FGFR3_HUMAN
ID FGFR3_HUMAN Reviewed; 806 AA.
AC P22607; D3DVP9; D3DVQ0; Q14308; Q16294; Q16608; Q59FL9;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 254.
DE RecName: Full=Fibroblast growth factor receptor 3;
DE Short=FGFR-3;
DE EC=2.7.10.1;
DE AltName: CD_antigen=CD333;
DE Flags: Precursor;
GN Name=FGFR3; Synonyms=JTK4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1847508; DOI=10.1073/pnas.88.4.1095;
RA Keegan K., Johnson D.E., Williams L.T., Hayman M.J.;
RT "Isolation of an additional member of the fibroblast growth factor receptor
RT family, FGFR-3.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:1095-1099(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBUNIT, FGF1- AND
RP FGF2-BINDING, SUBCELLULAR LOCATION, GLYCOSYLATION, AND DIMERIZATION.
RC TISSUE=Squamous cell carcinoma;
RX PubMed=11703096; DOI=10.1006/mcbr.2001.0306;
RA Terada M., Shimizu A., Sato N., Miyakaze S.I., Katayama H.,
RA Kurokawa-Seo M.;
RT "Fibroblast growth factor receptor 3 lacking the Ig IIIb and transmembrane
RT domains secreted from human squamous cell carcinoma DJM-1 binds to FGFs.";
RL Mol. Cell Biol. Res. Commun. 4:365-373(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-65; LEU-384; THR-441;
RP THR-717 AND PHE-726.
RG NIEHS SNPs program;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 76-806 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=1664411; DOI=10.1016/0888-7543(91)90041-c;
RA Thompson L.M., Plummer S., Schalling M., Altherr M.R., Gusella J.F.,
RA Housman D.E., Wasmuth J.J.;
RT "A gene encoding a fibroblast growth factor receptor isolated from the
RT Huntington disease gene region of human chromosome 4.";
RL Genomics 11:1133-1142(1991).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 614-681.
RX PubMed=2247464; DOI=10.1073/pnas.87.22.8913;
RA Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K.;
RT "Putative tyrosine kinases expressed in K-562 human leukemia cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 311-358 (ISOFORM 2).
RC TISSUE=Colon tumor;
RX PubMed=7923141;
RA Murgue B., Tsunekawa S., Rosenberg I., deBeaumont M., Podolsky D.K.;
RT "Identification of a novel variant form of fibroblast growth factor
RT receptor 3 (FGFR3 IIIb) in human colonic epithelium.";
RL Cancer Res. 54:5206-5211(1994).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 311-358 (ISOFORM 2).
RC TISSUE=Keratinocyte;
RX PubMed=7495869; DOI=10.1016/0167-4781(95)00156-b;
RA Scotet E., Houssaint E.;
RT "The choice between alternative IIIb and IIIc exons of the FGFR-3 gene is
RT not strictly tissue-specific.";
RL Biochim. Biophys. Acta 1264:238-242(1995).
RN [11]
RP INTERACTION WITH FGF1; FGF2; FGF4; FGF8 AND FGF9, 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 [12]
RP INVOLVEMENT IN SADDAN, VARIANT SADDAN MET-650, AND CHARACTERIZATION OF
RP VARIANT SADDAN MET-650.
RX PubMed=10053006; DOI=10.1086/302275;
RA Tavormina P.L., Bellus G.A., Webster M.K., Bamshad M.J., Fraley A.E.,
RA McIntosh I., Szabo J., Jiang W., Jabs E.W., Wilcox W.R., Wasmuth J.J.,
RA Donoghue D.J., Thompson L.M., Francomano C.A.;
RT "A novel skeletal dysplasia with developmental delay and acanthosis
RT nigricans is caused by a Lys650Met mutation in the fibroblast growth factor
RT receptor 3 gene.";
RL Am. J. Hum. Genet. 64:722-731(1999).
RN [13]
RP FUNCTION AS FGF9 RECEPTOR IN CHONDROCYTES AND IN ACTIVATION OF SIGNALING
RP PATHWAYS, SUBUNIT, SUBCELLULAR LOCATION, DEGRADATION, AUTOPHOSPHORYLATION,
RP AND CHARACTERIZATION OF VARIANT ACH ARG-380.
RX PubMed=10611230; DOI=10.1128/mcb.20.2.516-522.2000;
RA Monsonego-Ornan E., Adar R., Feferman T., Segev O., Yayon A.;
RT "The transmembrane mutation G380R in fibroblast growth factor receptor 3
RT uncouples ligand-mediated receptor activation from down-regulation.";
RL Mol. Cell. Biol. 20:516-522(2000).
RN [14]
RP FUNCTION IN STIMULATION OF CELL PROLIFERATION; PHOSPHORYLATION OF PIK3R1;
RP PTPN11/SHP2; STAT1; STAT3 AND MAP KINASES, PHOSPHORYLATION AT TYR-724,
RP MUTAGENESIS OF TYR-577; TYR-724; TYR-760 AND TYR-770, AND CHARACTERIZATION
RP OF VARIANT GLU-650.
RX PubMed=11294897; DOI=10.1091/mbc.12.4.931;
RA Hart K.C., Robertson S.C., Donoghue D.J.;
RT "Identification of tyrosine residues in constitutively activated fibroblast
RT growth factor receptor 3 involved in mitogenesis, Stat activation, and
RT phosphatidylinositol 3-kinase activation.";
RL Mol. Biol. Cell 12:931-942(2001).
RN [15]
RP UBIQUITINATION, PHOSPHORYLATION, CATALYTIC ACTIVITY, MUTAGENESIS OF
RP LYS-508, CHARACTERIZATION OF VARIANT ACH ARG-380, AND CHARACTERIZATION OF
RP VARIANT TD2 GLU-650.
RX PubMed=12297284; DOI=10.1016/s0014-5793(02)03255-6;
RA Monsonego-Ornan E., Adar R., Rom E., Yayon A.;
RT "FGF receptors ubiquitylation: dependence on tyrosine kinase activity and
RT role in downregulation.";
RL FEBS Lett. 528:83-89(2002).
RN [16]
RP FUNCTION AS PROTO-ONCOGENE IN ACTIVATION OF SIGNALING AND CELL
RP PROLIFERATION, FUNCTION IN PHOSPHORYLATION OF FRS2, CHARACTERIZATION OF
RP VARIANT GLU-650, AND AUTOPHOSPHORYLATION.
RX PubMed=14534538; DOI=10.1038/sj.onc.1206798;
RA Agazie Y.M., Movilla N., Ischenko I., Hayman M.J.;
RT "The phosphotyrosine phosphatase SHP2 is a critical mediator of
RT transformation induced by the oncogenic fibroblast growth factor receptor
RT 3.";
RL Oncogene 22:6909-6918(2003).
RN [17]
RP INTERACTION WITH FGF1; FGF8; FGF9; FGF17; FGF18; FGF19 AND FGF20, 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 [18]
RP INTERACTION WITH SOCS1 AND SOCS3, FUNCTION IN ACTIVATION OF STAT1 AND MAP
RP KINASES, GLYCOSYLATION, PHOSPHORYLATION, MUTAGENESIS OF LYS-508, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16410555; DOI=10.1242/jcs.02740;
RA Ben-Zvi T., Yayon A., Gertler A., Monsonego-Ornan E.;
RT "Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and
RT modulate fibroblast growth factor receptor signaling.";
RL J. Cell Sci. 119:380-387(2006).
RN [19]
RP FUNCTION IN REGULATION OF CHONDROCYTE PROLIFERATION AND IN ACTIVATION OF
RP PLCG1 AND STAT1, INTERACTION WITH FHF1 AND HEPARIN, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION, AND CHARACTERIZATION OF VARIANTS ARG-380; GLU-650 AND
RP MET-650.
RX PubMed=17561467; DOI=10.1016/j.bone.2006.11.030;
RA Harada D., Yamanaka Y., Ueda K., Nishimura R., Morishima T., Seino Y.,
RA Tanaka H.;
RT "Sustained phosphorylation of mutated FGFR3 is a crucial feature of genetic
RT dwarfism and induces apoptosis in the ATDC5 chondrogenic cell line via
RT PLCgamma-activated STAT1.";
RL Bone 41:273-281(2007).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF CBL, UBIQUITINATION, GLYCOSYLATION,
RP SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND CHARACTERIZATION OF VARIANTS
RP CYS-248; CYS-373 AND MET-650.
RX PubMed=17509076; DOI=10.1111/j.1742-4658.2007.05835.x;
RA Bonaventure J., Horne W.C., Baron R.;
RT "The localization of FGFR3 mutations causing thanatophoric dysplasia type I
RT differentially affects phosphorylation, processing and ubiquitylation of
RT the receptor.";
RL FEBS J. 274:3078-3093(2007).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF FRS2, CHARACTERIZATION OF VARIANT GLU-650,
RP ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RX PubMed=17145761; DOI=10.1074/jbc.m606144200;
RA Krejci P., Masri B., Salazar L., Farrington-Rock C., Prats H.,
RA Thompson L.M., Wilcox W.R.;
RT "Bisindolylmaleimide I suppresses fibroblast growth factor-mediated
RT activation of Erk MAP kinase in chondrocytes by preventing Shp2 association
RT with the Frs2 and Gab1 adaptor proteins.";
RL J. Biol. Chem. 282:2929-2936(2007).
RN [22]
RP INTERACTION WITH FGF19; FGF21 AND KLB.
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 [23]
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 [24]
RP FUNCTION IN ACTIVATION OF STAT1; STAT5; MAPK1/ERK2; MAPK3/ERK1 AND THE MAP
RP KINASE SIGNALING PATHWAY.
RX PubMed=19088846; DOI=10.1371/journal.pone.0003961;
RA Krejci P., Salazar L., Kashiwada T.A., Chlebova K., Salasova A.,
RA Thompson L.M., Bryja V., Kozubik A., Wilcox W.R.;
RT "Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal
RT dysplasia undermines dominant role of STAT1 in FGFR3 signaling in
RT cartilage.";
RL PLoS ONE 3:E3961-E3961(2008).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [26]
RP FUNCTION, INTERACTION WITH PIK3R1 AND PLCG1, AND PHOSPHORYLATION AT
RP TYR-760.
RX PubMed=19286672; DOI=10.1093/hmg/ddp116;
RA Salazar L., Kashiwada T., Krejci P., Muchowski P., Donoghue D.,
RA Wilcox W.R., Thompson L.M.;
RT "A novel interaction between fibroblast growth factor receptor 3 and the
RT p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation
RT of ERK by p85 in multiple myeloma cells.";
RL Hum. Mol. Genet. 18:1951-1961(2009).
RN [27]
RP REVIEW ON FUNCTION; ALTERNATIVE SPLICING; SIGNALING AND ROLE IN DISEASE.
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 [28]
RP REVIEW ON FUNCTION; LIGANDS; SIGNALING; ALTERNATIVE SPLICING; DOMAIN; ROLE
RP IN DISEASE; UBIQUITINATION AND DEGRADATION.
RX PubMed=15748888; DOI=10.1016/j.yexcr.2004.11.012;
RA L'Hote C.G., Knowles M.A.;
RT "Cell responses to FGFR3 signalling: growth, differentiation and
RT apoptosis.";
RL Exp. Cell Res. 304:417-431(2005).
RN [29]
RP REVIEW ON ROLE IN SKELETON DEVELOPMENT AND DISEASE.
RX PubMed=19066716; DOI=10.1007/s00774-008-0009-7;
RA Harada D., Yamanaka Y., Ueda K., Tanaka H., Seino Y.;
RT "FGFR3-related dwarfism and cell signaling.";
RL J. Bone Miner. Metab. 27:9-15(2009).
RN [30]
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 [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 32-365 IN COMPLEX WITH FGF1,
RP ACTIVITY REGULATION, AND DOMAIN.
RX PubMed=14732692; DOI=10.1073/pnas.0307287101;
RA Olsen S.K., Ibrahimi O.A., Raucci A., Zhang F., Eliseenkova A.V., Yayon A.,
RA Basilico C., Linhardt R.J., Schlessinger J., Mohammadi M.;
RT "Insights into the molecular basis for fibroblast growth factor receptor
RT autoinhibition and ligand-binding promiscuity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:935-940(2004).
RN [33]
RP VARIANT ACH ARG-380.
RX PubMed=8078586; DOI=10.1038/371252a0;
RA Rousseau F., Bonaventure J., Legeai-Mallet L., Pelet A., Rozet J.-M.,
RA Maroteaux P., le Merrer M., Munnich A.;
RT "Mutations in the gene encoding fibroblast growth factor receptor-3 in
RT achondroplasia.";
RL Nature 371:252-254(1994).
RN [34]
RP VARIANT ACH ARG-380.
RX PubMed=7847369;
RA Bellus G.A., Hefferon T.W., de Luna R.I., Hecht J.T., Horton W.A.,
RA Machado M., Kaitila I., McIntosh I., Francomano C.A.;
RT "Achondroplasia is defined by recurrent G380R mutations of FGFR3.";
RL Am. J. Hum. Genet. 56:368-373(1995).
RN [35]
RP VARIANT ACH CYS-375.
RX PubMed=7758520; DOI=10.1007/bf01954274;
RA Superti-Furga A., Eich G., Bucher H.U., Wisser J., Giedion A.,
RA Gitzelmann R., Steinmann B.;
RT "A glycine 375-to-cysteine substitution in the transmembrane domain of the
RT fibroblast growth factor receptor-3 in a newborn with achondroplasia.";
RL Eur. J. Pediatr. 154:215-219(1995).
RN [36]
RP VARIANT TD1 CYS-249.
RX PubMed=8589699; DOI=10.1093/hmg/4.11.2175;
RA Tavormina P.L., Rimoin D.L., Cohn D.H., Zhu Y.-Z., Shiang R., Wasmuth J.J.;
RT "Another mutation that results in the substitution of an unpaired cysteine
RT residue in the extracellular domain of FGFR3 in thanatophoric dysplasia
RT type I.";
RL Hum. Mol. Genet. 4:2175-2177(1995).
RN [37]
RP VARIANTS TD1 CYS-248 AND CYS-371, AND VARIANT TD2 GLU-650.
RX PubMed=7773297; DOI=10.1038/ng0395-321;
RA Tavormina P.L., Shiang R., Thompson L.M., Zhu Y.-Z., Wilkin D.J.,
RA Lachman R.S., Wilcox W.R., Rimoin D.L., Cohn D.H., Wasmuth J.J.;
RT "Thanatophoric dysplasia (types I and II) caused by distinct mutations in
RT fibroblast growth factor receptor 3.";
RL Nat. Genet. 9:321-328(1995).
RN [38]
RP VARIANT HYPOCHONDROPLASIA LYS-540.
RX PubMed=7670477; DOI=10.1038/ng0795-357;
RA Bellus G.A., McIntosh I., Smith E.A., Aylsworth A.S., Kaitila I.,
RA Horton W.A., Greenhaw G.A., Hecht J.T., Francomano C.A.;
RT "A recurrent mutation in the tyrosine kinase domain of fibroblast growth
RT factor receptor 3 causes hypochondroplasia.";
RL Nat. Genet. 10:357-359(1995).
RN [39]
RP VARIANT CAN GLU-391.
RX PubMed=7493034; DOI=10.1038/ng1295-462;
RA Meyers G.A., Orlow S.J., Munro I.R., Przylepa K.A., Jabs E.W.;
RT "Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in
RT Crouzon syndrome with acanthosis nigricans.";
RL Nat. Genet. 11:462-464(1995).
RN [40]
RP CHARACTERIZATION OF VARIANT ACH ARG-380.
RX PubMed=8599935; DOI=10.1002/j.1460-2075.1996.tb00384.x;
RA Webster M.K., Donoghue D.J.;
RT "Constitutive activation of fibroblast growth factor receptor 3 by the
RT transmembrane domain point mutation found in achondroplasia.";
RL EMBO J. 15:520-527(1996).
RN [41]
RP VARIANTS TD1 CYS-248; CYS-249; CYS-370 AND CYS-373.
RX PubMed=8845844; DOI=10.1093/hmg/5.4.509;
RA Rousseau F., el Ghouzzi V., Delezoide A.-L., Legeai-Mallet L.,
RA le Merrer M., Munnich A., Bonaventure J.;
RT "Missense FGFR3 mutations create cysteine residues in thanatophoric
RT dwarfism type I (TD1).";
RL Hum. Mol. Genet. 5:509-512(1996).
RN [42]
RP CHARACTERIZATION OF VARIANT TD2 GLU-650, CHARACTERIZATION OF VARIANT
RP GLN-650, AND PHOSPHORYLATION AT TYR-647 AND TYR-648.
RX PubMed=8754806; DOI=10.1128/mcb.16.8.4081;
RA Webster M.K., D'Avis P.Y., Robertson S.C., Donoghue D.J.;
RT "Profound ligand-independent kinase activation of fibroblast growth factor
RT receptor 3 by the activation loop mutation responsible for a lethal
RT skeletal dysplasia, thanatophoric dysplasia type II.";
RL Mol. Cell. Biol. 16:4081-4087(1996).
RN [43]
RP VARIANT MNKS ARG-250.
RX PubMed=9042914;
RA Muenke M., Gripp K.W., McDonald-Mcginn D.M., Gaudenz K., Whitaker L.A.,
RA Bartlett S.P., Markowitz R.I., Robin N.H., Nwokoro N., Mulvihill J.J.,
RA Losken H.W., Mulliken J.B., Guttmacher A.E., Wilroy R.S., Clarke L.A.,
RA Hollway G., Ades L.C., Haan E.A., Mulley J.C., Cohen M.M. Jr., Bellus G.A.,
RA Francomano C.A., Moloney D.M., Wall S.A., Wilkie A.O.M., Zackai E.H.;
RT "A unique point mutation in the fibroblast growth factor receptor 3 gene
RT (FGFR3) defines a new craniosynostosis syndrome.";
RL Am. J. Hum. Genet. 60:555-564(1997).
RN [44]
RP INVOLVEMENT IN MULTIPLE MYELOMA, AND VARIANTS CYS-373; GLU-650 AND MET-650.
RX PubMed=9207791; DOI=10.1038/ng0797-260;
RA Chesi M., Nardini E., Brents L.A., Schroeck E., Ried T., Kuehl W.M.,
RA Bergsagel P.L.;
RT "Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is
RT associated with increased expression and activating mutations of fibroblast
RT growth factor receptor 3.";
RL Nat. Genet. 16:260-264(1997).
RN [45]
RP VARIANT TD1 CYS-370.
RX PubMed=9790257; DOI=10.1507/endocrj.45.suppl_s171;
RA Katsumata N., Kuno T., Miyazaki S., Mikami S., Nagashima-Miyokawa A.,
RA Nimura A., Horikawa R., Tanaka T.;
RT "G370C mutation in the FGFR3 gene in a Japanese patient with thanatophoric
RT dysplasia.";
RL Endocr. J. 45:S171-S174(1998).
RN [46]
RP VARIANT HYPOCHONDROPLASIA VAL-538.
RX PubMed=10215410;
RX DOI=10.1002/(sici)1098-1004(1998)11:4<333::aid-humu18>3.0.co;2-g;
RA Grigelioniene G., Hagenaes L., Ekloef O., Neumeyer L., Haereid P.E.,
RA Anvret M.;
RT "A novel missense mutation Ile538Val in the fibroblast growth factor
RT receptor 3 in hypochondroplasia.";
RL Hum. Mutat. 11:333-333(1998).
RN [47]
RP VARIANT HYPOCHONDROPLASIA THR-540.
RX PubMed=9452043; DOI=10.1002/humu.1380110122;
RA Deutz-Terlouw P.P., Losekoot M., Aalfs C.M., Hennekam R.C.M., Bakker E.;
RT "Asn540Thr substitution in the fibroblast growth factor receptor 3 tyrosine
RT kinase domain causing hypochondroplasia.";
RL Hum. Mutat. Suppl. 1:S62-S65(1998).
RN [48]
RP VARIANT TD1 MET-650.
RX PubMed=10671061;
RA Kitoh H., Brodie S.G., Kupke K.G., Lachman R.S., Wilcox W.R.;
RT "Lys650Met substitution in the tyrosine kinase domain of the fibroblast
RT growth factor receptor gene causes thanatophoric dysplasia type I.";
RL Hum. Mutat. 12:362-363(1998).
RN [49]
RP VARIANT ARG-250.
RX PubMed=9525367; DOI=10.1016/s0140-6736(98)24012-8;
RA Hollway G.E., Suthers G.K., Battese K.M., Turner A.M., David D.J.,
RA Mulley J.C.;
RT "Deafness due to Pro250Arg mutation of FGFR3.";
RL Lancet 351:877-878(1998).
RN [50]
RP VARIANTS TD1 CYS-248; CYS-249 AND CYS-373.
RX PubMed=10360402;
RX DOI=10.1002/(sici)1096-8628(19990611)84:5<476::aid-ajmg12>3.0.co;2-x;
RA Brodie S.G., Kitoh H., Lachman R.S., Nolasco L.M., Mekikian P.B.,
RA Wilcox W.R.;
RT "Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by
RT FGFR3 mutations.";
RL Am. J. Med. Genet. 84:476-480(1999).
RN [51]
RP VARIANT MNKS ARG-250.
RX PubMed=9950359;
RA Lajeunie E., El Ghouzzi V., Le Merrer M., Munnich A., Bonaventure J.,
RA Renier D.;
RT "Sex related expressivity of the phenotype in coronal craniosynostosis
RT caused by the recurrent P250R FGFR3 mutation.";
RL J. Med. Genet. 36:9-13(1999).
RN [52]
RP VARIANTS BLC CYS-248; CYS-249; CYS-370 AND GLU-650, AND VARIANTS CERCA
RP CYS-248; CYS-249; CYS-370 AND GLU-650.
RX PubMed=10471491; DOI=10.1038/12615;
RA Cappellen D., De Oliveira C., Ricol D., Gil Diez de Medina S., Bourdin J.,
RA Sastre-Garau X., Chopin D., Thiery J.P., Radvanyi F.;
RT "Frequent activating mutations of FGFR3 in human bladder and cervix
RT carcinomas.";
RL Nat. Genet. 23:18-20(1999).
RN [53]
RP VARIANT HYPOCHONDROPLASIA GLN-650.
RX PubMed=11055896; DOI=10.1086/316892;
RA Bellus G.A., Spector E.B., Speiser P.W., Weaver C.A., Garber A.T.,
RA Bryke C.R., Israel J., Rosengren S.S., Webster M.K., Donoghue D.J.,
RA Francomano C.A.;
RT "Distinct missense mutations of the FGFR3 Lys650 codon modulate receptor
RT kinase activation and the severity of the skeletal dysplasia phenotype.";
RL Am. J. Hum. Genet. 67:1411-1421(2000).
RN [54]
RP VARIANT HYPOCHONDROPLASIA SER-540.
RX PubMed=10777366; DOI=10.1136/jmg.37.3.220;
RA Mortier G., Nuytinck L., Craen M., Renard J.-P., Leroy J.G., De Paepe A.;
RT "Clinical and radiographic features of a family with hypochondroplasia
RT owing to a novel asn540ser mutation in the fibroblast growth factor
RT receptor 3 gene.";
RL J. Med. Genet. 37:220-224(2000).
RN [55]
RP VARIANT MNKS ARG-250.
RX PubMed=11746040; DOI=10.1002/ajmg.10049;
RA Lowry R.B., Jabs E.W., Graham G.E., Gerritsen J., Fleming J.;
RT "Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and sprengel
RT shoulder with and without Pro250Arg mutation in the FGFR3 gene.";
RL Am. J. Med. Genet. 104:112-119(2001).
RN [56]
RP INVOLVEMENT IN MULTIPLE MYELOMA, AND VARIANT CYS-248.
RX PubMed=11529856; DOI=10.1046/j.1365-2141.2001.02957.x;
RA Intini D., Baldini L., Fabris S., Lombardi L., Ciceri G., Maiolo A.T.,
RA Neri A.;
RT "Analysis of FGFR3 gene mutations in multiple myeloma patients with
RT t(4;14).";
RL Br. J. Haematol. 114:362-364(2001).
RN [57]
RP VARIANT COLORECTAL CANCER LYS-322.
RX PubMed=11325814;
RA Jang J.-H., Shin K.-H., Park J.-G.;
RT "Mutations in fibroblast growth factor receptor 2 and fibroblast growth
RT factor receptor 3 genes associated with human gastric and colorectal
RT cancers.";
RL Cancer Res. 61:3541-3543(2001).
RN [58]
RP VARIANT BLC CANCER GLN-650.
RX PubMed=11314002; DOI=10.1038/sj.onc.1204110;
RA Sibley K., Cuthbert-Heavens D., Knowles M.A.;
RT "Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional
RT cell carcinoma.";
RL Oncogene 20:686-691(2001).
RN [59]
RP VARIANT HYPOCHONDROPLASIA SER-540.
RX PubMed=12707965; DOI=10.1002/ajmg.a.10238;
RA Thauvin-Robinet C., Faivre L., Lewin P., De Monleon J.-V., Francois C.,
RA Huet F., Couailler J.-F., Campos-Xavier A.B., Bonaventure J., Le Merrer M.;
RT "Hypochondroplasia and stature within normal limits: another family with an
RT Asn540-to-Ser mutation in the fibroblast growth factor receptor 3 gene.";
RL Am. J. Med. Genet. A 119:81-84(2003).
RN [60]
RP VARIANTS KERSEB CYS-248; CYS-249; CYS-370; CYS-371; CYS-373; GLU-650 AND
RP MET-650.
RX PubMed=15772091; DOI=10.1093/hmg/ddi127;
RA Logie A., Dunois-Larde C., Rosty C., Levrel O., Blanche M., Ribeiro A.,
RA Gasc J.-M., Jorcano J., Werner S., Sastre-Garau X., Thiery J.P.,
RA Radvanyi F.;
RT "Activating mutations of the tyrosine kinase receptor FGFR3 are associated
RT with benign skin tumors in mice and humans.";
RL Hum. Mol. Genet. 14:1153-1160(2005).
RN [61]
RP VARIANT CATSHLS HIS-621.
RX PubMed=17033969; DOI=10.1086/508433;
RA Toydemir R.M., Brassington A.E., Bayrak-Toydemir P., Krakowiak P.A.,
RA Jorde L.B., Whitby F.G., Longo N., Viskochil D.H., Carey J.C.,
RA Bamshad M.J.;
RT "A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing
RT loss (CATSHL) syndrome.";
RL Am. J. Hum. Genet. 79:935-941(2006).
RN [62]
RP VARIANTS KNEN CYS-248; CYS-370 AND ARG-380.
RX PubMed=16841094; DOI=10.1172/jci28163;
RA Hafner C., van Oers J.M.M., Vogt T., Landthaler M., Stoehr R., Blaszyk H.,
RA Hofstaedter F., Zwarthoff E.C., Hartmann A.;
RT "Mosaicism of activating FGFR3 mutations in human skin causes epidermal
RT nevi.";
RL J. Clin. Invest. 116:2201-2207(2006).
RN [63]
RP VARIANT LADDS ASN-513.
RX PubMed=16501574; DOI=10.1038/ng1757;
RA Rohmann E., Brunner H.G., Kayserili H., Uyguner O., Nuernberg G., Lew E.D.,
RA Dobbie A., Eswarakumar V.P., Uzumcu A., Ulubil-Emeroglu M., Leroy J.G.,
RA Li Y., Becker C., Lehnerdt K., Cremers C.W.R.J., Yueksel-Apak M.,
RA Nuernberg P., Kubisch C., Schlessinger J., van Bokhoven H., Wollnik B.;
RT "Mutations in different components of FGF signaling in LADD syndrome.";
RL Nat. Genet. 38:414-417(2006).
RN [64]
RP VARIANT CAN GLU-391.
RX PubMed=17935505; DOI=10.1111/j.1399-0004.2007.00884.x;
RA Arnaud-Lopez L., Fragoso R., Mantilla-Capacho J., Barros-Nunez P.;
RT "Crouzon with acanthosis nigricans. Further delineation of the syndrome.";
RL Clin. Genet. 72:405-410(2007).
RN [65]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-79; ARG-228; MET-338; LEU-384; ASN-646
RP AND GLU-650.
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 [66]
RP VARIANT TGCT GLU-650.
RX PubMed=19855393; DOI=10.1038/ng.470;
RA Goriely A., Hansen R.M., Taylor I.B., Olesen I.A., Jacobsen G.K.,
RA McGowan S.J., Pfeifer S.P., McVean G.A., Rajpert-De Meyts E., Wilkie A.O.;
RT "Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for
RT congenital disorders and testicular tumors.";
RL Nat. Genet. 41:1247-1252(2009).
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 cell proliferation, differentiation and apoptosis. Plays
CC an essential role in the regulation of chondrocyte differentiation,
CC proliferation and apoptosis, and is required for normal skeleton
CC development. Regulates both osteogenesis and postnatal bone
CC mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but
CC can also promote cancer cell proliferation. Required for normal
CC development of the inner ear. Phosphorylates PLCG1, CBL and FRS2.
CC Ligand binding leads to the activation of several signaling cascades.
CC Activation of PLCG1 leads to the production of the cellular signaling
CC 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 Plays a role in the regulation of vitamin D metabolism. Mutations that
CC lead to constitutive kinase activation or impair normal FGFR3
CC maturation, internalization and degradation lead to aberrant signaling.
CC Over-expressed or constitutively activated FGFR3 promotes activation of
CC PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its
CC capacity to bind FGF1 and FGF2 and hence may interfere with FGF
CC signaling. {ECO:0000269|PubMed:10611230, ECO:0000269|PubMed:11294897,
CC ECO:0000269|PubMed:11703096, ECO:0000269|PubMed:14534538,
CC ECO:0000269|PubMed:16410555, ECO:0000269|PubMed:16597617,
CC ECO:0000269|PubMed:17145761, ECO:0000269|PubMed:17311277,
CC ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17561467,
CC ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:19286672,
CC 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:12297284, ECO:0000269|PubMed:17145761};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. Ligand binding leads to dimerization and activation by
CC autophosphorylation on tyrosine residues. Inhibited by SU5402.
CC {ECO:0000269|PubMed:14732692, ECO:0000269|PubMed:17145761,
CC ECO:0000269|PubMed:17509076}.
CC -!- SUBUNIT: Monomer. Homodimer after ligand binding. Interacts with FGF1,
CC FGF2, FGF4, FGF6; FGF8, FGF9, FGF10, FGF17, FGF18, FGF19, FGF20 and
CC FGF23 (in vitro). Interacts with KLB. Affinity for fibroblast growth
CC factors (FGFs) is increased by heparan sulfate glycosaminoglycans that
CC function as coreceptors. Likewise, KLB increases the affinity for FGF19
CC and FGF21. Interacts with PIK3R1, PLCG1, SOCS1 and SOCS3. Isoform 3
CC forms disulfide-linked dimers. {ECO:0000269|PubMed:10611230,
CC ECO:0000269|PubMed:11703096, ECO:0000269|PubMed:14732692,
CC ECO:0000269|PubMed:16410555, ECO:0000269|PubMed:16597617,
CC ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:17623664,
CC ECO:0000269|PubMed:19286672, ECO:0000269|PubMed:8663044}.
CC -!- INTERACTION:
CC P22607; Q6H8Q1-8: ABLIM2; NbExp=3; IntAct=EBI-348399, EBI-16436655;
CC P22607; Q8NC06-3: ACBD4; NbExp=3; IntAct=EBI-348399, EBI-12811089;
CC P22607; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-348399, EBI-10173507;
CC P22607; Q8N302-2: AGGF1; NbExp=3; IntAct=EBI-348399, EBI-25838028;
CC P22607; Q9UKV8: AGO2; NbExp=3; IntAct=EBI-348399, EBI-528269;
CC P22607; P55008: AIF1; NbExp=3; IntAct=EBI-348399, EBI-9031341;
CC P22607; Q99996-3: AKAP9; NbExp=3; IntAct=EBI-348399, EBI-11022349;
CC P22607; Q9NQ31: AKIP1; NbExp=3; IntAct=EBI-348399, EBI-517035;
CC P22607; P53677-2: AP3M2; NbExp=3; IntAct=EBI-348399, EBI-12177015;
CC P22607; D3DTF8: APLN; NbExp=3; IntAct=EBI-348399, EBI-22002556;
CC P22607; Q9NXL2-1: ARHGEF38; NbExp=3; IntAct=EBI-348399, EBI-18172597;
CC P22607; Q9Y2Y0: ARL2BP; NbExp=3; IntAct=EBI-348399, EBI-3449344;
CC P22607; Q66PJ3-4: ARL6IP4; NbExp=3; IntAct=EBI-348399, EBI-5280499;
CC P22607; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-348399, EBI-10254793;
CC P22607; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-348399, EBI-9089489;
CC P22607; Q9UII2: ATP5IF1; NbExp=3; IntAct=EBI-348399, EBI-718459;
CC P22607; Q9ULK2-2: ATXN7L1; NbExp=3; IntAct=EBI-348399, EBI-21568482;
CC P22607; Q9H7T9: AUNIP; NbExp=3; IntAct=EBI-348399, EBI-10693257;
CC P22607; Q8TBE0: BAHD1; NbExp=3; IntAct=EBI-348399, EBI-742750;
CC P22607; Q9UQB8-6: BAIAP2; NbExp=3; IntAct=EBI-348399, EBI-9092016;
CC P22607; Q16520: BATF; NbExp=3; IntAct=EBI-348399, EBI-749503;
CC P22607; P54687-4: BCAT1; NbExp=3; IntAct=EBI-348399, EBI-25834445;
CC P22607; Q00994: BEX3; NbExp=3; IntAct=EBI-348399, EBI-741753;
CC P22607; Q5H9J7: BEX5; NbExp=3; IntAct=EBI-348399, EBI-10243741;
CC P22607; Q9H2G9: BLZF1; NbExp=3; IntAct=EBI-348399, EBI-2548012;
CC P22607; Q5PSV4: BRMS1L; NbExp=3; IntAct=EBI-348399, EBI-5666615;
CC P22607; Q9ULD4-2: BRPF3; NbExp=3; IntAct=EBI-348399, EBI-23662416;
CC P22607; Q9NSI6-4: BRWD1; NbExp=3; IntAct=EBI-348399, EBI-10693038;
CC P22607; Q6P5X5: C22orf39; NbExp=3; IntAct=EBI-348399, EBI-7317823;
CC P22607; Q3SXR2: C3orf36; NbExp=3; IntAct=EBI-348399, EBI-18036948;
CC P22607; Q96LL4: C8orf48; NbExp=3; IntAct=EBI-348399, EBI-751596;
CC P22607; P20807-4: CAPN3; NbExp=3; IntAct=EBI-348399, EBI-11532021;
CC P22607; O00257-3: CBX4; NbExp=3; IntAct=EBI-348399, EBI-4392727;
CC P22607; Q96HB5: CCDC120; NbExp=3; IntAct=EBI-348399, EBI-744556;
CC P22607; Q6ZP82: CCDC141; NbExp=3; IntAct=EBI-348399, EBI-928795;
CC P22607; Q5M9N0-2: CCDC158; NbExp=3; IntAct=EBI-348399, EBI-21796846;
CC P22607; Q96GN5-2: CDCA7L; NbExp=3; IntAct=EBI-348399, EBI-9091443;
CC P22607; P24941: CDK2; NbExp=3; IntAct=EBI-348399, EBI-375096;
CC P22607; O14519: CDK2AP1; NbExp=3; IntAct=EBI-348399, EBI-1052532;
CC P22607; P38936: CDKN1A; NbExp=3; IntAct=EBI-348399, EBI-375077;
CC P22607; O95674: CDS2; NbExp=3; IntAct=EBI-348399, EBI-3913685;
CC P22607; Q9H3R5: CENPH; NbExp=3; IntAct=EBI-348399, EBI-1003700;
CC P22607; Q9Y4F5-3: CEP170B; NbExp=3; IntAct=EBI-348399, EBI-12950757;
CC P22607; Q86XR8: CEP57; NbExp=3; IntAct=EBI-348399, EBI-308614;
CC P22607; Q494V2-2: CFAP100; NbExp=3; IntAct=EBI-348399, EBI-11953200;
CC P22607; Q8WUX9: CHMP7; NbExp=3; IntAct=EBI-348399, EBI-749253;
CC P22607; Q9H2A9: CHST8; NbExp=3; IntAct=EBI-348399, EBI-21642354;
CC P22607; Q9Y3D0: CIAO2B; NbExp=3; IntAct=EBI-348399, EBI-744045;
CC P22607; Q96BR5: COA7; NbExp=3; IntAct=EBI-348399, EBI-6269632;
CC P22607; P02458-1: COL2A1; NbExp=3; IntAct=EBI-348399, EBI-12375799;
CC P22607; P21964-2: COMT; NbExp=3; IntAct=EBI-348399, EBI-10200977;
CC P22607; Q86WV2: COX4I1; NbExp=3; IntAct=EBI-348399, EBI-10260134;
CC P22607; Q03060-25: CREM; NbExp=3; IntAct=EBI-348399, EBI-12884642;
CC P22607; Q8TB03: CXorf38; NbExp=3; IntAct=EBI-348399, EBI-12024320;
CC P22607; O60759: CYTIP; NbExp=3; IntAct=EBI-348399, EBI-997814;
CC P22607; Q9UJU6: DBNL; NbExp=3; IntAct=EBI-348399, EBI-751783;
CC P22607; Q6ZN54-2: DEF8; NbExp=3; IntAct=EBI-348399, EBI-12346463;
CC P22607; Q8NDP9: DKFZp547K2416; NbExp=3; IntAct=EBI-348399, EBI-25842538;
CC P22607; O60479: DLX3; NbExp=3; IntAct=EBI-348399, EBI-3908248;
CC P22607; Q96EY1-3: DNAJA3; NbExp=3; IntAct=EBI-348399, EBI-11526226;
CC P22607; Q9H147: DNTTIP1; NbExp=3; IntAct=EBI-348399, EBI-2795449;
CC P22607; Q92782-2: DPF1; NbExp=3; IntAct=EBI-348399, EBI-23669343;
CC P22607; Q7Z7J5: DPPA2; NbExp=3; IntAct=EBI-348399, EBI-741400;
CC P22607; Q14117: DPYS; NbExp=3; IntAct=EBI-348399, EBI-12275416;
CC P22607; Q9BPU6: DPYSL5; NbExp=3; IntAct=EBI-348399, EBI-724653;
CC P22607; Q9BVC3: DSCC1; NbExp=3; IntAct=EBI-348399, EBI-11143782;
CC P22607; Q9Y6W6: DUSP10; NbExp=3; IntAct=EBI-348399, EBI-3443946;
CC P22607; O14641: DVL2; NbExp=3; IntAct=EBI-348399, EBI-740850;
CC P22607; A0AVK6: E2F8; NbExp=3; IntAct=EBI-348399, EBI-7779316;
CC P22607; Q658K8: EEF1DP3; NbExp=3; IntAct=EBI-348399, EBI-10248874;
CC P22607; Q6UXG2-3: ELAPOR1; NbExp=3; IntAct=EBI-348399, EBI-12920100;
CC P22607; O00472: ELL2; NbExp=3; IntAct=EBI-348399, EBI-395274;
CC P22607; O43768-8: ENSA; NbExp=3; IntAct=EBI-348399, EBI-25853109;
CC P22607; Q6NXG1: ESRP1; NbExp=3; IntAct=EBI-348399, EBI-10213520;
CC P22607; Q15910-2: EZH2; NbExp=3; IntAct=EBI-348399, EBI-10699473;
CC P22607; Q96GL9: FAM163A; NbExp=3; IntAct=EBI-348399, EBI-11793142;
CC P22607; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-348399, EBI-12193763;
CC P22607; Q8NB25: FAM184A; NbExp=3; IntAct=EBI-348399, EBI-9917523;
CC P22607; Q86UY5: FAM83A; NbExp=3; IntAct=EBI-348399, EBI-1384254;
CC P22607; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-348399, EBI-8468186;
CC P22607; Q8TC84: FANK1; NbExp=3; IntAct=EBI-348399, EBI-21975404;
CC P22607; Q9UBX5: FBLN5; NbExp=3; IntAct=EBI-348399, EBI-947897;
CC P22607; Q9Y3I1: FBXO7; NbExp=3; IntAct=EBI-348399, EBI-1161222;
CC P22607; O94868-3: FCHSD2; NbExp=3; IntAct=EBI-348399, EBI-11958845;
CC P22607; P05230: FGF1; NbExp=3; IntAct=EBI-348399, EBI-698068;
CC P22607; P22607: FGFR3; NbExp=4; IntAct=EBI-348399, EBI-348399;
CC P22607; P15407: FOSL1; NbExp=3; IntAct=EBI-348399, EBI-744510;
CC P22607; P15408: FOSL2; NbExp=3; IntAct=EBI-348399, EBI-3893419;
CC P22607; P55318: FOXA3; NbExp=3; IntAct=EBI-348399, EBI-3910364;
CC P22607; Q06547-2: GABPB1; NbExp=3; IntAct=EBI-348399, EBI-618189;
CC P22607; Q06547-3: GABPB1; NbExp=3; IntAct=EBI-348399, EBI-9088619;
CC P22607; P15976-2: GATA1; NbExp=3; IntAct=EBI-348399, EBI-9090198;
CC P22607; P23769-2: GATA2; NbExp=3; IntAct=EBI-348399, EBI-21856389;
CC P22607; P23771: GATA3; NbExp=3; IntAct=EBI-348399, EBI-6664760;
CC P22607; Q49A26-4: GLYR1; NbExp=3; IntAct=EBI-348399, EBI-12143817;
CC P22607; Q7Z5G4: GOLGA7; NbExp=3; IntAct=EBI-348399, EBI-4403685;
CC P22607; Q9NWQ4-1: GPATCH2L; NbExp=3; IntAct=EBI-348399, EBI-11959863;
CC P22607; P52655: GTF2A1; NbExp=3; IntAct=EBI-348399, EBI-389518;
CC P22607; Q15486: GUSBP1; NbExp=4; IntAct=EBI-348399, EBI-712457;
CC P22607; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-348399, EBI-2514791;
CC P22607; Q9BT25: HAUS8; NbExp=3; IntAct=EBI-348399, EBI-2558143;
CC P22607; Q99075: HBEGF; NbExp=3; IntAct=EBI-348399, EBI-7211558;
CC P22607; A8K0U2: hCG_2001421; NbExp=3; IntAct=EBI-348399, EBI-25843825;
CC P22607; Q5T447-2: HECTD3; NbExp=3; IntAct=EBI-348399, EBI-25854793;
CC P22607; Q8IV36: HID1; NbExp=3; IntAct=EBI-348399, EBI-743438;
CC P22607; Q4VB01: HOXB1; NbExp=3; IntAct=EBI-348399, EBI-17494170;
CC P22607; P09629: HOXB7; NbExp=3; IntAct=EBI-348399, EBI-1248457;
CC P22607; O43248: HOXC11; NbExp=3; IntAct=EBI-348399, EBI-2652631;
CC P22607; Q53T59: HS1BP3; NbExp=3; IntAct=EBI-348399, EBI-11335623;
CC P22607; Q53GQ0: HSD17B12; NbExp=3; IntAct=EBI-348399, EBI-2963255;
CC P22607; P14060: HSD3B1; NbExp=3; IntAct=EBI-348399, EBI-17426018;
CC P22607; P08238: HSP90AB1; NbExp=2; IntAct=EBI-348399, EBI-352572;
CC P22607; Q96EW2-2: HSPBAP1; NbExp=3; IntAct=EBI-348399, EBI-25835621;
CC P22607; P10809: HSPD1; NbExp=3; IntAct=EBI-348399, EBI-352528;
CC P22607; Q8NDH6-2: ICA1L; NbExp=3; IntAct=EBI-348399, EBI-12141931;
CC P22607; P41134: ID1; NbExp=3; IntAct=EBI-348399, EBI-1215527;
CC P22607; Q8IY31-2: IFT20; NbExp=3; IntAct=EBI-348399, EBI-11742277;
CC P22607; P22692: IGFBP4; NbExp=3; IntAct=EBI-348399, EBI-2831948;
CC P22607; Q9NZH6: IL37; NbExp=3; IntAct=EBI-348399, EBI-3862125;
CC P22607; Q9NXX0: ILF3; NbExp=3; IntAct=EBI-348399, EBI-743980;
CC P22607; Q86VI3: IQGAP3; NbExp=3; IntAct=EBI-348399, EBI-1237354;
CC P22607; Q8NA54: IQUB; NbExp=3; IntAct=EBI-348399, EBI-10220600;
CC P22607; Q86U28: ISCA2; NbExp=3; IntAct=EBI-348399, EBI-10258659;
CC P22607; Q13352: ITGB3BP; NbExp=3; IntAct=EBI-348399, EBI-712105;
CC P22607; P05412: JUN; NbExp=3; IntAct=EBI-348399, EBI-852823;
CC P22607; P17275: JUNB; NbExp=3; IntAct=EBI-348399, EBI-748062;
CC P22607; Q8N5Z5: KCTD17; NbExp=3; IntAct=EBI-348399, EBI-743960;
CC P22607; Q7Z7F0-4: KHDC4; NbExp=3; IntAct=EBI-348399, EBI-9089060;
CC P22607; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-348399, EBI-14069005;
CC P22607; Q2M2Z5: KIZ; NbExp=3; IntAct=EBI-348399, EBI-2554344;
CC P22607; Q6P597: KLC3; NbExp=3; IntAct=EBI-348399, EBI-1643885;
CC P22607; P57682: KLF3; NbExp=3; IntAct=EBI-348399, EBI-8472267;
CC P22607; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-348399, EBI-714379;
CC P22607; Q9UH77: KLHL3; NbExp=3; IntAct=EBI-348399, EBI-8524663;
CC P22607; P08727: KRT19; NbExp=3; IntAct=EBI-348399, EBI-742756;
CC P22607; Q14525: KRT33B; NbExp=3; IntAct=EBI-348399, EBI-1049638;
CC P22607; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-348399, EBI-1048945;
CC P22607; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-348399, EBI-10241353;
CC P22607; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-348399, EBI-10261141;
CC P22607; Q6IAA8: LAMTOR1; NbExp=3; IntAct=EBI-348399, EBI-715385;
CC P22607; A0A0C4DGV4: LAMTOR5; NbExp=3; IntAct=EBI-348399, EBI-10173304;
CC P22607; Q14847-2: LASP1; NbExp=3; IntAct=EBI-348399, EBI-9088686;
CC P22607; Q9H2C1: LHX5; NbExp=3; IntAct=EBI-348399, EBI-25835523;
CC P22607; Q68G74: LHX8; NbExp=3; IntAct=EBI-348399, EBI-8474075;
CC P22607; Q8N0U6: LINC00518; NbExp=3; IntAct=EBI-348399, EBI-10264791;
CC P22607; Q1L5Z9: LONRF2; NbExp=3; IntAct=EBI-348399, EBI-2510853;
CC P22607; Q96JB6: LOXL4; NbExp=3; IntAct=EBI-348399, EBI-749562;
CC P22607; Q96LR2: LURAP1; NbExp=3; IntAct=EBI-348399, EBI-741355;
CC P22607; P0DP58-2: LYNX1; NbExp=3; IntAct=EBI-348399, EBI-21916939;
CC P22607; P27338: MAOB; NbExp=3; IntAct=EBI-348399, EBI-3911344;
CC P22607; Q9GZQ8: MAP1LC3B; NbExp=3; IntAct=EBI-348399, EBI-373144;
CC P22607; Q15759: MAPK11; NbExp=3; IntAct=EBI-348399, EBI-298304;
CC P22607; Q9NS73-5: MBIP; NbExp=3; IntAct=EBI-348399, EBI-10182361;
CC P22607; P33993-2: MCM7; NbExp=3; IntAct=EBI-348399, EBI-11741465;
CC P22607; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-348399, EBI-348259;
CC P22607; Q9HAF1: MEAF6; NbExp=3; IntAct=EBI-348399, EBI-399266;
CC P22607; Q9H8H3: METTL7A; NbExp=3; IntAct=EBI-348399, EBI-1390168;
CC P22607; D3DX41: MGC16703; NbExp=3; IntAct=EBI-348399, EBI-25850974;
CC P22607; Q8TAC0: MGC27345; NbExp=3; IntAct=EBI-348399, EBI-25851300;
CC P22607; Q53S70: MGC4677; NbExp=3; IntAct=EBI-348399, EBI-10242717;
CC P22607; Q5JXC2: MIIP; NbExp=3; IntAct=EBI-348399, EBI-2801965;
CC P22607; A0A0A0MR05: MLST8; NbExp=3; IntAct=EBI-348399, EBI-25835557;
CC P22607; Q00013: MPP1; NbExp=3; IntAct=EBI-348399, EBI-711788;
CC P22607; Q8TCY5: MRAP; NbExp=3; IntAct=EBI-348399, EBI-9538727;
CC P22607; Q6IN84-2: MRM1; NbExp=3; IntAct=EBI-348399, EBI-25835707;
CC P22607; O60783: MRPS14; NbExp=3; IntAct=EBI-348399, EBI-1045956;
CC P22607; Q96H12: MSANTD3; NbExp=3; IntAct=EBI-348399, EBI-8466227;
CC P22607; P01106: MYC; NbExp=3; IntAct=EBI-348399, EBI-447544;
CC P22607; Q9NPC6: MYOZ2; NbExp=3; IntAct=EBI-348399, EBI-746712;
CC P22607; P41271-2: NBL1; NbExp=3; IntAct=EBI-348399, EBI-12135485;
CC P22607; P14598: NCF1; NbExp=3; IntAct=EBI-348399, EBI-395044;
CC P22607; Q9GZM8: NDEL1; NbExp=3; IntAct=EBI-348399, EBI-928842;
CC P22607; Q8NC67-2: NETO2; NbExp=3; IntAct=EBI-348399, EBI-25852289;
CC P22607; Q16621: NFE2; NbExp=3; IntAct=EBI-348399, EBI-726369;
CC P22607; Q8N5V2: NGEF; NbExp=3; IntAct=EBI-348399, EBI-718372;
CC P22607; Q99743: NPAS2; NbExp=3; IntAct=EBI-348399, EBI-3932727;
CC P22607; Q14995: NR1D2; NbExp=3; IntAct=EBI-348399, EBI-6144053;
CC P22607; F1D8P7: NR1H2; NbExp=3; IntAct=EBI-348399, EBI-10177172;
CC P22607; Q6PHZ7: NR2C2; NbExp=3; IntAct=EBI-348399, EBI-2802743;
CC P22607; Q9BZ95-3: NSD3; NbExp=3; IntAct=EBI-348399, EBI-22002759;
CC P22607; Q96MF7: NSMCE2; NbExp=3; IntAct=EBI-348399, EBI-2557388;
CC P22607; Q4KMX9: OBSCN; NbExp=3; IntAct=EBI-348399, EBI-10490715;
CC P22607; A5D8V7: ODAD3; NbExp=3; IntAct=EBI-348399, EBI-8466445;
CC P22607; Q5BJF6-2: ODF2; NbExp=3; IntAct=EBI-348399, EBI-9090919;
CC P22607; Q3SX64: ODF3L2; NbExp=3; IntAct=EBI-348399, EBI-6660184;
CC P22607; O43482: OIP5; NbExp=3; IntAct=EBI-348399, EBI-536879;
CC P22607; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-348399, EBI-25830200;
CC P22607; Q8IVL6-2: P3H3; NbExp=3; IntAct=EBI-348399, EBI-12149899;
CC P22607; Q9H8K7: PAAT; NbExp=3; IntAct=EBI-348399, EBI-714785;
CC P22607; Q8N3R9: PALS1; NbExp=3; IntAct=EBI-348399, EBI-2513978;
CC P22607; Q495U3: PANX2; NbExp=3; IntAct=EBI-348399, EBI-17242559;
CC P22607; Q9NR21-5: PARP11; NbExp=3; IntAct=EBI-348399, EBI-17159452;
CC P22607; Q9BR81: PCDHGC3; NbExp=3; IntAct=EBI-348399, EBI-22012354;
CC P22607; Q5VU43-8: PDE4DIP; NbExp=3; IntAct=EBI-348399, EBI-25837868;
CC P22607; Q13956: PDE6H; NbExp=3; IntAct=EBI-348399, EBI-10231995;
CC P22607; O15534: PER1; NbExp=3; IntAct=EBI-348399, EBI-2557276;
CC P22607; O15212: PFDN6; NbExp=3; IntAct=EBI-348399, EBI-356973;
CC P22607; Q9BUL5: PHF23; NbExp=3; IntAct=EBI-348399, EBI-722852;
CC P22607; P14618: PKM; NbExp=3; IntAct=EBI-348399, EBI-353408;
CC P22607; Q9UPR0: PLCL2; NbExp=3; IntAct=EBI-348399, EBI-311059;
CC P22607; Q6ZR37: PLEKHG7; NbExp=3; IntAct=EBI-348399, EBI-12891828;
CC P22607; Q5SXH7-1: PLEKHS1; NbExp=3; IntAct=EBI-348399, EBI-26412802;
CC P22607; Q96T60: PNKP; NbExp=3; IntAct=EBI-348399, EBI-1045072;
CC P22607; P19388: POLR2E; NbExp=3; IntAct=EBI-348399, EBI-395189;
CC P22607; Q07869: PPARA; NbExp=3; IntAct=EBI-348399, EBI-78615;
CC P22607; Q9UNP9: PPIE; NbExp=3; IntAct=EBI-348399, EBI-591818;
CC P22607; O60927: PPP1R11; NbExp=3; IntAct=EBI-348399, EBI-1048104;
CC P22607; O60237-2: PPP1R12B; NbExp=3; IntAct=EBI-348399, EBI-10700351;
CC P22607; Q96I34: PPP1R16A; NbExp=3; IntAct=EBI-348399, EBI-710402;
CC P22607; Q6ZMI0-5: PPP1R21; NbExp=3; IntAct=EBI-348399, EBI-25835994;
CC P22607; O43741: PRKAB2; NbExp=3; IntAct=EBI-348399, EBI-1053424;
CC P22607; O60260-5: PRKN; NbExp=3; IntAct=EBI-348399, EBI-21251460;
CC P22607; Q86UA1: PRPF39; NbExp=3; IntAct=EBI-348399, EBI-2803203;
CC P22607; P62333: PSMC6; NbExp=3; IntAct=EBI-348399, EBI-357669;
CC P22607; Q06323: PSME1; NbExp=3; IntAct=EBI-348399, EBI-712149;
CC P22607; P06454-2: PTMA; NbExp=3; IntAct=EBI-348399, EBI-10194874;
CC P22607; Q8WUD1-2: RAB2B; NbExp=3; IntAct=EBI-348399, EBI-25835884;
CC P22607; Q9UNT1-2: RABL2B; NbExp=3; IntAct=EBI-348399, EBI-12256104;
CC P22607; Q15311: RALBP1; NbExp=3; IntAct=EBI-348399, EBI-749285;
CC P22607; Q9HD47-3: RANGRF; NbExp=3; IntAct=EBI-348399, EBI-9089733;
CC P22607; Q9NS23-4: RASSF1; NbExp=3; IntAct=EBI-348399, EBI-438710;
CC P22607; Q9NWB1-5: RBFOX1; NbExp=3; IntAct=EBI-348399, EBI-12123390;
CC P22607; Q9BWF3: RBM4; NbExp=3; IntAct=EBI-348399, EBI-2856454;
CC P22607; Q8TBY0: RBM46; NbExp=3; IntAct=EBI-348399, EBI-12068216;
CC P22607; Q9P2K3-2: RCOR3; NbExp=3; IntAct=EBI-348399, EBI-1504830;
CC P22607; Q04206: RELA; NbExp=3; IntAct=EBI-348399, EBI-73886;
CC P22607; P47804-3: RGR; NbExp=3; IntAct=EBI-348399, EBI-25834767;
CC P22607; Q15382: RHEB; NbExp=3; IntAct=EBI-348399, EBI-1055287;
CC P22607; Q8IXN7: RIMKLA; NbExp=3; IntAct=EBI-348399, EBI-21890191;
CC P22607; Q8WVD3: RNF138; NbExp=3; IntAct=EBI-348399, EBI-749039;
CC P22607; Q9H0X6: RNF208; NbExp=3; IntAct=EBI-348399, EBI-751555;
CC P22607; P62899: RPL31; NbExp=3; IntAct=EBI-348399, EBI-1053664;
CC P22607; P62244: RPS15A; NbExp=3; IntAct=EBI-348399, EBI-347895;
CC P22607; P62701: RPS4X; NbExp=3; IntAct=EBI-348399, EBI-354303;
CC P22607; Q66K80: RUSC1-AS1; NbExp=3; IntAct=EBI-348399, EBI-10248967;
CC P22607; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-348399, EBI-25837959;
CC P22607; Q86SQ7-2: SDCCAG8; NbExp=3; IntAct=EBI-348399, EBI-10696955;
CC P22607; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-348399, EBI-9089805;
CC P22607; Q13435: SF3B2; NbExp=3; IntAct=EBI-348399, EBI-749111;
CC P22607; O60902-3: SHOX2; NbExp=3; IntAct=EBI-348399, EBI-9092164;
CC P22607; Q9NSD5-3: SLC6A13; NbExp=3; IntAct=EBI-348399, EBI-25831241;
CC P22607; Q9UHI5: SLC7A8; NbExp=3; IntAct=EBI-348399, EBI-13292283;
CC P22607; Q12824: SMARCB1; NbExp=3; IntAct=EBI-348399, EBI-358419;
CC P22607; Q13573: SNW1; NbExp=3; IntAct=EBI-348399, EBI-632715;
CC P22607; O14544: SOCS6; NbExp=3; IntAct=EBI-348399, EBI-3929549;
CC P22607; Q02086-2: SP2; NbExp=3; IntAct=EBI-348399, EBI-9088579;
CC P22607; Q7Z6I5: SPATA12; NbExp=3; IntAct=EBI-348399, EBI-10696971;
CC P22607; Q86W54-2: SPATA24; NbExp=3; IntAct=EBI-348399, EBI-12041693;
CC P22607; Q496A3: SPATS1; NbExp=3; IntAct=EBI-348399, EBI-3923692;
CC P22607; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-348399, EBI-7082156;
CC P22607; Q9C004: SPRY4; NbExp=3; IntAct=EBI-348399, EBI-354861;
CC P22607; Q5W111-2: SPRYD7; NbExp=3; IntAct=EBI-348399, EBI-12408727;
CC P22607; Q99469: STAC; NbExp=3; IntAct=EBI-348399, EBI-2652799;
CC P22607; Q92783-2: STAM; NbExp=3; IntAct=EBI-348399, EBI-12025738;
CC P22607; O75886: STAM2; NbExp=3; IntAct=EBI-348399, EBI-373258;
CC P22607; Q13586: STIM1; NbExp=3; IntAct=EBI-348399, EBI-448878;
CC P22607; Q8N4C7: STX19; NbExp=3; IntAct=EBI-348399, EBI-8484990;
CC P22607; Q15814: TBCC; NbExp=3; IntAct=EBI-348399, EBI-15695297;
CC P22607; O15273: TCAP; NbExp=3; IntAct=EBI-348399, EBI-954089;
CC P22607; Q86WV5: TEN1; NbExp=3; IntAct=EBI-348399, EBI-2562799;
CC P22607; Q96A09: TENT5B; NbExp=3; IntAct=EBI-348399, EBI-752030;
CC P22607; P54274-2: TERF1; NbExp=3; IntAct=EBI-348399, EBI-711018;
CC P22607; Q6N021: TET2; NbExp=3; IntAct=EBI-348399, EBI-310727;
CC P22607; Q9BXU0: TEX12; NbExp=3; IntAct=EBI-348399, EBI-12090309;
CC P22607; Q5T0J7-2: TEX35; NbExp=3; IntAct=EBI-348399, EBI-12833746;
CC P22607; Q8WTV1: THAP3; NbExp=3; IntAct=EBI-348399, EBI-17438286;
CC P22607; Q5T1C6: THEM4; NbExp=3; IntAct=EBI-348399, EBI-7684443;
CC P22607; O60830: TIMM17B; NbExp=3; IntAct=EBI-348399, EBI-2372529;
CC P22607; Q9BZW5-2: TM6SF1; NbExp=3; IntAct=EBI-348399, EBI-25852210;
CC P22607; Q96B77: TMEM186; NbExp=3; IntAct=EBI-348399, EBI-9089409;
CC P22607; Q8N0U2: TMEM61; NbExp=3; IntAct=EBI-348399, EBI-25830583;
CC P22607; Q53NU3: tmp_locus_54; NbExp=3; IntAct=EBI-348399, EBI-10242677;
CC P22607; Q8IUR5-4: TMTC1; NbExp=3; IntAct=EBI-348399, EBI-9089156;
CC P22607; Q71RG4-4: TMUB2; NbExp=3; IntAct=EBI-348399, EBI-25831574;
CC P22607; P50616: TOB1; NbExp=3; IntAct=EBI-348399, EBI-723281;
CC P22607; Q9H496: TOR1AIP2; NbExp=3; IntAct=EBI-348399, EBI-2510146;
CC P22607; P36406: TRIM23; NbExp=3; IntAct=EBI-348399, EBI-740098;
CC P22607; Q9UPQ4-2: TRIM35; NbExp=3; IntAct=EBI-348399, EBI-17716262;
CC P22607; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-348399, EBI-11525489;
CC P22607; Q9Y3Q8: TSC22D4; NbExp=3; IntAct=EBI-348399, EBI-739485;
CC P22607; Q99598: TSNAX; NbExp=3; IntAct=EBI-348399, EBI-742638;
CC P22607; O60636: TSPAN2; NbExp=3; IntAct=EBI-348399, EBI-3914288;
CC P22607; Q6PF05: TTC23L; NbExp=3; IntAct=EBI-348399, EBI-8656864;
CC P22607; Q9UGJ1-2: TUBGCP4; NbExp=3; IntAct=EBI-348399, EBI-10964469;
CC P22607; P49459: UBE2A; NbExp=3; IntAct=EBI-348399, EBI-2339348;
CC P22607; Q13404: UBE2V1; NbExp=3; IntAct=EBI-348399, EBI-1050671;
CC P22607; P11441: UBL4A; NbExp=3; IntAct=EBI-348399, EBI-356983;
CC P22607; Q9HA47-2: UCK1; NbExp=3; IntAct=EBI-348399, EBI-16434682;
CC P22607; P22415: USF1; NbExp=3; IntAct=EBI-348399, EBI-1054489;
CC P22607; Q495M9: USH1G; NbExp=3; IntAct=EBI-348399, EBI-8601749;
CC P22607; Q9H270: VPS11; NbExp=3; IntAct=EBI-348399, EBI-373380;
CC P22607; Q8NEZ2: VPS37A; NbExp=3; IntAct=EBI-348399, EBI-2850578;
CC P22607; Q9P1Q0-4: VPS54; NbExp=3; IntAct=EBI-348399, EBI-25835297;
CC P22607; Q9NX94: WBP1L; NbExp=3; IntAct=EBI-348399, EBI-10316321;
CC P22607; Q8TBZ3-3: WDR20; NbExp=3; IntAct=EBI-348399, EBI-9089370;
CC P22607; O00755: WNT7A; NbExp=3; IntAct=EBI-348399, EBI-727198;
CC P22607; P19544-6: WT1; NbExp=3; IntAct=EBI-348399, EBI-11745701;
CC P22607; O43829: ZBTB14; NbExp=3; IntAct=EBI-348399, EBI-10176632;
CC P22607; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-348399, EBI-14104088;
CC P22607; Q9NP64: ZCCHC17; NbExp=3; IntAct=EBI-348399, EBI-746345;
CC P22607; Q8WUU4: ZNF296; NbExp=3; IntAct=EBI-348399, EBI-8834821;
CC P22607; Q96JL9-2: ZNF333; NbExp=3; IntAct=EBI-348399, EBI-25835852;
CC P22607; Q9C0F3: ZNF436; NbExp=3; IntAct=EBI-348399, EBI-8489702;
CC P22607; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-348399, EBI-745520;
CC P22607; Q3KNS6-3: ZNF829; NbExp=3; IntAct=EBI-348399, EBI-18036029;
CC P22607; B7Z3E8; NbExp=3; IntAct=EBI-348399, EBI-25831617;
CC P22607; Q7L8T7; NbExp=3; IntAct=EBI-348399, EBI-25831943;
CC P22607; Q7Z637; NbExp=3; IntAct=EBI-348399, EBI-25831475;
CC P22607; Q86V28; NbExp=3; IntAct=EBI-348399, EBI-10259496;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein. Cytoplasmic vesicle. Endoplasmic reticulum. Note=The
CC activated receptor is rapidly internalized and degraded. Detected in
CC intracellular vesicles after internalization of the autophosphorylated
CC receptor.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000250}; Single-
CC pass type I membrane protein {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cell membrane {ECO:0000250}; Single-
CC pass type I membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=IIIc;
CC IsoId=P22607-1; Sequence=Displayed;
CC Name=2; Synonyms=IIIb;
CC IsoId=P22607-2; Sequence=VSP_002988;
CC Name=3; Synonyms=FGFR3deltaTM;
CC IsoId=P22607-3; Sequence=VSP_002989;
CC Name=4;
CC IsoId=P22607-4; Sequence=VSP_040945;
CC -!- TISSUE SPECIFICITY: Expressed in brain, kidney and testis. Very low or
CC no expression in spleen, heart, and muscle. In 20- to 22-week old
CC fetuses it is expressed at high level in kidney, lung, small intestine
CC and brain, and to a lower degree in spleen, liver, and muscle. Isoform
CC 2 is detected in epithelial cells. Isoform 1 is not detected in
CC epithelial cells. Isoform 1 and isoform 2 are detected in fibroblastic
CC cells. {ECO:0000269|PubMed:1664411}.
CC -!- DOMAIN: The second and third Ig-like domains directly interact with
CC fibroblast growth factors (FGF) and heparan sulfate proteoglycans.
CC {ECO:0000269|PubMed:14732692}.
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.
CC Phosphorylation at Tyr-724 is essential for stimulation of cell
CC proliferation and activation of PIK3R1, STAT1 and MAP kinase signaling.
CC Phosphorylation at Tyr-760 is required for interaction with PIK3R1 and
CC PLCG1. {ECO:0000269|PubMed:11294897, ECO:0000269|PubMed:19286672}.
CC -!- PTM: Ubiquitinated. Is rapidly ubiquitinated after ligand binding and
CC autophosphorylation, leading to receptor internalization and
CC degradation. Subject to both proteasomal and lysosomal degradation.
CC {ECO:0000269|PubMed:12297284, ECO:0000269|PubMed:17509076}.
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:11703096, ECO:0000269|PubMed:16410555,
CC ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17509076}.
CC -!- DISEASE: Achondroplasia (ACH) [MIM:100800]: A frequent form of short-
CC limb dwarfism. It is characterized by a long, narrow trunk, short
CC extremities, particularly in the proximal (rhizomelic) segments, a
CC large head with frontal bossing, hypoplasia of the midface and a
CC trident configuration of the hands. ACH is an autosomal dominant
CC disease. {ECO:0000269|PubMed:10611230, ECO:0000269|PubMed:12297284,
CC ECO:0000269|PubMed:7758520, ECO:0000269|PubMed:7847369,
CC ECO:0000269|PubMed:8078586, ECO:0000269|PubMed:8599935}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Crouzon syndrome with acanthosis nigricans (CAN) [MIM:612247]:
CC Classic Crouzon disease which is caused by mutations in the FGFR2 gene
CC is characterized by craniosynostosis (premature fusion of the skull
CC sutures), and facial hypoplasia. Crouzon syndrome with acanthosis
CC nigricans (a skin disorder characterized by pigmentation anomalies),
CC CAN, is considered to be an independent disorder from classic Crouzon
CC syndrome. CAN is characterized by additional more severe physical
CC manifestation, such as Chiari malformation, hydrocephalus, and atresia
CC or stenosis of the choanas, and is caused by a specific mutation (Ala-
CC 391 to Glu) in the transmembrane domain of FGFR3. It is proposed to
CC have an autosomal dominant mode of inheritance.
CC {ECO:0000269|PubMed:17935505, ECO:0000269|PubMed:7493034}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Thanatophoric dysplasia 1 (TD1) [MIM:187600]: A neonatal
CC lethal skeletal dysplasia. Affected individuals manifest severe
CC shortening of the limbs with macrocephaly, narrow thorax, short ribs,
CC and curved femurs. {ECO:0000269|PubMed:10360402,
CC ECO:0000269|PubMed:10671061, ECO:0000269|PubMed:7773297,
CC ECO:0000269|PubMed:8589699, ECO:0000269|PubMed:8845844,
CC ECO:0000269|PubMed:9790257}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Thanatophoric dysplasia 2 (TD2) [MIM:187601]: A neonatal
CC lethal skeletal dysplasia causing severe shortening of the limbs,
CC narrow thorax and short ribs. Patients with thanatophoric dysplasia
CC type 2 have straight femurs and cloverleaf skull.
CC {ECO:0000269|PubMed:12297284, ECO:0000269|PubMed:7773297,
CC ECO:0000269|PubMed:8754806}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Hypochondroplasia (HCH) [MIM:146000]: Autosomal dominant
CC disease and is characterized by disproportionate short stature. It
CC resembles achondroplasia, but with a less severe phenotype.
CC {ECO:0000269|PubMed:10215410, ECO:0000269|PubMed:10777366,
CC ECO:0000269|PubMed:11055896, ECO:0000269|PubMed:12707965,
CC ECO:0000269|PubMed:7670477, ECO:0000269|PubMed:9452043}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Bladder cancer (BLC) [MIM:109800]: A malignancy originating in
CC tissues of the urinary bladder. It often presents with multiple tumors
CC appearing at different times and at different sites in the bladder.
CC Most bladder cancers are transitional cell carcinomas that begin in
CC cells that normally make up the inner lining of the bladder. Other
CC types of bladder cancer include squamous cell carcinoma (cancer that
CC begins in thin, flat cells) and adenocarcinoma (cancer that begins in
CC cells that make and release mucus and other fluids). Bladder cancer is
CC a complex disorder with both genetic and environmental influences.
CC {ECO:0000269|PubMed:10471491, ECO:0000269|PubMed:11314002}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry. Somatic mutations can constitutively
CC activate FGFR3.
CC -!- DISEASE: Cervical cancer (CERCA) [MIM:603956]: A malignant neoplasm of
CC the cervix, typically originating from a dysplastic or premalignant
CC lesion previously present at the active squamocolumnar junction. The
CC transformation from mild dysplastic to invasive carcinoma generally
CC occurs slowly within several years, although the rate of this process
CC varies widely. Carcinoma in situ is particularly known to precede
CC invasive cervical cancer in most cases. Cervical cancer is strongly
CC associated with infection by oncogenic types of human papillomavirus.
CC {ECO:0000269|PubMed:10471491}. Note=The gene represented in this entry
CC is involved in disease pathogenesis.
CC -!- DISEASE: Camptodactyly, tall stature, and hearing loss syndrome
CC (CATSHLS) [MIM:610474]: An autosomal dominant syndrome characterized by
CC permanent and irreducible flexion of one or more fingers of the hand
CC and/or feet, tall stature, scoliosis and/or a pectus excavatum, and
CC hearing loss. Affected individuals have developmental delay and/or
CC intellectual disability, and several of these have microcephaly.
CC Radiographic findings included tall vertebral bodies with irregular
CC borders and broad femoral metaphyses with long tubular shafts. On
CC audiological exam, each tested member have bilateral sensorineural
CC hearing loss and absent otoacoustic emissions. The hearing loss was
CC congenital or developed in early infancy, progressed variably in early
CC childhood, and range from mild to severe. Computed tomography and
CC magnetic resonance imaging reveal that the brain, middle ear, and inner
CC ear are structurally normal. {ECO:0000269|PubMed:17033969}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Multiple myeloma (MM) [MIM:254500]: A malignant tumor of
CC plasma cells usually arising in the bone marrow and characterized by
CC diffuse involvement of the skeletal system, hyperglobulinemia, Bence-
CC Jones proteinuria and anemia. Complications of multiple myeloma are
CC bone pain, hypercalcemia, renal failure and spinal cord compression.
CC The aberrant antibodies that are produced lead to impaired humoral
CC immunity and patients have a high prevalence of infection. Amyloidosis
CC may develop in some patients. Multiple myeloma is part of a spectrum of
CC diseases ranging from monoclonal gammopathy of unknown significance
CC (MGUS) to plasma cell leukemia. {ECO:0000269|PubMed:11529856,
CC ECO:0000269|PubMed:9207791}. Note=The gene represented in this entry
CC may be involved in disease pathogenesis. A chromosomal aberration
CC involving FGFR3 is found in multiple myeloma. Translocation
CC t(4;14)(p16.3;q32.3) with the IgH locus.
CC -!- DISEASE: Lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:149730]:
CC An autosomal dominant ectodermal dysplasia, a heterogeneous group of
CC disorders due to abnormal development of two or more ectodermal
CC structures. Lacrimo-auriculo-dento-digital syndrome is characterized by
CC aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped
CC ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb
CC segments anomalies. In addition to these cardinal features, facial
CC dysmorphism, malformations of the kidney and respiratory system and
CC abnormal genitalia have been reported. Craniosynostosis and severe
CC syndactyly are not observed. {ECO:0000269|PubMed:16501574}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Keratinocytic non-epidermolytic nevus (KNEN) [MIM:162900]:
CC Epidermal nevi of the common, non-organoid and non-epidermolytic type
CC are benign skin lesions and may vary in their extent from a single
CC (usually linear) lesion to widespread and systematized involvement.
CC They may be present at birth or develop early during childhood.
CC {ECO:0000269|PubMed:16841094}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Muenke syndrome (MNKS) [MIM:602849]: A condition characterized
CC by premature closure of coronal suture of skull during development
CC (coronal craniosynostosis), which affects the shape of the head and
CC face. It may be uni- or bilateral. When bilateral, it is characterized
CC by a skull with a small antero-posterior diameter (brachycephaly),
CC often with a decrease in the depth of the orbits and hypoplasia of the
CC maxillae. Unilateral closure of the coronal sutures leads to flattening
CC of the orbit on the involved side (plagiocephaly). The intellect is
CC normal. In addition to coronal craniosynostosis some affected
CC individuals show skeletal abnormalities of hands and feet,
CC sensorineural hearing loss, intellectual disability and respiratory
CC insufficiency. {ECO:0000269|PubMed:11746040,
CC ECO:0000269|PubMed:9042914, ECO:0000269|PubMed:9950359}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Keratosis, seborrheic (KERSEB) [MIM:182000]: A common benign
CC skin tumor. Seborrheic keratoses usually begin with the appearance of
CC one or more sharply defined, light brown, flat macules. The lesions may
CC be sparse or numerous. As they initially grow, they develop a velvety
CC to finely verrucous surface, followed by an uneven warty surface with
CC multiple plugged follicles and a dull or lackluster appearance.
CC {ECO:0000269|PubMed:15772091}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common
CC malignancy in males representing 95% of all testicular neoplasms. TGCTs
CC have various pathologic subtypes including: unclassified intratubular
CC germ cell neoplasia, seminoma (including cases with
CC syncytiotrophoblastic cells), spermatocytic seminoma, embryonal
CC carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.
CC {ECO:0000269|PubMed:19855393}. Note=The gene represented in this entry
CC may be involved in disease pathogenesis.
CC -!- DISEASE: Achondroplasia, severe, with developmental delay and
CC acanthosis nigricans (SADDAN) [MIM:616482]: A severe form of
CC achondroplasia associated with developmental delay and acanthosis
CC nigricans. Patients manifest short-limb dwarfism, with a long, narrow
CC trunk, short extremities, particularly in the proximal (rhizomelic)
CC segments, a large head with frontal bossing, hypoplasia of the midface
CC and a trident configuration of the hands. Acanthosis nigricans is a
CC skin condition characterized by brown-pigmented, velvety verrucosities
CC in body folds and creases. {ECO:0000269|PubMed:10053006}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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=BAD92678.1; 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/FGFRID99.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fgfr3/";
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; M58051; AAA52450.1; -; mRNA.
DR EMBL; AF245114; AAF63380.1; -; mRNA.
DR EMBL; AB209441; BAD92678.1; ALT_INIT; mRNA.
DR EMBL; AY768549; AAU89726.1; -; Genomic_DNA.
DR EMBL; AC016773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471131; EAW82564.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82565.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82566.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82567.1; -; Genomic_DNA.
DR EMBL; M64347; AAA58470.1; -; mRNA.
DR EMBL; M59374; AAA63209.1; -; mRNA.
DR EMBL; S76733; AAB33323.1; -; Genomic_DNA.
DR EMBL; X84939; CAA59334.1; -; mRNA.
DR EMBL; U22410; AAA67781.1; -; Genomic_DNA.
DR CCDS; CCDS3353.1; -. [P22607-1]
DR CCDS; CCDS3354.1; -. [P22607-3]
DR CCDS; CCDS54706.1; -. [P22607-2]
DR PIR; A38576; TVHUF3.
DR RefSeq; NP_000133.1; NM_000142.4. [P22607-1]
DR RefSeq; NP_001156685.1; NM_001163213.1. [P22607-2]
DR RefSeq; NP_075254.1; NM_022965.3. [P22607-3]
DR PDB; 1RY7; X-ray; 3.20 A; B=33-365.
DR PDB; 2LZL; NMR; -; A/B=357-399.
DR PDB; 4K33; X-ray; 2.34 A; A=449-759.
DR PDB; 6LVM; X-ray; 2.53 A; A=472-759.
DR PDB; 6PNX; X-ray; 2.20 A; A/B=451-759.
DR PDB; 7DHL; X-ray; 2.57 A; A=472-759.
DR PDBsum; 1RY7; -.
DR PDBsum; 2LZL; -.
DR PDBsum; 4K33; -.
DR PDBsum; 6LVM; -.
DR PDBsum; 6PNX; -.
DR PDBsum; 7DHL; -.
DR AlphaFoldDB; P22607; -.
DR BMRB; P22607; -.
DR SASBDB; P22607; -.
DR SMR; P22607; -.
DR BioGRID; 108552; 158.
DR DIP; DIP-4016N; -.
DR IntAct; P22607; 357.
DR MINT; P22607; -.
DR STRING; 9606.ENSP00000339824; -.
DR BindingDB; P22607; -.
DR ChEMBL; CHEMBL2742; -.
DR DrugBank; DB12147; Erdafitinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB11886; Infigratinib.
DR DrugBank; DB09078; Lenvatinib.
DR DrugBank; DB09079; Nintedanib.
DR DrugBank; DB06589; Pazopanib.
DR DrugBank; DB15102; Pemigatinib.
DR DrugBank; DB08901; Ponatinib.
DR DrugBank; DB15685; Selpercatinib.
DR DrugBank; DB05014; XL999.
DR DrugCentral; P22607; -.
DR GuidetoPHARMACOLOGY; 1810; -.
DR GlyGen; P22607; 7 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P22607; -.
DR PhosphoSitePlus; P22607; -.
DR BioMuta; FGFR3; -.
DR DMDM; 120050; -.
DR EPD; P22607; -.
DR jPOST; P22607; -.
DR MassIVE; P22607; -.
DR PaxDb; P22607; -.
DR PeptideAtlas; P22607; -.
DR PRIDE; P22607; -.
DR ProteomicsDB; 54005; -. [P22607-1]
DR ProteomicsDB; 54006; -. [P22607-2]
DR ProteomicsDB; 54007; -. [P22607-3]
DR ProteomicsDB; 54008; -. [P22607-4]
DR ABCD; P22607; 3 sequenced antibodies.
DR Antibodypedia; 3787; 699 antibodies from 45 providers.
DR DNASU; 2261; -.
DR Ensembl; ENST00000340107.8; ENSP00000339824.4; ENSG00000068078.20. [P22607-2]
DR Ensembl; ENST00000352904.6; ENSP00000231803.1; ENSG00000068078.20. [P22607-3]
DR Ensembl; ENST00000440486.8; ENSP00000414914.2; ENSG00000068078.20. [P22607-1]
DR GeneID; 2261; -.
DR KEGG; hsa:2261; -.
DR MANE-Select; ENST00000440486.8; ENSP00000414914.2; NM_000142.5; NP_000133.1.
DR UCSC; uc003gdr.3; human. [P22607-1]
DR CTD; 2261; -.
DR DisGeNET; 2261; -.
DR GeneCards; FGFR3; -.
DR GeneReviews; FGFR3; -.
DR HGNC; HGNC:3690; FGFR3.
DR HPA; ENSG00000068078; Tissue enhanced (brain, esophagus, skin).
DR MalaCards; FGFR3; -.
DR MIM; 100800; phenotype.
DR MIM; 109800; phenotype.
DR MIM; 134934; gene.
DR MIM; 146000; phenotype.
DR MIM; 149730; phenotype.
DR MIM; 162900; phenotype.
DR MIM; 182000; phenotype.
DR MIM; 187600; phenotype.
DR MIM; 187601; phenotype.
DR MIM; 254500; phenotype.
DR MIM; 273300; phenotype.
DR MIM; 602849; phenotype.
DR MIM; 603956; phenotype.
DR MIM; 610474; phenotype.
DR MIM; 612247; phenotype.
DR MIM; 616482; phenotype.
DR neXtProt; NX_P22607; -.
DR OpenTargets; ENSG00000068078; -.
DR Orphanet; 15; Achondroplasia.
DR Orphanet; 85164; Camptodactyly-tall stature-scoliosis-hearing loss syndrome.
DR Orphanet; 93262; Crouzon syndrome-acanthosis nigricans syndrome.
DR Orphanet; 251579; Giant cell glioblastoma.
DR Orphanet; 251576; Gliosarcoma.
DR Orphanet; 429; Hypochondroplasia.
DR Orphanet; 2363; Lacrimoauriculodentodigital syndrome.
DR Orphanet; 53271; Muenke syndrome.
DR Orphanet; 35099; Non-syndromic bicoronal craniosynostosis.
DR Orphanet; 794; Saethre-Chotzen syndrome.
DR Orphanet; 85165; Severe achondroplasia-developmental delay-acanthosis nigricans syndrome.
DR Orphanet; 1860; Thanatophoric dysplasia type 1.
DR Orphanet; 93274; Thanatophoric dysplasia type 2.
DR PharmGKB; PA28129; -.
DR VEuPathDB; HostDB:ENSG00000068078; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000159880; -.
DR HOGENOM; CLU_000288_74_3_1; -.
DR InParanoid; P22607; -.
DR OMA; PTIYWLK; -.
DR OrthoDB; 220433at2759; -.
DR PhylomeDB; P22607; -.
DR TreeFam; TF316307; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P22607; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3.
DR Reactome; R-HSA-190371; FGFR3b ligand binding and activation. [P22607-2]
DR Reactome; R-HSA-190372; FGFR3c ligand binding and activation. [P22607-1]
DR Reactome; R-HSA-2033515; t(4;14) translocations of FGFR3.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3.
DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3.
DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-HSA-5655332; Signaling by FGFR3 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-8853334; Signaling by FGFR3 fusions in cancer.
DR SignaLink; P22607; -.
DR SIGNOR; P22607; -.
DR BioGRID-ORCS; 2261; 15 hits in 1115 CRISPR screens.
DR ChiTaRS; FGFR3; human.
DR EvolutionaryTrace; P22607; -.
DR GeneWiki; Fibroblast_growth_factor_receptor_3; -.
DR GenomeRNAi; 2261; -.
DR Pharos; P22607; Tclin.
DR PRO; PR:P22607; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P22607; protein.
DR Bgee; ENSG00000068078; Expressed in upper leg skin and 179 other tissues.
DR ExpressionAtlas; P22607; baseline and differential.
DR Genevisible; P22607; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0030133; C:transport vesicle; IDA:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0070977; P:bone maturation; ISS:BHF-UCL.
DR GO; GO:0030282; P:bone mineralization; ISS:BHF-UCL.
DR GO; GO:0060349; P:bone morphogenesis; ISS:BHF-UCL.
DR GO; GO:0007267; P:cell-cell signaling; IEA:Ensembl.
DR GO; GO:0002062; P:chondrocyte differentiation; TAS:UniProtKB.
DR GO; GO:0035988; P:chondrocyte proliferation; TAS:UniProtKB.
DR GO; GO:0003416; P:endochondral bone growth; TAS:UniProtKB.
DR GO; GO:0001958; P:endochondral ossification; TAS:UniProtKB.
DR GO; GO:1902178; P:fibroblast growth factor receptor apoptotic signaling pathway; IMP:UniProtKB.
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:0048640; P:negative regulation of developmental growth; ISS:BHF-UCL.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IMP:UniProtKB.
DR GO; GO:0010518; P:positive regulation of phospholipase activity; IMP:UniProtKB.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 3.
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; 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; 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; Apoptosis; ATP-binding; Cell membrane;
KW Chromosomal rearrangement; Craniosynostosis; Cytoplasmic vesicle; Deafness;
KW Disease variant; Disulfide bond; Dwarfism; Ectodermal dysplasia;
KW Endoplasmic reticulum; Glycoprotein; Immunoglobulin domain; Kinase;
KW Lacrimo-auriculo-dento-digital syndrome; Membrane; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Secreted; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..22
FT CHAIN 23..806
FT /note="Fibroblast growth factor receptor 3"
FT /id="PRO_0000016785"
FT TOPO_DOM 23..375
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 376..396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 397..806
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..126
FT /note="Ig-like C2-type 1"
FT DOMAIN 151..244
FT /note="Ig-like C2-type 2"
FT DOMAIN 253..355
FT /note="Ig-like C2-type 3"
FT DOMAIN 472..761
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 126..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 765..806
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 770..787
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 617
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 478..486
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 508
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61851"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61851"
FT MOD_RES 647
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:8754806"
FT MOD_RES 648
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:8754806"
FT MOD_RES 724
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11294897"
FT MOD_RES 760
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19286672"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 225
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 315
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 61..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 176..228
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 275..339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 311..422
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11703096"
FT /id="VSP_002989"
FT VAR_SEQ 311..358
FT /note="TAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLP ->
FT SWISESVEADVRLRLANVSERDGGEYLCRATNFIGVAEKAFWLSVHGPRA (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:7495869"
FT /id="VSP_002988"
FT VAR_SEQ 654..806
FT /note="GRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFK
FT LLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTDEYLDLS
FT APFEQYSPGGQDTPSSSSSGDDSVFAHDLLPPAPPSSGGSRT -> LVLWGPALGDLHA
FT GGLPVPRHPCGGALQAAEGGPPHGQARQLHTRPVHDHAGVLACRALPEAHLQAAGGGPG
FT PCPYRDVHRRVPGPVGAFRAVLPGWPGHPQLQLLRGRLRVCPRPAAPGPTQQWGLADVK
FT GHWSPTM (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_040945"
FT VARIANT 65
FT /note="G -> R (in dbSNP:rs2305178)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_022167"
FT VARIANT 79
FT /note="T -> S (in a lung adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042207"
FT VARIANT 228
FT /note="C -> R (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042208"
FT VARIANT 248
FT /note="R -> C (in KERSEB, BLC, keratinocytic non-
FT epidermolytic nevus and TD1; severe and lethal; also found
FT as somatic mutation in one patient with multiple myeloma;
FT constitutive dimerization and kinase activation;
FT dbSNP:rs121913482)"
FT /evidence="ECO:0000269|PubMed:10360402,
FT ECO:0000269|PubMed:10471491, ECO:0000269|PubMed:11529856,
FT ECO:0000269|PubMed:15772091, ECO:0000269|PubMed:16841094,
FT ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:7773297,
FT ECO:0000269|PubMed:8845844"
FT /id="VAR_004148"
FT VARIANT 249
FT /note="S -> C (in KERSEB, BLC, cervical cancer and TD1;
FT dbSNP:rs121913483)"
FT /evidence="ECO:0000269|PubMed:10360402,
FT ECO:0000269|PubMed:10471491, ECO:0000269|PubMed:15772091,
FT ECO:0000269|PubMed:8589699, ECO:0000269|PubMed:8845844"
FT /id="VAR_004149"
FT VARIANT 250
FT /note="P -> R (in MNKS; also some individuals with
FT autosomal dominant congenital sensorineural deafness
FT without craniosynostosis; dbSNP:rs4647924)"
FT /evidence="ECO:0000269|PubMed:11746040,
FT ECO:0000269|PubMed:9042914, ECO:0000269|PubMed:9525367,
FT ECO:0000269|PubMed:9950359"
FT /id="VAR_004150"
FT VARIANT 322
FT /note="E -> K (in colorectal cancer; dbSNP:rs121913111)"
FT /evidence="ECO:0000269|PubMed:11325814"
FT /id="VAR_018388"
FT VARIANT 338
FT /note="T -> M"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042209"
FT VARIANT 370
FT /note="G -> C (in KERSEB, BLC, keratinocytic non-
FT epidermolytic nevus and TD1; dbSNP:rs121913479)"
FT /evidence="ECO:0000269|PubMed:10471491,
FT ECO:0000269|PubMed:15772091, ECO:0000269|PubMed:16841094,
FT ECO:0000269|PubMed:8845844, ECO:0000269|PubMed:9790257"
FT /id="VAR_004151"
FT VARIANT 371
FT /note="S -> C (in KERSEB and TD1; dbSNP:rs121913484)"
FT /evidence="ECO:0000269|PubMed:15772091,
FT ECO:0000269|PubMed:7773297"
FT /id="VAR_004152"
FT VARIANT 373
FT /note="Y -> C (in KERSEB and TD1; disulfide-linked dimer
FT with constitutive kinase activation; dbSNP:rs121913485)"
FT /evidence="ECO:0000269|PubMed:10360402,
FT ECO:0000269|PubMed:15772091, ECO:0000269|PubMed:17509076,
FT ECO:0000269|PubMed:8845844, ECO:0000269|PubMed:9207791"
FT /id="VAR_004153"
FT VARIANT 375
FT /note="G -> C (in ACH; dbSNP:rs75790268)"
FT /evidence="ECO:0000269|PubMed:7758520"
FT /id="VAR_004154"
FT VARIANT 380
FT /note="G -> R (in keratinocytic non-epidermolytic nevus and
FT ACH; very common mutation; constitutively activated kinase
FT with impaired internalization and degradation, resulting in
FT prolonged FGFR3 signaling; dbSNP:rs28931614)"
FT /evidence="ECO:0000269|PubMed:10611230,
FT ECO:0000269|PubMed:12297284, ECO:0000269|PubMed:16841094,
FT ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:7847369,
FT ECO:0000269|PubMed:8078586, ECO:0000269|PubMed:8599935"
FT /id="VAR_004155"
FT VARIANT 384
FT /note="F -> L (in dbSNP:rs17881656)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.4"
FT /id="VAR_022168"
FT VARIANT 391
FT /note="A -> E (in CAN; dbSNP:rs28931615)"
FT /evidence="ECO:0000269|PubMed:17935505,
FT ECO:0000269|PubMed:7493034"
FT /id="VAR_004156"
FT VARIANT 441
FT /note="A -> T (in dbSNP:rs17884368)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_022169"
FT VARIANT 513
FT /note="D -> N (in LADDS; dbSNP:rs121913112)"
FT /evidence="ECO:0000269|PubMed:16501574"
FT /id="VAR_029887"
FT VARIANT 538
FT /note="I -> V (in hypochondroplasia; dbSNP:rs80053154)"
FT /evidence="ECO:0000269|PubMed:10215410"
FT /id="VAR_004157"
FT VARIANT 540
FT /note="N -> K (in hypochondroplasia; dbSNP:rs28933068)"
FT /evidence="ECO:0000269|PubMed:7670477"
FT /id="VAR_004158"
FT VARIANT 540
FT /note="N -> S (in hypochondroplasia; mild;
FT dbSNP:rs77722678)"
FT /evidence="ECO:0000269|PubMed:10777366,
FT ECO:0000269|PubMed:12707965"
FT /id="VAR_018389"
FT VARIANT 540
FT /note="N -> T (in hypochondroplasia; dbSNP:rs77722678)"
FT /evidence="ECO:0000269|PubMed:9452043"
FT /id="VAR_004159"
FT VARIANT 621
FT /note="R -> H (in CATSHLS; dbSNP:rs121913113)"
FT /evidence="ECO:0000269|PubMed:17033969"
FT /id="VAR_029108"
FT VARIANT 646
FT /note="D -> N"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042210"
FT VARIANT 650
FT /note="K -> E (in KERSEB, TD2, TGCT and BLC; bladder
FT transitional cell carcinoma; somatic mutation;
FT constitutively activated kinase with impaired
FT internalization and degradation, resulting in prolonged
FT FGFR3 signaling; dbSNP:rs78311289)"
FT /evidence="ECO:0000269|PubMed:10471491,
FT ECO:0000269|PubMed:11294897, ECO:0000269|PubMed:12297284,
FT ECO:0000269|PubMed:14534538, ECO:0000269|PubMed:15772091,
FT ECO:0000269|PubMed:17145761, ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:19855393,
FT ECO:0000269|PubMed:7773297, ECO:0000269|PubMed:8754806,
FT ECO:0000269|PubMed:9207791"
FT /id="VAR_004160"
FT VARIANT 650
FT /note="K -> M (in KERSEB, ACH, TD1 and SADDAN;
FT constitutively activated kinase with impaired
FT internalization and degradation, resulting in prolonged
FT FGFR3 signaling; dbSNP:rs121913105)"
FT /evidence="ECO:0000269|PubMed:10053006,
FT ECO:0000269|PubMed:10671061, ECO:0000269|PubMed:15772091,
FT ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17561467,
FT ECO:0000269|PubMed:9207791"
FT /id="VAR_004161"
FT VARIANT 650
FT /note="K -> Q (in hypochondroplasia and BLC; in
FT hypochondroplasia the form is milder than that seen in
FT individuals with the K-540 or M-650 mutations;
FT constitutively activated kinase; dbSNP:rs78311289)"
FT /evidence="ECO:0000269|PubMed:11055896,
FT ECO:0000269|PubMed:11314002, ECO:0000269|PubMed:8754806"
FT /id="VAR_018390"
FT VARIANT 717
FT /note="A -> T (in dbSNP:rs17882190)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_022170"
FT VARIANT 726
FT /note="I -> F (in dbSNP:rs17880763)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_022171"
FT MUTAGEN 508
FT /note="K->A: Loss of kinase activity. Abolishes
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:12297284,
FT ECO:0000269|PubMed:16410555"
FT MUTAGEN 577
FT /note="Y->F: Minor effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:11294897"
FT MUTAGEN 650
FT /note="K->D: Constitutively activated kinase."
FT MUTAGEN 650
FT /note="K->L: Constitutively activated kinase."
FT MUTAGEN 724
FT /note="Y->F: Strongly reduced kinase activity. Strongly
FT reduced mitogen activity."
FT /evidence="ECO:0000269|PubMed:11294897"
FT MUTAGEN 760
FT /note="Y->F: Minor effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:11294897"
FT MUTAGEN 770
FT /note="Y->F: Minor effect on kinase activity. Increased
FT mitogen activity."
FT /evidence="ECO:0000269|PubMed:11294897"
FT CONFLICT 395
FT /note="L -> V (in Ref. 7; AAA58470)"
FT /evidence="ECO:0000305"
FT CONFLICT 421
FT /note="R -> RQ (in Ref. 3; BAD92678)"
FT /evidence="ECO:0000305"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:1RY7"
FT TURN 208..211
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:1RY7"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 226..232
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 235..246
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 263..268
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:1RY7"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 335..345
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 348..357
FT /evidence="ECO:0007829|PDB:1RY7"
FT STRAND 369..372
FT /evidence="ECO:0007829|PDB:2LZL"
FT HELIX 374..398
FT /evidence="ECO:0007829|PDB:2LZL"
FT TURN 463..465
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 469..471
FT /evidence="ECO:0007829|PDB:6PNX"
FT STRAND 472..480
FT /evidence="ECO:0007829|PDB:6PNX"
FT STRAND 485..493
FT /evidence="ECO:0007829|PDB:6PNX"
FT STRAND 502..509
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 516..532
FT /evidence="ECO:0007829|PDB:6PNX"
FT STRAND 541..545
FT /evidence="ECO:0007829|PDB:6PNX"
FT STRAND 547..550
FT /evidence="ECO:0007829|PDB:6PNX"
FT STRAND 552..556
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 563..568
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 591..610
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 620..622
FT /evidence="ECO:0007829|PDB:6PNX"
FT STRAND 623..625
FT /evidence="ECO:0007829|PDB:6PNX"
FT STRAND 631..633
FT /evidence="ECO:0007829|PDB:6PNX"
FT TURN 643..645
FT /evidence="ECO:0007829|PDB:6LVM"
FT STRAND 646..649
FT /evidence="ECO:0007829|PDB:4K33"
FT HELIX 658..660
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 663..668
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 673..688
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 700..702
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 703..708
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 721..730
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 735..737
FT /evidence="ECO:0007829|PDB:6PNX"
FT HELIX 741..754
FT /evidence="ECO:0007829|PDB:6PNX"
SQ SEQUENCE 806 AA; 87710 MW; BC5EA75EA46F447E CRC64;
MGAPACALAL CVAVAIVAGA SSESLGTEQR VVGRAAEVPG PEPGQQEQLV FGSGDAVELS
CPPPGGGPMG PTVWVKDGTG LVPSERVLVG PQRLQVLNAS HEDSGAYSCR QRLTQRVLCH
FSVRVTDAPS SGDDEDGEDE AEDTGVDTGA PYWTRPERMD KKLLAVPAAN TVRFRCPAAG
NPTPSISWLK NGREFRGEHR IGGIKLRHQQ WSLVMESVVP SDRGNYTCVV ENKFGSIRQT
YTLDVLERSP HRPILQAGLP ANQTAVLGSD VEFHCKVYSD AQPHIQWLKH VEVNGSKVGP
DGTPYVTVLK TAGANTTDKE LEVLSLHNVT FEDAGEYTCL AGNSIGFSHH SAWLVVLPAE
EELVEADEAG SVYAGILSYG VGFFLFILVV AAVTLCRLRS PPKKGLGSPT VHKISRFPLK
RQVSLESNAS MSSNTPLVRI ARLSSGEGPT LANVSELELP ADPKWELSRA RLTLGKPLGE
GCFGQVVMAE AIGIDKDRAA KPVTVAVKML KDDATDKDLS DLVSEMEMMK MIGKHKNIIN
LLGACTQGGP LYVLVEYAAK GNLREFLRAR RPPGLDYSFD TCKPPEEQLT FKDLVSCAYQ
VARGMEYLAS QKCIHRDLAA RNVLVTEDNV MKIADFGLAR DVHNLDYYKK TTNGRLPVKW
MAPEALFDRV YTHQSDVWSF GVLLWEIFTL GGSPYPGIPV EELFKLLKEG HRMDKPANCT
HDLYMIMREC WHAAPSQRPT FKQLVEDLDR VLTVTSTDEY LDLSAPFEQY SPGGQDTPSS
SSSGDDSVFA HDLLPPAPPS SGGSRT
