[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). DOI=10.1073/pnas.88.4.1095; PubMed=1847508 [NCBI, ExPASy, EBI, Israel, Japan] Keegan K., Johnson D.E., Williams L.T., Hayman M.J.; "Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3."; Proc. Natl. Acad. Sci. U.S.A. 88:1095-1099(1991).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). DOI=10.1006/mcbr.2001.0306; PubMed=11703096 [NCBI, ExPASy, EBI, Israel, Japan] Terada M., Shimizu A., Sato N., Miyakaze S.I., Katayama H., Kurokawa-Seo M.; "Fibroblast growth factor receptor 3 lacking the Ig IIIb and transmembrane domains secreted from human squamous cell carcinoma DJM-1 binds to FGFs."; Mol. Cell Biol. Res. Commun. 4:365-373(2001).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-65; LEU-384; THR-441; THR-717 AND PHE-726. NIEHS SNPs program; Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
[4]	NUCLEOTIDE SEQUENCE [MRNA] OF 76-806 (ISOFORM 1), AND TISSUE SPECIFICITY. TISSUE=Fetal brain; DOI=10.1016/0888-7543(91)90041-C; PubMed=1664411 [NCBI, ExPASy, EBI, Israel, Japan] Thompson L.M., Plummer S., Schalling M., Altherr M.R., Gusella J.F., Housman D.E., Wasmuth J.J.; "A gene encoding a fibroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4."; Genomics 11:1133-1142(1991).
[5]	NUCLEOTIDE SEQUENCE [MRNA] OF 614-681. DOI=10.1073/pnas.87.22.8913; PubMed=2247464 [NCBI, ExPASy, EBI, Israel, Japan] Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K.; "Putative tyrosine kinases expressed in K-562 human leukemia cells."; Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990).
[6]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 311-358 (ISOFORM 2). TISSUE=Colon tumor; PubMed=7923141 [NCBI, ExPASy, EBI, Israel, Japan] Murgue B., Tsunekawa S., Rosenberg I., deBeaumont M., Podolsky D.K.; "Identification of a novel variant form of fibroblast growth factor receptor 3 (FGFR3 IIIb) in human colonic epithelium."; Cancer Res. 54:5206-5211(1994).
[7]	NUCLEOTIDE SEQUENCE [MRNA] OF 311-358 (ISOFORM 2). TISSUE=Keratinocyte; DOI=10.1016/0167-4781(95)00156-B; PubMed=7495869 [NCBI, ExPASy, EBI, Israel, Japan] Scotet E., Houssaint E.; "The choice between alternative IIIb and IIIc exons of the FGFR-3 gene is not strictly tissue-specific."; Biochim. Biophys. Acta 1264:238-242(1995).
[8]	X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 32-365 IN COMPLEX WITH FGF1. DOI=10.1073/pnas.0307287101; PubMed=14732692 [NCBI, ExPASy, EBI, Israel, Japan] Olsen S.K., Ibrahimi O.A., Raucci A., Zhang F., Eliseenkova A.V., Yayon A., Basilico C., Linhardt R.J., Schlessinger J., Mohammadi M.; "Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity."; Proc. Natl. Acad. Sci. U.S.A. 101:935-940(2004).
[9]	VARIANT ACH ARG-380. DOI=10.1038/371252a0; PubMed=8078586 [NCBI, ExPASy, EBI, Israel, Japan] Rousseau F., Bonaventure J., Legeai-Mallet L., Pelet A., Rozet J.-M., Maroteaux P., le Merrer M., Munnich A.; "Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia."; Nature 371:252-254(1994).
[10]	VARIANT ACH ARG-380. PubMed=7847369 [NCBI, ExPASy, EBI, Israel, Japan] Bellus G.A., Hefferon T.W., de Luna R.I., Hecht J.T., Horton W.A., Machado M., Kaitila I., McIntosh I., Francomano C.A.; "Achondroplasia is defined by recurrent G380R mutations of FGFR3."; Am. J. Hum. Genet. 56:368-373(1995).
[11]	VARIANT ACH CYS-375. DOI=10.1007/s004310050278; PubMed=7758520 [NCBI, ExPASy, EBI, Israel, Japan] Superti-Furga A., Eich G., Bucher H.U., Wisser J., Giedion A., Gitzelmann R., Steinmann B.; "A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia."; Eur. J. Pediatr. 154:215-219(1995).
[12]	VARIANT TD CYS-249. DOI=10.1093/hmg/4.11.2175; PubMed=8589699 [NCBI, ExPASy, EBI, Israel, Japan] Tavormina P.L., Rimoin D.L., Cohn D.H., Zhu Y.-Z., Shiang R., Wasmuth J.J.; "Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I."; Hum. Mol. Genet. 4:2175-2177(1995).
[13]	VARIANTS TD CYS-248; CYS-371 AND GLU-650. DOI=10.1038/ng0395-321; PubMed=7773297 [NCBI, ExPASy, EBI, Israel, Japan] Tavormina P.L., Shiang R., Thompson L.M., Zhu Y.-Z., Wilkin D.J., Lachman R.S., Wilcox W.R., Rimoin D.L., Cohn D.H., Wasmuth J.J.; "Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3."; Nat. Genet. 9:321-328(1995).
[14]	VARIANT HYPOCHONDROPLASIA LYS-540. DOI=10.1038/ng0795-357; PubMed=7670477 [NCBI, ExPASy, EBI, Israel, Japan] Bellus G.A., McIntosh I., Smith E.A., Aylsworth A.S., Kaitila I., Horton W.A., Greenhaw G.A., Hecht J.T., Francomano C.A.; "A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia."; Nat. Genet. 10:357-359(1995).
[15]	VARIANT CAN GLU-391. DOI=10.1038/ng1295-462; PubMed=7493034 [NCBI, ExPASy, EBI, Israel, Japan] Meyers G.A., Orlow S.J., Munro I.R., Przylepa K.A., Jabs E.W.; "Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans."; Nat. Genet. 11:462-464(1995).
[16]	CHARACTERIZATION OF VARIANT ACH ARG-380. PubMed=8599935 [NCBI, ExPASy, EBI, Israel, Japan] Webster M.K., Donoghue D.J.; "Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia."; EMBO J. 15:520-527(1996).
[17]	VARIANTS TD CYS-248; CYS-249; CYS-370 AND CYS-373. DOI=10.1093/hmg/5.4.509; PubMed=8845844 [NCBI, ExPASy, EBI, Israel, Japan] Rousseau F., el Ghouzzi V., Delezoide A.-L., Legeai-Mallet L., le Merrer M., Munnich A., Bonaventure J.; "Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)."; Hum. Mol. Genet. 5:509-512(1996).
[18]	VARIANT MNKS ARG-250. PubMed=9042914 [NCBI, ExPASy, EBI, Israel, Japan] Muenke M., Gripp K.W., McDonald-Mcginn D.M., Gaudenz K., Whitaker L.A., Bartlett S.P., Markowitz R.I., Robin N.H., Nwokoro N., Mulvihill J.J., Losken H.W., Mulliken J.B., Guttmacher A.E., Wilroy R.S., Clarke L.A., Hollway G., Ades L.C., Haan E.A., Mulley J.C., Cohen M.M. Jr., Bellus G.A., Francomano C.A., Moloney D.M., Wall S.A., Wilkie A.O.M., Zackai E.H.; "A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome."; Am. J. Hum. Genet. 60:555-564(1997).
[19]	INVOLVEMENT IN MULTIPLE MYELOMA, AND VARIANTS CYS-373; GLU-650 AND MET-650. DOI=10.1038/ng0797-260; PubMed=9207791 [NCBI, ExPASy, EBI, Israel, Japan] Chesi M., Nardini E., Brents L.A., Schroeck E., Ried T., Kuehl W.M., Bergsagel P.L.; "Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3."; Nat. Genet. 16:260-264(1997).
[20]	VARIANT TD CYS-370. PubMed=9790257 [NCBI, ExPASy, EBI, Israel, Japan] Katsumata N., Kuno T., Miyazaki S., Mikami S., Nagashima-Miyokawa A., Nimura A., Horikawa R., Tanaka T.; "G370C mutation in the FGFR3 gene in a Japanese patient with thanatophoric dysplasia."; Endocr. J. 45:S171-S174(1998).
[21]	VARIANT HYPOCHONDROPLASIA VAL-538. DOI=10.1002/(SICI)1098-1004(1998)11:4<333::AID-HUMU17>3.3.CO;2-A; PubMed=10215410 [NCBI, ExPASy, EBI, Israel, Japan] Grigelioniene G., Hagenaes L., Ekloef O., Neumeyer L., Haereid P.E., Anvret M.; "A novel missense mutation Ile538Val in the fibroblast growth factor receptor 3 in hypochondroplasia."; Hum. Mutat. 11:333-333(1998).
[22]	VARIANT HYPOCHONDROPLASIA THR-540. PubMed=9452043 [NCBI, ExPASy, EBI, Israel, Japan] Deutz-Terlouw P.P., Losekoot M., Aalfs C.M., Hennekam R.C.M., Bakker E.; "Asn540Thr substitution in the fibroblast growth factor receptor 3 tyrosine kinase domain causing hypochondroplasia."; Hum. Mutat. Suppl. 1:S62-S65(1998).
[23]	VARIANT TD MET-650. PubMed=10671061 [NCBI, ExPASy, EBI, Israel, Japan] Kitoh H., Brodie S.G., Kupke K.G., Lachman R.S., Wilcox W.R.; "Lys650Met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia type I."; Hum. Mutat. 12:362-363(1998).
[24]	VARIANT ARG-250. DOI=10.1016/S0140-6736(98)24012-8; PubMed=9525367 [NCBI, ExPASy, EBI, Israel, Japan] Hollway G.E., Suthers G.K., Battese K.M., Turner A.M., David D.J., Mulley J.C.; "Deafness due to Pro250Arg mutation of FGFR3."; Lancet 351:877-878(1998).
[25]	VARIANTS PLSD-SD CYS-248; CYS-249 AND CYS-373. DOI=10.1002/(SICI)1096-8628(19990611)84:5<476::AID-AJMG12>3.3.CO;2-O; PubMed=10360402 [NCBI, ExPASy, EBI, Israel, Japan] Brodie S.G., Kitoh H., Lachman R.S., Nolasco L.M., Mekikian P.B., Wilcox W.R.; "Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations."; Am. J. Med. Genet. 84:476-480(1999).
[26]	VARIANT MNKS ARG-250. PubMed=9950359 [NCBI, ExPASy, EBI, Israel, Japan] Lajeunie E., El Ghouzzi V., Le Merrer M., Munnich A., Bonaventure J., Renier D.; "Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation."; J. Med. Genet. 36:9-13(1999).
[27]	VARIANTS BLADDER AND CERVIX CANCERS CYS-248; CYS-249; CYS-370 AND GLU-650. DOI=10.1038/12615; PubMed=10471491 [NCBI, ExPASy, EBI, Israel, Japan] Cappellen D., De Oliveira C., Ricol D., Gil Diez de Medina S., Bourdin J., Sastre-Garau X., Chopin D., Thiery J.P., Radvanyi F.; "Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas."; Nat. Genet. 23:18-20(1999).
[28]	VARIANT HYPOCHONDROPLASIA GLN-650. DOI=10.1086/316892; PubMed=11055896 [NCBI, ExPASy, EBI, Israel, Japan] Bellus G.A., Spector E.B., Speiser P.W., Weaver C.A., Garber A.T., Bryke C.R., Israel J., Rosengren S.S., Webster M.K., Donoghue D.J., Francomano C.A.; "Distinct missense mutations of the FGFR3 Lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype."; Am. J. Hum. Genet. 67:1411-1421(2000).
[29]	VARIANT HYPOCHONDROPLASIA SER-540. DOI=10.1136/jmg.37.3.220; PubMed=10777366 [NCBI, ExPASy, EBI, Israel, Japan] Mortier G., Nuytinck L., Craen M., Renard J.-P., Leroy J.G., De Paepe A.; "Clinical and radiographic features of a family with hypochondroplasia owing to a novel asn540ser mutation in the fibroblast growth factor receptor 3 gene."; J. Med. Genet. 37:220-224(2000).
[30]	VARIANT MNKS ARG-250. DOI=10.1002/ajmg.10049; PubMed=11746040 [NCBI, ExPASy, EBI, Israel, Japan] Lowry R.B., Jabs E.W., Graham G.E., Gerritsen J., Fleming J.; "Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and sprengel shoulder with and without Pro250Arg mutation in the FGFR3 gene."; Am. J. Med. Genet. 104:112-119(2001).
[31]	INVOLVEMENT IN MULTIPLE MYELOMA, AND VARIANT CYS-248. DOI=10.1046/j.1365-2141.2001.02957.x; PubMed=11529856 [NCBI, ExPASy, EBI, Israel, Japan] Intini D., Baldini L., Fabris S., Lombardi L., Ciceri G., Maiolo A.T., Neri A.; "Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14)."; Br. J. Haematol. 114:362-364(2001).
[32]	VARIANT COLORECTAL CANCER LYS-322. PubMed=11325814 [NCBI, ExPASy, EBI, Israel, Japan] Jang J.-H., Shin K.-H., Park J.-G.; "Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers."; Cancer Res. 61:3541-3543(2001).
[33]	VARIANT BLADDER CANCER GLN-650. DOI=10.1038/sj.onc.1204110; PubMed=11314002 [NCBI, ExPASy, EBI, Israel, Japan] Sibley K., Cuthbert-Heavens D., Knowles M.A.; "Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma."; Oncogene 20:686-691(2001).
[34]	VARIANT HYPOCHONDROPLASIA SER-540. DOI=10.1002/ajmg.a.10238; PubMed=12707965 [NCBI, ExPASy, EBI, Israel, Japan] Thauvin-Robinet C., Faivre L., Lewin P., De Monleon J.-V., Francois C., Huet F., Couailler J.-F., Campos-Xavier A.B., Bonaventure J., Le Merrer M.; "Hlypochondroplasia and stature within normal limits: another family with an Asn540-to-Ser mutation in the fibroblast growth factor receptor 3 gene."; Am. J. Med. Genet. A 119:81-84(2003).
[35]	VARIANT CATSHL SYNDROME HIS-621. DOI=10.1086/508433; PubMed=17033969 [NCBI, ExPASy, EBI, Israel, Japan] Toydemir R.M., Brassington A.E., Bayrak-Toydemir P., Krakowiak P.A., Jorde L.B., Whitby F.G., Longo N., Viskochil D.H., Carey J.C., Bamshad M.J.; "A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome."; Am. J. Hum. Genet. 79:935-941(2006).
[36]	VARIANTS KERATINOCYTIC NON-EPIDERMOLYTIC NEVUS CYS-248; CYS-370 AND ARG-380. DOI=10.1172/JCI28163; PubMed=16841094 [NCBI, ExPASy, EBI, Israel, Japan] Hafner C., van Oers J.M.M., Vogt T., Landthaler M., Stoehr R., Blaszyk H., Hofstaedter F., Zwarthoff E.C., Hartmann A.; "Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi."; J. Clin. Invest. 116:2201-2207(2006).
[37]	VARIANT LADDS ASN-513. DOI=10.1038/ng1757; PubMed=16501574 [NCBI, ExPASy, EBI, Israel, Japan] Rohmann E., Brunner H.G., Kayserili H., Uyguner O., Nuernberg G., Lew E.D., Dobbie A., Eswarakumar V.P., Uzumcu A., Ulubil-Emeroglu M., Leroy J.G., Li Y., Becker C., Lehnerdt K., Cremers C.W.R.J., Yueksel-Apak M., Nuernberg P., Kubisch C., Schlessinger J., van Bokhoven H., Wollnik B.; "Mutations in different components of FGF signaling in LADD syndrome."; Nat. Genet. 38:414-417(2006).
[38]	VARIANT CAN GLU-391. DOI=10.1111/j.1399-0004.2007.00884.x; PubMed=17935505 [NCBI, ExPASy, EBI, Israel, Japan] Arnaud-Lopez L., Fragoso R., Mantilla-Capacho J., Barros-Nunez P.; "Crouzon with acanthosis nigricans. Further delineation of the syndrome."; Clin. Genet. 72:405-410(2007).
[39]	VARIANTS [LARGE SCALE ANALYSIS] SER-79; ARG-228; MET-338; LEU-384; ASN-646 AND GLU-650. DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan] Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; "Patterns of somatic mutation in human cancer genomes."; Nature 446:153-158(2007).

Comments

FUNCTION: Receptor for acidic and basic fibroblast growth factors. Preferentially binds FGF1.
CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
INTERACTION:
Self; NbExp=1; IntAct=EBI-348399, EBI-348399;
P05230:FGF1; NbExp=2; IntAct=EBI-348399, EBI-698068;
Q9Y4H4:GPSM3; NbExp=1; IntAct=EBI-348399, EBI-347538;
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.

ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing.

Name	1
Synonyms	IIIc
Isoform ID	P22607-1
This is the isoform sequence displayed in this entry.

Name	2
Synonyms	IIIb
Isoform ID	P22607-2
Features which should be applied to build the isoform sequence: VSP_002988.

Name	3
Isoform ID	P22607-3
Features which should be applied to build the isoform sequence: VSP_002989.

TISSUE SPECIFICITY: Expressed in brain, kidney and testis. Very low or no expression in spleen, heart, and muscle. In 20- to 22-week old fetuses it is expressed at high level in kidney, lung, small intestine and brain, and to a lower degree in spleen, liver, and muscle. Epithelial cells show exclusively isoform 2 transcripts while fibroblastic cells show a mixture of isoform 1 and isoform 2.
DISEASE: Defects in FGFR3 are the cause of achondroplasia (ACH) [MIM:100800]. ACH is an autosomal dominant disease and is the most frequent form of short-limb dwarfism. It is characterized by a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands.
DISEASE: Defects in FGFR3 are the cause of Crouzon syndrome with acanthosis nigricans (CAN) [MIM:612247]. Classic Crouzon disease which is caused by mutations in the FGFR2 gene is characterized by craniosynostosis (premature fusion of the skull sutures), and facial hypoplasia. Crouzon syndrome with acanthosis nigricans (a skin disorder characterized by pigmentation anomalies), CAN, is considered to be an independant disorder from classic Crouzon syndrome. CAN is characterized by additional more severe physical manifestation, such as Chiari malformation, hydrocephalus, and atresia or stenosis of the choanas, and is caused by a specific mutation (Ala-391 to Glu) in the transmembrane domain of FGFR3. It is proposed to have an autosonal dominant mode of inheritance.
DISEASE: Defects in FGFR3 are the cause of platyspondylic lethal skeletal dysplasia Sand Diego type (PLSD-SD) [MIM:270230]. Platyspondylic lethal skeletal dysplasias (PLSDs) are a heterogeneous group of chondrodysplasias characterized by severe platyspondyly and limb shortening. PLSD-SD is characterized by postnatal growth deficiency, mild developmental delay, short trunk, craniofacial abnormalities, platyspondyly, delayed ossification, generalized osteoporosis and thin ribs.
DISEASE: Defects in FGFR3 are a cause of thanatophoric dysplasia (TD) [MIM:187600, 187601]; also known as thanatophoric dwarfism. TD is the most common neonatal lethal skeletal dysplasia. Affected individuals display features similar to those seen in homozygous achondroplasia. It causes severe shortening of the limbs with macrocephaly, narrow thorax and short ribs. In the most common subtype, TD1, femur are curved, while in TD2, straight femurs are associated with cloverleaf skull. Mutations affecting different functional domains of FGFR3 cause different forms of this lethal disorder.
DISEASE: Defects in FGFR3 are a cause of hypochondroplasia (HCH) [MIM:146000]. HCH is an autosomal dominant disease and is characterized by disproportionate short stature. It resembles achondroplasia, but with a less severe phenotype.
DISEASE: Defects in FGFR3 are a cause of bladder cancer [MIM:109800]. Somatic mutations can constitutively activate FGFR3.
DISEASE: Defects in FGFR3 are a cause of cervical cancer [MIM:603956].
DISEASE: Defects in FGFR3 are the cause of camptodactyly tall stature and hearing loss syndrome (CATSHL syndrome) [MIM:610474]. CATSHL syndrome is an autosomal dominant syndrome characterized by permanent and irreducible flexion of one or more fingers of the hand and/or feet, tall stature, scoliosis and/or a pectus excavatum, and hearing loss. Affected individuals have developmental delay and/or mental retardation, and several of these have microcephaly. Radiographic findings included tall vertebral bodies with irregular borders and broad femoral metaphyses with long tubular shafts. On audiological exam, each tested member have bilateral sensorineural hearing loss and absent otoacoustic emissions. The hearing loss was congenital or developed in early infancy, progressed variably in early childhood, and range from mild to severe. Computed tomography and magnetic resonance imaging reveal that the brain, middle ear, and inner ear are structurally normal.
DISEASE: A chromosomal aberration involving FGFR3 may be a cause of multiple myeloma (MM) [MIM:254500]. Translocation t(4;14)(p16.3;q32.3) with the IgH locus.
DISEASE: Defects in FGFR3 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:149730]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.
DISEASE: Defects in FGFR3 are a cause of keratinocytic non-epidermolytic nevus [MIM:162900]; also called pigmented moles. Epidermal nevi of the common, non-organoid and non-epidermolytic type are benign skin lesions and may vary in their extent from a single (usually linear) lesion to widespread and systematized involvement. They may be present at birth or develop early during childhood.
DISEASE: Defects in FGFR3 are a cause of Muenke syndrome (MNKS) [MIM:602849]; also known as Muenke non-syndromic coronal craniosynostosis. MNKS is a condition characterized by premature closure of coronal suture of skull during development (coronal craniosynostosis), which affects the shape of the head and face. It may be uni- or bilateral. When bilateral, it is characterized by a skull with a small antero-posterior diameter (brachycephaly), often with a decrease in the depth of the orbits and hypoplasia of the maxillae. Unilateral closure of the coronal sutures leads to flattening of the orbit on the involved side (plagiocephaly). The intellect is normal. In addition to coronal craniosynostosis some affected individuals show skeletal abnormalities of hands and feet, sensorineural hearing loss, mental retardation and respiratory insufficiency.
SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
SIMILARITY: Contains 3 Ig-like C2-type (immunoglobulin-like) domains.
SIMILARITY: Contains 1 protein kinase domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/FGFR99.html";.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=FGFR3";.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/fgfr3/";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M58051; AAA52450.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF245114; AAF63380.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY768549; AAU89726.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M64347; AAA58470.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M59374; AAA63209.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S76733; AAB33323.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X84939; CAA59334.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U22410; AAA67781.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00027174; -.
IPI00220253; -.
IPI00220254; -.

A38576; TVHUF3.

NP_000133.1; -.

3D structure databases

PDB

1RY7; X-ray; 3.20 A; B=33-365.

[ExPASy / RCSB / EBI]

1RY7; -.

P22607; 458-755.

Protein-protein interaction databases

DIP

DIP:4016N; -.

IntAct

P22607; 22.

PTM databases

PhosphoSite

P22607; -.

Enzyme and pathway databases

BRENDA

2.7.10.1; 247.

Pathway_Interaction_DB

fgf_pathway; FGF signaling pathway.

Reactome

REACT_9470; Signaling by FGFR.

Organism-specific databases

GC04P001762; -.

HIX0031383; -.

HGNC:3690; FGFR3.

CAB004231; -.

100800; phenotype. [NCBI / EBI]
109800; phenotype. [NCBI / EBI]
134934; gene. [NCBI / EBI]
146000; phenotype. [NCBI / EBI]
149730; phenotype. [NCBI / EBI]
162900; phenotype. [NCBI / EBI]
187600; phenotype. [NCBI / EBI]
187601; phenotype. [NCBI / EBI]
254500; phenotype. [NCBI / EBI]
270230; phenotype. [NCBI / EBI]
602849; phenotype. [NCBI / EBI]
603956; phenotype. [NCBI / EBI]
610474; phenotype. [NCBI / EBI]
612247; phenotype. [NCBI / EBI]

Orphanet

15; Achondroplasia.
85164; Camptodactyly - tall stature - scoliosis - hearing loss.
93262; Crouzon syndrome - acanthosis nigricans.
1555; Cutis gyrata - acanthosis nigricans - craniosynostosis.
429; Hypochondroplasia.
35099; Isolated brachycephaly.
2343; Isolated cloverleaf skull syndrome.
35098; Isolated plagiocephaly.
2363; Lacrimo-auriculo-dento-digital syndrome.
53271; Muenke syndrome.
794; Saethre-Chotzen syndrome.
85165; Severe achondroplasia - developmental delay - acanthosis nigricans.
2655; Thanatophoric dwarfism.

PharmGKB

PA28129; -.

Gene expression databases

P22607; -.

P22607; -.

HS_FGFR3; -.

ENSG00000068078; Homo sapiens.

Ontologies

GO:0005887;	Cellular component: integral to plasma membrane (traceable author statement from ProtInc).
GO:0005524;	Molecular function: ATP binding (inferred from electronic annotation from UniProtKB-KW).
GO:0005007;	Molecular function: fibroblast growth factor receptor activity (non-traceable author statement from UniProtKB).
GO:0042802;	Molecular function: identical protein binding (inferred from physical interaction from IntAct).
GO:0016049;	Biological process: cell growth (non-traceable author statement from UniProtKB).
GO:0008543;	Biological process: fibroblast growth factor receptor signaling pathway (traceable author statement from ProtInc).
GO:0007259;	Biological process: JAK-STAT cascade (traceable author statement from ProtInc).
GO:0000165;	Biological process: MAPKKK cascade (traceable author statement from ProtInc).
GO:0006468;	Biological process: protein amino acid phosphorylation (inferred from electronic annotation from InterPro).
GO:0007605;	Biological process: sensory perception of sound (inferred from electronic annotation from UniProtKB-KW).
GO:0001501;	Biological process: skeletal system development (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR016248; Fibroblast_GF_rcpt.
IPR013151; Ig.
IPR007110; Ig-like.
IPR013783; Ig-like_fold.
IPR013098; Ig_I-set.
IPR003599; Ig_sub.
IPR003598; Ig_sub2.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_BS.
IPR001245; Tyr_pkinase.
IPR008266; Tyr_pkinase_AS.
Graphical view of domain structure.

Gene3D

G3DSA:2.60.40.10; Ig-like_fold; 3.

Pfam

PF07679; I-set; 1.
PF00047; ig; 2.
PF07714; Pkinase_Tyr; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF000628; FGFR; 1.

PRINTS

PR00109; TYRKINASE.

ProDom

PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00409; IG; 1.
SM00408; IGc2; 2.
SM00219; TyrKc; 1.
SMART graphical view of domain structure.

PROSITE

PS50835; IG_LIKE; 3.
PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00109; PROTEIN_KINASE_TYR; 1.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

P22607; -.

Genome annotation databases

Ensembl

ENSG00000068078; Homo sapiens. [Contig view]

GeneID

2261; -.

KEGG

hsa:2261; -.

Phylogenomic databases

HOVERGEN

P22607; -.

Other

DB00039; Palifermin.

9179; -.

FGFR3; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Alternative splicing; ATP-binding; Chromosomal rearrangement; Craniosynostosis; Deafness; Disease mutation; Disulfide bond; Dwarfism; Ectodermal dysplasia; Glycoprotein; Immunoglobulin domain; Kinase; Lacrimo-auriculo-dento-digital syndrome; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; Repeat; Signal; Transferase; Transmembrane; Tyrosine-protein kinase.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 22`	`22`
`CHAIN`	`23 806`	`784`	`Fibroblast growth factor receptor 3.`	`PRO_0000016785`
`TOPO_DOM`	`23 375`	`353`	`Extracellular (Potential).`
`TRANSMEM`	`376 396`	`21`	`Potential.`
`TOPO_DOM`	`397 806`	`410`	`Cytoplasmic (Potential).`
`DOMAIN`	`24 126`	`103`	`Ig-like C2-type 1.`
`DOMAIN`	`151 244`	`94`	`Ig-like C2-type 2.`
`DOMAIN`	`253 355`	`103`	`Ig-like C2-type 3.`
`DOMAIN`	`472 761`	`290`	`Protein kinase.`
`NP_BIND`	`478 486`	`9`	`ATP (By similarity).`
`ACT_SITE`	`617 617`		`Proton acceptor (By similarity).`
`BINDING`	`508 508`		`ATP (By similarity).`
`MOD_RES`	`647 647`		`Phosphotyrosine (By similarity).`
`MOD_RES`	`648 648`		`Phosphotyrosine; by autocatalysis (By similarity).`
`CARBOHYD`	`98 98`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`225 225`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`262 262`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`294 294`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`315 315`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`328 328`		`N-linked (GlcNAc...) (Potential).`
`DISULFID`	`61 109`		`Potential.`
`DISULFID`	`176 228`		`Potential.`
`DISULFID`	`275 339`		`Potential.`
`VAR_SEQ`	`311 422`		`Missing (in isoform 3).`	`VSP_002989`
`VAR_SEQ`	`311 358`		`TAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHH` `SAWLVVLP -> SWISESVEADVRLRLANVSERDGGEYLCRATNFIGVAEKA` `FWLSVHGPRA (in isoform 2).`	`VSP_002988`
`VARIANT`	`65 65`	`1`	`G -> R (in dbSNP:rs2305178 [NCBI]).`	`VAR_022167`
`VARIANT`	`79 79`	`1`	`T -> S (in a lung adenocarcinoma sample; somatic mutation).`	`VAR_042207`
`VARIANT`	`228 228`	`1`	`C -> R (in a colorectal adenocarcinoma sample; somatic mutation).`	`VAR_042208`
`VARIANT`	`248 248`	`1`	`R -> C (in bladder cancer, PLSD-SD, keratinocytic non-epidermolytic nevus and TD; severe and lethal; also found as somatic mutation in one patient with multiple myeloma).`	`VAR_004148`
`VARIANT`	`249 249`	`1`	`S -> C (in bladder cancer, cervical cancer, PLSD-SD and TD; type 1).`	`VAR_004149`
`VARIANT`	`250 250`	`1`	`P -> R (in MNKS; also some individuals with autosomal dominant congenital sensorineural deafness without craniosynostosis; dbSNP:rs4647924 [NCBI]).`	`VAR_004150`
`VARIANT`	`322 322`	`1`	`E -> K (in colorectal cancer).`	`VAR_018388`
`VARIANT`	`338 338`	`1`	`T -> M.`	`VAR_042209`
`VARIANT`	`370 370`	`1`	`G -> C (in bladder cancer, keratinocytic non-epidermolytic nevus and TD; type 1).`	`VAR_004151`
`VARIANT`	`371 371`	`1`	`S -> C (in TD; type 1).`	`VAR_004152`
`VARIANT`	`373 373`	`1`	`Y -> C (in PLSD-SD and TD; type 1).`	`VAR_004153`
`VARIANT`	`375 375`	`1`	`G -> C (in ACH).`	`VAR_004154`
`VARIANT`	`380 380`	`1`	`G -> R (in keratinocytic non-epidermolytic nevus and ACH; results in constitutive activation; very common mutation; dbSNP:rs28931614 [NCBI]).`	`VAR_004155`
`VARIANT`	`384 384`	`1`	`F -> L (in dbSNP:rs17881656 [NCBI]).`	`VAR_022168`
`VARIANT`	`391 391`	`1`	`A -> E (in CAN; dbSNP:rs28931615 [NCBI]).`	`VAR_004156`
`VARIANT`	`441 441`	`1`	`A -> T (in dbSNP:rs17884368 [NCBI]).`	`VAR_022169`
`VARIANT`	`513 513`	`1`	`D -> N (in LADDS).`	`VAR_029887 [3D]`
`VARIANT`	`538 538`	`1`	`I -> V (in hypochondroplasia).`	`VAR_004157 [3D]`
`VARIANT`	`540 540`	`1`	`N -> K (in hypochondroplasia).`	`VAR_004158 [3D]`
`VARIANT`	`540 540`	`1`	`N -> S (in hypochondroplasia; mild).`	`VAR_018389 [3D]`
`VARIANT`	`540 540`	`1`	`N -> T (in hypochondroplasia).`	`VAR_004159 [3D]`
`VARIANT`	`621 621`	`1`	`R -> H (in CATSHL syndrome).`	`VAR_029108 [3D]`
`VARIANT`	`646 646`	`1`	`D -> N.`	`VAR_042210 [3D]`
`VARIANT`	`650 650`	`1`	`K -> E (in TD and bladder cancer samples; bladder transitional cell carcinoma; somatic mutation).`	`VAR_004160 [3D]`
`VARIANT`	`650 650`	`1`	`K -> M (in ACH and TD; type 1).`	`VAR_004161 [3D]`
`VARIANT`	`650 650`	`1`	`K -> Q (in hypochondroplasia and bladder cancer; in hypochondroplasia the form is milder than that seen in individuals with the K-540 or M-650 mutations).`	`VAR_018390 [3D]`
`VARIANT`	`717 717`	`1`	`A -> T (in dbSNP:rs17882190 [NCBI]).`	`VAR_022170 [3D]`
`VARIANT`	`726 726`	`1`	`I -> F (in dbSNP:rs17880763 [NCBI]).`	`VAR_022171 [3D]`
`CONFLICT`	`395 395`		`L -> V (in Ref. 4; AAA58470).`
`STRAND`	`163 167`	`5`
`STRAND`	`172 175`	`4`
`STRAND`	`185 187`	`3`
`TURN`	`208 211`	`4`
`STRAND`	`212 215`	`4`
`HELIX`	`220 222`	`3`
`STRAND`	`226 232`	`7`
`STRAND`	`235 246`	`12`
`STRAND`	`263 268`	`6`
`STRAND`	`271 273`	`3`
`STRAND`	`283 289`	`7`
`HELIX`	`293 295`	`3`
`STRAND`	`302 304`	`3`
`STRAND`	`324 326`	`3`
`STRAND`	`335 345`	`11`
`STRAND`	`348 357`	`10`

Sequence information

Length: 806 AA [This is the length of the unprocessed precursor]

Molecular weight: 87710 Da [This is the MW of the unprocessed precursor]

CRC64: BC5EA75EA46F447E [This is a checksum on the sequence]

        10         20         30         40         50         60 
MGAPACALAL CVAVAIVAGA SSESLGTEQR VVGRAAEVPG PEPGQQEQLV FGSGDAVELS 

        70         80         90        100        110        120 
CPPPGGGPMG PTVWVKDGTG LVPSERVLVG PQRLQVLNAS HEDSGAYSCR QRLTQRVLCH 

       130        140        150        160        170        180 
FSVRVTDAPS SGDDEDGEDE AEDTGVDTGA PYWTRPERMD KKLLAVPAAN TVRFRCPAAG 

       190        200        210        220        230        240 
NPTPSISWLK NGREFRGEHR IGGIKLRHQQ WSLVMESVVP SDRGNYTCVV ENKFGSIRQT 

       250        260        270        280        290        300 
YTLDVLERSP HRPILQAGLP ANQTAVLGSD VEFHCKVYSD AQPHIQWLKH VEVNGSKVGP 

       310        320        330        340        350        360 
DGTPYVTVLK TAGANTTDKE LEVLSLHNVT FEDAGEYTCL AGNSIGFSHH SAWLVVLPAE 

       370        380        390        400        410        420 
EELVEADEAG SVYAGILSYG VGFFLFILVV AAVTLCRLRS PPKKGLGSPT VHKISRFPLK 

       430        440        450        460        470        480 
RQVSLESNAS MSSNTPLVRI ARLSSGEGPT LANVSELELP ADPKWELSRA RLTLGKPLGE 

       490        500        510        520        530        540 
GCFGQVVMAE AIGIDKDRAA KPVTVAVKML KDDATDKDLS DLVSEMEMMK MIGKHKNIIN 

       550        560        570        580        590        600 
LLGACTQGGP LYVLVEYAAK GNLREFLRAR RPPGLDYSFD TCKPPEEQLT FKDLVSCAYQ 

       610        620        630        640        650        660 
VARGMEYLAS QKCIHRDLAA RNVLVTEDNV MKIADFGLAR DVHNLDYYKK TTNGRLPVKW 

       670        680        690        700        710        720 
MAPEALFDRV YTHQSDVWSF GVLLWEIFTL GGSPYPGIPV EELFKLLKEG HRMDKPANCT 

       730        740        750        760        770        780 
HDLYMIMREC WHAAPSQRPT FKQLVEDLDR VLTVTSTDEY LDLSAPFEQY SPGGQDTPSS 

       790        800 
SSSGDDSVFA HDLLPPAPPS SGGSRT

P22607 in FASTA format

View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools