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 27-MAR-2024, entry version 263. 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; 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>3.3.co;2-o; 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 LADD2 ASN-513, AND INVOLVEMENT IN LADD2. 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 a 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; Q16543: CDC37; NbExp=3; IntAct=EBI-348399, EBI-295634; 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=4; 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; Q3SX64: CIMAP1D; NbExp=3; IntAct=EBI-348399, EBI-6660184; 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=4; IntAct=EBI-348399, EBI-2963255; CC P22607; P14060: HSD3B1; NbExp=3; IntAct=EBI-348399, EBI-17426018; CC P22607; P08238: HSP90AB1; NbExp=4; 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; O43504: LAMTOR5; NbExp=3; IntAct=EBI-348399, EBI-713382; 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; 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; 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=4; 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; Q9H8H3: TMT1A; NbExp=3; IntAct=EBI-348399, EBI-1390168; 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 2 (LADD2) CC [MIM:620192]: A form of lacrimo-auriculo-dento-digital syndrome, an CC autosomal dominant disease characterized by aplastic/hypoplastic CC lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, CC hypodontia and enamel hypoplasia, and distal limb segments anomalies. CC In addition to these cardinal features, facial dysmorphism, CC malformations of the kidney and respiratory system and abnormal CC genitalia have been reported. Craniosynostosis and severe syndactyly CC are not observed. {ECO:0000269|PubMed:16501574}. Note=The disease may CC be caused by variants affecting the gene represented in this 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="https://atlasgeneticsoncology.org/gene/99/FGFR"; 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 PDB; 7YSU; EM; 3.20 A; C/E=148-358. DR PDBsum; 1RY7; -. DR PDBsum; 2LZL; -. DR PDBsum; 4K33; -. DR PDBsum; 6LVM; -. DR PDBsum; 6PNX; -. DR PDBsum; 7DHL; -. DR PDBsum; 7YSU; -. DR AlphaFoldDB; P22607; -. DR BMRB; P22607; -. DR EMDB; EMD-34082; -. DR SASBDB; P22607; -. DR SMR; P22607; -. DR BioGRID; 108552; 349. DR DIP; DIP-4016N; -. DR IntAct; P22607; 559. DR MINT; P22607; -. DR STRING; 9606.ENSP00000339824; -. DR BindingDB; P22607; -. DR ChEMBL; CHEMBL2742; -. DR DrugBank; DB12147; Erdafitinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB15149; Futibatinib. 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 GlyCosmos; P22607; 6 sites, No reported glycans. DR GlyGen; P22607; 7 sites, 1 O-linked glycan (1 site). DR iPTMnet; P22607; -. DR PhosphoSitePlus; P22607; -. DR BioMuta; FGFR3; -. DR DMDM; 120050; -. DR CPTAC; CPTAC-3180; -. DR CPTAC; CPTAC-3181; -. DR EPD; P22607; -. DR jPOST; P22607; -. DR MassIVE; P22607; -. DR PaxDb; 9606-ENSP00000339824; -. DR PeptideAtlas; 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; 844 antibodies from 45 providers. DR DNASU; 2261; -. DR Ensembl; ENST00000340107.9; 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 AGR; HGNC:3690; -. 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; 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 MIM; 620192; 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; RPANCTH; -. DR OrthoDB; 1614410at2759; -. 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 1201 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 181 other cell types or tissues. DR ExpressionAtlas; P22607; baseline and differential. 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: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: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:0016310; P:phosphorylation; IEA:UniProtKB-KW. 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:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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:0007259; P:receptor signaling pathway via JAK-STAT; IMP: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 CDD; cd05857; IgI_2_FGFR; 1. DR Gene3D; 6.10.250.1740; -; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 3. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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; 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 PANTHER; PTHR24416:SF505; FIBROBLAST GROWTH FACTOR RECEPTOR 3; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR Pfam; PF21165; FGFR3_TM; 1. DR Pfam; PF07679; I-set; 1. DR Pfam; PF13927; Ig_3; 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; Immunoglobulin; 3. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; P22607; HS. 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 FT non-epidermolytic nevus and TD1; severe and lethal; also FT found as somatic mutation in one patient with multiple FT myeloma; 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 FT non-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 LADD2; uncertain significance; FT 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 152..154 FT /evidence="ECO:0007829|PDB:7YSU" FT HELIX 156..158 FT /evidence="ECO:0007829|PDB:7YSU" 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 TURN 319..321 FT /evidence="ECO:0007829|PDB:7YSU" FT STRAND 324..326 FT /evidence="ECO:0007829|PDB:1RY7" FT STRAND 331..333 FT /evidence="ECO:0007829|PDB:7YSU" 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 //