Fibroblast growth factor receptor 4

Details

Name
Fibroblast growth factor receptor 4
Synonyms
  • 2.7.10.1
  • FGFR-4
  • JTK2
  • TKF
Gene Name
FGFR4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002393|Fibroblast growth factor receptor 4
MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRA
ERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDS
LTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTP
TIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLD
VLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFP
YVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTA
AAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSL
ESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQ
VVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVC
TQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGM
QYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEA
LFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYG
LMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDS
VFSHDPLPLGSSSFPFGSGVQT
Number of residues
802
Molecular Weight
87953.535
Theoretical pI
6.81
GO Classification
Functions
ATP binding / fibroblast growth factor binding / fibroblast growth factor-activated receptor activity / heparin binding / protein tyrosine kinase activity
Processes
activation of MAPKK activity / axon guidance / cell migration / epidermal growth factor receptor signaling pathway / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / glucose homeostasis / innate immune response / insulin receptor signaling pathway / MAPK cascade / neurotrophin TRK receptor signaling pathway / peptidyl-tyrosine phosphorylation / phosphate ion homeostasis / phosphatidylinositol-mediated signaling / positive regulation of cell proliferation / positive regulation of DNA biosynthetic process / positive regulation of ERK1 and ERK2 cascade / positive regulation of gene expression / positive regulation of metalloenzyme activity / positive regulation of proteolysis / protein autophosphorylation / Ras protein signal transduction / regulation of bile acid biosynthetic process / regulation of cholesterol homeostasis / regulation of extracellular matrix disassembly / regulation of lipid metabolic process / small GTPase mediated signal transduction / vascular endothelial growth factor receptor signaling pathway
Components
cytoplasm / endoplasmic reticulum / endosome / extracellular region / Golgi apparatus / integral component of plasma membrane / nucleoplasm / plasma membrane / transport vesicle
General Function
Protein tyrosine kinase activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
370-390
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021287|Fibroblast growth factor receptor 4 (FGFR4)
ATGCGGCTGCTGCTGGCCCTGTTGGGGGTCCTGCTGAGTGTGCCTGGGCCTCCAGTCTTG
TCCCTGGAGGCCTCTGAGGAAGTGGAGCTTGAGCCCTGCCTGGCTCCCAGCCTGGAGCAG
CAAGAGCAGGAGCTGACAGTAGCCCTTGGGCAGCCTGTGCGTCTGTGCTGTGGGCGGGCT
GAGCGTGGTGGCCACTGGTACAAGGAGGGCAGTCGCCTGGCACCTGCTGGCCGTGTACGG
GGCTGGAGGGGCCGCCTAGAGATTGCCAGCTTCCTACCTGAGGATGCTGGCCGCTACCTC
TGCCTGGCACGAGGCTCCATGATCGTCCTGCAGAATCTCACCTTGATTACAGGTGACTCC
TTGACCTCCAGCAACGATGATGAGGACCCCAAGTCCCATAGGGACCCCTCGAATAGGCAC
AGTTACCCCCAGCAAGCACCCTACTGGACACACCCCCAGCGCATGGAGAAGAAACTGCAT
GCAGTACCTGCGGGGAACACCGTCAAGTTCCGCTGTCCAGCTGCAGGCAACCCCACGCCC
ACCATCCGCTGGCTTAAGGATGGACAGGCCTTTCATGGGGAGAACCGCATTGGAGGCATT
CGGCTGCGCCATCAGCACTGGAGTCTCGTGATGGAGAGCGTGGTGCCCTCGGACCGCGGC
ACATACACCTGCCTGGTAGAGAACGCTGTGGGCAGCATCCGCTATAACTACCTGCTAGAT
GTGCTGGAGCGGTCCCCGCACCGGCCCATCCTGCAGGCCGGGCTCCCGGCCAACACCACA
GCCGTGGTGGGCAGCGACGTGGAGCTGCTGTGCAAGGTGTACAGCGATGCCCAGCCCCAC
ATCCAGTGGCTGAAGCACATCGTCATCAACGGCAGCAGCTTCGGAGCCGACGGTTTCCCC
TATGTGCAAGTCCTAAAGACTGCAGACATCAATAGCTCAGAGGTGGAGGTCCTGTACCTG
CGGAACGTGTCAGCCGAGGACGCAGGCGAGTACACCTGCCTCGCAGGCAATTCCATCGGC
CTCTCCTACCAGTCTGCCTGGCTCACGGTGCTGCCAGAGGAGGACCCCACATGGACCGCA
GCAGCGCCCGAGGCCAGTTCTCCCTGGAGTCAGGCTCTTCCGGCAAGTCAAGCTCATCCC
TGGTACGAGGCGTGCGTCTCTCCTCCAGCGGCCCCGCCTTGCTCGCCGGCCTCGCTGGTG
CTTGGGAAGCCCCTAGGCGAGGGCTGCTTTGGCCAGGTAGTACGTGCAGAGGCCTTTGGC
ATGGACCCTGCCCGGCCTGACCAAGCCAGCACTGTGGCCGTCAAGATGCTCAAAGACAAC
GCCTCTGACAAGGACCTGGCCGACCTGGTCTCGGAGATGGAGGTGATGAAGCTGATCGGC
CGACACAAGAACATCATCAACCTGCTTGGTGTCTGCACCCAGGAAGGGCCCCTGTACGTG
ATCGTGGAGTGCGCCGCCAAGGGAAACCTGCGGGAGTTCCTGCGGGCCCGGCGCCCCCCA
GGCCCCGACCTCAGCCCCGACGGTCCTCGGAGCAGTGAGGGGCCGCTCTCCTTCCCAGTC
CTGGTCTCCTGCGCCTACCAGGTGGCCCGAGGCATGCAGTATCTGGAGTCCCGGAAGTGT
ATCCACCGGGACCTGGCTGCCCGCAATGTGCTGGTGACTGAGGACAATGTGATGAAGATT
GCTGACTTTGGGCTGGCCCGCGGCGTCCACCACATTGACTACTATAAGAAAACCAGCAAC
GGCCGCCTGCCTGTGAAGTGGATGGCGCCCGAGGCCTTGTTTGACCGGGTGTACACACAC
CAGAGTGACGTGTGGTCTTTTGGGATCCTGCTATGGGAGATCTTCACCCTCGGGGGCTCC
CCGTATCCTGGCATCCCGGTGGAGGAGCTGTTCTCGCTGCTGCGGGAGGGACATCGGATG
GACCGACCCCCACACTGCCCCCCAGAGCTGTACGGGCTGATGCGTGAGTGCTGGCACGCA
GCGCCCTCCCAGAGGCCTACCTTCAAGCAGCTGGTGGAGGCGCTGGACAAGGTCCTGCTG
GCCGTCTCTGAGGAGTACCTCGACCTCCGCCTGACCTTCGGACCCTATTCCCCCTCTGGT
GGGGACGCCAGCAGCACCTGCTCCTCCAGCGATTCTGTCTTCAGCCACGACCCCCTGCCA
TTGGGATCCAGCTCCTTCCCCTTCGGGTCTGGGGTGCAGACATGA
Chromosome Location
5
Locus
5q35.1-qter
External Identifiers
ResourceLink
UniProtKB IDP22455
UniProtKB Entry NameFGFR4_HUMAN
GenBank Protein ID31372
GenBank Gene IDX57205
GenAtlas IDFGFR4
HGNC IDHGNC:3691
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00039PaliferminapprovedunknownDetails
DB08901Ponatinibapproved, investigationalunknowninhibitorDetails
DB09078Lenvatinibapproved, investigationalyesinhibitorDetails
DB01109Heparinapproved, investigationalunknownDetails
DB12147Erdafitinibapproved, investigationalyesinhibitorDetails
DB15102Pemigatinibapproved, investigationalunknowninhibitorDetails