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P22455 (FGFR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 161. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fibroblast growth factor receptor 4

Short name=FGFR-4
EC=2.7.10.1
Alternative name(s):
CD_antigen=CD334
Gene names
Name:FGFR4
Synonyms:JTK2, TKF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length802 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26 Ref.30

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.16 Ref.19 Ref.20 Ref.21

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. Ref.20

Subunit structure

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. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.21 Ref.22 Ref.24 Ref.26

Subcellular location

Cell membrane; Single-pass type I membrane protein. Endosome. Endoplasmic reticulum. Note: Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane. Ref.3 Ref.5 Ref.20 Ref.21 Ref.22

Isoform 2: Secreted Ref.3 Ref.5 Ref.20 Ref.21 Ref.22.

Isoform 3: Cytoplasm Ref.3 Ref.5 Ref.20 Ref.21 Ref.22.

Tissue specificity

Expressed in gastrointestinal epithelial cells, pancreas, and gastric and pancreatic cancer cell lines. Ref.3

Post-translational modification

N-glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF19. Ref.19 Ref.22

Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated. Ref.19 Ref.22

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. Ref.14 Ref.19 Ref.21 Ref.22 Ref.24

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 componentCell membrane
Cytoplasm
Endoplasmic reticulum
Endosome
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

alveolar secondary septum development

Inferred from electronic annotation. Source: Ensembl

cell migration

Inferred from mutant phenotype Ref.30. Source: UniProtKB

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Inferred from direct assay Ref.26. Source: UniProtKB

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

organ induction

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.20Ref.22. Source: UniProtKB

phosphate ion homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of DNA biosynthetic process

Inferred from mutant phenotype Ref.26. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype Ref.26. Source: UniProtKB

positive regulation of cell proliferation

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of metalloenzyme activity

Inferred from mutant phenotype Ref.24. Source: UniProtKB

positive regulation of proteolysis

Inferred from mutant phenotype Ref.24. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.24. Source: UniProtKB

regulation of bile acid biosynthetic process

Inferred from mutant phenotype Ref.18Ref.22. Source: UniProtKB

regulation of cholesterol homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of extracellular matrix disassembly

Inferred from mutant phenotype Ref.30. Source: UniProtKB

regulation of lipid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

endoplasmic reticulum

Inferred from direct assay Ref.22. Source: UniProtKB

endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from direct assay Ref.22. Source: UniProtKB

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

fibroblast growth factor binding

Inferred from direct assay Ref.20Ref.15. Source: UniProtKB

fibroblast growth factor-activated receptor activity

Inferred from direct assay Ref.20Ref.26Ref.15. Source: UniProtKB

heparin binding

Inferred from direct assay Ref.20. Source: UniProtKB

protein tyrosine kinase activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P22455-1)

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: P22455-2)

Also known as: Soluble-form;

The sequence of this isoform differs from the canonical sequence as follows:
     353-416: EEDPTWTAAA...QKLSRFPLAR → GTGRIPHLTCDSLTPAGRTKSPTL
Isoform 3 (identifier: P22455-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-210: Missing.
Note: Lacks a signal peptide. Constitutively phosphorylated.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.13
Chain22 – 802781Fibroblast growth factor receptor 4
PRO_0000016787

Regions

Topological domain22 – 369348Extracellular Potential
Transmembrane370 – 39021Helical; Potential
Topological domain391 – 802412Cytoplasmic Potential
Domain22 – 11897Ig-like C2-type 1
Domain152 – 24089Ig-like C2-type 2
Domain249 – 349101Ig-like C2-type 3
Domain467 – 755289Protein kinase
Nucleotide binding473 – 4819ATP By similarity

Sites

Active site6121Proton acceptor By similarity
Binding site5031ATP By similarity

Amino acid modifications

Modified residue6421Phosphotyrosine; by autocatalysis Ref.21
Modified residue6431Phosphotyrosine; by autocatalysis Ref.21
Modified residue7541Phosphotyrosine; by autocatalysis Ref.14
Glycosylation1121N-linked (GlcNAc...) Potential
Glycosylation2581N-linked (GlcNAc...) Potential
Glycosylation2901N-linked (GlcNAc...) Potential
Glycosylation3111N-linked (GlcNAc...) Potential
Glycosylation3221N-linked (GlcNAc...) Potential
Disulfide bond57 ↔ 101 By similarity
Disulfide bond172 ↔ 224 By similarity
Disulfide bond271 ↔ 333 By similarity

Natural variations

Alternative sequence1 – 210210Missing in isoform 3.
VSP_053542
Alternative sequence353 – 41664EEDPT…FPLAR → GTGRIPHLTCDSLTPAGRTK SPTL in isoform 2.
VSP_035108
Natural variant101V → I. Ref.6 Ref.8 Ref.27
Corresponds to variant rs1966265 [ dbSNP | Ensembl ].
VAR_029185
Natural variant1361P → L. Ref.3 Ref.6 Ref.7 Ref.8 Ref.10 Ref.27
Corresponds to variant rs376618 [ dbSNP | Ensembl ].
VAR_042211
Natural variant1791T → A. Ref.27
Corresponds to variant rs55675160 [ dbSNP | Ensembl ].
VAR_042212
Natural variant3881G → R Prolonged FGFR4 activity, increased cell motility and tumor cell invasion, possibly due to increased stability of the protease MMP14. Ref.5 Ref.6 Ref.8 Ref.21 Ref.30
Corresponds to variant rs351855 [ dbSNP | Ensembl ].
VAR_014797
Natural variant4261G → S. Ref.27
Corresponds to variant rs55879131 [ dbSNP | Ensembl ].
VAR_046102
Natural variant5161D → N. Ref.27
Corresponds to variant rs34158682 [ dbSNP | Ensembl ].
VAR_042213
Natural variant5291R → Q.
Corresponds to variant rs34284947 [ dbSNP | Ensembl ].
VAR_049720
Natural variant5501V → M in breast pleomorphic lobular sample; somatic mutation. Ref.27
VAR_046103
Natural variant7121P → T in a lung adenocarcinoma sample; somatic mutation. Ref.27
VAR_046104
Natural variant7721S → N in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.27
VAR_046105

Experimental info

Mutagenesis5031K → R: Loss of kinase activity. Ref.16 Ref.19
Mutagenesis7541Y → F: Loss of interaction with PLCG1. Ref.14
Sequence conflict1211L → S in AAF27432. Ref.3
Sequence conflict1941E → G in AAF27432. Ref.3
Sequence conflict2971D → V in CAA40490. Ref.1

Secondary structure

........................................................ 802
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 27, 2001. Version 2.
Checksum: B22B259831BB889F

FASTA80287,954
        10         20         30         40         50         60 
MRLLLALLGV LLSVPGPPVL SLEASEEVEL EPCLAPSLEQ QEQELTVALG QPVRLCCGRA 

        70         80         90        100        110        120 
ERGGHWYKEG SRLAPAGRVR GWRGRLEIAS FLPEDAGRYL CLARGSMIVL QNLTLITGDS 

       130        140        150        160        170        180 
LTSSNDDEDP KSHRDPSNRH SYPQQAPYWT HPQRMEKKLH AVPAGNTVKF RCPAAGNPTP 

       190        200        210        220        230        240 
TIRWLKDGQA FHGENRIGGI RLRHQHWSLV MESVVPSDRG TYTCLVENAV GSIRYNYLLD 

       250        260        270        280        290        300 
VLERSPHRPI LQAGLPANTT AVVGSDVELL CKVYSDAQPH IQWLKHIVIN GSSFGADGFP 

       310        320        330        340        350        360 
YVQVLKTADI NSSEVEVLYL RNVSAEDAGE YTCLAGNSIG LSYQSAWLTV LPEEDPTWTA 

       370        380        390        400        410        420 
AAPEARYTDI ILYASGSLAL AVLLLLAGLY RGQALHGRHP RPPATVQKLS RFPLARQFSL 

       430        440        450        460        470        480 
ESGSSGKSSS SLVRGVRLSS SGPALLAGLV SLDLPLDPLW EFPRDRLVLG KPLGEGCFGQ 

       490        500        510        520        530        540 
VVRAEAFGMD PARPDQASTV AVKMLKDNAS DKDLADLVSE MEVMKLIGRH KNIINLLGVC 

       550        560        570        580        590        600 
TQEGPLYVIV ECAAKGNLRE FLRARRPPGP DLSPDGPRSS EGPLSFPVLV SCAYQVARGM 

       610        620        630        640        650        660 
QYLESRKCIH RDLAARNVLV TEDNVMKIAD FGLARGVHHI DYYKKTSNGR LPVKWMAPEA 

       670        680        690        700        710        720 
LFDRVYTHQS DVWSFGILLW EIFTLGGSPY PGIPVEELFS LLREGHRMDR PPHCPPELYG 

       730        740        750        760        770        780 
LMRECWHAAP SQRPTFKQLV EALDKVLLAV SEEYLDLRLT FGPYSPSGGD ASSTCSSSDS 

       790        800 
VFSHDPLPLG SSSFPFGSGV QT 

« Hide

Isoform 2 (Soluble-form) [UniParc].

Checksum: BECABBA4E04A35BC
Show »

FASTA76283,452
Isoform 3 [UniParc].

Checksum: 26B7B22E4DAF8A87
Show »

FASTA59264,640

References

« Hide 'large scale' references
[1]"FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern."
Partanen J.M., Maekelae T.P., Eerola E., Korhonen J., Hirvonen H., Claesson-Welsh L., Alitalo K.
EMBO J. 10:1347-1354(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Fibroblast growth factor receptor 4 is a high affinity receptor for both acidic and basic fibroblast growth factor but not for keratinocyte growth factor."
Ron D., Reich R., Chedid M., Lengel C., Cohen O.E., Chan A.M., Neufeld G., Miki T., Tronick S.R.
J. Biol. Chem. 268:5388-5394(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION AS RECEPTOR FOR FGF1 AND FGF2.
Tissue: Mammary gland.
[3]"Identification of a novel alternative splicing of human FGF receptor 4: soluble-form splice variant expressed in human gastrointestinal epithelial cells."
Takaishi S., Sawada M., Morita Y., Seno H., Fukuzawa H., Chiba T.
Biochem. Biophys. Res. Commun. 267:658-662(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LEU-136, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
Tissue: Intestine.
[4]"Genomic structure and complete sequence of the human FGFR4 gene."
Kostrzewa M., Muller U.
Mamm. Genome 9:131-135(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Targeted expression of a human pituitary tumor-derived isoform of FGF receptor-4 recapitulates pituitary tumorigenesis."
Ezzat S., Zheng L., Zhu X.F., Wu G.E., Asa S.L.
J. Clin. Invest. 109:69-78(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION (ISOFORM 3), VARIANT ARG-388.
Tissue: Pituitary.
[6]"PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma."
Marshall A.D., van der Ent M.A., Grosveld G.C.
Mol. Carcinog. 51:807-815(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ILE-10; LEU-136 AND ARG-388.
[7]"Sequence variation in fibroblast growth factor receptors 3 and 4."
Lind D.L., Cox D.R.
Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-136.
[8]NIEHS SNPs program
Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-10; LEU-136 AND ARG-388.
[9]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LEU-136.
[11]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Muscle.
[12]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 609-676.
Tissue: Blood.
[13]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-38.
[14]"Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1."
Vainikka S., Joukov V., Wennstrom S., Bergman M., Pelicci P.G., Alitalo K.
J. Biol. Chem. 269:18320-18326(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS FGF1 RECEPTOR AND IN ACTIVATION OF SIGNALING VIA PLCG1 AND PIK3R1, INTERACTION WITH PLCG1, PHOSPHORYLATION AT TYR-754, MUTAGENESIS OF TYR-754.
[15]"Receptor specificity of the fibroblast growth factor family."
Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A., Coulier F., Gao G., Goldfarb M.
J. Biol. Chem. 271:15292-15297(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FGF1; FGF2; FGF4; FGF6; FGF8 AND FGF9, FUNCTION IN CELL PROLIFERATION.
[16]"N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling."
Cavallaro U., Niedermeyer J., Fuxa M., Christofori G.
Nat. Cell Biol. 3:650-657(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL DIFFERENTIATION, MUTAGENESIS OF LYS-503, CATALYTIC ACTIVITY, IDENTIFICATION IN A COMPLEX WITH NCAM1; CDH2; PLCG1; FRS2; SRC; SHC; GAP43 AND CTTN.
[17]"Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family."
Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M.
J. Biol. Chem. 281:15694-15700(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FGF1; FGF17; FGF18; FGF19; FGF21 AND FGF23, FUNCTION IN STIMULATION OF CELL PROLIFERATION.
[18]"Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21."
Kurosu H., Choi M., Ogawa Y., Dickson A.S., Goetz R., Eliseenkova A.V., Mohammadi M., Rosenblatt K.P., Kliewer S.A., Kuro-o M.
J. Biol. Chem. 282:26687-26695(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FGF19; FGF21 AND KLB, FUNCTION IN SIGNALING AND IN REGULATION OF CYP7A1 AND BILE ACID SYNTHESIS.
[19]"Fibroblast growth factor receptor-induced phosphorylation of STAT1 at the Golgi apparatus without translocation to the nucleus."
Citores L., Bai L., Sorensen V., Olsnes S.
J. Cell. Physiol. 212:148-156(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN STAT1 PHOSPHORYLATION, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-503, GLYCOSYLATION, PHOSPHORYLATION.
[20]"Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis."
Haugsten E.M., Malecki J., Bjorklund S.M., Olsnes S., Wesche J.
Mol. Biol. Cell 19:3390-3403(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION AS FGF1 RECEPTOR AND IN ACTIVATION OF PLCG1; FRS2; MAPK1/ERK2 AND MAPK3/ERK1, ENZYME REGULATION, UBIQUITINATION, SUBCELLULAR LOCATION.
[21]"Altered fibroblast growth factor receptor 4 stability promotes prostate cancer progression."
Wang J., Yu W., Cai Y., Ren C., Ittmann M.M.
Neoplasia 10:847-856(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION AS FGF2 RECEPTOR AND IN STIMULATION OF CELL PROLIFERATION, SUBCELLULAR LOCATION, INTERACTION WITH FGF2 AND HIP1, PHOSPHORYLATION AT TYR-642 AND TYR-643, CHARACTERIZATION OF VARIANT ARG-388.
[22]"Glycosylation of fibroblast growth factor receptor 4 is a key regulator of fibroblast growth factor 19-mediated down-regulation of cytochrome P450 7A1."
Triantis V., Saeland E., Bijl N., Oude-Elferink R.P., Jansen P.L.
Hepatology 52:656-666(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN FGF19 SIGNALING AND IN REGULATION OF BILE ACID SYNTHESIS VIA CYP7A1, INTERACTION WITH FGF19; KL AND KLB, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, GLYCOSYLATION.
[23]"FGF19-induced hepatocyte proliferation is mediated through FGFR4 activation."
Wu X., Ge H., Lemon B., Vonderfecht S., Weiszmann J., Hecht R., Gupte J., Hager T., Wang Z., Lindberg R., Li Y.
J. Biol. Chem. 285:5165-5170(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN HEPATOCYTE PROLIFERATION AND FGF19 SIGNALING.
[24]"FGF receptor-4 (FGFR4) polymorphism acts as an activity switch of a membrane type 1 matrix metalloproteinase-FGFR4 complex."
Sugiyama N., Varjosalo M., Meller P., Lohi J., Chan K.M., Zhou Z., Alitalo K., Taipale J., Keski-Oja J., Lehti K.
Proc. Natl. Acad. Sci. U.S.A. 107:15786-15791(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DOWN-REGULATION OF MMP14, AUTOPHOSPHORYLATION, INTERACTION WITH MMP14.
[25]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"Sulfated glycosaminoglycans are required for specific and sensitive fibroblast growth factor (FGF) 19 signaling via FGF receptor 4 and betaKlotho."
Nakamura M., Uehara Y., Asada M., Honda E., Nagai N., Kimata K., Suzuki M., Imamura T.
J. Biol. Chem. 286:26418-26423(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN FGF19 SIGNALING, FUNCTION IN STIMULATION OF CELL PROLIFERATION AND ACTIVATION OF MAPK1/ERK2 AND MAPK3/ERK1, INTERACTION WITH FGF19; KLB AND SULFATED GLYCOSAMINOGLYCANS.
[27]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-10; LEU-136; ALA-179; SER-426; ASN-516; MET-550; THR-712 AND ASN-772.
[28]"Cellular signaling by fibroblast growth factor receptors."
Eswarakumar V.P., Lax I., Schlessinger J.
Cytokine Growth Factor Rev. 16:139-149(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON LIGAND SELECTIVITY AND SIGNALING.
[29]"Fibroblast growth factor signalling: from development to cancer."
Turner N., Grose R.
Nat. Rev. Cancer 10:116-129(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION IN FGF SIGNALING.
[30]"Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation."
Sugiyama N., Varjosalo M., Meller P., Lohi J., Hyytiainen M., Kilpinen S., Kallioniemi O., Ingvarsen S., Engelholm L.H., Taipale J., Alitalo K., Keski-Oja J., Lehti K.
Cancer Res. 70:7851-7861(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT ARG-388, FUNCTION IN TUMOR CELL INVASION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRTVHUF4. S15345.
RefSeqNP_002002.3. NM_002011.3.
NP_075252.2. NM_022963.2.
NP_998812.1. NM_213647.1.
XP_005265895.1. XM_005265838.2.
UniGeneHs.165950.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1QCTmodel-B/E36-353[»]
ProteinModelPortalP22455.
SMRP22455. Positions 21-355, 454-747.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108555. 6 interactions.
DIPDIP-5149N.
IntActP22455. 1 interaction.
STRING9606.ENSP00000292408.

Chemistry

BindingDBP22455.
ChEMBLCHEMBL3973.
DrugBankDB00039. Palifermin.
GuidetoPHARMACOLOGY1811.

Protein family/group databases

MEROPSI43.001.

PTM databases

PhosphoSiteP22455.

Polymorphism databases

DMDM13432140.

Proteomic databases

PaxDbP22455.
PRIDEP22455.

Protocols and materials databases

DNASU2264.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000292408; ENSP00000292408; ENSG00000160867. [P22455-1]
ENST00000292410; ENSP00000292410; ENSG00000160867. [P22455-2]
ENST00000393637; ENSP00000377254; ENSG00000160867. [P22455-2]
ENST00000502906; ENSP00000424960; ENSG00000160867. [P22455-1]
GeneID2264.
KEGGhsa:2264.
UCSCuc003mfl.3. human. [P22455-1]
uc003mfo.3. human. [P22455-2]

Organism-specific databases

CTD2264.
GeneCardsGC05P176513.
HGNCHGNC:3691. FGFR4.
HPACAB005196.
HPA027273.
HPA027369.
HPA028251.
MIM134935. gene.
neXtProtNX_P22455.
PharmGKBPA28130.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000263410.
HOVERGENHBG000345.
KOK05095.
OMAGQDFHGE.
OrthoDBEOG7NGQ9N.
PhylomeDBP22455.
TreeFamTF316307.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP22455.
BgeeP22455.
CleanExHS_FGFR4.
GenevestigatorP22455.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
InterProIPR016248. 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.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFPIRSF000628. FGFR. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50835. IG_LIKE. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFGFR4. human.
GeneWikiFibroblast_growth_factor_receptor_4.
GenomeRNAi2264.
NextBio35516406.
PROP22455.
SOURCESearch...

Entry information

Entry nameFGFR4_HUMAN
AccessionPrimary (citable) accession number: P22455
Secondary accession number(s): G3JVM2 expand/collapse secondary AC list , G3JVM5, G3JVM7, G3JVM9, O43785, Q14309, Q71TW8, Q8TDA0, Q96KE5
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: April 27, 2001
Last modified: April 16, 2014
This is version 161 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries