Reviewed,
UniProtKB/Swiss-Prot P22607 (FGFR3_HUMAN)
Last modified
November 3, 2009.
Version 136.
History...
Clusters with 100%,
90%,
50% identity |
Documents (8) |
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Names and origin
| Protein names | Recommended name: Fibroblast growth factor receptor 3 Short name=FGFR-3 EC=2.7.10.1 Alternative name(s): CD_antigen=CD333 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 806 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (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. |
| Subcellular location | |
| 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. Ref.4 |
| Involvement in 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. Ref.9 Ref.10 Ref.11 Ref.16 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 autosomal dominant mode of inheritance. Ref.15 Ref.27 Ref.32 Ref.33 Ref.39 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. Ref.25 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. Ref.12 Ref.13 Ref.17 Ref.20 Ref.23 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. Defects in FGFR3 are a cause of bladder cancer [MIM:109800]. Somatic mutations can constitutively activate FGFR3. Ref.33 Defects in FGFR3 are a cause of cervical cancer [MIM:603956]. 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. 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. 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. Ref.38 Defects in FGFR3 are a cause of keratinocytic non-epidermolytic nevus [MIM:162900]; also known as 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. 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. Ref.18 Ref.26 Ref.30 Defects in FGFR3 are a cause of keratosis seborrheic (KERSEB) [MIM:182000]. A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance. Ref.35 |
| Sequence similarities | Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily. Contains 3 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| itself | 1 | EBI-348399,EBI-348399 | ||
| FGF1 | P05230 | 2 | EBI-348399,EBI-698068 | |
| GPSM3 | Q9Y4H4 | 1 | EBI-348399,EBI-347538 |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P22607-1) Also known as: IIIc; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P22607-2) Also known as: IIIb; The sequence of this isoform differs from the canonical sequence as follows: 311-358: TAGANTTDKE...HHSAWLVVLP → SWISESVEAD...FWLSVHGPRA | ||||||
| Isoform 3 (identifier: P22607-3) The sequence of this isoform differs from the canonical sequence as follows: 311-422: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 22 | 22 | ||||||||||||||||||||||||||||||||||||||
| Chain | 23 – 806 | 784 | Fibroblast growth factor receptor 3 | PRO_0000016785 | ||||||||||||||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||||||||||||||
| Topological domain | 23 – 375 | 353 | Extracellular Potential | |||||||||||||||||||||||||||||||||||||
| Transmembrane | 376 – 396 | 21 | Potential | |||||||||||||||||||||||||||||||||||||
| Topological domain | 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 | |||||||||||||||||||||||||||||||||||||
| Nucleotide binding | 478 – 486 | 9 | ATP By similarity | |||||||||||||||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||||||||||||||
| Active site | 617 | 1 | Proton acceptor By similarity | |||||||||||||||||||||||||||||||||||||
| Binding site | 508 | 1 | ATP By similarity | |||||||||||||||||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||||||||||||||||
| Modified residue | 647 | 1 | Phosphotyrosine By similarity | |||||||||||||||||||||||||||||||||||||
| Modified residue | 648 | 1 | Phosphotyrosine; by autocatalysis By similarity | |||||||||||||||||||||||||||||||||||||
| Glycosylation | 98 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||||||||
| Glycosylation | 225 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||||||||
| Glycosylation | 262 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||||||||
| Glycosylation | 294 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||||||||
| Glycosylation | 315 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||||||||
| Glycosylation | 328 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||||||||
| Disulfide bond | 61 ↔ 109 | Potential | ||||||||||||||||||||||||||||||||||||||
| Disulfide bond | 176 ↔ 228 | Potential | ||||||||||||||||||||||||||||||||||||||
| Disulfide bond | 275 ↔ 339 | Potential | ||||||||||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 311 – 422 | 112 | Missing in isoform 3. | VSP_002989 | ||||||||||||||||||||||||||||||||||||
| Alternative sequence | 311 – 358 | 48 | TAGAN…LVVLP → SWISESVEADVRLRLANVSE RDGGEYLCRATNFIGVAEKA FWLSVHGPRA in isoform 2. | VSP_002988 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 65 | 1 | G → R: dbSNP rs2305178. Ref.3 | VAR_022167 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 79 | 1 | T → S in a lung adenocarcinoma sample; somatic mutation. Ref.40 | VAR_042207 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 228 | 1 | C → R in a colorectal adenocarcinoma sample; somatic mutation. Ref.40 | VAR_042208 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 248 | 1 | R → C in KERSEB, bladder cancer, PLSD-SD, keratinocytic non-epidermolytic nevus and TD; severe and lethal; also found as somatic mutation in one patient with multiple myeloma. Ref.27 Ref.25 Ref.13 Ref.17 Ref.35 Ref.31 Ref.37 | VAR_004148 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 249 | 1 | S → C in KERSEB, bladder cancer, cervical cancer, PLSD-SD and TD; type 1. Ref.27 Ref.25 Ref.12 Ref.17 Ref.35 | VAR_004149 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 250 | 1 | P → R in MNKS; also some individuals with autosomal dominant congenital sensorineural deafness without craniosynostosis. dbSNP rs4647924. Ref.18 Ref.26 Ref.30 Ref.24 | VAR_004150 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 322 | 1 | E → K in colorectal cancer. Ref.32 | VAR_018388 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 338 | 1 | T → M | VAR_042209 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 370 | 1 | G → C in KERSEB, bladder cancer, keratinocytic non-epidermolytic nevus and TD; type 1. Ref.27 Ref.17 Ref.20 Ref.35 Ref.37 | VAR_004151 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 371 | 1 | S → C in KERSEB and TD; type 1. Ref.13 Ref.35 | VAR_004152 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 373 | 1 | Y → C in KERSEB, PLSD-SD and TD; type 1. Ref.25 Ref.17 Ref.35 Ref.19 | VAR_004153 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 375 | 1 | G → C in ACH. Ref.11 | VAR_004154 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 380 | 1 | G → R in keratinocytic non-epidermolytic nevus and ACH; results in constitutive activation; very common mutation. dbSNP rs28931614. Ref.9 Ref.10 Ref.16 Ref.37 | VAR_004155 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 384 | 1 | F → L: dbSNP rs17881656. Ref.3 Ref.40 | VAR_022168 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 391 | 1 | A → E in CAN. dbSNP rs28931615. Ref.15 Ref.39 | VAR_004156 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 441 | 1 | A → T: dbSNP rs17884368. Ref.3 | VAR_022169 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 513 | 1 | D → N in LADDS. Ref.38 | VAR_029887 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 538 | 1 | I → V in hypochondroplasia. Ref.21 | VAR_004157 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 540 | 1 | N → K in hypochondroplasia. Ref.14 | VAR_004158 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 540 | 1 | N → S in hypochondroplasia; mild. Ref.29 Ref.34 | VAR_018389 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 540 | 1 | N → T in hypochondroplasia. Ref.22 | VAR_004159 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 621 | 1 | R → H in CATSHL syndrome. Ref.36 | VAR_029108 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 646 | 1 | D → N | VAR_042210 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 650 | 1 | K → E in KERSEB, TD and bladder cancer samples; bladder transitional cell carcinoma; somatic mutation. Ref.27 Ref.13 Ref.35 Ref.40 Ref.19 | VAR_004160 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 650 | 1 | K → M in KERSEB, ACH and TD; type 1. Ref.23 Ref.35 Ref.19 | VAR_004161 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 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. Ref.33 Ref.28 | VAR_018390 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 717 | 1 | A → T: dbSNP rs17882190. Ref.3 | VAR_022170 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 726 | 1 | I → F: dbSNP rs17880763. Ref.3 | VAR_022171 | ||||||||||||||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 395 | 1 | L → V in AAA58470. Ref.4 | |||||||||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||||
| Beta strand | 163 – 167 | 5 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 172 – 175 | 4 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 185 – 187 | 3 | ||||||||||||||||||||||||||||||||||||||
| Turn | 208 – 211 | 4 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 212 – 215 | 4 | ||||||||||||||||||||||||||||||||||||||
| Helix | 220 – 222 | 3 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 226 – 232 | 7 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 235 – 246 | 12 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 263 – 268 | 6 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 271 – 273 | 3 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 283 – 289 | 7 | ||||||||||||||||||||||||||||||||||||||
| Helix | 293 – 295 | 3 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 302 – 304 | 3 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 324 – 326 | 3 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 335 – 345 | 11 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 348 – 357 | 10 | ||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3." Keegan K., Johnson D.E., Williams L.T., Hayman M.J. Proc. Natl. Acad. Sci. U.S.A. 88:1095-1099(1991) [PubMed: 1847508] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "Fibroblast growth factor receptor 3 lacking the Ig IIIb and transmembrane domains secreted from human squamous cell carcinoma DJM-1 binds to FGFs." Terada M., Shimizu A., Sato N., Miyakaze S.I., Katayama H., Kurokawa-Seo M. Mol. Cell Biol. Res. Commun. 4:365-373(2001) [PubMed: 11703096] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). |
| [3] | NIEHS SNPs program Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-65; LEU-384; THR-441; THR-717 AND PHE-726. |
| [4] | "A gene encoding a fibroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4." Thompson L.M., Plummer S., Schalling M., Altherr M.R., Gusella J.F., Housman D.E., Wasmuth J.J. Genomics 11:1133-1142(1991) [PubMed: 1664411] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 76-806 (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Fetal brain. |
| [5] | "Putative tyrosine kinases expressed in K-562 human leukemia cells." Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K. Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990) [PubMed: 2247464] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 614-681. |
| [6] | "Identification of a novel variant form of fibroblast growth factor receptor 3 (FGFR3 IIIb) in human colonic epithelium." Murgue B., Tsunekawa S., Rosenberg I., deBeaumont M., Podolsky D.K. Cancer Res. 54:5206-5211(1994) [PubMed: 7923141] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 311-358 (ISOFORM 2). Tissue: Colon tumor. |
| [7] | "The choice between alternative IIIb and IIIc exons of the FGFR-3 gene is not strictly tissue-specific." Scotet E., Houssaint E. Biochim. Biophys. Acta 1264:238-242(1995) [PubMed: 7495869] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 311-358 (ISOFORM 2). Tissue: Keratinocyte. |
| [8] | "Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity." Olsen S.K., Ibrahimi O.A., Raucci A., Zhang F., Eliseenkova A.V., Yayon A., Basilico C., Linhardt R.J., Schlessinger J., Mohammadi M. Proc. Natl. Acad. Sci. U.S.A. 101:935-940(2004) [PubMed: 14732692] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 32-365 IN COMPLEX WITH FGF1. |
| [9] | "Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia." Rousseau F., Bonaventure J., Legeai-Mallet L., Pelet A., Rozet J.-M., Maroteaux P., le Merrer M., Munnich A. Nature 371:252-254(1994) [PubMed: 8078586] [Abstract] Cited for: VARIANT ACH ARG-380. |
| [10] | "Achondroplasia is defined by recurrent G380R mutations of FGFR3." 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. Am. J. Hum. Genet. 56:368-373(1995) [PubMed: 7847369] [Abstract] Cited for: VARIANT ACH ARG-380. |
| [11] | "A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia." Superti-Furga A., Eich G., Bucher H.U., Wisser J., Giedion A., Gitzelmann R., Steinmann B. Eur. J. Pediatr. 154:215-219(1995) [PubMed: 7758520] [Abstract] Cited for: VARIANT ACH CYS-375. |
| [12] | "Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I." Tavormina P.L., Rimoin D.L., Cohn D.H., Zhu Y.-Z., Shiang R., Wasmuth J.J. Hum. Mol. Genet. 4:2175-2177(1995) [PubMed: 8589699] [Abstract] Cited for: VARIANT TD CYS-249. |
| [13] | "Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3." 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. Nat. Genet. 9:321-328(1995) [PubMed: 7773297] [Abstract] Cited for: VARIANTS TD CYS-248; CYS-371 AND GLU-650. |
| [14] | "A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia." 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. Nat. Genet. 10:357-359(1995) [PubMed: 7670477] [Abstract] Cited for: VARIANT HYPOCHONDROPLASIA LYS-540. |
| [15] | "Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans." Meyers G.A., Orlow S.J., Munro I.R., Przylepa K.A., Jabs E.W. Nat. Genet. 11:462-464(1995) [PubMed: 7493034] [Abstract] Cited for: VARIANT CAN GLU-391. |
| [16] | "Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia." Webster M.K., Donoghue D.J. EMBO J. 15:520-527(1996) [PubMed: 8599935] [Abstract] Cited for: CHARACTERIZATION OF VARIANT ACH ARG-380. |
| [17] | "Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)." Rousseau F., el Ghouzzi V., Delezoide A.-L., Legeai-Mallet L., le Merrer M., Munnich A., Bonaventure J. Hum. Mol. Genet. 5:509-512(1996) [PubMed: 8845844] [Abstract] Cited for: VARIANTS TD CYS-248; CYS-249; CYS-370 AND CYS-373. |
| [18] | "A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome." 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. Zackai E.H.Am. J. Hum. Genet. 60:555-564(1997) [PubMed: 9042914] [Abstract] Cited for: VARIANT MNKS ARG-250. |
| [19] | "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." Chesi M., Nardini E., Brents L.A., Schroeck E., Ried T., Kuehl W.M., Bergsagel P.L. Nat. Genet. 16:260-264(1997) [PubMed: 9207791] [Abstract] Cited for: INVOLVEMENT IN MULTIPLE MYELOMA, VARIANTS CYS-373; GLU-650 AND MET-650. |
| [20] | "G370C mutation in the FGFR3 gene in a Japanese patient with thanatophoric dysplasia." Katsumata N., Kuno T., Miyazaki S., Mikami S., Nagashima-Miyokawa A., Nimura A., Horikawa R., Tanaka T. Endocr. J. 45:S171-S174(1998) [PubMed: 9790257] [Abstract] Cited for: VARIANT TD CYS-370. |
| [21] | "A novel missense mutation Ile538Val in the fibroblast growth factor receptor 3 in hypochondroplasia." Grigelioniene G., Hagenaes L., Ekloef O., Neumeyer L., Haereid P.E., Anvret M. Hum. Mutat. 11:333-333(1998) [PubMed: 10215410] [Abstract] Cited for: VARIANT HYPOCHONDROPLASIA VAL-538. |
| [22] | "Asn540Thr substitution in the fibroblast growth factor receptor 3 tyrosine kinase domain causing hypochondroplasia." Deutz-Terlouw P.P., Losekoot M., Aalfs C.M., Hennekam R.C.M., Bakker E. Hum. Mutat. Suppl. 1:S62-S65(1998) [PubMed: 9452043] [Abstract] Cited for: VARIANT HYPOCHONDROPLASIA THR-540. |
| [23] | "Lys650Met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia type I." Kitoh H., Brodie S.G., Kupke K.G., Lachman R.S., Wilcox W.R. Hum. Mutat. 12:362-363(1998) [PubMed: 10671061] [Abstract] Cited for: VARIANT TD MET-650. |
| [24] | "Deafness due to Pro250Arg mutation of FGFR3." Hollway G.E., Suthers G.K., Battese K.M., Turner A.M., David D.J., Mulley J.C. Lancet 351:877-878(1998) [PubMed: 9525367] [Abstract] Cited for: VARIANT ARG-250. |
| [25] | "Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations." Brodie S.G., Kitoh H., Lachman R.S., Nolasco L.M., Mekikian P.B., Wilcox W.R. Am. J. Med. Genet. 84:476-480(1999) [PubMed: 10360402] [Abstract] Cited for: VARIANTS PLSD-SD CYS-248; CYS-249 AND CYS-373. |
| [26] | "Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation." Lajeunie E., El Ghouzzi V., Le Merrer M., Munnich A., Bonaventure J., Renier D. J. Med. Genet. 36:9-13(1999) [PubMed: 9950359] [Abstract] Cited for: VARIANT MNKS ARG-250. |
| [27] | "Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas." Cappellen D., De Oliveira C., Ricol D., Gil Diez de Medina S., Bourdin J., Sastre-Garau X., Chopin D., Thiery J.P., Radvanyi F. Nat. Genet. 23:18-20(1999) [PubMed: 10471491] [Abstract] Cited for: VARIANTS BLADDER AND CERVIX CANCERS CYS-248; CYS-249; CYS-370 AND GLU-650. |
| [28] | "Distinct missense mutations of the FGFR3 Lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype." 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. Am. J. Hum. Genet. 67:1411-1421(2000) [PubMed: 11055896] [Abstract] Cited for: VARIANT HYPOCHONDROPLASIA GLN-650. |
| [29] | "Clinical and radiographic features of a family with hypochondroplasia owing to a novel asn540ser mutation in the fibroblast growth factor receptor 3 gene." Mortier G., Nuytinck L., Craen M., Renard J.-P., Leroy J.G., De Paepe A. J. Med. Genet. 37:220-224(2000) [PubMed: 10777366] [Abstract] Cited for: VARIANT HYPOCHONDROPLASIA SER-540. |
| [30] | "Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and sprengel shoulder with and without Pro250Arg mutation in the FGFR3 gene." Lowry R.B., Jabs E.W., Graham G.E., Gerritsen J., Fleming J. Am. J. Med. Genet. 104:112-119(2001) [PubMed: 11746040] [Abstract] Cited for: VARIANT MNKS ARG-250. |
| [31] | "Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14)." Intini D., Baldini L., Fabris S., Lombardi L., Ciceri G., Maiolo A.T., Neri A. Br. J. Haematol. 114:362-364(2001) [PubMed: 11529856] [Abstract] Cited for: INVOLVEMENT IN MULTIPLE MYELOMA, VARIANT CYS-248. |
| [32] | "Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers." Jang J.-H., Shin K.-H., Park J.-G. Cancer Res. 61:3541-3543(2001) [PubMed: 11325814] [Abstract] Cited for: VARIANT COLORECTAL CANCER LYS-322. |
| [33] | "Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma." Sibley K., Cuthbert-Heavens D., Knowles M.A. Oncogene 20:686-691(2001) [PubMed: 11314002] [Abstract] Cited for: VARIANT BLADDER CANCER GLN-650. |
| [34] | "Hlypochondroplasia and stature within normal limits: another family with an Asn540-to-Ser mutation in the fibroblast growth factor receptor 3 gene." 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. Am. J. Med. Genet. A 119:81-84(2003) [PubMed: 12707965] [Abstract] Cited for: VARIANT HYPOCHONDROPLASIA SER-540. |
| [35] | "Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans." Logie A., Dunois-Larde C., Rosty C., Levrel O., Blanche M., Ribeiro A., Gasc J.-M., Jorcano J., Werner S., Sastre-Garau X., Thiery J.P., Radvanyi F. Hum. Mol. Genet. 14:1153-1160(2005) [PubMed: 15772091] [Abstract] Cited for: VARIANTS KERSEB CYS-248; CYS-249; CYS-370; CYS-371; CYS-373; GLU-650 AND MET-650. |
| [36] | "A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome." 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. Am. J. Hum. Genet. 79:935-941(2006) [PubMed: 17033969] [Abstract] Cited for: VARIANT CATSHL SYNDROME HIS-621. |
| [37] | "Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi." Hafner C., van Oers J.M.M., Vogt T., Landthaler M., Stoehr R., Blaszyk H., Hofstaedter F., Zwarthoff E.C., Hartmann A. J. Clin. Invest. 116:2201-2207(2006) [PubMed: 16841094] [Abstract] Cited for: VARIANTS KERATINOCYTIC NON-EPIDERMOLYTIC NEVUS CYS-248; CYS-370 AND ARG-380. |
| [38] | "Mutations in different components of FGF signaling in LADD syndrome." 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. Wollnik B.Nat. Genet. 38:414-417(2006) [PubMed: 16501574] [Abstract] Cited for: VARIANT LADDS ASN-513. |
| [39] | "Crouzon with acanthosis nigricans. Further delineation of the syndrome." Arnaud-Lopez L., Fragoso R., Mantilla-Capacho J., Barros-Nunez P. Clin. Genet. 72:405-410(2007) [PubMed: 17935505] [Abstract] Cited for: VARIANT CAN GLU-391. |
| [40] | "Patterns of somatic mutation in human cancer genomes." 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. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-79; ARG-228; MET-338; LEU-384; ASN-646 AND GLU-650. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M58051 mRNA. Translation: AAA52450.1. AF245114 mRNA. Translation: AAF63380.1. AY768549 Genomic DNA. Translation: AAU89726.1. M64347 mRNA. Translation: AAA58470.1. M59374 mRNA. Translation: AAA63209.1. S76733 Genomic DNA. Translation: AAB33323.1. X84939 mRNA. Translation: CAA59334.1. U22410 Genomic DNA. Translation: AAA67781.1. | |||||||||||||
| IPI | IPI00027174. IPI00220253. IPI00220254. | ||||||||||||
| PIR | TVHUF3. A38576. | ||||||||||||
| RefSeq | NP_000133.1. NP_075254.1. | ||||||||||||
| UniGene | Hs.1420 | ||||||||||||
3D structure databases | |||||||||||||
| |||||||||||||
| SMR | P22607. Positions 458-755. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP:4016N. | ||||||||||||
| IntAct | P22607. 22 interactions. | ||||||||||||
| STRING | P22607. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | P22607. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | P22607. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000260795; ENSP00000260795; ENSG00000068078; Homo sapiens. [Genome view] ENST00000312875; ENSP00000323596; ENSG00000068078; Homo sapiens. [Genome view] ENST00000340107; ENSP00000339824; ENSG00000068078; Homo sapiens. [Genome view] ENST00000352904; ENSP00000231803; ENSG00000068078; Homo sapiens. [Genome view] ENST00000360915; ENSP00000354170; ENSG00000068078; Homo sapiens. [Genome view] ENST00000412135; ENSP00000412903; ENSG00000068078; Homo sapiens. [Genome view] ENST00000440486; ENSP00000414914; ENSG00000068078; Homo sapiens. [Genome view] | ||||||||||||
| GeneID | 2261. | ||||||||||||
| KEGG | hsa:2261. | ||||||||||||
| UCSC | uc003gdr.2. human. uc003gds.2. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 2261. | ||||||||||||
| GeneCards | GC04P001762. | ||||||||||||
| H-InvDB | HIX0031383. | ||||||||||||
| HGNC | HGNC:3690. FGFR3. | ||||||||||||
| HPA | CAB004231. | ||||||||||||
| MIM | 100800. phenotype. 109800. phenotype. 134934. gene. 146000. phenotype. 149730. phenotype. 162900. phenotype. 182000. phenotype. 187600. phenotype. 187601. phenotype. 254500. phenotype. 270230. phenotype. 602849. phenotype. 603956. phenotype. 610474. phenotype. 612247. phenotype. | ||||||||||||
| 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. 1860. Thanatophoric dwarfism, type I. 93274. Thanatophoric dwarfism, type II. | ||||||||||||
| PharmGKB | PA28129. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOVERGEN | 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. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P22607. | ||||||||||||
| Bgee | P22607. | ||||||||||||
| CleanEx | HS_FGFR3. | ||||||||||||
| Genevestigator | P22607. | ||||||||||||
| GermOnline | ENSG00000068078. Homo sapiens. | ||||||||||||
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] | ||||||||||||
| Gene3D | G3DSA:2.60.40.10. Ig-like_fold. 3 hits. | ||||||||||||
| Pfam | PF07679. I-set. 1 hit. PF00047. ig. 2 hits. PF07714. Pkinase_Tyr. 1 hit. [Graphical view] | ||||||||||||
| PIRSF | PIRSF000628. FGFR. 1 hit. | ||||||||||||
| PRINTS | PR00109. TYRKINASE. | ||||||||||||
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] | ||||||||||||
| SMART | SM00409. IG. 1 hit. SM00408. IGc2. 2 hits. SM00219. TyrKc. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS50835. IG_LIKE. 3 hits. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| DrugBank | DB00039. Palifermin. | ||||||||||||
| NextBio | 9179. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | FGFR3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P22607 Secondary accession number(s): Q14308, Q16294, Q16608 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human cell differentiation molecules CD nomenclature of surface proteins of human leucocytes and list of entries |
| Human chromosome 4 Human chromosome 4: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


