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P22455

- FGFR4_HUMAN

UniProt

P22455 - FGFR4_HUMAN

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Protein

Fibroblast growth factor receptor 4

Gene
FGFR4, JTK2, TKF
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling.14 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.4 Publications

Enzyme regulationi

Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei503 – 5031ATP By similarity
Active sitei612 – 6121Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi473 – 4819ATP By similarity

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
Complete GO annotation...

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.5 Publications
Isoform 2 : Secreted 5 Publications
Isoform 3 : Cytoplasm 5 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 369348Extracellular Reviewed predictionAdd
BLAST
Transmembranei370 – 39021Helical; Reviewed predictionAdd
BLAST
Topological domaini391 – 802412Cytoplasmic Reviewed predictionAdd
BLAST

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
Complete GO annotation...

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 ↔ 101 By similarity
Glycosylationi112 – 1121N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi172 ↔ 224 By similarity
Glycosylationi258 – 2581N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi271 ↔ 333 By similarity
Glycosylationi290 – 2901N-linked (GlcNAc...) Reviewed prediction
Glycosylationi311 – 3111N-linked (GlcNAc...) Reviewed prediction
Glycosylationi322 – 3221N-linked (GlcNAc...) Reviewed prediction
Modified residuei642 – 6421Phosphotyrosine; by autocatalysis1 Publication
Modified residuei643 – 6431Phosphotyrosine; by autocatalysis1 Publication
Modified residuei754 – 7541Phosphotyrosine; by autocatalysis1 Publication

Post-translational modificationi

N-glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF19.2 Publications
Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated.2 Publications
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.5 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. 1 interaction.
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.

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 kinaseAdd
BLAST

Sequence similaritiesi

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

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. 5 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. VSP_053542Add
BLAST
Alternative sequencei353 – 41664EEDPT…FPLAR → GTGRIPHLTCDSLTPAGRTK SPTL in isoform 2. VSP_035108Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti121 – 1211L → S in AAF27432. 1 Publication
Sequence conflicti194 – 1941E → G in AAF27432. 1 Publication
Sequence conflicti297 – 2971D → V in CAA40490. 1 Publication

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]
ENST00000292410; ENSP00000292410; ENSG00000160867. [P22455-2]
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. 1 interaction.
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 ]
ENST00000292410 ; ENSP00000292410 ; ENSG00000160867 . [P22455-2 ]
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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 165 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

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