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P22455

- FGFR4_HUMAN

UniProt

P22455 - FGFR4_HUMAN

Protein

Fibroblast growth factor receptor 4

Gene

FGFR4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 166 (01 Oct 2014)
      Sequence version 2 (27 Apr 2001)
      Previous versions | rss
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    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.4 PublicationsPROSITE-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.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei503 – 5031ATPPROSITE-ProRule annotation
    Active sitei612 – 6121Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi473 – 4819ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. fibroblast growth factor-activated receptor activity Source: UniProtKB
    3. fibroblast growth factor binding Source: UniProtKB
    4. heparin binding Source: UniProtKB
    5. protein tyrosine kinase activity Source: Reactome

    GO - Biological processi

    1. alveolar secondary septum development Source: Ensembl
    2. cell migration Source: UniProtKB
    3. epidermal growth factor receptor signaling pathway Source: Reactome
    4. Fc-epsilon receptor signaling pathway Source: Reactome
    5. fibroblast growth factor receptor signaling pathway Source: UniProtKB
    6. glucose homeostasis Source: UniProtKB
    7. innate immune response Source: Reactome
    8. insulin receptor signaling pathway Source: Reactome
    9. neurotrophin TRK receptor signaling pathway Source: Reactome
    10. organ induction Source: Ensembl
    11. peptidyl-tyrosine phosphorylation Source: UniProtKB
    12. phosphate ion homeostasis Source: UniProtKB
    13. phosphatidylinositol-mediated signaling Source: Reactome
    14. positive regulation of cell proliferation Source: UniProtKB
    15. positive regulation of DNA biosynthetic process Source: UniProtKB
    16. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    17. positive regulation of metalloenzyme activity Source: UniProtKB
    18. positive regulation of proteolysis Source: UniProtKB
    19. protein autophosphorylation Source: UniProtKB
    20. regulation of bile acid biosynthetic process Source: UniProtKB
    21. regulation of cholesterol homeostasis Source: UniProtKB
    22. regulation of extracellular matrix disassembly Source: UniProtKB
    23. regulation of lipid metabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 2681.
    ReactomeiREACT_111046. betaKlotho-mediated ligand binding.
    REACT_111184. Negative regulation of FGFR signaling.
    REACT_121286. Signaling by FGFR4 mutants.
    REACT_121398. Signaling by FGFR mutants.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_21247. FRS2-mediated cascade.
    REACT_21270. PI-3K cascade.
    REACT_21310. Phospholipase C-mediated cascade.
    REACT_21374. SHC-mediated cascade.
    REACT_75829. PIP3 activates AKT signaling.
    REACT_9452. FGFR4 ligand binding and activation.
    REACT_976. PI3K Cascade.

    Protein family/group databases

    MEROPSiI43.001.

    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
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:3691. FGFR4.

    Subcellular locationi

    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.
    Isoform 3 : Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. endoplasmic reticulum Source: UniProtKB
    3. endosome Source: UniProtKB-SubCell
    4. extracellular region Source: UniProtKB-SubCell
    5. integral component of plasma membrane Source: UniProtKB
    6. nucleus Source: HPA
    7. plasma membrane Source: Reactome

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi503 – 5031K → R: Loss of kinase activity. 2 Publications
    Mutagenesisi754 – 7541Y → F: Loss of interaction with PLCG1. 1 Publication

    Organism-specific databases

    PharmGKBiPA28130.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 21211 PublicationAdd
    BLAST
    Chaini22 – 802781Fibroblast growth factor receptor 4PRO_0000016787Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi57 ↔ 101PROSITE-ProRule annotation
    Glycosylationi112 – 1121N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi172 ↔ 224PROSITE-ProRule annotation
    Glycosylationi258 – 2581N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi271 ↔ 333PROSITE-ProRule annotation
    Glycosylationi290 – 2901N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi311 – 3111N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi322 – 3221N-linked (GlcNAc...)Sequence Analysis
    Modified residuei642 – 6421Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei643 – 6431Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei754 – 7541Phosphotyrosine; by autocatalysis2 Publications

    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.
    PRIDEiP22455.

    PTM databases

    PhosphoSiteiP22455.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    ArrayExpressiP22455.
    BgeeiP22455.
    CleanExiHS_FGFR4.
    GenevestigatoriP22455.

    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 HIP1.9 Publications

    Protein-protein interaction databases

    BioGridi108555. 6 interactions.
    DIPiDIP-5149N.
    IntActiP22455. 4 interactions.
    STRINGi9606.ENSP00000292408.

    Structurei

    Secondary structure

    1
    802
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi45 – 473
    Beta strandi65 – 673
    Beta strandi75 – 817
    Helixi93 – 953
    Beta strandi100 – 1023
    Beta strandi114 – 1163
    Beta strandi160 – 1634
    Beta strandi168 – 1714
    Turni176 – 1783
    Turni180 – 1834
    Beta strandi189 – 1913
    Turni192 – 1943
    Beta strandi199 – 2057
    Beta strandi208 – 2136
    Helixi216 – 2183
    Beta strandi220 – 2278
    Beta strandi229 – 24214
    Beta strandi256 – 2605
    Beta strandi263 – 2653
    Beta strandi267 – 2715
    Beta strandi273 – 2753
    Beta strandi277 – 2859
    Beta strandi295 – 2984
    Beta strandi301 – 3044
    Beta strandi312 – 32211
    Helixi325 – 3273
    Beta strandi331 – 3366
    Beta strandi342 – 3498

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1QCTmodel-B/E36-353[»]
    ProteinModelPortaliP22455.
    SMRiP22455. Positions 21-355, 454-747.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini22 – 369348ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini391 – 802412CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei370 – 39021HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini22 – 11897Ig-like C2-type 1Add
    BLAST
    Domaini152 – 24089Ig-like C2-type 2Add
    BLAST
    Domaini249 – 349101Ig-like C2-type 3Add
    BLAST
    Domaini467 – 755289Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    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

    eggNOGiCOG0515.
    HOGENOMiHOG000263410.
    HOVERGENiHBG000345.
    KOiK05095.
    OMAiDRPPHCP.
    OrthoDBiEOG7NGQ9N.
    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.
    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. 2 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. 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. Align

    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

    MRLLLALLGV LLSVPGPPVL SLEASEEVEL EPCLAPSLEQ QEQELTVALG    50
    QPVRLCCGRA ERGGHWYKEG SRLAPAGRVR GWRGRLEIAS FLPEDAGRYL 100
    CLARGSMIVL QNLTLITGDS LTSSNDDEDP KSHRDPSNRH SYPQQAPYWT 150
    HPQRMEKKLH AVPAGNTVKF RCPAAGNPTP TIRWLKDGQA FHGENRIGGI 200
    RLRHQHWSLV MESVVPSDRG TYTCLVENAV GSIRYNYLLD VLERSPHRPI 250
    LQAGLPANTT AVVGSDVELL CKVYSDAQPH IQWLKHIVIN GSSFGADGFP 300
    YVQVLKTADI NSSEVEVLYL RNVSAEDAGE YTCLAGNSIG LSYQSAWLTV 350
    LPEEDPTWTA AAPEARYTDI ILYASGSLAL AVLLLLAGLY RGQALHGRHP 400
    RPPATVQKLS RFPLARQFSL ESGSSGKSSS SLVRGVRLSS SGPALLAGLV 450
    SLDLPLDPLW EFPRDRLVLG KPLGEGCFGQ VVRAEAFGMD PARPDQASTV 500
    AVKMLKDNAS DKDLADLVSE MEVMKLIGRH KNIINLLGVC TQEGPLYVIV 550
    ECAAKGNLRE FLRARRPPGP DLSPDGPRSS EGPLSFPVLV SCAYQVARGM 600
    QYLESRKCIH RDLAARNVLV TEDNVMKIAD FGLARGVHHI DYYKKTSNGR 650
    LPVKWMAPEA LFDRVYTHQS DVWSFGILLW EIFTLGGSPY PGIPVEELFS 700
    LLREGHRMDR PPHCPPELYG LMRECWHAAP SQRPTFKQLV EALDKVLLAV 750
    SEEYLDLRLT FGPYSPSGGD ASSTCSSSDS VFSHDPLPLG SSSFPFGSGV 800
    QT 802
    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti121 – 1211L → S in AAF27432. (PubMed:10631118)Curated
    Sequence conflicti194 – 1941E → G in AAF27432. (PubMed:10631118)Curated
    Sequence conflicti297 – 2971D → V in CAA40490. (PubMed:1709094)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti10 – 101V → I.3 Publications
    Corresponds to variant rs1966265 [ dbSNP | Ensembl ].
    VAR_029185
    Natural varianti136 – 1361P → L.6 Publications
    Corresponds to variant rs376618 [ dbSNP | Ensembl ].
    VAR_042211
    Natural varianti179 – 1791T → A.1 Publication
    Corresponds to variant rs55675160 [ dbSNP | Ensembl ].
    VAR_042212
    Natural varianti388 – 3881G → R Prolonged FGFR4 activity, increased cell motility and tumor cell invasion, possibly due to increased stability of the protease MMP14. 3 Publications
    Corresponds to variant rs351855 [ dbSNP | Ensembl ].
    VAR_014797
    Natural varianti426 – 4261G → S.1 Publication
    Corresponds to variant rs55879131 [ dbSNP | Ensembl ].
    VAR_046102
    Natural varianti516 – 5161D → N.1 Publication
    Corresponds to variant rs34158682 [ dbSNP | Ensembl ].
    VAR_042213
    Natural varianti529 – 5291R → Q.
    Corresponds to variant rs34284947 [ dbSNP | Ensembl ].
    VAR_049720
    Natural varianti550 – 5501V → M in breast pleomorphic lobular sample; somatic mutation. 1 Publication
    VAR_046103
    Natural varianti712 – 7121P → T in a lung adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_046104
    Natural varianti772 – 7721S → N in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication
    VAR_046105

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 210210Missing in isoform 3. 1 PublicationVSP_053542Add
    BLAST
    Alternative sequencei353 – 41664EEDPT…FPLAR → GTGRIPHLTCDSLTPAGRTK SPTL in isoform 2. 1 PublicationVSP_035108Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_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_005265838.2. [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.3. human. [P22455-1]
    uc003mfo.3. human. [P22455-2]

    Polymorphism databases

    DMDMi13432140.

    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS4410.1. [P22455-1 ]
    CCDS4411.1. [P22455-2 ]
    PIRi S15345. TVHUF4.
    RefSeqi 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_005265838.2. [P22455-1 ]
    UniGenei Hs.165950.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1QCT model - B/E 36-353 [» ]
    ProteinModelPortali P22455.
    SMRi P22455. Positions 21-355, 454-747.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108555. 6 interactions.
    DIPi DIP-5149N.
    IntActi P22455. 4 interactions.
    STRINGi 9606.ENSP00000292408.

    Chemistry

    BindingDBi P22455.
    ChEMBLi CHEMBL3973.
    DrugBanki DB00039. Palifermin.
    GuidetoPHARMACOLOGYi 1811.

    Protein family/group databases

    MEROPSi I43.001.

    PTM databases

    PhosphoSitei P22455.

    Polymorphism databases

    DMDMi 13432140.

    Proteomic databases

    MaxQBi P22455.
    PaxDbi P22455.
    PRIDEi P22455.

    Protocols and materials databases

    DNASUi 2264.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000292408 ; ENSP00000292408 ; ENSG00000160867 . [P22455-1 ]
    ENST00000393637 ; ENSP00000377254 ; ENSG00000160867 . [P22455-2 ]
    ENST00000502906 ; ENSP00000424960 ; ENSG00000160867 . [P22455-1 ]
    GeneIDi 2264.
    KEGGi hsa:2264.
    UCSCi uc003mfl.3. human. [P22455-1 ]
    uc003mfo.3. human. [P22455-2 ]

    Organism-specific databases

    CTDi 2264.
    GeneCardsi GC05P176513.
    HGNCi HGNC:3691. FGFR4.
    HPAi CAB005196.
    HPA027273.
    HPA027369.
    HPA028251.
    MIMi 134935. gene.
    neXtProti NX_P22455.
    PharmGKBi PA28130.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000263410.
    HOVERGENi HBG000345.
    KOi K05095.
    OMAi DRPPHCP.
    OrthoDBi EOG7NGQ9N.
    PhylomeDBi P22455.
    TreeFami TF316307.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    Reactomei REACT_111046. betaKlotho-mediated ligand binding.
    REACT_111184. Negative regulation of FGFR signaling.
    REACT_121286. Signaling by FGFR4 mutants.
    REACT_121398. Signaling by FGFR mutants.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_21247. FRS2-mediated cascade.
    REACT_21270. PI-3K cascade.
    REACT_21310. Phospholipase C-mediated cascade.
    REACT_21374. SHC-mediated cascade.
    REACT_75829. PIP3 activates AKT signaling.
    REACT_9452. FGFR4 ligand binding and activation.
    REACT_976. PI3K Cascade.

    Miscellaneous databases

    ChiTaRSi FGFR4. human.
    GeneWikii Fibroblast_growth_factor_receptor_4.
    GenomeRNAii 2264.
    NextBioi 35516406.
    PROi P22455.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P22455.
    Bgeei P22455.
    CleanExi HS_FGFR4.
    Genevestigatori P22455.

    Family and domain databases

    Gene3Di 2.60.40.10. 3 hits.
    InterProi 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.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view ]
    Pfami PF07679. I-set. 2 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. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. 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. 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. 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.
      , 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.

    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: October 1, 2014
    This is version 166 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

    External Data

    Dasty 3