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Reviewed, UniProtKB/Swiss-Prot P22455 (FGFR4_HUMAN)

Last modified February 9, 2010. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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) [Complete 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

Receptor for acidic fibroblast growth factor. Does not bind to basic fibroblast growth factor. Binds FGF19.

Catalytic activity

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

Subunit structure

Interacts with KLB By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein. Note: Isoform 2 may be secreted. Ref.3

Tissue specificity

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

Post-translational modification

Glycosylated By similarity.

Phosphorylated on tyrosine residue By similarity. Phosphorylation requires the presence of a functional (phosphorylated) FGFR1 and not necessarily by means of FGFR heterodimerization 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.

Alternative products

This entry describes 2 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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.10
Chain22 – 802781Fibroblast growth factor receptor 4
PRO_0000016787

Regions

Topological domain22 – 369348Extracellular Potential
Transmembrane370 – 39021 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 residue5731Phosphoserine Ref.11
Modified residue6431Phosphotyrosine; by autocatalysis By similarity
Glycosylation1121N-linked (GlcNAc...) Potential
Glycosylation2581N-linked (GlcNAc...) Potential
Glycosylation2901N-linked (GlcNAc...) Potential
Glycosylation3111N-linked (GlcNAc...) Potential
Glycosylation3221N-linked (GlcNAc...) Potential
Disulfide bond57 ↔ 101 Potential
Disulfide bond172 ↔ 224 Potential
Disulfide bond271 ↔ 333 Potential

Natural variations

Alternative sequence353 – 41664EEDPT…FPLAR → GTGRIPHLTCDSLTPAGRTK SPTL in isoform 2.
VSP_035108
Natural variant101V → I: dbSNP rs1966265. Ref.6 Ref.12
VAR_029185
Natural variant1361P → L: dbSNP rs376618. Ref.3 Ref.6 Ref.12 Ref.5 Ref.7
VAR_042211
Natural variant1791T → A: dbSNP rs55675160. Ref.12
VAR_042212
Natural variant3881G → R: dbSNP rs351855. Ref.6
VAR_014797
Natural variant4261G → S: dbSNP rs55879131. Ref.12
VAR_046102
Natural variant5161D → N: dbSNP rs34158682. Ref.12
VAR_042213
Natural variant5291R → Q: dbSNP rs34284947.
VAR_049720
Natural variant5501V → M in breast pleomorphic lobular sample; somatic mutation. Ref.12
VAR_046103
Natural variant7121P → T in a lung adenocarcinoma sample; somatic mutation. Ref.12
VAR_046104
Natural variant7721S → N in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.12
VAR_046105

Experimental info

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).

Checksum: BECABBA4E04A35BC
Show »

FASTA76283,452

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: 1709094] [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: 7680645] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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: 10631118] [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: 9457674] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"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.
[6]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.
[7]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.
[8]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Muscle.
[9]"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: 2247464] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 609-676.
Tissue: Blood.
[10]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-38.
[11]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-573, MASS SPECTROMETRY.
[12]"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: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-10; LEU-136; ALA-179; SER-426; ASN-516; MET-550; THR-712 AND ASN-772.
+Additional computationally mapped references.

Web resources

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.
AF487555 Genomic DNA. Translation: AAM13666.1.
EF571596 Genomic DNA. Translation: ABQ01235.1.
CH471195 Genomic DNA. Translation: EAW85036.1.
BC011847 mRNA. Translation: AAH11847.1.
M59373 mRNA. Translation: AAA63208.1.
IPIIPI00304578.
IPI00420109.
PIRTVHUF4. S15345.
RefSeqNP_002002.3.
NP_075252.2.
NP_998812.1.
UniGeneHs.165950

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1QCTmodel-B/E36-353[»]
SMRP22455. Positions 146-355, 454-747, 464-773.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-5149N.
STRINGP22455.

PTM databases

PhosphoSiteP22455.

Proteomic databases

PRIDEP22455.

Genome annotation databases

EnsemblENST00000292408; ENSP00000292408; ENSG00000160867; Homo sapiens. [Genome view]
ENST00000393648; ENSP00000377259; ENSG00000160867; Homo sapiens. [Genome view]
GeneID2264.
KEGGhsa:2264.
UCSCuc003mfl.1. human.

Organism-specific databases

CTD2264.
GeneCardsGC05P176446.
H-InvDBHIX0005452.
HGNCHGNC:3691. FGFR4.
HPACAB005196.
MIM134935. gene.
PharmGKBPA28130.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG11483.
HOVERGENP22455.
OrthoDBEOG93JFPX.
PhylomeDBP22455.

Enzyme and pathway databases

BRENDA2.7.10.1. 247.
Pathway_Interaction_DBfgf_pathway. FGF signaling pathway.
ReactomeREACT_9470. Signaling by FGFR.

Gene expression databases

ArrayExpressP22455.
BgeeP22455.
CleanExHS_FGFR4.
GenevestigatorP22455.
GermOnlineENSG00000160867. Homo sapiens.

Family and domain databases

InterProIPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR020933. Tyr_kin_fibroblast_GF_rcpt_reg.
IPR016248. Tyr_kinase_fibroblast_GF_rcpt.
IPR020635. Tyr_Pkinase_cat_dom.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
[Graphical view]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 3 hits.
PANTHERPTHR23256:SF276. Tyr_kinase_fibroblast_GF_rcpt. 1 hit.
PTHR23256. Tyr_prot_kinase. 1 hit.
PIRSFPIRSF000628. FGFR. 1 hit.
SMARTSM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
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 Resources

DrugBankDB00039. Palifermin.
NextBio9195.
SOURCESearch...

Entry information

Entry nameFGFR4_HUMAN
AccessionPrimary (citable) accession number: P22455
Secondary accession number(s): O43785 expand/collapse secondary AC list , Q14309, Q71TW8, Q8TDA0
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: April 27, 2001
Last modified: February 9, 2010
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents