P18460 (FGFR3_CHICK) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fibroblast growth factor receptor 3
Short name=FGFR-3
EC=2.7.10.1

Alternative name(s):
Tyrosine kinase receptor CEK2

Gene names

Name:	FGFR3
Synonyms:	CEK2

Organism

Gallus gallus (Chicken) [Reference proteome]

Taxonomic identifier

9031 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Sauropsida › Sauria › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galliformes › Phasianidae › Phasianinae › Gallus

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 transcript level

General annotation (Comments)

Function	Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway By similarity.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues By similarity.
Subunit structure	Monomer. Homodimer after ligand binding By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity.
Domain	The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans By similarity.
Post-translational modification	Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer By similarity.
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
Biological process	Apoptosis
Cellular component	Cell membrane Membrane
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from electronic annotation. Source: Compara alveolar secondary septum development Inferred from electronic annotation. Source: Compara apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW axonogenesis involved in innervation Inferred from electronic annotation. Source: Compara bone morphogenesis Inferred from electronic annotation. Source: Compara cartilage development Inferred from electronic annotation. Source: Compara central nervous system myelination Inferred from electronic annotation. Source: Compara cochlea development Inferred from electronic annotation. Source: Compara digestive tract morphogenesis Inferred from electronic annotation. Source: Compara epithelial cell fate commitment Inferred from electronic annotation. Source: Compara inner ear receptor cell differentiation Inferred from electronic annotation. Source: Compara lens fiber cell development Inferred from electronic annotation. Source: Compara lens morphogenesis in camera-type eye Inferred from electronic annotation. Source: Compara morphogenesis of an epithelium Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of astrocyte differentiation Inferred from electronic annotation. Source: Compara negative regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of mitosis Inferred from electronic annotation. Source: Compara negative regulation of smoothened signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of endothelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of phosphatidylinositol 3-kinase activity Inferred from electronic annotation. Source: Compara positive regulation of phospholipase activity Inferred from electronic annotation. Source: Compara positive regulation of protein ubiquitination Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat1 protein Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from electronic annotation. Source: Compara response to axon injury Inferred from electronic annotation. Source: Compara somatic stem cell maintenance Inferred from electronic annotation. Source: Compara substantia nigra development Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Inferred from electronic annotation. Source: Compara internal side of plasma membrane Inferred from electronic annotation. Source: Compara lysosome Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW fibroblast growth factor-activated receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 806	787	Fibroblast growth factor receptor 3		PRO_0000016790
Regions
	Topological domain	20 – 364	345	Extracellular Potential
	Transmembrane	365 – 389	25	Helical; Potential
	Topological domain	390 – 806	417	Cytoplasmic Potential
	Domain	24 – 124	101	Ig-like C2-type 1
	Domain	150 – 238	89	Ig-like C2-type 2
	Domain	247 – 349	103	Ig-like C2-type 3
	Domain	466 – 755	290	Protein kinase
	Nucleotide binding	472 – 480	9	ATP By similarity
	Compositional bias	131 – 141	11	Asp/Glu-rich (highly acidic)
Sites
	Active site	611	1	Proton acceptor By similarity
	Binding site	502	1	ATP By similarity
Amino acid modifications
	Modified residue	641	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	642	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	718	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	754	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	83	1	N-linked (GlcNAc...) Potential
	Glycosylation	96	1	N-linked (GlcNAc...) Potential
	Glycosylation	118	1	N-linked (GlcNAc...) Potential
	Glycosylation	219	1	N-linked (GlcNAc...) Potential
	Glycosylation	256	1	N-linked (GlcNAc...) Potential
	Glycosylation	288	1	N-linked (GlcNAc...) Potential
	Glycosylation	309	1	N-linked (GlcNAc...) Potential
	Glycosylation	322	1	N-linked (GlcNAc...) Potential
	Disulfide bond	61 ↔ 107		By similarity
	Disulfide bond	170 ↔ 222		By similarity
	Disulfide bond	269 ↔ 333		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P18460 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: B38B3C6D5F2314B6	FASTA	806	89,730
	10 20 30 40 50 60 MRAAWGSVWC LCLAAAVGAL PAARRRGAER SGGQAAEYLR SETAFLEELV FGSGDTIELS 70 80 90 100 110 120 CNTQSSSVSV FWFKDGIGIA PSNRTHIGQK LLKIINVSYD DSGLYSCKPR HSNEVLGNFT 130 140 150 160 170 180 VRVTDSPSSG DDEDDDDESE DTGVPFWTRP DKMEKKLLAV PAANTVRFRC PAGGNPTPTI 190 200 210 220 230 240 YWLKNGKEFK GEHRIGGIKL RHQQWSLVME SVVPSDRGNY TCVVENKYGN IRHTYQLDVL 250 260 270 280 290 300 ERSPHRPILQ AGLPANQTVV VGSNVEFHCK VYSDAQPHIQ WLKHVEVNGS KYGPDGTPYV 310 320 330 340 350 360 TVLKTAGVNT TDKELEILYL RNVTFEDAGE YTCLAGNSIG FSHHSAWLTV LPAEELMEMD 370 380 390 400 410 420 DSGSVYAGIL SYGTGLVLFI LVLVIVIICR MKMPNKKAMN TTTVQKVSKF PLKRQQVSLE 430 440 450 460 470 480 SNSSMNSNTP LVRITRLSSS DGPMLANVSE LELPPDPKWE LARSRLTLGK PLGEGCFGQV 490 500 510 520 530 540 VMAEAIGIDK DKPNKAITVA VKMLKDDATD KDLSDLVSEM EMMKMIGKHK NIINLLGACT 550 560 570 580 590 600 QDGPLYVLVE YASKGNLREY LRARRPPGMD YSFDTCKLPE EQLTFKDLVS CAYQVARGME 610 620 630 640 650 660 YLASQKCIHR DLAARNVLVT EDNVMKIADF GLARDVHNID YYKKTTNGRL PVKWMAPEAL 670 680 690 700 710 720 FDRVYTHQSD VWSFGVLLWE IFTLGGSPYP GIPVEELFKL LKEGHRMDKP ANCTHDLYMI 730 740 750 760 770 780 MRECWHAVPS QRPTFKQLVE DLDRVLTMTS TDEYLDLSVP FEQYSPAGQD THSTCSSGDD 790 800 SVFAHDLLPD EPCLPKHVPC NGVIRT

References

[1]	"A distinctive family of embryonic protein-tyrosine kinase receptors." Pasquale E.B. Proc. Natl. Acad. Sci. U.S.A. 87:5812-5816(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	M35195 mRNA. Translation: AAA48664.1.
IPI	IPI00579747.
PIR	A35963.
RefSeq	NP_990840.2. NM_205509.2.
UniGene	Gga.14066.
3D structure databases
ProteinModelPortal	P18460.
SMR	P18460. Positions 145-355, 453-750.
ModBase	Search...
Protein-protein interaction databases
STRING	9031.ENSGALP00000001710.
Proteomic databases
PaxDb	P18460.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	396515.
KEGG	gga:396515.
Organism-specific databases
CTD	2261.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000263410.
HOVERGEN	HBG000345.
InParanoid	P18460.
KO	K05094.
Enzyme and pathway databases
BRENDA	2.7.10.1. 1306.
Family and domain databases
Gene3D	2.60.40.10. 3 hits.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003598. Ig_sub2. IPR013151. Immunoglobulin. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR016248. Tyr_kinase_fibroblast_GF_rcpt. [Graphical view]
Pfam	PF07679. I-set. 2 hits. PF00047. ig. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PIRSF	PIRSF000628. FGFR. 1 hit.
PRINTS	PR00109. TYRKINASE.
SMART	SM00408. IGc2. 3 hits. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
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
NextBio	20816552.

Entry information

Entry name

FGFR3_CHICK

Accession

Primary (citable) accession number: P18460

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	April 3, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program