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Protein

Fibroblast growth factor receptor 4

Gene

Fgfr4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 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. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4 (By similarity).By similarity1 Publication

Catalytic activityi

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

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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei501ATPPROSITE-ProRule annotation1
Active sitei610Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi471 – 479ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-109704. PI3K Cascade.
R-RNO-1257604. PIP3 activates AKT signaling.
R-RNO-1307965. betaKlotho-mediated ligand binding.
R-RNO-190322. FGFR4 ligand binding and activation.
R-RNO-5654228. Phospholipase C-mediated cascade, FGFR4.
R-RNO-5654712. FRS-mediated FGFR4 signaling.
R-RNO-5654719. SHC-mediated cascade:FGFR4.
R-RNO-5654720. PI-3K cascade:FGFR4.
R-RNO-5654733. Negative regulation of FGFR4 signaling.
R-RNO-5673001. RAF/MAP kinase cascade.
R-RNO-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor 4 (EC:2.7.10.1)
Short name:
FGFR-4
Alternative name(s):
CD_antigen: CD334
Gene namesi
Name:Fgfr4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi2612. Fgfr4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini17 – 367ExtracellularSequence analysisAdd BLAST351
Transmembranei368 – 388HelicalSequence analysisAdd BLAST21
Topological domaini389 – 800CytoplasmicSequence analysisAdd BLAST412

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
ChainiPRO_000022754817 – 800Fibroblast growth factor receptor 4Add BLAST784

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 98PROSITE-ProRule annotation
Glycosylationi109N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi168 ↔ 220PROSITE-ProRule annotation
Glycosylationi254N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi267 ↔ 329PROSITE-ProRule annotation
Glycosylationi286N-linked (GlcNAc...)Sequence analysis1
Glycosylationi307N-linked (GlcNAc...)Sequence analysis1
Modified residuei571PhosphoserineBy similarity1
Modified residuei640Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei641Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei752Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

N-glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF19 (By similarity).By similarity
Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated (By similarity).By similarity
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).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ498D6.
PRIDEiQ498D6.

PTM databases

iPTMnetiQ498D6.
PhosphoSitePlusiQ498D6.

Expressioni

Gene expression databases

BgeeiENSRNOG00000016763.
GenevisibleiQ498D6. RN.

Interactioni

Subunit structurei

Monomer. Homodimer after ligand binding. Interacts with FGF1, FGF2, FGF4, FGF6, FGF8, FGF9, FGF16, FGF17, FGF18, FGF19, FGF21 and FGF23 (in vitro). Binding affinity for FGF family members is enhanced by interactions between FGFs and heparan sulfate proteoglycans. Interacts with KLB; this strongly increases the affinity for FGF19 and FGF23. Affinity for FGF19 is strongly increased by KLB and sulfated glycosaminoglycans. KLB and KL both interact with the core-glycosylated FGFR4 in the endoplasmic reticulum and promote its degradation, so that only FGFR4 with fully mature N-glycans is expressed at the cell surface. Identified in a complex with NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with MMP14 and HIP1. Interacts with STAT3 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000050988.

Structurei

3D structure databases

ProteinModelPortaliQ498D6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 115Ig-like C2-type 1Add BLAST99
Domaini148 – 236Ig-like C2-type 2Add BLAST89
Domaini245 – 345Ig-like C2-type 3Add BLAST101
Domaini465 – 753Protein kinasePROSITE-ProRule annotationAdd BLAST289

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiQ498D6.
KOiK05095.
OMAiQDFHGEH.
PhylomeDBiQ498D6.
TreeFamiTF316307.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000628. FGFR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q498D6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWLLLALLSI FQETPAFSLE ASEEMEQEPC PAPISEQQEQ VLTVALGQPV
60 70 80 90 100
RLCCGRTERG RHWYKEGSRL ASAGRVRGWR GRLEIASFLP EDAGRYLCLA
110 120 130 140 150
RGSMTVVHNL TLIMDDSLPS INNEDPKTLS SSSSGHSYLQ QAPYWTHPQR
160 170 180 190 200
MEKKLHAVPA GNTVKFRCPA AGNPMPTIHW LKNGQAFHGE NRIGGIRLRH
210 220 230 240 250
QHWSLVMESV VPSDRGTYTC LVENSLGSIR YSYLLDVLER SPHRPILQAG
260 270 280 290 300
LPANTTAVVG SNVELLCKVY SDAQPHIQWL KHIVINGSSF GADGFPYVQV
310 320 330 340 350
LKTTDINSSE VEVLYLRNVS AEDAGEYTCL AGNSIGLSYQ SAWLTVLPAE
360 370 380 390 400
EEDLAWTTAT SEARYTDIIL YVSGSLALVL LLLLAGVYHR QAIHGHHSRQ
410 420 430 440 450
PVTVQKLSRF PLARQFSLES RSSGKSSLSL VRGVRLSSSG PPLLTGLVSL
460 470 480 490 500
DLPLDPLWEF PRDRLVLGKP LGEGCFGQVV RAEALGMDSS RPDQTSTVAV
510 520 530 540 550
KMLKDNASDK DLADLISEME MMKLIGRHKN IINLLGVCTQ EGPLYVIVEY
560 570 580 590 600
AAKGNLREFL RARRPPGPDL SPDGPRSSEG PLSFPALVSC AYQVARGMQY
610 620 630 640 650
LESRKCIHRD LAARNVLVTE DDVMKIADFG LARGVHHIDY YKKTSNGRLP
660 670 680 690 700
VKWMAPEALF DRVYTHQSDV WSFGILLWEI FTLGGSPYPG IPVEELFSLL
710 720 730 740 750
REGHRMERPP NCPSELYGLM RECWHAAPSQ RPTFKQLVEA LDKVLLAVSE
760 770 780 790 800
EYLDLRLTFG PYSPNNGDAS STCSSSDSVF SHDPLPLEPS PFPFPEAQTT
Length:800
Mass (Da):88,708
Last modified:September 13, 2005 - v1
Checksum:i4D3CF9C152C9A4EE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC100260 mRNA. Translation: AAI00261.1.
RefSeqiNP_001103374.1. NM_001109904.1.
UniGeneiRn.24104.

Genome annotation databases

EnsembliENSRNOT00000042394; ENSRNOP00000050988; ENSRNOG00000016763.
ENSRNOT00000082836; ENSRNOP00000069871; ENSRNOG00000016763.
GeneIDi25114.
KEGGirno:25114.
UCSCiRGD:2612. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC100260 mRNA. Translation: AAI00261.1.
RefSeqiNP_001103374.1. NM_001109904.1.
UniGeneiRn.24104.

3D structure databases

ProteinModelPortaliQ498D6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000050988.

PTM databases

iPTMnetiQ498D6.
PhosphoSitePlusiQ498D6.

Proteomic databases

PaxDbiQ498D6.
PRIDEiQ498D6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000042394; ENSRNOP00000050988; ENSRNOG00000016763.
ENSRNOT00000082836; ENSRNOP00000069871; ENSRNOG00000016763.
GeneIDi25114.
KEGGirno:25114.
UCSCiRGD:2612. rat.

Organism-specific databases

CTDi2264.
RGDi2612. Fgfr4.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiQ498D6.
KOiK05095.
OMAiQDFHGEH.
PhylomeDBiQ498D6.
TreeFamiTF316307.

Enzyme and pathway databases

ReactomeiR-RNO-109704. PI3K Cascade.
R-RNO-1257604. PIP3 activates AKT signaling.
R-RNO-1307965. betaKlotho-mediated ligand binding.
R-RNO-190322. FGFR4 ligand binding and activation.
R-RNO-5654228. Phospholipase C-mediated cascade, FGFR4.
R-RNO-5654712. FRS-mediated FGFR4 signaling.
R-RNO-5654719. SHC-mediated cascade:FGFR4.
R-RNO-5654720. PI-3K cascade:FGFR4.
R-RNO-5654733. Negative regulation of FGFR4 signaling.
R-RNO-5673001. RAF/MAP kinase cascade.
R-RNO-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

Miscellaneous databases

PROiQ498D6.

Gene expression databases

BgeeiENSRNOG00000016763.
GenevisibleiQ498D6. RN.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000628. FGFR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFGFR4_RAT
AccessioniPrimary (citable) accession number: Q498D6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: September 13, 2005
Last modified: November 2, 2016
This is version 109 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.