Reviewed, UniProtKB/Swiss-Prot P22607 (FGFR3_HUMAN)

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

Name:	FGFR3
Synonyms:	JTK4

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	Membrane; Single-pass type I membrane protein.
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

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Craniosynostosis Deafness Disease mutation Dwarfism Ectodermal dysplasia Lacrimo-auriculo-dento-digital syndrome
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	JAK-STAT cascade Traceable author statement. Source: ProtInc MAPKKK cascade Traceable author statement. Source: ProtInc cell growth Non-traceable author statement. Source: UniProtKB fibroblast growth factor receptor signaling pathway Traceable author statement. Source: ProtInc protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro skeletal system development Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW fibroblast growth factor receptor activity Ref.6 Non-traceable author statement. Source: UniProtKB identical protein binding Ref.8 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

806

Helix Strand Turn

Details...

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

	Sequence		Length	Mass (Da)
	Isoform 1 (IIIc) [UniParc]. Last modified August 1, 1991. Version 1. Checksum: BC5EA75EA46F447E	FASTA	806	87,710
	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
	Isoform 2 (IIIb). Checksum: E08CE2C9FD56D8F9	FASTA	808	88,157
	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 SWISESVEAD VRLRLANVSE RDGGEYLCRA TNFIGVAEKA FWLSVHGPRA 370 380 390 400 410 420 AEEELVEADE AGSVYAGILS YGVGFFLFIL VVAAVTLCRL RSPPKKGLGS PTVHKISRFP 430 440 450 460 470 480 LKRQVSLESN ASMSSNTPLV RIARLSSGEG PTLANVSELE LPADPKWELS RARLTLGKPL 490 500 510 520 530 540 GEGCFGQVVM AEAIGIDKDR AAKPVTVAVK MLKDDATDKD LSDLVSEMEM MKMIGKHKNI 550 560 570 580 590 600 INLLGACTQG GPLYVLVEYA AKGNLREFLR ARRPPGLDYS FDTCKPPEEQ LTFKDLVSCA 610 620 630 640 650 660 YQVARGMEYL ASQKCIHRDL AARNVLVTED NVMKIADFGL ARDVHNLDYY KKTTNGRLPV 670 680 690 700 710 720 KWMAPEALFD RVYTHQSDVW SFGVLLWEIF TLGGSPYPGI PVEELFKLLK EGHRMDKPAN 730 740 750 760 770 780 CTHDLYMIMR ECWHAAPSQR PTFKQLVEDL DRVLTVTSTD EYLDLSAPFE QYSPGGQDTP 790 800 SSSSSGDDSV FAHDLLPPAP PSSGGSRT
	Isoform 3. Checksum: 4493C5990FD68964	FASTA	694	75,696
	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 VSLESNASMS SNTPLVRIAR LSSGEGPTLA NVSELELPAD PKWELSRARL 370 380 390 400 410 420 TLGKPLGEGC FGQVVMAEAI GIDKDRAAKP VTVAVKMLKD DATDKDLSDL VSEMEMMKMI 430 440 450 460 470 480 GKHKNIINLL GACTQGGPLY VLVEYAAKGN LREFLRARRP PGLDYSFDTC KPPEEQLTFK 490 500 510 520 530 540 DLVSCAYQVA RGMEYLASQK CIHRDLAARN VLVTEDNVMK IADFGLARDV HNLDYYKKTT 550 560 570 580 590 600 NGRLPVKWMA PEALFDRVYT HQSDVWSFGV LLWEIFTLGG SPYPGIPVEE LFKLLKEGHR 610 620 630 640 650 660 MDKPANCTHD LYMIMRECWH AAPSQRPTFK QLVEDLDRVL TVTSTDEYLD LSAPFEQYSP 670 680 690 GGQDTPSSSS SGDDSVFAHD LLPPAPPSSG GSRT

References

	« Hide 'large scale' referencesShow '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. , 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. 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. , Schlessinger J., van Bokhoven H., 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. , 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. 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

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RY7	X-ray	3.20	B	33-365	[»]

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

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1991
Last modified:	November 3, 2009
This is version 136 of the entry and version 1 of the sequence. [Complete 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.