Reviewed,
UniProtKB/Swiss-Prot P22607 (FGFR3_HUMAN)
Last modified
November 25, 2008.
Version 123.
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 |
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| Organism | Homo sapiens (Human) | ||||
| 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. |
| 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. Defects in FGFR3 are a cause of Crouzon syndrome (CS) [MIM:123500]; also called craniofacial dysostosis type I (CFD1). Crouzon syndrome is characterized by craniosynostosis (premature fusion of the skull sutures), hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism. 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. 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. 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. 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. 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. 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. |
| 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. | VAR_022167 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 79 | 1 | T → S in a lung adenocarcinoma sample; somatic mutation. | VAR_042207 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 228 | 1 | C → R in a colorectal adenocarcinoma sample; somatic mutation. | VAR_042208 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 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 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 249 | 1 | S → C in bladder cancer, cervical cancer, PLSD-SD and TD; type 1. | VAR_004149 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 250 | 1 | P → R in MNKS; also some individuals with autosomal dominant congenital sensorineural deafness without craniosynostosis. dbSNP rs4647924. | VAR_004150 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 322 | 1 | E → K in colorectal cancer. | VAR_018388 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 338 | 1 | T → M | VAR_042209 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 370 | 1 | G → C in bladder cancer, keratinocytic non-epidermolytic nevus and TD; type 1. | VAR_004151 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 371 | 1 | S → C in TD; type 1. | VAR_004152 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 373 | 1 | Y → C in PLSD-SD and TD; type 1. | VAR_004153 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 375 | 1 | G → C in ACH. | VAR_004154 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 380 | 1 | G → R in keratinocytic non-epidermolytic nevus and ACH; results in constitutive activation; very common mutation. dbSNP rs28931614. | VAR_004155 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 384 | 1 | F → L: dbSNP rs17881656. | VAR_022168 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 391 | 1 | A → E in Crouzon syndrome with acanthosis nigricans. dbSNP rs28931615. | VAR_004156 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 441 | 1 | A → T: dbSNP rs17884368. | VAR_022169 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 513 | 1 | D → N in LADDS. | VAR_029887 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 538 | 1 | I → V in hypochondroplasia. | VAR_004157 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 540 | 1 | N → K in hypochondroplasia. | VAR_004158 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 540 | 1 | N → S in hypochondroplasia; mild. | VAR_018389 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 540 | 1 | N → T in hypochondroplasia. | VAR_004159 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 621 | 1 | R → H in CATSHL syndrome. | VAR_029108 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 646 | 1 | D → N | VAR_042210 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 650 | 1 | K → E in TD and bladder cancer samples; bladder transitional cell carcinoma; somatic mutation. | VAR_004160 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 650 | 1 | K → M in ACH and TD; type 1. | 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. | VAR_018390 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 717 | 1 | A → T: dbSNP rs17882190. | VAR_022170 | ||||||||||||||||||||||||||||||||||||
| Natural variant | 726 | 1 | I → F: dbSNP rs17880763. | 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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Clusters with