard P., Cabrol S.,
RA Carel J.-C., Delemarre-van de Waal H., Goulet-Salmon B., Kottler M.-L.,
RA Richard O., Sanchez-Franco F., Saura R., Young J., Petit C.,
RA Hardelin J.-P.;
RT "Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann
RT syndrome.";
RL Nat. Genet. 33:463-465(2003).
RN [69]
RP VARIANT HH2 SER-745.
RX PubMed=15001591; DOI=10.1210/jc.2003-030476;
RA Sato N., Katsumata N., Kagami M., Hasegawa T., Hori N., Kawakita S.,
RA Minowada S., Shimotsuka A., Shishiba Y., Yokozawa M., Yasuda T.,
RA Nagasaki K., Hasegawa D., Hasegawa Y., Tachibana K., Naiki Y., Horikawa R.,
RA Tanaka T., Ogata T.;
RT "Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1)
RT and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families
RT and 18 sporadic patients.";
RL J. Clin. Endocrinol. Metab. 89:1079-1088(2004).
RN [70]
RP VARIANTS OGD ILE-330; CYS-374 AND ARG-381, AND CHARACTERIZATION OF VARIANT
RP OGD CYS-374.
RX PubMed=15625620; DOI=10.1086/427956;
RA White K.E., Cabral J.M., Davis S.I., Fishburn T., Evans W.E., Ichikawa S.,
RA Fields J., Yu X., Shaw N.J., McLellan N.J., McKeown C., FitzPatrick D.,
RA Yu K., Ornitz D.M., Econs M.J.;
RT "Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1
RT in bone elongation.";
RL Am. J. Hum. Genet. 76:361-367(2005).
RN [71]
RP VARIANTS HH2 ILE-102; ALA-129; MET-273 AND THR-520.
RX PubMed=15605412; DOI=10.1002/humu.9298;
RA Albuisson J., Pecheux C., Carel J.-C., Lacombe D., Leheup B., Lapuzina P.,
RA Bouchard P., Legius E., Matthijs G., Wasniewska M., Delpech M., Young J.,
RA Hardelin J.-P., Dode C.;
RT "Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2).";
RL Hum. Mutat. 25:98-99(2005).
RN [72]
RP VARIANTS HH2 ARG-687 AND SER-745.
RX PubMed=15845591; DOI=10.1093/humrep/dei052;
RA Sato N., Hasegawa T., Hori N., Fukami M., Yoshimura Y., Ogata T.;
RT "Gonadotrophin therapy in Kallmann syndrome caused by heterozygous
RT mutations of the gene for fibroblast growth factor receptor 1: report of
RT three families: case report.";
RL Hum. Reprod. 20:2173-2178(2005).
RN [73]
RP VARIANTS OGD ILE-330 AND ARG-381.
RX PubMed=16470795; DOI=10.1002/ajmg.a.31106;
RA Farrow E.G., Davis S.I., Mooney S.D., Beighton P., Mascarenhas L.,
RA Gutierrez Y.R., Pitukcheewanont P., White K.E.;
RT "Extended mutational analyses of FGFR1 in osteoglophonic dysplasia.";
RL Am. J. Med. Genet. A 140:537-539(2006).
RN [74]
RP VARIANTS HH2 SER-48; PRO-245; TRP-250; VAL-343; LEU-366; SER-722 AND
RP ILE-795.
RX PubMed=16882753; DOI=10.1210/jc.2005-2793;
RA Trarbach E.B., Costa E.M.F., Versiani B., de Castro M., Baptista M.T.M.,
RA Garmes H.M., de Mendonca B.B., Latronico A.C.;
RT "Novel fibroblast growth factor receptor 1 mutations in patients with
RT congenital hypogonadotropic hypogonadism with and without anosmia.";
RL J. Clin. Endocrinol. Metab. 91:4006-4012(2006).
RN [75]
RP VARIANTS HH2 CYS-78; ILE-102; HIS-224; ASP-237; GLN-254; MET-273; GLY-274
RP CYS-339; CYS-346; VAL-538; ARG-703 AND SER-703, AND VARIANT VAL-769.
RX PubMed=16764984; DOI=10.1016/j.mce.2006.04.021;
RA Pitteloud N., Meysing A., Quinton R., Acierno J.S. Jr., Dwyer A.A.,
RA Plummer L., Fliers E., Boepple P., Hayes F., Seminara S., Hughes V.A.,
RA Ma J., Bouloux P., Mohammadi M., Crowley W.F. Jr.;
RT "Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome
RT with a wide spectrum of reproductive phenotypes.";
RL Mol. Cell. Endocrinol. 254:60-69(2006).
RN [76]
RP VARIANTS HH2 SER-178; GLY-622 AND GLN-622.
RX PubMed=16757108; DOI=10.1016/j.mce.2006.04.006;
RA Zenaty D., Bretones P., Lambe C., Guemas I., David M., Leger J.,
RA de Roux N.;
RT "Paediatric phenotype of Kallmann syndrome due to mutations of fibroblast
RT growth factor receptor 1 (FGFR1).";
RL Mol. Cell. Endocrinol. 254:78-83(2006).
RN [77]
RP VARIANTS HH2 SER-237; HIS-722 AND LYS-724, AND CHARACTERIZATION OF VARIANTS
RP HH2 SER-237; HIS-722 AND LYS-724.
RX PubMed=16606836; DOI=10.1073/pnas.0600962103;
RA Pitteloud N., Acierno J.S. Jr., Meysing A., Eliseenkova A.V., Ma J.,
RA Ibrahimi O.A., Metzger D.L., Hayes F.J., Dwyer A.A., Hughes V.A.,
RA Yialamas M., Hall J.E., Grant E., Mohammadi M., Crowley W.F. Jr.;
RT "Mutations in fibroblast growth factor receptor 1 cause both Kallmann
RT syndrome and normosmic idiopathic hypogonadotropic hypogonadism.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:6281-6286(2006).
RN [78]
RP VARIANTS HH2 PHE-101; TRP-250; ASP-270; ARG-283; 324-GLU--ARG-822 DEL;
RP CYS-332; ARG-621; 661-ARG--ARG-822 DEL; PHE-685 AND PHE-693, AND VARIANTS
RP LYS-77; SER-772 AND CYS-822.
RX PubMed=17154279; DOI=10.1002/humu.9470;
RA Dode C., Fouveaut C., Mortier G., Janssens S., Bertherat J., Mahoudeau J.,
RA Kottler M.-L., Chabrolle C., Gancel A., Francois I., Devriendt K.,
RA Wolczynski S., Pugeat M., Pineiro-Garcia A., Murat A., Bouchard P.,
RA Young J., Delpech M., Hardelin J.-P.;
RT "Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence
RT that the FGFR1c isoform is required in olfactory bulb and palate
RT morphogenesis.";
RL Hum. Mutat. 28:97-98(2007).
RN [79]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-125; THR-252 AND LEU-664.
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 [80]
RP VARIANTS HH2 CYS-99; SER-117; ASP-228; THR-239; GLN-250; LEU-470; ASN-618
RP AND PRO-671, AND CHARACTERIZATION OF VARIANTS HH2 CYS-99; SER-117; ASP-228;
RP THR-239; GLN-250; LEU-470; ASN-618 AND PRO-671.
RX PubMed=19820032; DOI=10.1210/jc.2009-0179;
RA Raivio T., Sidis Y., Plummer L., Chen H., Ma J., Mukherjee A.,
RA Jacobson-Dickman E., Quinton R., Van Vliet G., Lavoie H., Hughes V.A.,
RA Dwyer A., Hayes F.J., Xu S., Sparks S., Kaiser U.B., Mohammadi M.,
RA Pitteloud N.;
RT "Impaired fibroblast growth factor receptor 1 signaling as a cause of
RT normosmic idiopathic hypogonadotropic hypogonadism.";
RL J. Clin. Endocrinol. Metab. 94:4380-4390(2009).
RN [81]
RP VARIANT HH2 GLN-250.
RX PubMed=21700882; DOI=10.1073/pnas.1102284108;
RA Tornberg J., Sykiotis G.P., Keefe K., Plummer L., Hoang X., Hall J.E.,
RA Quinton R., Seminara S.B., Hughes V., Van Vliet G., Van Uum S.,
RA Crowley W.F., Habuchi H., Kimata K., Pitteloud N., Bulow H.E.;
RT "Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular
RT sugar modifications, is mutated in patients with idiopathic
RT hypogonadotrophic hypogonadism.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:11524-11529(2011).
RN [82]
RP VARIANT HH2 ARG-687.
RX PubMed=22927827; DOI=10.1371/journal.pgen.1002896;
RA Hanchate N.K., Giacobini P., Lhuillier P., Parkash J., Espy C.,
RA Fouveaut C., Leroy C., Baron S., Campagne C., Vanacker C., Collier F.,
RA Cruaud C., Meyer V., Garcia-Pinero A., Dewailly D., Cortet-Rudelli C.,
RA Gersak K., Metz C., Chabrier G., Pugeat M., Young J., Hardelin J.P.,
RA Prevot V., Dode C.;
RT "SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with
RT Kallmann syndrome.";
RL PLoS Genet. 8:E1002896-E1002896(2012).
RN [83]
RP VARIANTS HH2 SER-117; ASP-228; THR-239; GLN-250; SER-342; ARG-348; LEU-470;
RP THR-483; ASN-618; LYS-670; GLY-692; HIS-722; LYS-724 AND TYR-768.
RX PubMed=23643382; DOI=10.1016/j.ajhg.2013.04.008;
RA Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B.,
RA Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M.,
RA Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A.,
RA Kumanov P., Young J., Yialamas M.A., Hall J.E., Van Vliet G.,
RA Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K.,
RA Pitteloud N.;
RT "Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in
RT individuals with congenital hypogonadotropic hypogonadism.";
RL Am. J. Hum. Genet. 92:725-743(2013).
RN [84]
RP INVOLVEMENT IN HRTFDS, AND VARIANTS HRTFDS SER-165; SER-191; ARG-490;
RP TYR-623; LYS-628 AND TYR-725.
RX PubMed=23812909; DOI=10.1136/jmedgenet-2013-101603;
RA Simonis N., Migeotte I., Lambert N., Perazzolo C., de Silva D.C.,
RA Dimitrov B., Heinrichs C., Janssens S., Kerr B., Mortier G., Van Vliet G.,
RA Lepage P., Casimir G., Abramowicz M., Smits G., Vilain C.;
RT "FGFR1 mutations cause Hartsfield syndrome, the unique association of
RT holoprosencephaly and ectrodactyly.";
RL J. Med. Genet. 50:585-592(2013).
RN [85]
RP CHROMOSOMAL TRANSLOCATION WITH RANBP2.
RX PubMed=23041776; DOI=10.1038/leu.2012.286;
RA Gervais C., Dano L., Perrusson N., Helias C., Jeandidier E., Galoisy A.C.,
RA Ittel A., Herbrecht R., Bilger K., Mauvieux L.;
RT "A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene,
RT RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm.";
RL Leukemia 27:1186-1188(2013).
RN [86]
RP VARIANT HRTFDS THR-627.
RX PubMed=24888332; DOI=10.1002/ajmg.a.36621;
RA Dhamija R., Kirmani S., Wang X., Ferber M.J., Wieben E.D., Lazaridis K.N.,
RA Babovic-Vuksanovic D.;
RT "Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield
RT syndrome: A case of gonadal mosaicism.";
RL Am. J. Med. Genet. A 164:2356-2359(2014).
RN [87]
RP VARIANTS HH2 ARG-70; ILE-116; ALA-174; GLN-250 AND ARG-348.
RX PubMed=25077900; DOI=10.1210/jc.2014-2110;
RA Marcos S., Sarfati J., Leroy C., Fouveaut C., Parent P., Metz C.,
RA Wolczynski S., Gerard M., Bieth E., Kurtz F., Verier-Mine O., Perrin L.,
RA Archambeaud F., Cabrol S., Rodien P., Hove H., Prescott T., Lacombe D.,
RA Christin-Maitre S., Touraine P., Hieronimus S., Dewailly D., Young J.,
RA Pugeat M., Hardelin J.P., Dode C.;
RT "The prevalence of CHD7 missense versus truncating mutations is higher in
RT patients with Kallmann syndrome than in typical CHARGE patients.";
RL J. Clin. Endocrinol. Metab. 99:E2138-2143(2014).
RN [88]
RP VARIANTS HH2 CYS-4; CYS-96 AND VAL-719, AND VARIANT HH2 THR-353 (ISOFORM
RP 19).
RX PubMed=26277103; DOI=10.1016/j.fertnstert.2015.07.1142;
RA Goncalves C., Bastos M., Pignatelli D., Borges T., Araguees J.M.,
RA Fonseca F., Pereira B.D., Socorro S., Lemos M.C.;
RT "Novel FGFR1 mutations in Kallmann syndrome and normosmic idiopathic
RT hypogonadotropic hypogonadism: evidence for the involvement of an
RT alternatively spliced isoform.";
RL Fertil. Steril. 0:0-0(2015).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor
CC for fibroblast growth factors and plays an essential role in the
CC regulation of embryonic development, cell proliferation,
CC differentiation and migration. Required for normal mesoderm patterning
CC and correct axial organization during embryonic development, normal
CC skeletogenesis and normal development of the gonadotropin-releasing
CC hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and
CC SHB. Ligand binding leads to the activation of several signaling
CC cascades. Activation of PLCG1 leads to the production of the cellular
CC signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate.
CC Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and
CC SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the
CC MAP kinase signaling pathway, as well as of the AKT1 signaling pathway.
CC Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the
CC nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the
CC regulation of transcription. FGFR1 signaling is down-regulated by
CC IL17RD/SEF, and by FGFR1 ubiquitination, internalization and
CC degradation. {ECO:0000250|UniProtKB:P16092,
CC ECO:0000269|PubMed:10830168, ECO:0000269|PubMed:11353842,
CC ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:1379697,
CC ECO:0000269|PubMed:1379698, ECO:0000269|PubMed:15117958,
CC ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277,
CC ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18480409,
CC ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:19261810,
CC ECO:0000269|PubMed:19665973, ECO:0000269|PubMed:20133753,
CC ECO:0000269|PubMed:20139426, ECO:0000269|PubMed:21765395,
CC ECO:0000269|PubMed:8622701, ECO:0000269|PubMed:8663044}.
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 ECO:0000269|PubMed:1379697, ECO:0000269|PubMed:15117958,
CC ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:19224897,
CC ECO:0000269|PubMed:19665973, ECO:0000269|PubMed:20133753,
CC ECO:0000269|PubMed:8622701};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. Ligand binding leads to dimerization and activation by
CC sequential autophosphorylation on tyrosine residues. Inhibited by ARQ
CC 069; this compound maintains the kinase in an inactive conformation and
CC inhibits autophosphorylation. Inhibited by PD173074.
CC {ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:19224897,
CC ECO:0000269|PubMed:21454610, ECO:0000269|PubMed:8622701}.
CC -!- SUBUNIT: Monomer. Homodimer after ligand binding. Interacts
CC predominantly with FGF1 and FGF2, but can also interact with FGF3,
CC FGF4, FGF5, FGF6, FGF8, FGF10, FGF19, FGF21, FGF22 and FGF23 (in vitro)
CC (PubMed:1697263, PubMed:1722683, PubMed:8663044, PubMed:9655399,
CC PubMed:12181353, PubMed:16597617, PubMed:17623664). Ligand specificity
CC is determined by tissue-specific expression of isoforms, and
CC differences in the third Ig-like domain are crucial for ligand
CC specificity. Affinity for fibroblast growth factors (FGFs) is increased
CC by heparan sulfate glycosaminoglycans that function as coreceptors.
CC Likewise, KLB increases the affinity for FGF19, FGF21 and FGF23
CC (PubMed:19966287). Interacts (phosphorylated on Tyr-766) with PLCG1
CC (via SH2 domains) (PubMed:1656221, PubMed:1379697, PubMed:21765395).
CC Interacts with FRS2 (PubMed:21765395). Interacts with RPS6KA1
CC (PubMed:15117958). Interacts (via C-terminus) with NEDD4 (via WW3
CC domain) (PubMed:21765395). Interacts with KL (By similarity). Interacts
CC with SHB (via SH2 domain) (PubMed:12181353). Interacts with GRB10
CC (PubMed:10454568). Interacts with ANOS1; this interaction does not
CC interfere with FGF2-binding to FGFR1, but prevents binding of heparin-
CC bound FGF2 (PubMed:19696444). Interacts with SOX2 and SOX3. Interacts
CC with FLRT1, FLRT2 and FLRT3 (By similarity). Found in a ternary complex
CC with FGF1 and ITGAV:ITGB3 (PubMed:20422052, PubMed:18441324).
CC {ECO:0000250|UniProtKB:P16092, ECO:0000269|PubMed:10454568,
CC ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:1379697,
CC ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:1656221,
CC ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:1697263,
CC ECO:0000269|PubMed:1722683, ECO:0000269|PubMed:17623664,
CC ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:19696444,
CC ECO:0000269|PubMed:19966287, ECO:0000269|PubMed:20422052,
CC ECO:0000269|PubMed:21765395, ECO:0000269|PubMed:8663044,
CC ECO:0000269|PubMed:9655399}.
CC -!- INTERACTION:
CC P11362; P23352: ANOS1; NbExp=7; IntAct=EBI-1028277, EBI-5272188;
CC P11362; P12830: CDH1; NbExp=3; IntAct=EBI-1028277, EBI-727477;
CC P11362; P05230: FGF1; NbExp=4; IntAct=EBI-1028277, EBI-698068;
CC P11362; P09038: FGF2; NbExp=7; IntAct=EBI-1028277, EBI-977447;
CC P11362; Q9GZV9: FGF23; NbExp=2; IntAct=EBI-1028277, EBI-6594125;
CC P11362; P11362: FGFR1; NbExp=4; IntAct=EBI-1028277, EBI-1028277;
CC P11362; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1028277, EBI-352572;
CC P11362; P08908: HTR1A; NbExp=9; IntAct=EBI-1028277, EBI-6570214;
CC P11362; P46934: NEDD4; NbExp=26; IntAct=EBI-1028277, EBI-726944;
CC P11362; Q8IVI9: NOSTRIN; NbExp=5; IntAct=EBI-1028277, EBI-1391643;
CC P11362; P27986: PIK3R1; NbExp=5; IntAct=EBI-1028277, EBI-79464;
CC P11362; P19174: PLCG1; NbExp=9; IntAct=EBI-1028277, EBI-79387;
CC P11362; O88900: Grb14; Xeno; NbExp=3; IntAct=EBI-1028277, EBI-7639197;
CC P11362; O35082: Kl; Xeno; NbExp=2; IntAct=EBI-1028277, EBI-1570828;
CC P11362; P10686: Plcg1; Xeno; NbExp=4; IntAct=EBI-1028277, EBI-520788;
CC P11362-2; Q02363: ID2; NbExp=3; IntAct=EBI-25852941, EBI-713450;
CC P11362-2; Q9BRX2: PELO; NbExp=3; IntAct=EBI-25852941, EBI-1043580;
CC P11362-7; P09038: FGF2; NbExp=2; IntAct=EBI-15609945, EBI-977447;
CC P11362-7; O35082: Kl; Xeno; NbExp=3; IntAct=EBI-15609945, EBI-1570828;
CC P11362-14; P09038: FGF2; NbExp=2; IntAct=EBI-6622185, EBI-977447;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Nucleus. Cytoplasm, cytosol. Cytoplasmic vesicle. Note=After
CC ligand binding, both receptor and ligand are rapidly internalized. Can
CC translocate to the nucleus after internalization, or by translocation
CC from the endoplasmic reticulum or Golgi apparatus to the cytosol, and
CC from there to the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=21;
CC Name=1; Synonyms=Alpha A1, IV;
CC IsoId=P11362-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha A2;
CC IsoId=P11362-8; Sequence=VSP_009842, VSP_009843;
CC Name=3; Synonyms=Alpha A3;
CC IsoId=P11362-17; Sequence=VSP_009836, VSP_009837;
CC Name=4; Synonyms=Alpha B1;
CC IsoId=P11362-2; Sequence=VSP_002960;
CC Name=5; Synonyms=Alpha B2;
CC IsoId=P11362-9; Sequence=VSP_002960, VSP_009842, VSP_009843;
CC Name=6; Synonyms=Beta A1, II, H2;
CC IsoId=P11362-3; Sequence=VSP_002958;
CC Name=7; Synonyms=Beta A2;
CC IsoId=P11362-10; Sequence=VSP_002958, VSP_009842, VSP_009843;
CC Name=8; Synonyms=Beta B1;
CC IsoId=P11362-4; Sequence=VSP_002958, VSP_002960;
CC Name=9; Synonyms=Beta B2;
CC IsoId=P11362-11; Sequence=VSP_002958, VSP_002960, VSP_009842,
CC VSP_009843;
CC Name=10; Synonyms=Gamma A1;
CC IsoId=P11362-5; Sequence=VSP_002957;
CC Name=11; Synonyms=Gamma A2;
CC IsoId=P11362-12; Sequence=VSP_002957, VSP_009842, VSP_009843;
CC Name=12; Synonyms=Gamma B1;
CC IsoId=P11362-6; Sequence=VSP_002957, VSP_002960;
CC Name=13; Synonyms=Gamma B2;
CC IsoId=P11362-13; Sequence=VSP_002957, VSP_002960, VSP_009842,
CC VSP_009843;
CC Name=14; Synonyms=A, III;
CC IsoId=P11362-7; Sequence=VSP_002959;
CC Name=15; Synonyms=I, H3;
CC IsoId=P11362-14; Sequence=VSP_002958, VSP_002959;
CC Name=16; Synonyms=V;
CC IsoId=P11362-15; Sequence=VSP_009838, VSP_009839;
CC Name=17; Synonyms=H4;
CC IsoId=P11362-16; Sequence=VSP_002958, VSP_009840, VSP_009841;
CC Name=18; Synonyms=H5;
CC IsoId=P11362-18; Sequence=VSP_002958, VSP_002959, VSP_009840,
CC VSP_009841;
CC Name=19;
CC IsoId=P11362-19; Sequence=VSP_038470, VSP_002959, VSP_038471;
CC Name=20;
CC IsoId=P11362-20; Sequence=VSP_041916, VSP_041918;
CC Name=21;
CC IsoId=P11362-21; Sequence=VSP_041917, VSP_002959;
CC -!- TISSUE SPECIFICITY: Detected in astrocytoma, neuroblastoma and adrenal
CC cortex cell lines. Some isoforms are detected in foreskin fibroblast
CC cell lines, however isoform 17, isoform 18 and isoform 19 are not
CC detected in these cells. {ECO:0000269|PubMed:1652059}.
CC -!- DOMAIN: The second and third Ig-like domains directly interact with
CC fibroblast growth factors (FGF) and heparan sulfate proteoglycans.
CC Isoforms lacking the first Ig-like domain have higher affinity for
CC fibroblast growth factors (FGF) and heparan sulfate proteoglycans than
CC isoforms with all three Ig-like domains.
CC -!- PTM: Autophosphorylated. Binding of FGF family members together with
CC heparan sulfate proteoglycan or heparin promotes receptor dimerization
CC and autophosphorylation on tyrosine residues. Autophosphorylation
CC occurs in trans between the two FGFR molecules present in the dimer and
CC proceeds in a highly ordered manner. Initial autophosphorylation at
CC Tyr-653 increases the kinase activity by a factor of 50 to 100. After
CC this, Tyr-583 becomes phosphorylated, followed by phosphorylation of
CC Tyr-463, Tyr-766, Tyr-583 and Tyr-585. In a third stage, Tyr-654 is
CC autophosphorylated, resulting in a further tenfold increase of kinase
CC activity. Phosphotyrosine residues provide docking sites for
CC interacting proteins and so are crucial for FGFR1 function and its
CC regulation. {ECO:0000269|PubMed:16507368, ECO:0000269|PubMed:19224897,
CC ECO:0000269|PubMed:19665973, ECO:0000269|PubMed:8622701}.
CC -!- PTM: Ubiquitinated. FGFR1 is rapidly ubiquitinated by NEDD4 after
CC autophosphorylation, leading to internalization and lysosomal
CC degradation. CBL is recruited to activated FGFR1 via FRS2 and GRB2, and
CC mediates ubiquitination and subsequent degradation of FGFR1.
CC {ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:21765395}.
CC -!- PTM: N-glycosylated in the endoplasmic reticulum. The N-glycan chains
CC undergo further maturation to an Endo H-resistant form in the Golgi
CC apparatus. {ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16481405,
CC ECO:0000269|PubMed:17311277}.
CC -!- DISEASE: Pfeiffer syndrome (PS) [MIM:101600]: A syndrome characterized
CC by the association of craniosynostosis, broad and deviated thumbs and
CC big toes, and partial syndactyly of the fingers and toes. Three
CC subtypes are known: mild autosomal dominant form (type 1); cloverleaf
CC skull, elbow ankylosis, early death, sporadic (type 2);
CC craniosynostosis, early demise, sporadic (type 3).
CC {ECO:0000269|PubMed:7874169}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Hypogonadotropic hypogonadism 2 with or without anosmia (HH2)
CC [MIM:147950]: A disorder characterized by absent or incomplete sexual
CC maturation by the age of 18 years, in conjunction with low levels of
CC circulating gonadotropins and testosterone and no other abnormalities
CC of the hypothalamic-pituitary axis. In some cases, it is associated
CC with non-reproductive phenotypes, such as anosmia, cleft palate, and
CC sensorineural hearing loss. Anosmia or hyposmia is related to the
CC absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism
CC is due to deficiency in gonadotropin-releasing hormone and probably
CC results from a failure of embryonic migration of gonadotropin-releasing
CC hormone-synthesizing neurons. In the presence of anosmia, idiopathic
CC hypogonadotropic hypogonadism is referred to as Kallmann syndrome,
CC whereas in the presence of a normal sense of smell, it has been termed
CC normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
CC {ECO:0000269|PubMed:12627230, ECO:0000269|PubMed:15001591,
CC ECO:0000269|PubMed:15605412, ECO:0000269|PubMed:15845591,
CC ECO:0000269|PubMed:16606836, ECO:0000269|PubMed:16757108,
CC ECO:0000269|PubMed:16764984, ECO:0000269|PubMed:16882753,
CC ECO:0000269|PubMed:17154279, ECO:0000269|PubMed:19820032,
CC ECO:0000269|PubMed:21700882, ECO:0000269|PubMed:22927827,
CC ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900,
CC ECO:0000269|PubMed:26277103}. Note=The disease is caused by variants
CC affecting distinct genetic loci, including the gene represented in this
CC entry. Some patients carrying mutations in FGFR1 also have a mutation
CC other HH-associated genes including DUSP6, FGF8, FGF17, FLRT3, GNRH1,
CC GNRHR, HS6ST1, IL17RD, ANOS1, KISS1R, NSMF, PROKR2, SPRY4 and TACR3
CC (PubMed:23643382). {ECO:0000269|PubMed:23643382}.
CC -!- DISEASE: Osteoglophonic dysplasia (OGD) [MIM:166250]: Characterized by
CC craniosynostosis, prominent supraorbital ridge, and depressed nasal
CC bridge, as well as by rhizomelic dwarfism and nonossifying bone
CC lesions. Inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:15625620, ECO:0000269|PubMed:16470795}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hartsfield syndrome (HRTFDS) [MIM:615465]: A syndrome
CC characterized by the triad of holoprosencephaly, ectrodactyly, and
CC cleft/lip palate. Profound intellectual disability is also present.
CC Multiple other congenital anomalies usually occur.
CC {ECO:0000269|PubMed:23812909, ECO:0000269|PubMed:24888332}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Trigonocephaly 1 (TRIGNO1) [MIM:190440]: A keel-shaped
CC deformation of the forehead, caused by premature fusion of the metopic
CC sutures. It results in a triangular shape of the head.
CC {ECO:0000269|PubMed:11173846}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Chromosomal aberrations involving FGFR1 are a cause of
CC chromosome 8p11 myeloproliferative syndrome. Translocation
CC t(8;13)(p11;q12) with ZMYM2. Translocation t(6;8)(q27;p11) with CEP43.
CC Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. Translocation
CC t(8;9)(p12;q33) with CNTRL. Translocation t(2;8)(q12;p11) with RANBP2.
CC Chromosome 8p11 myeloproliferative syndrome is characterized by myeloid
CC hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma.
CC In general it progresses to acute myeloid leukemia. The fusion proteins
CC FGFR1OP2-FGFR1, CEP43-FGFR1 or FGFR1-CEP43 may exhibit constitutive
CC kinase activity and be responsible for the transforming activity. The
CC fusion protein CNTRL-FGFR1 is found in the cytoplasm, exhibits
CC constitutive kinase activity and may be responsible for the
CC transforming activity. {ECO:0000269|PubMed:10688839,
CC ECO:0000269|PubMed:15034873, ECO:0000269|PubMed:16946300,
CC ECO:0000269|PubMed:17389761, ECO:0000269|PubMed:23041776,
CC ECO:0000269|PubMed:9716603, ECO:0000269|PubMed:9949182}.
CC -!- DISEASE: Encephalocraniocutaneous lipomatosis (ECCL) [MIM:613001]: A
CC sporadically occurring, neurocutaneous disorder characterized by ocular
CC anomalies, skin lesions, and central nervous system anomalies. Clinical
CC features include a well-demarcated hairless fatty nevus on the scalp,
CC benign ocular tumors, intracranial and intraspinal lipomas, and
CC congenital abnormalities of the meninges. Seizures, spasticity, and
CC intellectual disability can be present. {ECO:0000269|PubMed:19224897,
CC ECO:0000269|PubMed:26942290}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Jackson-Weiss syndrome (JWS) [MIM:123150]: An autosomal
CC dominant craniosynostosis syndrome characterized by craniofacial
CC abnormalities and abnormality of the feet: broad great toes with medial
CC deviation and tarsal-metatarsal coalescence.
CC {ECO:0000269|PubMed:10861678}. 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. Fibroblast growth factor receptor subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92156.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FGFR1ID113.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fgfr1/";
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; M37722; AAA75007.1; -; mRNA.
DR EMBL; X52833; CAA37015.1; -; mRNA.
DR EMBL; M34185; AAA35836.1; -; mRNA.
DR EMBL; M34186; AAA35837.1; -; mRNA.
DR EMBL; M34187; AAA35838.1; -; mRNA.
DR EMBL; M34188; AAA35839.1; -; mRNA.
DR EMBL; X51803; CAA36101.1; -; mRNA.
DR EMBL; M34641; AAA35835.1; -; mRNA.
DR EMBL; M60485; AAA35840.1; -; mRNA.
DR EMBL; X57118; CAA40400.1; -; mRNA.
DR EMBL; X57119; CAA40401.1; -; mRNA.
DR EMBL; X57120; CAA40402.1; -; mRNA.
DR EMBL; X57121; CAA40403.1; -; mRNA.
DR EMBL; X57122; CAA40404.1; -; mRNA.
DR EMBL; M63887; AAA35958.1; -; mRNA.
DR EMBL; M63888; AAA35959.1; -; mRNA.
DR EMBL; M63889; AAA35960.1; -; mRNA.
DR EMBL; X66945; CAA47375.1; -; mRNA.
DR EMBL; FJ809917; ACO38646.1; -; mRNA.
DR EMBL; AK291754; BAF84443.1; -; mRNA.
DR EMBL; AK292470; BAF85159.1; -; mRNA.
DR EMBL; AK309947; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AB208919; BAD92156.1; ALT_INIT; mRNA.
DR EMBL; AK222718; BAD96438.1; -; mRNA.
DR EMBL; AY585209; AAS79322.1; -; Genomic_DNA.
DR EMBL; AC087623; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015035; AAH15035.1; -; mRNA.
DR EMBL; BC018128; AAH18128.1; -; mRNA.
DR EMBL; BC091494; AAH91494.1; -; mRNA.
DR EMBL; Y00665; CAA68679.1; -; mRNA.
DR CCDS; CCDS43730.1; -. [P11362-3]
DR CCDS; CCDS43731.1; -. [P11362-14]
DR CCDS; CCDS43732.1; -. [P11362-7]
DR CCDS; CCDS55221.1; -. [P11362-20]
DR CCDS; CCDS55222.1; -. [P11362-2]
DR CCDS; CCDS55223.1; -. [P11362-21]
DR CCDS; CCDS6107.2; -. [P11362-1]
DR PIR; A41266; A41266.
DR PIR; C36464; C36464.
DR PIR; C40862; C40862.
DR PIR; S11692; TVHUFG.
DR PIR; S19167; A40862.
DR RefSeq; NP_001167534.1; NM_001174063.1. [P11362-2]
DR RefSeq; NP_001167535.1; NM_001174064.1. [P11362-20]
DR RefSeq; NP_001167536.1; NM_001174065.1. [P11362-7]
DR RefSeq; NP_001167537.1; NM_001174066.1. [P11362-3]
DR RefSeq; NP_001167538.1; NM_001174067.1. [P11362-21]
DR RefSeq; NP_056934.2; NM_015850.3. [P11362-7]
DR RefSeq; NP_075593.1; NM_023105.2. [P11362-3]
DR RefSeq; NP_075594.1; NM_023106.2. [P11362-14]
DR RefSeq; NP_075598.2; NM_023110.2. [P11362-1]
DR PDB; 1AGW; X-ray; 2.40 A; A/B=456-765.
DR PDB; 1CVS; X-ray; 2.80 A; C/D=141-365.
DR PDB; 1EVT; X-ray; 2.80 A; C/D=141-365.
DR PDB; 1FGI; X-ray; 2.50 A; A/B=456-765.
DR PDB; 1FGK; X-ray; 2.00 A; A/B=456-765.
DR PDB; 1FQ9; X-ray; 3.00 A; C/D=141-365.
DR PDB; 1XR0; NMR; -; A=409-430.
DR PDB; 2CR3; NMR; -; A=38-123.
DR PDB; 2FGI; X-ray; 2.50 A; A/B=456-765.
DR PDB; 3C4F; X-ray; 2.07 A; A/B=464-765.
DR PDB; 3DPK; X-ray; 1.95 A; A=577-615.
DR PDB; 3GQI; X-ray; 2.50 A; A=458-774.
DR PDB; 3GQL; X-ray; 2.80 A; A/B/C=458-774.
DR PDB; 3JS2; X-ray; 2.20 A; A/B=458-765.
DR PDB; 3KRJ; X-ray; 2.10 A; A=577-597.
DR PDB; 3KRL; X-ray; 2.40 A; A=577-597.
DR PDB; 3KXX; X-ray; 3.20 A; A/B/C/D=458-765.
DR PDB; 3KY2; X-ray; 2.70 A; A/B=458-765.
DR PDB; 3OJV; X-ray; 2.60 A; C/D=142-365.
DR PDB; 3RHX; X-ray; 2.01 A; A/B=461-765.
DR PDB; 3TT0; X-ray; 2.80 A; A/B=456-765.
DR PDB; 4F63; X-ray; 2.55 A; A/B=458-765.
DR PDB; 4F64; X-ray; 2.05 A; A/B=458-765.
DR PDB; 4F65; X-ray; 2.26 A; A/B=458-765.
DR PDB; 4NK9; X-ray; 2.57 A; A/B=458-765.
DR PDB; 4NKA; X-ray; 2.19 A; A/B=458-765.
DR PDB; 4NKS; X-ray; 2.50 A; A/B=458-765.
DR PDB; 4RWI; X-ray; 2.29 A; A/B=458-765.
DR PDB; 4RWJ; X-ray; 2.49 A; A/B=458-765.
DR PDB; 4RWK; X-ray; 2.98 A; A/B=458-765.
DR PDB; 4RWL; X-ray; 2.19 A; A/B=458-765.
DR PDB; 4UWB; X-ray; 2.31 A; A/B=458-765.
DR PDB; 4UWC; X-ray; 1.96 A; A/B=458-765.
DR PDB; 4UWY; X-ray; 2.31 A; A/B=458-765.
DR PDB; 4V01; X-ray; 2.33 A; A/B=458-765.
DR PDB; 4V04; X-ray; 2.12 A; A/B=458-765.
DR PDB; 4V05; X-ray; 2.57 A; A/B=458-765.
DR PDB; 4WUN; X-ray; 1.65 A; A/B=459-765.
DR PDB; 4ZSA; X-ray; 2.00 A; A/B=458-765.
DR PDB; 5A46; X-ray; 2.63 A; A/B=437-822.
DR PDB; 5A4C; X-ray; 2.09 A; A/B=461-765.
DR PDB; 5AM6; X-ray; 1.96 A; A/B=458-765.
DR PDB; 5AM7; X-ray; 1.96 A; A/B=458-765.
DR PDB; 5B7V; X-ray; 2.15 A; A/B=456-765.
DR PDB; 5EW8; X-ray; 1.63 A; A/B=458-765.
DR PDB; 5FLF; X-ray; 2.58 A; A/B/C/D/E=458-765.
DR PDB; 5O49; X-ray; 1.91 A; A/B=458-765.
DR PDB; 5O4A; X-ray; 2.01 A; A/B=458-765.
DR PDB; 5UQ0; X-ray; 2.30 A; A/B=459-765.
DR PDB; 5UR1; X-ray; 2.20 A; A/B=459-765.
DR PDB; 5VND; X-ray; 2.20 A; A/B=458-765.
DR PDB; 5W21; X-ray; 3.00 A; C=142-365.
DR PDB; 5W59; X-ray; 2.50 A; B=142-365.
DR PDB; 5Z0S; X-ray; 2.45 A; A/B=458-765.
DR PDB; 5ZV2; X-ray; 2.86 A; A/B=461-764.
DR PDB; 6C18; X-ray; 2.30 A; A/B=459-765.
DR PDB; 6C19; X-ray; 2.12 A; A/B=459-765.
DR PDB; 6C1B; X-ray; 2.00 A; A/B=459-765.
DR PDB; 6C1C; X-ray; 2.15 A; A/B=459-765.
DR PDB; 6C1O; X-ray; 2.29 A; A/B=459-765.
DR PDB; 6ITJ; X-ray; 1.99 A; A/B=458-765.
DR PDB; 6MZQ; X-ray; 2.00 A; A/B=459-765.
DR PDB; 6MZW; X-ray; 2.20 A; A/B=459-765.
DR PDB; 6NVL; X-ray; 2.70 A; A/B/C/D=458-765.
DR PDB; 6P68; X-ray; 2.90 A; A/B/C=458-765.
DR PDB; 6P69; X-ray; 2.20 A; A/B=458-765.
DR PDB; 7OZB; X-ray; 1.71 A; AAA/BBB=458-765.
DR PDB; 7OZD; X-ray; 1.82 A; AAA/BBB=458-765.
DR PDB; 7OZF; X-ray; 1.82 A; AAA/BBB=458-765.
DR PDBsum; 1AGW; -.
DR PDBsum; 1CVS; -.
DR PDBsum; 1EVT; -.
DR PDBsum; 1FGI; -.
DR PDBsum; 1FGK; -.
DR PDBsum; 1FQ9; -.
DR PDBsum; 1XR0; -.
DR PDBsum; 2CR3; -.
DR PDBsum; 2FGI; -.
DR PDBsum; 3C4F; -.
DR PDBsum; 3DPK; -.
DR PDBsum; 3GQI; -.
DR PDBsum; 3GQL; -.
DR PDBsum; 3JS2; -.
DR PDBsum; 3KRJ; -.
DR PDBsum; 3KRL; -.
DR PDBsum; 3KXX; -.
DR PDBsum; 3KY2; -.
DR PDBsum; 3OJV; -.
DR PDBsum; 3RHX; -.
DR PDBsum; 3TT0; -.
DR PDBsum; 4F63; -.
DR PDBsum; 4F64; -.
DR PDBsum; 4F65; -.
DR PDBsum; 4NK9; -.
DR PDBsum; 4NKA; -.
DR PDBsum; 4NKS; -.
DR PDBsum; 4RWI; -.
DR PDBsum; 4RWJ; -.
DR PDBsum; 4RWK; -.
DR PDBsum; 4RWL; -.
DR PDBsum; 4UWB; -.
DR PDBsum; 4UWC; -.
DR PDBsum; 4UWY; -.
DR PDBsum; 4V01; -.
DR PDBsum; 4V04; -.
DR PDBsum; 4V05; -.
DR PDBsum; 4WUN; -.
DR PDBsum; 4ZSA; -.
DR PDBsum; 5A46; -.
DR PDBsum; 5A4C; -.
DR PDBsum; 5AM6; -.
DR PDBsum; 5AM7; -.
DR PDBsum; 5B7V; -.
DR PDBsum; 5EW8; -.
DR PDBsum; 5FLF; -.
DR PDBsum; 5O49; -.
DR PDBsum; 5O4A; -.
DR PDBsum; 5UQ0; -.
DR PDBsum; 5UR1; -.
DR PDBsum; 5VND; -.
DR PDBsum; 5W21; -.
DR PDBsum; 5W59; -.
DR PDBsum; 5Z0S; -.
DR PDBsum; 5ZV2; -.
DR PDBsum; 6C18; -.
DR PDBsum; 6C19; -.
DR PDBsum; 6C1B; -.
DR PDBsum; 6C1C; -.
DR PDBsum; 6C1O; -.
DR PDBsum; 6ITJ; -.
DR PDBsum; 6MZQ; -.
DR PDBsum; 6MZW; -.
DR PDBsum; 6NVL; -.
DR PDBsum; 6P68; -.
DR PDBsum; 6P69; -.
DR PDBsum; 7OZB; -.
DR PDBsum; 7OZD; -.
DR PDBsum; 7OZF; -.
DR AlphaFoldDB; P11362; -.
DR BMRB; P11362; -.
DR SMR; P11362; -.
DR BioGRID; 108551; 338.
DR CORUM; P11362; -.
DR DIP; DIP-4019N; -.
DR IntAct; P11362; 168.
DR MINT; P11362; -.
DR STRING; 9606.ENSP00000393312; -.
DR BindingDB; P11362; -.
DR ChEMBL; CHEMBL3650; -.
DR DrugBank; DB07840; (E)-[4-(3,5-Difluorophenyl)-3H-pyrrolo[2,3-b]pyridin-3-ylidene](3-methoxyphenyl)methanol.
DR DrugBank; DB07525; 3-(3-methoxybenzyl)-1H-pyrrolo[2,3-b]pyridine.
DR DrugBank; DB08577; 3-[(3-(2-CARBOXYETHYL)-4-METHYLPYRROL-2-YL)METHYLENE]-2-INDOLINONE.
DR DrugBank; DB02058; 3-[4-(1-formylpiperazin-4-yl)-benzylidenyl]-2-indolinone.
DR DrugBank; DB12147; Erdafitinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB01109; Heparin.
DR DrugBank; DB11886; Infigratinib.
DR DrugBank; DB09078; Lenvatinib.
DR DrugBank; DB09079; Nintedanib.
DR DrugBank; DB00039; Palifermin.
DR DrugBank; DB15102; Pemigatinib.
DR DrugBank; DB08901; Ponatinib.
DR DrugBank; DB15822; Pralsetinib.
DR DrugBank; DB08896; Regorafenib.
DR DrugBank; DB15685; Selpercatinib.
DR DrugBank; DB00398; Sorafenib.
DR DrugBank; DB11800; Tivozanib.
DR DrugBank; DB05014; XL999.
DR DrugCentral; P11362; -.
DR GuidetoPHARMACOLOGY; 1808; -.
DR TCDB; 8.A.23.1.7; the basigin (basigin) family.
DR CarbonylDB; P11362; -.
DR GlyConnect; 1239; 8 N-Linked glycans (4 sites).
DR GlyGen; P11362; 10 sites, 10 N-linked glycans (4 sites).
DR iPTMnet; P11362; -.
DR PhosphoSitePlus; P11362; -.
DR SwissPalm; P11362; -.
DR BioMuta; FGFR1; -.
DR DMDM; 120046; -.
DR CPTAC; CPTAC-1773; -.
DR CPTAC; CPTAC-1780; -.
DR EPD; P11362; -.
DR jPOST; P11362; -.
DR MassIVE; P11362; -.
DR MaxQB; P11362; -.
DR PaxDb; P11362; -.
DR PeptideAtlas; P11362; -.
DR PRIDE; P11362; -.
DR ProteomicsDB; 52745; -. [P11362-1]
DR ProteomicsDB; 52746; -. [P11362-10]
DR ProteomicsDB; 52747; -. [P11362-11]
DR ProteomicsDB; 52748; -. [P11362-12]
DR ProteomicsDB; 52749; -. [P11362-13]
DR ProteomicsDB; 52750; -. [P11362-14]
DR ProteomicsDB; 52751; -. [P11362-15]
DR ProteomicsDB; 52752; -. [P11362-16]
DR ProteomicsDB; 52754; -. [P11362-18]
DR ProteomicsDB; 52755; -. [P11362-19]
DR ProteomicsDB; 52756; -. [P11362-2]
DR ProteomicsDB; 52757; -. [P11362-20]
DR ProteomicsDB; 52758; -. [P11362-21]
DR ProteomicsDB; 52759; -. [P11362-3]
DR ProteomicsDB; 52760; -. [P11362-4]
DR ProteomicsDB; 52761; -. [P11362-5]
DR ProteomicsDB; 52762; -. [P11362-6]
DR ProteomicsDB; 52763; -. [P11362-7]
DR ProteomicsDB; 52764; -. [P11362-8]
DR ProteomicsDB; 52765; -. [P11362-9]
DR ABCD; P11362; 7 sequenced antibodies.
DR Antibodypedia; 11015; 2522 antibodies from 48 providers.
DR DNASU; 2260; -.
DR Ensembl; ENST00000326324.10; ENSP00000327229.6; ENSG00000077782.22. [P11362-14]
DR Ensembl; ENST00000335922.9; ENSP00000337247.5; ENSG00000077782.22. [P11362-20]
DR Ensembl; ENST00000356207.9; ENSP00000348537.5; ENSG00000077782.22. [P11362-3]
DR Ensembl; ENST00000397091.9; ENSP00000380280.5; ENSG00000077782.22. [P11362-7]
DR Ensembl; ENST00000397108.8; ENSP00000380297.4; ENSG00000077782.22. [P11362-7]
DR Ensembl; ENST00000397113.6; ENSP00000380302.2; ENSG00000077782.22. [P11362-7]
DR Ensembl; ENST00000447712.7; ENSP00000400162.2; ENSG00000077782.22. [P11362-1]
DR Ensembl; ENST00000484370.5; ENSP00000433163.1; ENSG00000077782.22. [P11362-15]
DR Ensembl; ENST00000532791.5; ENSP00000432972.1; ENSG00000077782.22. [P11362-2]
DR GeneID; 2260; -.
DR KEGG; hsa:2260; -.
DR MANE-Select; ENST00000447712.7; ENSP00000400162.2; NM_023110.3; NP_075598.2.
DR UCSC; uc003xlp.4; human. [P11362-1]
DR CTD; 2260; -.
DR DisGeNET; 2260; -.
DR GeneCards; FGFR1; -.
DR GeneReviews; FGFR1; -.
DR HGNC; HGNC:3688; FGFR1.
DR HPA; ENSG00000077782; Low tissue specificity.
DR MalaCards; FGFR1; -.
DR MIM; 101600; phenotype.
DR MIM; 123150; phenotype.
DR MIM; 136350; gene.
DR MIM; 147950; phenotype.
DR MIM; 166250; phenotype.
DR MIM; 190440; phenotype.
DR MIM; 613001; phenotype.
DR MIM; 615465; phenotype.
DR neXtProt; NX_P11362; -.
DR OpenTargets; ENSG00000077782; -.
DR Orphanet; 2396; Encephalocraniocutaneous lipomatosis.
DR Orphanet; 251579; Giant cell glioblastoma.
DR Orphanet; 251576; Gliosarcoma.
DR Orphanet; 2117; Hartsfield syndrome.
DR Orphanet; 478; Kallmann syndrome.
DR Orphanet; 93924; Lobar holoprosencephaly.
DR Orphanet; 280200; Microform holoprosencephaly.
DR Orphanet; 168953; Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement.
DR Orphanet; 2227; NON RARE IN EUROPE: Hypodontia.
DR Orphanet; 3366; Non-syndromic metopic craniosynostosis.
DR Orphanet; 432; Normosmic congenital hypogonadotropic hypogonadism.
DR Orphanet; 99798; Oligodontia.
DR Orphanet; 2645; Osteoglosphonic dysplasia.
DR Orphanet; 93258; Pfeiffer syndrome type 1.
DR Orphanet; 251615; Pilomyxoid astrocytoma.
DR Orphanet; 314950; Primary hypereosinophilic syndrome.
DR Orphanet; 220386; Semilobar holoprosencephaly.
DR Orphanet; 3157; Septo-optic dysplasia spectrum.
DR PharmGKB; PA28127; -.
DR VEuPathDB; HostDB:ENSG00000077782; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000155860; -.
DR HOGENOM; CLU_000288_74_3_1; -.
DR InParanoid; P11362; -.
DR OMA; YACVTNS; -.
DR OrthoDB; 220433at2759; -.
DR PhylomeDB; P11362; -.
DR TreeFam; TF316307; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P11362; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1839120; Signaling by FGFR1 amplification mutants.
DR Reactome; R-HSA-1839122; Signaling by activated point mutants of FGFR1.
DR Reactome; R-HSA-190370; FGFR1b ligand binding and activation. [P11362-19]
DR Reactome; R-HSA-190373; FGFR1c ligand binding and activation. [P11362-1]
DR Reactome; R-HSA-190374; FGFR1c and Klotho ligand binding and activation. [P11362-1]
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-375165; NCAM signaling for neurite out-growth. [P11362-1]
DR Reactome; R-HSA-445144; Signal transduction by L1. [P11362-1]
DR Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1.
DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1.
DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1.
DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1.
DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling.
DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease.
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-8853336; Signaling by plasma membrane FGFR1 fusions.
DR SignaLink; P11362; -.
DR SIGNOR; P11362; -.
DR BioGRID-ORCS; 2260; 65 hits in 1111 CRISPR screens.
DR ChiTaRS; FGFR1; human.
DR EvolutionaryTrace; P11362; -.
DR GeneWiki; Fibroblast_growth_factor_receptor_1; -.
DR GenomeRNAi; 2260; -.
DR Pharos; P11362; Tclin.
DR PRO; PR:P11362; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P11362; protein.
DR Bgee; ENSG00000077782; Expressed in buccal mucosa cell and 207 other tissues.
DR ExpressionAtlas; P11362; baseline and differential.
DR Genevisible; P11362; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0017134; F:fibroblast growth factor binding; IDA:UniProtKB.
DR GO; GO:0005007; F:fibroblast growth factor receptor activity; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0090722; F:receptor-receptor interaction; IDA:ParkinsonsUK-UCL.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; TAS:UniProtKB.
DR GO; GO:0043009; P:chordate embryonic development; TAS:UniProtKB.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; TAS:ProtInc.
DR GO; GO:0001764; P:neuron migration; TAS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IGI:BHF-UCL.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:2000546; P:positive regulation of endothelial cell chemotaxis to fibroblast growth factor; IDA:BHF-UCL.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; TAS:UniProtKB.
DR GO; GO:0010518; P:positive regulation of phospholipase activity; TAS:UniProtKB.
DR GO; GO:0010863; P:positive regulation of phospholipase C activity; IDA:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IGI:BHF-UCL.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IGI:BHF-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; NAS:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; TAS:UniProtKB.
DR GO; GO:2001239; P:regulation of extrinsic apoptotic signaling pathway in absence of ligand; TAS:BHF-UCL.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0048705; P:skeletal system morphogenesis; TAS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd05098; PTKc_FGFR1; 1.
DR Gene3D; 2.60.40.10; -; 3.
DR IDEAL; IID00650; -.
DR InterPro; IPR028174; FGF_rcpt_1.
DR InterPro; IPR016248; FGF_rcpt_fam.
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; IPR013151; Immunoglobulin.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF000628; FGFR; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Chromosomal rearrangement; Craniosynostosis; Cytoplasm;
KW Cytoplasmic vesicle; Direct protein sequencing; Disease variant;
KW Disulfide bond; Dwarfism; Glycoprotein; Heparin-binding; Holoprosencephaly;
KW Hypogonadotropic hypogonadism; Immunoglobulin domain;
KW Intellectual disability; Kallmann syndrome; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; Signal; Transcription; Transcription regulation; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..21
FT CHAIN 22..822
FT /note="Fibroblast growth factor receptor 1"
FT /id="PRO_0000016780"
FT TOPO_DOM 22..376
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 398..822
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..119
FT /note="Ig-like C2-type 1"
FT DOMAIN 158..246
FT /note="Ig-like C2-type 2"
FT DOMAIN 255..357
FT /note="Ig-like C2-type 3"
FT DOMAIN 478..767
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 120..154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 160..177
FT /note="Heparin-binding"
FT REGION 778..822
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..137
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 778..794
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 623
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028,
FT ECO:0000269|PubMed:19224897"
FT BINDING 484..490
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 514
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 562..564
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 568
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 627
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 641
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT SITE 428..429
FT /note="Breakpoint for translocation to form CEP43-FGFR1 or
FT FGFR1-CEP43 fusion proteins"
FT /evidence="ECO:0000269|PubMed:9949182"
FT SITE 428..429
FT /note="Breakpoint for translocation to form CNTRL-FGFR1 OR
FT FGFR1-CNTRL fusion proteins"
FT /evidence="ECO:0000269|PubMed:10688839"
FT SITE 428..429
FT /note="Breakpoint for translocation to form FGFR1OP2-FGFR1"
FT /evidence="ECO:0000269|PubMed:15034873,
FT ECO:0000269|PubMed:16946300, ECO:0000269|PubMed:17389761"
FT SITE 766
FT /note="Mediates interaction with PLCG1 and SHB"
FT MOD_RES 463
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16507368,
FT ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:8622701"
FT MOD_RES 583
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16507368,
FT ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:8622701"
FT MOD_RES 585
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16507368,
FT ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:8622701"
FT MOD_RES 653
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16507368,
FT ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:19665973,
FT ECO:0000269|PubMed:8622701"
FT MOD_RES 654
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16507368,
FT ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:19665973,
FT ECO:0000269|PubMed:8622701"
FT MOD_RES 730
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19224897,
FT ECO:0000269|PubMed:8622701"
FT MOD_RES 766
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19665973"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 330
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 55..101
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 178..230
FT DISULFID 277..341
FT VAR_SEQ 1..160
FT /note="Missing (in isoform 10, isoform 11, isoform 12 and
FT isoform 13)"
FT /evidence="ECO:0000303|PubMed:1846977"
FT /id="VSP_002957"
FT VAR_SEQ 1..30
FT /note="MWSWKCLLFWAVLVTATLCTARPSPTLPEQ -> MAAVTRDFGEMLLHSGRV
FT LPAE (in isoform 20)"
FT /evidence="ECO:0000303|Ref.12"
FT /id="VSP_041916"
FT VAR_SEQ 1
FT /note="M -> MEARVSLKRRIELTVEYPWRCGALSPTSNCRTGM (in isoform
FT 21)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041917"
FT VAR_SEQ 31..119
FT /note="Missing (in isoform 6, isoform 7, isoform 8, isoform
FT 9, isoform 15, isoform 17 and isoform 18)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:1650441,
FT ECO:0000303|PubMed:1846977, ECO:0000303|PubMed:2162671,
FT ECO:0000303|PubMed:2167437, ECO:0000303|PubMed:7520751"
FT /id="VSP_002958"
FT VAR_SEQ 32..61
FT /note="QPWGAPVEVESFLVHPGDLLQLRCRLRDDV -> CPDLQEAKSCSASFHSIT
FT PLPFGLGTRLSD (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1846977"
FT /id="VSP_009836"
FT VAR_SEQ 62..822
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1846977"
FT /id="VSP_009837"
FT VAR_SEQ 119
FT /note="S -> SVPI (in isoform 19)"
FT /evidence="ECO:0000303|PubMed:1652059,
FT ECO:0000303|PubMed:20139426"
FT /id="VSP_038470"
FT VAR_SEQ 120..150
FT /note="DALPSSEDDDDDDDSSSEEKETDNTKPNRMP -> ACPDLQEAKWCSASFHS
FT ITPLPFGLGTRLSD (in isoform 16)"
FT /evidence="ECO:0000303|PubMed:1650441"
FT /id="VSP_009838"
FT VAR_SEQ 148..149
FT /note="Missing (in isoform 14, isoform 15, isoform 18,
FT isoform 19 and isoform 21)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:1650441,
FT ECO:0000303|PubMed:1652059, ECO:0000303|PubMed:1662973,
FT ECO:0000303|PubMed:1722683, ECO:0000303|PubMed:20139426,
FT ECO:0000303|PubMed:2162671, ECO:0000303|PubMed:2167437,
FT ECO:0000303|PubMed:7520751, ECO:0000303|Ref.12"
FT /id="VSP_002959"
FT VAR_SEQ 151..822
FT /note="Missing (in isoform 16)"
FT /evidence="ECO:0000303|PubMed:1650441"
FT /id="VSP_009839"
FT VAR_SEQ 313..391
FT /note="TAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLEALEE
FT RPAVMTSPLYLEIIIYCTGAFLISCMV -> VIMAPVFVGQSTGKETTVSGAQVPVGRL
FT SCPRMGSFLTLQAHTLHLSRDLATSPRTSNRGHKVEVSWEQRAAGMGGAGL (in
FT isoform 17 and isoform 18)"
FT /evidence="ECO:0000303|PubMed:2167437"
FT /id="VSP_009840"
FT VAR_SEQ 313..360
FT /note="TAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLE ->
FT HSGINSSDAEVLTLFNVTEAQSGEYVCKVSNYIGEANQSAWLTVTRP (in isoform
FT 19)"
FT /evidence="ECO:0000303|PubMed:1652059,
FT ECO:0000303|PubMed:20139426"
FT /id="VSP_038471"
FT VAR_SEQ 392..822
FT /note="Missing (in isoform 17 and isoform 18)"
FT /evidence="ECO:0000303|PubMed:2167437"
FT /id="VSP_009841"
FT VAR_SEQ 427..428
FT /note="Missing (in isoform 20)"
FT /evidence="ECO:0000303|Ref.12"
FT /id="VSP_041918"
FT VAR_SEQ 428..429
FT /note="Missing (in isoform 4, isoform 5, isoform 8, isoform
FT 9, isoform 12 and isoform 13)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1846977"
FT /id="VSP_002960"
FT VAR_SEQ 619..662
FT /note="CIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNGRL -> VWNL
FT KAPLVHTPRPGSQECPGDRGQCDEDSRLWPRTGHSPHRLL (in isoform 2,
FT isoform 5, isoform 7, isoform 9, isoform 11 and isoform
FT 13)"
FT /evidence="ECO:0000303|PubMed:1846977"
FT /id="VSP_009842"
FT VAR_SEQ 663..822
FT /note="Missing (in isoform 2, isoform 5, isoform 7, isoform
FT 9, isoform 11 and isoform 13)"
FT /evidence="ECO:0000303|PubMed:1846977"
FT /id="VSP_009843"
FT VARIANT 4
FT /note="W -> C (in HH2; unknown pathological significance;
FT dbSNP:rs760884357)"
FT /evidence="ECO:0000269|PubMed:26277103"
FT /id="VAR_074012"
FT VARIANT 22
FT /note="R -> S (in dbSNP:rs17175750)"
FT /evidence="ECO:0000269|Ref.13"
FT /id="VAR_019290"
FT VARIANT 48
FT /note="G -> S (in HH2; phenotype consistent with normosmic
FT idiopathic hypogonadotropic hypogonadism;
FT dbSNP:rs121909640)"
FT /evidence="ECO:0000269|PubMed:16882753"
FT /id="VAR_030968"
FT VARIANT 70
FT /note="G -> R (in HH2; dbSNP:rs140254426)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072993"
FT VARIANT 77
FT /note="N -> K (in dbSNP:rs767195580)"
FT /evidence="ECO:0000269|PubMed:17154279"
FT /id="VAR_030969"
FT VARIANT 78
FT /note="R -> C (in HH2; dbSNP:rs1554570706)"
FT /evidence="ECO:0000269|PubMed:16764984"
FT /id="VAR_030970"
FT VARIANT 96
FT /note="S -> C (in HH2; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:26277103"
FT /id="VAR_074013"
FT VARIANT 97
FT /note="G -> D (in HH2)"
FT /evidence="ECO:0000269|PubMed:12627230"
FT /id="VAR_017885"
FT VARIANT 99
FT /note="Y -> C (in HH2; impairs the tertiary folding
FT resulting in incomplete glycosylation and reduced cell
FT surface expression; dbSNP:rs727505373)"
FT /evidence="ECO:0000269|PubMed:12627230,
FT ECO:0000269|PubMed:19820032"
FT /id="VAR_017886"
FT VARIANT 101
FT /note="C -> F (in HH2)"
FT /evidence="ECO:0000269|PubMed:17154279"
FT /id="VAR_030971"
FT VARIANT 102
FT /note="V -> I (in HH2; dbSNP:rs55642501)"
FT /evidence="ECO:0000269|PubMed:15605412,
FT ECO:0000269|PubMed:16764984"
FT /id="VAR_030972"
FT VARIANT 116
FT /note="V -> I (in HH2; dbSNP:rs747842199)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072994"
FT VARIANT 117
FT /note="N -> S (in HH2; some patients also carry GNRHR
FT mutations; dbSNP:rs780765366)"
FT /evidence="ECO:0000269|PubMed:19820032,
FT ECO:0000269|PubMed:23643382"
FT /id="VAR_069288"
FT VARIANT 125
FT /note="S -> L (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation; dbSNP:rs121913473)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042201"
FT VARIANT 129
FT /note="D -> A (in HH2; dbSNP:rs765615419)"
FT /evidence="ECO:0000269|PubMed:15605412"
FT /id="VAR_030973"
FT VARIANT 165
FT /note="L -> S (in HRTFDS; dbSNP:rs397515481)"
FT /evidence="ECO:0000269|PubMed:23812909"
FT /id="VAR_070851"
FT VARIANT 167
FT /note="A -> S (in HH2; with cleft palate, corpus callosum
FT agenesis, unilateral deafness and fusion of fourth and
FT fifth metacarpal bones; dbSNP:rs121909630)"
FT /evidence="ECO:0000269|PubMed:12627230"
FT /id="VAR_017887"
FT VARIANT 174
FT /note="V -> A (in HH2)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072995"
FT VARIANT 178
FT /note="C -> S (in HH2; with severe ear anomalies)"
FT /evidence="ECO:0000269|PubMed:16757108"
FT /id="VAR_030974"
FT VARIANT 191
FT /note="L -> S (in HRTFDS; dbSNP:rs869025669)"
FT /evidence="ECO:0000269|PubMed:23812909"
FT /id="VAR_070852"
FT VARIANT 213
FT /note="W -> G (in dbSNP:rs17851623)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030975"
FT VARIANT 224
FT /note="D -> H (in HH2)"
FT /evidence="ECO:0000269|PubMed:16764984"
FT /id="VAR_030976"
FT VARIANT 228
FT /note="Y -> D (in HH2; some patients also carry KISS1R
FT mutations; impairs the tertiary folding resulting in
FT incomplete glycosylation and reduced cell surface
FT expression)"
FT /evidence="ECO:0000269|PubMed:19820032,
FT ECO:0000269|PubMed:23643382"
FT /id="VAR_069289"
FT VARIANT 237
FT /note="G -> D (in HH2)"
FT /evidence="ECO:0000269|PubMed:16764984"
FT /id="VAR_030977"
FT VARIANT 237
FT /note="G -> S (in HH2; with or without anosmia; also found
FT in a family member with isolated anosmia; may impair proper
FT folding; dbSNP:rs121909635)"
FT /evidence="ECO:0000269|PubMed:16606836"
FT /id="VAR_030978"
FT VARIANT 239
FT /note="I -> T (in HH2; some patients also carry PROKR2 and
FT GNRH1 mutations; impairs the tertiary folding resulting in
FT incomplete glycosylation and reduced cell surface
FT expression)"
FT /evidence="ECO:0000269|PubMed:19820032,
FT ECO:0000269|PubMed:23643382"
FT /id="VAR_069290"
FT VARIANT 245
FT /note="L -> P (in HH2)"
FT /evidence="ECO:0000269|PubMed:16882753"
FT /id="VAR_030979"
FT VARIANT 250
FT /note="R -> Q (in HH2; with or without anosmia; results in
FT Kallmann syndrome in the presence of HS6ST1 mutation TRP-
FT 306; reduces receptor affinity for fibroblast growth
FT factor; dbSNP:rs121909645)"
FT /evidence="ECO:0000269|PubMed:19820032,
FT ECO:0000269|PubMed:21700882, ECO:0000269|PubMed:23643382,
FT ECO:0000269|PubMed:25077900"
FT /id="VAR_069291"
FT VARIANT 250
FT /note="R -> W (in HH2)"
FT /evidence="ECO:0000269|PubMed:16882753,
FT ECO:0000269|PubMed:17154279"
FT /id="VAR_030980"
FT VARIANT 252
FT /note="P -> R (in PS and JWS; dbSNP:rs121909627)"
FT /evidence="ECO:0000269|PubMed:10861678,
FT ECO:0000269|PubMed:7874169"
FT /id="VAR_004111"
FT VARIANT 252
FT /note="P -> T (in a lung bronchoalveolar carcinoma sample;
FT somatic mutation; dbSNP:rs121913472)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042202"
FT VARIANT 254
FT /note="R -> Q (in HH2)"
FT /evidence="ECO:0000269|PubMed:16764984"
FT /id="VAR_030981"
FT VARIANT 270
FT /note="G -> D (in HH2)"
FT /evidence="ECO:0000269|PubMed:17154279"
FT /id="VAR_030982"
FT VARIANT 273
FT /note="V -> M (in HH2; dbSNP:rs1131691929)"
FT /evidence="ECO:0000269|PubMed:15605412,
FT ECO:0000269|PubMed:16764984"
FT /id="VAR_030983"
FT VARIANT 274
FT /note="E -> G (in HH2; also found in a family member with
FT isolated anosmia; dbSNP:rs727505369)"
FT /id="VAR_030984"
FT VARIANT 277
FT /note="C -> Y (in HH2)"
FT /evidence="ECO:0000269|PubMed:12627230"
FT /id="VAR_017888"
FT VARIANT 283
FT /note="P -> R (in HH2)"
FT /evidence="ECO:0000269|PubMed:17154279"
FT /id="VAR_030985"
FT VARIANT 300
FT /note="I -> T (in TRIGNO1; dbSNP:rs121909633)"
FT /evidence="ECO:0000269|PubMed:11173846"
FT /id="VAR_030986"
FT VARIANT 324..822
FT /note="Missing (in HH2)"
FT /evidence="ECO:0000269|PubMed:17154279"
FT /id="VAR_080328"
FT VARIANT 330
FT /note="N -> I (in OGD; dbSNP:rs121909632)"
FT /evidence="ECO:0000269|PubMed:15625620,
FT ECO:0000269|PubMed:16470795"
FT /id="VAR_030987"
FT VARIANT 332
FT /note="S -> C (in HH2)"
FT /evidence="ECO:0000269|PubMed:17154279"
FT /id="VAR_030988"
FT VARIANT 339
FT /note="Y -> C (in HH2)"
FT /evidence="ECO:0000269|PubMed:16764984"
FT /id="VAR_030989"
FT VARIANT 342
FT /note="L -> S (in HH2; phenotype consistent with Kallmann
FT syndrome; the patient also carries a splice site mutation
FT in NSMF; dbSNP:rs121909638)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069954"
FT VARIANT 343
FT /note="A -> V (in HH2)"
FT /evidence="ECO:0000269|PubMed:16882753"
FT /id="VAR_030990"
FT VARIANT 346
FT /note="S -> C (in HH2; also found in a family member with
FT isolated anosmia)"
FT /evidence="ECO:0000269|PubMed:16764984"
FT /id="VAR_030991"
FT VARIANT 348
FT /note="G -> R (in HH2; phenotype consistent with Kallmann
FT syndrome; the patient also carries a mutation in IL17RD;
FT dbSNP:rs886037634)"
FT /evidence="ECO:0000269|PubMed:23643382,
FT ECO:0000269|PubMed:25077900"
FT /id="VAR_069955"
FT VARIANT 366
FT /note="P -> L (in HH2; with or without anosmia;
FT dbSNP:rs121909641)"
FT /evidence="ECO:0000269|PubMed:16882753"
FT /id="VAR_030992"
FT VARIANT 374
FT /note="Y -> C (in OGD; elevated basal activity and
FT increased FGF2-mediated activity; dbSNP:rs121909631)"
FT /evidence="ECO:0000269|PubMed:15625620"
FT /id="VAR_030993"
FT VARIANT 381
FT /note="C -> R (in OGD; dbSNP:rs121909634)"
FT /evidence="ECO:0000269|PubMed:15625620,
FT ECO:0000269|PubMed:16470795"
FT /id="VAR_030994"
FT VARIANT 470
FT /note="R -> L (in HH2; some patients also carry GNRHR
FT mutations; dbSNP:rs121909637)"
FT /evidence="ECO:0000269|PubMed:19820032,
FT ECO:0000269|PubMed:23643382"
FT /id="VAR_069292"
FT VARIANT 483
FT /note="P -> T (in HH2; phenotype consistent with Kallmann
FT syndrome; the patient also carries a rare variant in SPRY4;
FT dbSNP:rs397515444)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069956"
FT VARIANT 490
FT /note="G -> R (in HRTFDS; dbSNP:rs869025670)"
FT /evidence="ECO:0000269|PubMed:23812909"
FT /id="VAR_070853"
FT VARIANT 520
FT /note="A -> T (in HH2; dbSNP:rs749758370)"
FT /evidence="ECO:0000269|PubMed:15605412"
FT /id="VAR_030995"
FT VARIANT 538
FT /note="I -> V (in HH2)"
FT /evidence="ECO:0000269|PubMed:16764984"
FT /id="VAR_030996"
FT VARIANT 546
FT /note="N -> K (in ECCL; somatic mutation; activating
FT mutation; strongly increased speed of the first
FT autophosphorylation and loss of the normal sequential order
FT of autophosphorylation; dbSNP:rs779707422)"
FT /evidence="ECO:0000269|PubMed:19224897,
FT ECO:0000269|PubMed:26942290"
FT /id="VAR_075853"
FT VARIANT 561
FT /note="V -> M"
FT /evidence="ECO:0000269|PubMed:26942290"
FT /id="VAR_075854"
FT VARIANT 607
FT /note="V -> M (in HH2; with bimanual synkinesis;
FT dbSNP:rs121909629)"
FT /evidence="ECO:0000269|PubMed:12627230"
FT /id="VAR_017889"
FT VARIANT 618
FT /note="K -> N (in HH2; some patients also carry GNRHR
FT mutations; impairs tyrosine kinase activity)"
FT /evidence="ECO:0000269|PubMed:19820032,
FT ECO:0000269|PubMed:23643382"
FT /id="VAR_069293"
FT VARIANT 621
FT /note="H -> R (in HH2)"
FT /evidence="ECO:0000269|PubMed:17154279"
FT /id="VAR_030997"
FT VARIANT 622..822
FT /note="Missing (in HH2)"
FT /evidence="ECO:0000269|PubMed:12627230"
FT /id="VAR_080329"
FT VARIANT 622
FT /note="R -> G (in HH2; with severe ear anomalies;
FT dbSNP:rs121909628)"
FT /evidence="ECO:0000269|PubMed:16757108"
FT /id="VAR_030998"
FT VARIANT 622
FT /note="R -> Q (in HH2)"
FT /evidence="ECO:0000269|PubMed:16757108"
FT /id="VAR_030999"
FT VARIANT 623
FT /note="D -> Y (in HRTFDS; dbSNP:rs398122946)"
FT /evidence="ECO:0000269|PubMed:23812909"
FT /id="VAR_070854"
FT VARIANT 627
FT /note="R -> T (in HRTFDS; dbSNP:rs869025671)"
FT /evidence="ECO:0000269|PubMed:24888332"
FT /id="VAR_071460"
FT VARIANT 628
FT /note="N -> K (in HRTFDS; dbSNP:rs869025672)"
FT /evidence="ECO:0000269|PubMed:23812909"
FT /id="VAR_070855"
FT VARIANT 656
FT /note="K -> E (in ECCL; somatic mutation;
FT dbSNP:rs869320694)"
FT /evidence="ECO:0000269|PubMed:26942290"
FT /id="VAR_075855"
FT VARIANT 661..822
FT /note="Missing (in HH2)"
FT /evidence="ECO:0000269|PubMed:17154279"
FT /id="VAR_080330"
FT VARIANT 664
FT /note="V -> L (in a lung large cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042203"
FT VARIANT 666
FT /note="W -> R (in HH2; with cleft palate;
FT dbSNP:rs1563433902)"
FT /evidence="ECO:0000269|PubMed:12627230"
FT /id="VAR_017890"
FT VARIANT 670
FT /note="E -> K (in HH2; phenotype consistent with Kallmann
FT syndrome; the patient also carries a rare variant in FLRT3;
FT dbSNP:rs397515446)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069957"
FT VARIANT 671
FT /note="A -> P (in HH2)"
FT /evidence="ECO:0000269|PubMed:19820032"
FT /id="VAR_069294"
FT VARIANT 685
FT /note="S -> F (in HH2)"
FT /evidence="ECO:0000269|PubMed:17154279"
FT /id="VAR_031000"
FT VARIANT 687
FT /note="G -> R (in HH2; dbSNP:rs727505376)"
FT /evidence="ECO:0000269|PubMed:15845591,
FT ECO:0000269|PubMed:22927827"
FT /id="VAR_031001"
FT VARIANT 692
FT /note="E -> G (in HH2; phenotype consistent with Kallmann
FT syndrome; the patient also carries a rare variant in DUSP6;
FT dbSNP:rs397515445)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069958"
FT VARIANT 693
FT /note="I -> F (in HH2)"
FT /evidence="ECO:0000269|PubMed:17154279"
FT /id="VAR_031002"
FT VARIANT 703
FT /note="G -> R (in HH2)"
FT /evidence="ECO:0000269|PubMed:16764984"
FT /id="VAR_031003"
FT VARIANT 703
FT /note="G -> S (in HH2; dbSNP:rs768957161)"
FT /evidence="ECO:0000269|PubMed:16764984"
FT /id="VAR_031004"
FT VARIANT 719
FT /note="M -> R (in HH2)"
FT /evidence="ECO:0000269|PubMed:12627230"
FT /id="VAR_017891"
FT VARIANT 719
FT /note="M -> V (in HH2; unknown pathological significance;
FT dbSNP:rs1085307879)"
FT /evidence="ECO:0000269|PubMed:26277103"
FT /id="VAR_074014"
FT VARIANT 722
FT /note="P -> H (in HH2; associated with K-724; also found in
FT a family member with isolated anosmia; reduced tyrosine
FT kinase activity; dbSNP:rs267606805)"
FT /evidence="ECO:0000269|PubMed:16606836,
FT ECO:0000269|PubMed:23643382"
FT /id="VAR_031005"
FT VARIANT 722
FT /note="P -> S (in HH2; dbSNP:rs121909642)"
FT /evidence="ECO:0000269|PubMed:16882753"
FT /id="VAR_031006"
FT VARIANT 724
FT /note="N -> K (in HH2; associated with H-722; also found in
FT a family member with isolated anosmia; reduced tyrosine
FT kinase activity; dbSNP:rs267606806)"
FT /evidence="ECO:0000269|PubMed:16606836,
FT ECO:0000269|PubMed:23643382"
FT /id="VAR_031007"
FT VARIANT 725
FT /note="C -> Y (in HRTFDS; dbSNP:rs398122945)"
FT /evidence="ECO:0000269|PubMed:23812909"
FT /id="VAR_070856"
FT VARIANT 745
FT /note="P -> S (in HH2)"
FT /evidence="ECO:0000269|PubMed:15001591,
FT ECO:0000269|PubMed:15845591"
FT /id="VAR_031008"
FT VARIANT 768
FT /note="D -> Y (in HH2; the patient also carries a rare
FT variant in FGF8; dbSNP:rs121909644)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069959"
FT VARIANT 769
FT /note="L -> V (in dbSNP:rs2956723)"
FT /evidence="ECO:0000269|PubMed:16764984"
FT /id="VAR_031009"
FT VARIANT 772
FT /note="P -> S (in dbSNP:rs56234888)"
FT /evidence="ECO:0000269|PubMed:12627230,
FT ECO:0000269|PubMed:17154279"
FT /id="VAR_017892"
FT VARIANT 795
FT /note="V -> I (in HH2; also found in a family member with
FT isolated anosmia; dbSNP:rs781328162)"
FT /evidence="ECO:0000269|PubMed:16882753"
FT /id="VAR_031010"
FT VARIANT 818
FT /note="G -> R (in dbSNP:rs17182456)"
FT /evidence="ECO:0000269|Ref.13"
FT /id="VAR_019291"
FT VARIANT 822
FT /note="R -> C (in dbSNP:rs17182463)"
FT /evidence="ECO:0000269|PubMed:17154279, ECO:0000269|Ref.13"
FT /id="VAR_019292"
FT MUTAGEN 514
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15117958"
FT MUTAGEN 577
FT /note="R->E: Strongly reduced autophosphorylation in
FT response to FGF signaling. No effect on in vitro kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:20133753"
FT MUTAGEN 609
FT /note="R->V: Abolishes interaction with PLCG1."
FT MUTAGEN 623
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:19224897"
FT MUTAGEN 653
FT /note="Y->F: No effect on kinase activity. Loss of
FT autophosphorylation and kinase activity; when associated
FT with F-654."
FT /evidence="ECO:0000269|PubMed:8622701"
FT MUTAGEN 654
FT /note="Y->F: Reduced kinase activity. Loss of
FT autophosphorylation and kinase activity; when associated
FT with F-653."
FT /evidence="ECO:0000269|PubMed:8622701"
FT MUTAGEN 755
FT /note="D->V: Abolishes interaction with PLCG1."
FT MUTAGEN 766
FT /note="Y->F: Abolishes interaction with PLCG1 and SHB.
FT Decreases phosphorylation of FRS2, activation of RAS and
FT MAP kinase signaling and stimulation of cell
FT proliferation."
FT /evidence="ECO:0000269|PubMed:12181353,
FT ECO:0000269|PubMed:1379697, ECO:0000269|PubMed:1379698,
FT ECO:0000269|PubMed:7516330"
FT CONFLICT 24
FT /note="S -> C (in Ref. 8; AAA35958/AAA35959)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="K -> E (in Ref. 3; AAA35837)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="G -> S (in Ref. 5; AAA35835)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="E -> G (in Ref. 16; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="S -> F (in Ref. 12; BAD96438)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="V -> A (in Ref. 8; AAA35958/AAA35959)"
FT /evidence="ECO:0000305"
FT CONFLICT 364
FT /note="E -> Q (in Ref. 18; CAA68679)"
FT /evidence="ECO:0000305"
FT CONFLICT 469
FT /note="P -> L (in Ref. 1; AAA75007)"
FT /evidence="ECO:0000305"
FT CONFLICT 482
FT /note="K -> R (in Ref. 12; BAD96438)"
FT /evidence="ECO:0000305"
FT CONFLICT 576
FT /note="R -> W (in Ref. 12; BAD96438)"
FT /evidence="ECO:0000305"
FT CONFLICT 817
FT /note="G -> R (in Ref. 4; CAA36101)"
FT /evidence="ECO:0000305"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:2CR3"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:2CR3"
FT STRAND 63..72
FT /evidence="ECO:0007829|PDB:2CR3"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:2CR3"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:2CR3"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:2CR3"
FT STRAND 97..105
FT /evidence="ECO:0007829|PDB:2CR3"
FT STRAND 108..116
FT /evidence="ECO:0007829|PDB:2CR3"
FT STRAND 151..156
FT /evidence="ECO:0007829|PDB:5W59"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 187..192
FT /evidence="ECO:0007829|PDB:5W59"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:5W59"
FT TURN 210..213
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 214..217
FT /evidence="ECO:0007829|PDB:5W59"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 226..234
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 237..248
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 265..268
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:5W21"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 286..293
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:1CVS"
FT STRAND 307..313
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 316..318
FT /evidence="ECO:0007829|PDB:3OJV"
FT HELIX 320..323
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:5W59"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:1CVS"
FT STRAND 337..345
FT /evidence="ECO:0007829|PDB:5W59"
FT STRAND 348..359
FT /evidence="ECO:0007829|PDB:5W59"
FT TURN 461..463
FT /evidence="ECO:0007829|PDB:5O49"
FT TURN 469..471
FT /evidence="ECO:0007829|PDB:5EW8"
FT HELIX 475..477
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 478..486
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 488..499
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 501..503
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 508..516
FT /evidence="ECO:0007829|PDB:5EW8"
FT HELIX 522..538
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 547..551
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 558..562
FT /evidence="ECO:0007829|PDB:5EW8"
FT HELIX 569..574
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 582..584
FT /evidence="ECO:0007829|PDB:6MZQ"
FT STRAND 585..588
FT /evidence="ECO:0007829|PDB:3KXX"
FT HELIX 591..593
FT /evidence="ECO:0007829|PDB:3KXX"
FT HELIX 597..616
FT /evidence="ECO:0007829|PDB:5EW8"
FT HELIX 626..628
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 629..631
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 637..639
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 641..643
FT /evidence="ECO:0007829|PDB:3JS2"
FT HELIX 648..650
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 653..655
FT /evidence="ECO:0007829|PDB:4UWY"
FT STRAND 658..660
FT /evidence="ECO:0007829|PDB:5AM7"
FT HELIX 663..666
FT /evidence="ECO:0007829|PDB:5EW8"
FT HELIX 669..674
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 676..678
FT /evidence="ECO:0007829|PDB:3GQI"
FT HELIX 679..694
FT /evidence="ECO:0007829|PDB:5EW8"
FT HELIX 706..714
FT /evidence="ECO:0007829|PDB:5EW8"
FT STRAND 722..724
FT /evidence="ECO:0007829|PDB:4RWL"
FT HELIX 727..736
FT /evidence="ECO:0007829|PDB:5EW8"
FT HELIX 741..743
FT /evidence="ECO:0007829|PDB:5EW8"
FT HELIX 747..760
FT /evidence="ECO:0007829|PDB:5EW8"
FT VARIANT P11362-19:353
FT /note="A -> T (in HH2; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:26277103"
FT /id="VAR_082843"
SQ SEQUENCE 822 AA; 91868 MW; 93A01B5D78C3E72C CRC64;
MWSWKCLLFW AVLVTATLCT ARPSPTLPEQ AQPWGAPVEV ESFLVHPGDL LQLRCRLRDD
VQSINWLRDG VQLAESNRTR ITGEEVEVQD SVPADSGLYA CVTSSPSGSD TTYFSVNVSD
ALPSSEDDDD DDDSSSEEKE TDNTKPNRMP VAPYWTSPEK MEKKLHAVPA AKTVKFKCPS
SGTPNPTLRW LKNGKEFKPD HRIGGYKVRY ATWSIIMDSV VPSDKGNYTC IVENEYGSIN
HTYQLDVVER SPHRPILQAG LPANKTVALG SNVEFMCKVY SDPQPHIQWL KHIEVNGSKI
GPDNLPYVQI LKTAGVNTTD KEMEVLHLRN VSFEDAGEYT CLAGNSIGLS HHSAWLTVLE
ALEERPAVMT SPLYLEIIIY CTGAFLISCM VGSVIVYKMK SGTKKSDFHS QMAVHKLAKS
IPLRRQVTVS ADSSASMNSG VLLVRPSRLS SSGTPMLAGV SEYELPEDPR WELPRDRLVL
GKPLGEGCFG QVVLAEAIGL DKDKPNRVTK VAVKMLKSDA TEKDLSDLIS EMEMMKMIGK
HKNIINLLGA CTQDGPLYVI VEYASKGNLR EYLQARRPPG LEYCYNPSHN PEEQLSSKDL
VSCAYQVARG MEYLASKKCI HRDLAARNVL VTEDNVMKIA DFGLARDIHH IDYYKKTTNG
RLPVKWMAPE ALFDRIYTHQ SDVWSFGVLL WEIFTLGGSP YPGVPVEELF KLLKEGHRMD
KPSNCTNELY MMMRDCWHAV PSQRPTFKQL VEDLDRIVAL TSNQEYLDLS MPLDQYSPSF
PDTRSSTCSS GEDSVFSHEP LPEEPCLPRH PAQLANGGLK RR
