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Q9I8X3

- FGFR3_DANRE

UniProt

Q9I8X3 - FGFR3_DANRE

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Protein
Fibroblast growth factor receptor 3
Gene
fgfr3
Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed - Annotation score: 4 out of 5 - Experimental evidence at transcript leveli

Functioni

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 activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei496 – 4961ATP By similarity
Active sitei605 – 6051Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi466 – 4749ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. fibroblast growth factor-activated receptor activity Source: InterPro
Complete GO annotation...

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. positive regulation of cell proliferation Source: InterPro
  3. skeletal system development Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor 3 (EC:2.7.10.1)
Short name:
FGFR-3
Gene namesi
Name:fgfr3
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
ProteomesiUP000000437: Unplaced

Organism-specific databases

ZFINiZDB-GENE-000816-1. fgfr3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 363343Extracellular Reviewed prediction
Add
BLAST
Transmembranei364 – 38421Helical; Reviewed prediction
Add
BLAST
Topological domaini385 – 800416Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020 Reviewed prediction
Add
BLAST
Chaini21 – 800780Fibroblast growth factor receptor 3
PRO_0000249205Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi55 ↔ 101 By similarity
Glycosylationi77 – 771N-linked (GlcNAc...) Reviewed prediction
Glycosylationi90 – 901N-linked (GlcNAc...) Reviewed prediction
Glycosylationi112 – 1121N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi169 ↔ 221 By similarity
Glycosylationi218 – 2181N-linked (GlcNAc...) Reviewed prediction
Glycosylationi255 – 2551N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi268 ↔ 332 By similarity
Glycosylationi287 – 2871N-linked (GlcNAc...) Reviewed prediction
Glycosylationi308 – 3081N-linked (GlcNAc...) Reviewed prediction
Glycosylationi321 – 3211N-linked (GlcNAc...) Reviewed prediction
Modified residuei635 – 6351Phosphotyrosine; by autocatalysis By similarity
Modified residuei636 – 6361Phosphotyrosine; by autocatalysis By similarity
Modified residuei712 – 7121Phosphotyrosine; by autocatalysis By similarity
Modified residuei748 – 7481Phosphotyrosine; by autocatalysis By similarity

Post-translational modificationi

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.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiQ9I8X3.

Expressioni

Developmental stagei

Expression occurs in the axial mesoderm, the diencephalon, the anterior hindbrain and the anterior spinal cord. In the hindbrain, a differential expression was detected at several levels of intensity, with the highest expression in the posterior rhombomere 1 that is morphologically distinct from the anterior part, which develops into the cerebellum.1 Publication

Interactioni

Subunit structurei

Monomer. Homodimer after ligand binding By similarity.

Structurei

3D structure databases

ProteinModelPortaliQ9I8X3.
SMRiQ9I8X3. Positions 143-354, 446-744.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini21 – 122102Ig-like C2-type 1
Add
BLAST
Domaini144 – 23794Ig-like C2-type 2
Add
BLAST
Domaini246 – 348103Ig-like C2-type 3
Add
BLAST
Domaini460 – 739280Protein kinase
Add
BLAST

Domaini

The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans By similarity.

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
HOVERGENiHBG000345.
InParanoidiQ9I8X3.
KOiK05094.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR028176. FGF_rcpt_3.
IPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PANTHERiPTHR24416:SF128. PTHR24416:SF128. 1 hit.
PfamiPF07679. I-set. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000628. FGFR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9I8X3-1 [UniParc]FASTAAdd to Basket

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MVPLCLLLYL ATLVFPPVYS AHLLSPEPTD WVSSEVEVFL EDYVAGVGDT    50
VVLSCTPQDF LLPIVWQKDG DAVSSSNRTR VGQKALRIIN VSYEDSGVYS 100
CRHAHKSMLL SNYTVKVIDS LSSGDDEDYD EDEDEAGNGN AEAPYWTRSD 150
RMEKKLLAVP AANTVKFRCP AAGNPTPSIH WLKNGKEFKG EQRMGGIKLR 200
HQQWSLVMES AVPSDRGNYT CVVQNKYGSI KHTYQLDVLE RSPHRPILQA 250
GLPANQTVVV GSDVEFHCKV YSDAQPHIQW LKHIEVNGSQ YGPNGAPYVN 300
VLKTAGINTT DKELEILYLT NVSFEDAGQY TCLAGNSIGY NHHSAWLTVL 350
PAVEMEREDD YADILIYVTS CVLFILTMVI IILCRMWINT QKTLPAPPVQ 400
KLSKFPLKRQ VSLESNSSMN SNTPLVRIAR LSSSDGPMLP NVSELELPSD 450
PKWEFTRTKL TLGKPLGEGC FGQVVMAEAI GIDKEKPNKP LTVAVKMLKD 500
DGTDKDLSDL VSEMEMMKMI GKHKNIINLL GACTQDGPLY VLVEYASKGN 550
LREYLRARRP PGMDYSFDTC KIPNETLTFK DLVSCAYQVA RGMEYLASKK 600
CIHRDPAARN VLVTEDNVMK IADFGLARDV HNIDYYKKTT NGRLPVKWMA 650
PEALFDRVYT HQSDVWSYGV LLWEIFTLGG SPYPGIPVEE LFKLLKEGHR 700
MDKPANCTHE LYMIMRECWH AVPSQRPTFR QLVEDHDRVL SMTSTDEYLD 750
LSVPFEQYSP TCPDSNSTCS SGDDSVFAHD PLPEEPCLPK HHHSNGVIRT 800
Length:800
Mass (Da):89,716
Last modified:October 1, 2000 - v1
Checksum:i8092DC0272A5BAD1
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF157560 mRNA. Translation: AAF80344.1.
RefSeqiNP_571681.1. NM_131606.1.
UniGeneiDr.10434.

Genome annotation databases

GeneIDi58129.
KEGGidre:58129.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF157560 mRNA. Translation: AAF80344.1 .
RefSeqi NP_571681.1. NM_131606.1.
UniGenei Dr.10434.

3D structure databases

ProteinModelPortali Q9I8X3.
SMRi Q9I8X3. Positions 143-354, 446-744.
ModBasei Search...

Proteomic databases

PRIDEi Q9I8X3.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 58129.
KEGGi dre:58129.

Organism-specific databases

CTDi 2261.
ZFINi ZDB-GENE-000816-1. fgfr3.

Phylogenomic databases

eggNOGi COG0515.
HOVERGENi HBG000345.
InParanoidi Q9I8X3.
KOi K05094.

Miscellaneous databases

NextBioi 20892380.

Family and domain databases

Gene3Di 2.60.40.10. 3 hits.
InterProi IPR028176. FGF_rcpt_3.
IPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view ]
PANTHERi PTHR24416:SF128. PTHR24416:SF128. 1 hit.
Pfami PF07679. I-set. 3 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PIRSFi PIRSF000628. FGFR. 1 hit.
PRINTSi PR00109. TYRKINASE.
SMARTi SM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "fgfr3 and regionalization of anterior neural tube in zebrafish."
    Sleptsova-Friedrich I., Li Y., Emelyanov A., Ekker M., Korzh V., Ge R.
    Mech. Dev. 102:213-217(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiFGFR3_DANRE
AccessioniPrimary (citable) accession number: Q9I8X3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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