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Protein

Fibroblast growth factor receptor 4

Gene

FGFR4

Organism
Homo sapiens (Human)
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. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.14 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation4 Publications

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei503ATPPROSITE-ProRule annotation1
Active sitei612Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi473 – 481ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • cell migration Source: UniProtKB
  • fibroblast growth factor receptor signaling pathway Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • MAPK cascade Source: Reactome
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • phosphate ion homeostasis Source: UniProtKB
  • phosphatidylinositol-mediated signaling Source: Reactome
  • positive regulation of catalytic activity Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of DNA biosynthetic process Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of proteolysis Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • regulation of bile acid biosynthetic process Source: UniProtKB
  • regulation of cholesterol homeostasis Source: UniProtKB
  • regulation of extracellular matrix disassembly Source: UniProtKB
  • regulation of lipid metabolic process Source: UniProtKB
  • regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS08543-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-109704. PI3K Cascade.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1307965. betaKlotho-mediated ligand binding.
R-HSA-1839128. FGFR4 mutant receptor activation.
R-HSA-190322. FGFR4 ligand binding and activation.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5654228. Phospholipase C-mediated cascade, FGFR4.
R-HSA-5654712. FRS-mediated FGFR4 signaling.
R-HSA-5654719. SHC-mediated cascade:FGFR4.
R-HSA-5654720. PI-3K cascade:FGFR4.
R-HSA-5654733. Negative regulation of FGFR4 signaling.
R-HSA-5655291. Signaling by FGFR4 in disease.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SIGNORiP22455.

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
Synonyms:JTK2, TKF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:3691. FGFR4.

Subcellular locationi

Isoform 3 :
  • Cytoplasm 1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 369ExtracellularSequence analysisAdd BLAST348
Transmembranei370 – 390HelicalSequence analysisAdd BLAST21
Topological domaini391 – 802CytoplasmicSequence analysisAdd BLAST412

GO - Cellular componenti

  • cytoplasm Source: HPA
  • endoplasmic reticulum Source: UniProtKB
  • endosome Source: UniProtKB-SubCell
  • extracellular region Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • nucleoplasm Source: HPA
  • plasma membrane Source: UniProtKB
  • transport vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Endosome, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Prostate cancer (PC)4 Publications
The gene represented in this entry is involved in disease pathogenesis. FGFR4 variant Arg-388 has been associated with prostate cancer as well as cancers of the breast, colon, head and neck, larynx, lung, skin. Arg-388 predisposes cancer patients for accelerated disease progression and is associated with poor prognosis.10 Publications
Disease descriptionA malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
See also OMIM:176807
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014797388G → R in PC; also found in other types of cancer; associated with increased disease susceptibility, accelerated cancer progression and poor prognosis; results in prolonged FGFR4 activity; causes increased cell motility and tumor cell invasion possibly due to increased stability of the protease MMP14; increased interaction with STAT3; results in STAT3 phosphorylation and signaling activation. 8 PublicationsCorresponds to variant rs351855dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi503K → R: Loss of kinase activity. 2 Publications1
Mutagenesisi754Y → F: Loss of interaction with PLCG1. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2264.
MIMi176807. phenotype.
OpenTargetsiENSG00000160867.
PharmGKBiPA28130.

Chemistry databases

ChEMBLiCHEMBL3973.
DrugBankiDB09078. Lenvatinib.
DB00039. Palifermin.
DB08901. Ponatinib.
GuidetoPHARMACOLOGYi1811.

Polymorphism and mutation databases

BioMutaiFGFR4.
DMDMi13432140.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 211 PublicationAdd BLAST21
ChainiPRO_000001678722 – 802Fibroblast growth factor receptor 4Add BLAST781

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi57 ↔ 101PROSITE-ProRule annotation
Glycosylationi112N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi172 ↔ 224PROSITE-ProRule annotation
Glycosylationi258N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi271 ↔ 333PROSITE-ProRule annotation
Glycosylationi290N-linked (GlcNAc...)Sequence analysis1
Glycosylationi311N-linked (GlcNAc...)Sequence analysis1
Glycosylationi322N-linked (GlcNAc...)Sequence analysis1
Modified residuei573PhosphoserineCombined sources1
Modified residuei642Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei643Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei754Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

N-glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF19.
Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated.1 Publication
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.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP22455.
PaxDbiP22455.
PeptideAtlasiP22455.
PRIDEiP22455.

PTM databases

iPTMnetiP22455.
PhosphoSitePlusiP22455.

Expressioni

Tissue specificityi

Expressed in gastrointestinal epithelial cells, pancreas, and gastric and pancreatic cancer cell lines.1 Publication

Gene expression databases

BgeeiENSG00000160867.
CleanExiHS_FGFR4.
ExpressionAtlasiP22455. baseline and differential.
GenevisibleiP22455. HS.

Organism-specific databases

HPAiCAB005196.
HPA027273.
HPA027369.
HPA028251.

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 (PubMed:11433297, PubMed:16597617, PubMed:17623664, PubMed:18670643, PubMed:20683963, PubMed:20798051, PubMed:21653700, PubMed:7518429, PubMed:8663044). Interacts with STAT3 (PubMed:26675719).10 Publications

GO - Molecular functioni

  • fibroblast growth factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108555. 31 interactors.
DIPiDIP-5149N.
IntActiP22455. 23 interactors.
STRINGi9606.ENSP00000292408.

Chemistry databases

BindingDBiP22455.

Structurei

Secondary structure

1802
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi445 – 448Combined sources4
Turni458 – 460Combined sources3
Helixi464 – 466Combined sources3
Beta strandi467 – 474Combined sources8
Beta strandi480 – 487Combined sources8
Beta strandi490 – 493Combined sources4
Beta strandi497 – 504Combined sources8
Helixi511 – 527Combined sources17
Beta strandi536 – 540Combined sources5
Beta strandi542 – 544Combined sources3
Beta strandi547 – 551Combined sources5
Helixi558 – 563Combined sources6
Beta strandi572 – 574Combined sources3
Helixi586 – 605Combined sources20
Helixi615 – 617Combined sources3
Beta strandi618 – 620Combined sources3
Beta strandi626 – 628Combined sources3
Turni631 – 635Combined sources5
Helixi637 – 639Combined sources3
Beta strandi642 – 644Combined sources3
Helixi652 – 655Combined sources4
Helixi658 – 663Combined sources6
Helixi668 – 683Combined sources16
Beta strandi689 – 692Combined sources4
Helixi695 – 703Combined sources9
Helixi716 – 725Combined sources10
Helixi730 – 732Combined sources3
Helixi736 – 748Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QCTmodel-B/E36-353[»]
4QQ5X-ray2.20A445-753[»]
4QQCX-ray2.40A445-753[»]
4QQJX-ray1.68A445-753[»]
4QQTX-ray1.50A445-753[»]
4QRCX-ray1.90A445-753[»]
4R6VX-ray2.35A445-753[»]
4TYEX-ray2.80A447-753[»]
4TYGX-ray2.40A447-753[»]
4TYIX-ray3.40A447-753[»]
4TYJX-ray2.45A447-753[»]
4UXQX-ray1.85A447-753[»]
4XCUX-ray1.71A449-751[»]
5JKGX-ray2.35A445-753[»]
ProteinModelPortaliP22455.
SMRiP22455.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 118Ig-like C2-type 1Add BLAST97
Domaini152 – 240Ig-like C2-type 2Add BLAST89
Domaini249 – 349Ig-like C2-type 3Add BLAST101
Domaini467 – 755Protein 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.
InParanoidiP22455.
KOiK05095.
OMAiQDFHGEH.
OrthoDBiEOG091G0CQZ.
PhylomeDBiP22455.
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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P22455-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MRLLLALLGV LLSVPGPPVL SLEASEEVEL EPCLAPSLEQ QEQELTVALG
60 70 80 90 100
QPVRLCCGRA ERGGHWYKEG SRLAPAGRVR GWRGRLEIAS FLPEDAGRYL
110 120 130 140 150
CLARGSMIVL QNLTLITGDS LTSSNDDEDP KSHRDPSNRH SYPQQAPYWT
160 170 180 190 200
HPQRMEKKLH AVPAGNTVKF RCPAAGNPTP TIRWLKDGQA FHGENRIGGI
210 220 230 240 250
RLRHQHWSLV MESVVPSDRG TYTCLVENAV GSIRYNYLLD VLERSPHRPI
260 270 280 290 300
LQAGLPANTT AVVGSDVELL CKVYSDAQPH IQWLKHIVIN GSSFGADGFP
310 320 330 340 350
YVQVLKTADI NSSEVEVLYL RNVSAEDAGE YTCLAGNSIG LSYQSAWLTV
360 370 380 390 400
LPEEDPTWTA AAPEARYTDI ILYASGSLAL AVLLLLAGLY RGQALHGRHP
410 420 430 440 450
RPPATVQKLS RFPLARQFSL ESGSSGKSSS SLVRGVRLSS SGPALLAGLV
460 470 480 490 500
SLDLPLDPLW EFPRDRLVLG KPLGEGCFGQ VVRAEAFGMD PARPDQASTV
510 520 530 540 550
AVKMLKDNAS DKDLADLVSE MEVMKLIGRH KNIINLLGVC TQEGPLYVIV
560 570 580 590 600
ECAAKGNLRE FLRARRPPGP DLSPDGPRSS EGPLSFPVLV SCAYQVARGM
610 620 630 640 650
QYLESRKCIH RDLAARNVLV TEDNVMKIAD FGLARGVHHI DYYKKTSNGR
660 670 680 690 700
LPVKWMAPEA LFDRVYTHQS DVWSFGILLW EIFTLGGSPY PGIPVEELFS
710 720 730 740 750
LLREGHRMDR PPHCPPELYG LMRECWHAAP SQRPTFKQLV EALDKVLLAV
760 770 780 790 800
SEEYLDLRLT FGPYSPSGGD ASSTCSSSDS VFSHDPLPLG SSSFPFGSGV

QT
Length:802
Mass (Da):87,954
Last modified:April 27, 2001 - v2
Checksum:iB22B259831BB889F
GO
Isoform 2 (identifier: P22455-2) [UniParc]FASTAAdd to basket
Also known as: Soluble-form

The sequence of this isoform differs from the canonical sequence as follows:
     353-416: EEDPTWTAAA...QKLSRFPLAR → GTGRIPHLTCDSLTPAGRTKSPTL

Show »
Length:762
Mass (Da):83,452
Checksum:iBECABBA4E04A35BC
GO
Isoform 3 (identifier: P22455-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-210: Missing.

Note: Lacks a signal peptide. Constitutively phosphorylated.
Show »
Length:592
Mass (Da):64,640
Checksum:i26B7B22E4DAF8A87
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121L → S in AAF27432 (PubMed:10631118).Curated1
Sequence conflicti194E → G in AAF27432 (PubMed:10631118).Curated1
Sequence conflicti297D → V in CAA40490 (PubMed:1709094).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02918510V → I.3 PublicationsCorresponds to variant rs1966265dbSNPEnsembl.1
Natural variantiVAR_042211136P → L.6 PublicationsCorresponds to variant rs376618dbSNPEnsembl.1
Natural variantiVAR_042212179T → A.1 PublicationCorresponds to variant rs55675160dbSNPEnsembl.1
Natural variantiVAR_014797388G → R in PC; also found in other types of cancer; associated with increased disease susceptibility, accelerated cancer progression and poor prognosis; results in prolonged FGFR4 activity; causes increased cell motility and tumor cell invasion possibly due to increased stability of the protease MMP14; increased interaction with STAT3; results in STAT3 phosphorylation and signaling activation. 8 PublicationsCorresponds to variant rs351855dbSNPEnsembl.1
Natural variantiVAR_046102426G → S.1 PublicationCorresponds to variant rs55879131dbSNPEnsembl.1
Natural variantiVAR_042213516D → N.1 PublicationCorresponds to variant rs34158682dbSNPEnsembl.1
Natural variantiVAR_049720529R → Q.Corresponds to variant rs34284947dbSNPEnsembl.1
Natural variantiVAR_046103550V → M in breast pleomorphic lobular sample; somatic mutation. 1 PublicationCorresponds to variant rs774571806dbSNPEnsembl.1
Natural variantiVAR_046104712P → T in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_046105772S → N in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0535421 – 210Missing in isoform 3. 1 PublicationAdd BLAST210
Alternative sequenceiVSP_035108353 – 416EEDPT…FPLAR → GTGRIPHLTCDSLTPAGRTK SPTL in isoform 2. 1 PublicationAdd BLAST64

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57205 mRNA. Translation: CAA40490.1.
L03840 mRNA. Translation: AAB59389.1.
AF202063 mRNA. Translation: AAF27432.1.
Y13901 Genomic DNA. Translation: CAA74200.1.
AF359246 mRNA. Translation: AAK51435.1.
JN007471 mRNA. Translation: AEO19712.1.
JN007472 mRNA. Translation: AEO19713.1.
JN007473 mRNA. Translation: AEO19714.1.
JN007474 mRNA. Translation: AEO19715.1.
JN007475 mRNA. Translation: AEO19716.1.
JN007476 mRNA. Translation: AEO19717.1.
JN007477 mRNA. Translation: AEO19718.1.
JN007478 mRNA. Translation: AEO19719.1.
JN007479 mRNA. Translation: AEO19720.1.
JN007480 mRNA. Translation: AEO19721.1.
JN007481 mRNA. Translation: AEO19722.1.
JN007482 mRNA. Translation: AEO19723.1.
AF487555 Genomic DNA. Translation: AAM13666.1.
EF571596 Genomic DNA. Translation: ABQ01235.1.
AC027314 Genomic DNA. No translation available.
CH471195 Genomic DNA. Translation: EAW85036.1.
BC011847 mRNA. Translation: AAH11847.1.
M59373 mRNA. Translation: AAA63208.1.
CCDSiCCDS4410.1. [P22455-1]
CCDS4411.1. [P22455-2]
PIRiS15345. TVHUF4.
RefSeqiNP_001278909.1. NM_001291980.1.
NP_002002.3. NM_002011.4. [P22455-1]
NP_075252.2. NM_022963.3. [P22455-2]
NP_998812.1. NM_213647.2. [P22455-1]
XP_005265895.1. XM_005265838.3. [P22455-1]
UniGeneiHs.165950.

Genome annotation databases

EnsembliENST00000292408; ENSP00000292408; ENSG00000160867. [P22455-1]
ENST00000393637; ENSP00000377254; ENSG00000160867. [P22455-2]
ENST00000502906; ENSP00000424960; ENSG00000160867. [P22455-1]
GeneIDi2264.
KEGGihsa:2264.
UCSCiuc003mfl.4. human. [P22455-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57205 mRNA. Translation: CAA40490.1.
L03840 mRNA. Translation: AAB59389.1.
AF202063 mRNA. Translation: AAF27432.1.
Y13901 Genomic DNA. Translation: CAA74200.1.
AF359246 mRNA. Translation: AAK51435.1.
JN007471 mRNA. Translation: AEO19712.1.
JN007472 mRNA. Translation: AEO19713.1.
JN007473 mRNA. Translation: AEO19714.1.
JN007474 mRNA. Translation: AEO19715.1.
JN007475 mRNA. Translation: AEO19716.1.
JN007476 mRNA. Translation: AEO19717.1.
JN007477 mRNA. Translation: AEO19718.1.
JN007478 mRNA. Translation: AEO19719.1.
JN007479 mRNA. Translation: AEO19720.1.
JN007480 mRNA. Translation: AEO19721.1.
JN007481 mRNA. Translation: AEO19722.1.
JN007482 mRNA. Translation: AEO19723.1.
AF487555 Genomic DNA. Translation: AAM13666.1.
EF571596 Genomic DNA. Translation: ABQ01235.1.
AC027314 Genomic DNA. No translation available.
CH471195 Genomic DNA. Translation: EAW85036.1.
BC011847 mRNA. Translation: AAH11847.1.
M59373 mRNA. Translation: AAA63208.1.
CCDSiCCDS4410.1. [P22455-1]
CCDS4411.1. [P22455-2]
PIRiS15345. TVHUF4.
RefSeqiNP_001278909.1. NM_001291980.1.
NP_002002.3. NM_002011.4. [P22455-1]
NP_075252.2. NM_022963.3. [P22455-2]
NP_998812.1. NM_213647.2. [P22455-1]
XP_005265895.1. XM_005265838.3. [P22455-1]
UniGeneiHs.165950.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QCTmodel-B/E36-353[»]
4QQ5X-ray2.20A445-753[»]
4QQCX-ray2.40A445-753[»]
4QQJX-ray1.68A445-753[»]
4QQTX-ray1.50A445-753[»]
4QRCX-ray1.90A445-753[»]
4R6VX-ray2.35A445-753[»]
4TYEX-ray2.80A447-753[»]
4TYGX-ray2.40A447-753[»]
4TYIX-ray3.40A447-753[»]
4TYJX-ray2.45A447-753[»]
4UXQX-ray1.85A447-753[»]
4XCUX-ray1.71A449-751[»]
5JKGX-ray2.35A445-753[»]
ProteinModelPortaliP22455.
SMRiP22455.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108555. 31 interactors.
DIPiDIP-5149N.
IntActiP22455. 23 interactors.
STRINGi9606.ENSP00000292408.

Chemistry databases

BindingDBiP22455.
ChEMBLiCHEMBL3973.
DrugBankiDB09078. Lenvatinib.
DB00039. Palifermin.
DB08901. Ponatinib.
GuidetoPHARMACOLOGYi1811.

PTM databases

iPTMnetiP22455.
PhosphoSitePlusiP22455.

Polymorphism and mutation databases

BioMutaiFGFR4.
DMDMi13432140.

Proteomic databases

MaxQBiP22455.
PaxDbiP22455.
PeptideAtlasiP22455.
PRIDEiP22455.

Protocols and materials databases

DNASUi2264.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000292408; ENSP00000292408; ENSG00000160867. [P22455-1]
ENST00000393637; ENSP00000377254; ENSG00000160867. [P22455-2]
ENST00000502906; ENSP00000424960; ENSG00000160867. [P22455-1]
GeneIDi2264.
KEGGihsa:2264.
UCSCiuc003mfl.4. human. [P22455-1]

Organism-specific databases

CTDi2264.
DisGeNETi2264.
GeneCardsiFGFR4.
HGNCiHGNC:3691. FGFR4.
HPAiCAB005196.
HPA027273.
HPA027369.
HPA028251.
MIMi134935. gene.
176807. phenotype.
neXtProtiNX_P22455.
OpenTargetsiENSG00000160867.
PharmGKBiPA28130.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiP22455.
KOiK05095.
OMAiQDFHGEH.
OrthoDBiEOG091G0CQZ.
PhylomeDBiP22455.
TreeFamiTF316307.

Enzyme and pathway databases

BioCyciZFISH:HS08543-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-109704. PI3K Cascade.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1307965. betaKlotho-mediated ligand binding.
R-HSA-1839128. FGFR4 mutant receptor activation.
R-HSA-190322. FGFR4 ligand binding and activation.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5654228. Phospholipase C-mediated cascade, FGFR4.
R-HSA-5654712. FRS-mediated FGFR4 signaling.
R-HSA-5654719. SHC-mediated cascade:FGFR4.
R-HSA-5654720. PI-3K cascade:FGFR4.
R-HSA-5654733. Negative regulation of FGFR4 signaling.
R-HSA-5655291. Signaling by FGFR4 in disease.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SIGNORiP22455.

Miscellaneous databases

ChiTaRSiFGFR4. human.
GeneWikiiFibroblast_growth_factor_receptor_4.
GenomeRNAii2264.
PROiP22455.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160867.
CleanExiHS_FGFR4.
ExpressionAtlasiP22455. baseline and differential.
GenevisibleiP22455. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P22455
Secondary accession number(s): G3JVM2
, G3JVM5, G3JVM7, G3JVM9, O43785, Q14309, Q71TW8, Q8TDA0, Q96KE5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: April 27, 2001
Last modified: November 30, 2016
This is version 189 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  8. 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.