| IED ID | IndEnz0002005736 |
| Enzyme Type ID | protease005736 |
| Protein Name |
Fibroblast growth factor receptor 4 FGFR-4 EC 2.7.10.1 Protein-tyrosine kinase receptor MPK-11 CD antigen CD334 |
| Gene Name | Fgfr4 Fgfr-4 Mpk-11 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MWLLLALLSIFQGTPALSLEASEEMEQEPCLAPILEQQEQVLTVALGQPVRLCCGRTERGRHWYKEGSRLASAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMTVVHNLTLLMDDSLTSISNDEDPKTLSSSSSGHVYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPMPTIHWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENSLGSIRYSYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHVVINGSSFGADGFPYVQVLKTTDINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDLTWTTATPEARYTDIILYVSGSLVLLVLLLLAGVYHRQVIRGHYSRQPVTIQKLSRFPLARQFSLESRSSGKSSLSLVRGVRLSSSGPPLLTGLVNLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPSRPDQTSTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPALVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDDVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFEILLWEIFTLGGSPYPGIPVEELFSLLREGHRMERPPNCPSELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPFSPSNGDASSTCSSSDSVFSHDPLPLEPSPFPFSDSQTT |
| Enzyme Length | 799 |
| Uniprot Accession Number | Q03142 |
| Absorption | |
| Active Site | ACT_SITE 609; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10028" |
| Activity Regulation | ACTIVITY REGULATION: Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity). {ECO:0000250}. |
| Binding Site | BINDING 500; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; |
| DNA Binding | |
| EC Number | 2.7.10.1 |
| Enzyme Function | 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. Plays a role in postnatal lung development. May be involved in the development of skeletal muscle cell lineages. {ECO:0000269|PubMed:10809780, ECO:0000269|PubMed:17664243, ECO:0000269|PubMed:19237543, ECO:0000269|PubMed:21561999, ECO:0000269|PubMed:9716527}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 470..478; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Features | Active site (1); Alternative sequence (1); Binding site (1); Chain (1); Compositional bias (1); Disulfide bond (3); Domain (4); Glycosylation (5); Modified residue (4); Mutagenesis (1); Nucleotide binding (1); Region (1); Sequence conflict (8); Signal peptide (1); Topological domain (2); Transmembrane (1) |
| Keywords | ATP-binding;Alternative splicing;Cell membrane;Disulfide bond;Endoplasmic reticulum;Endosome;Glycoprotein;Immunoglobulin domain;Kinase;Membrane;Nucleotide-binding;Phosphoprotein;Receptor;Reference proteome;Repeat;Signal;Transferase;Transmembrane;Transmembrane helix;Tyrosine-protein kinase;Ubl conjugation |
| Interact With | O35082; Q99N32 |
| Induction | INDUCTION: Isoform 1 and isoform 2 are up-regulated by estradiol during myogenic differentiation and down-regulated in fully developed myotubes. {ECO:0000269|PubMed:18186042}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18186042}; Single-pass type I membrane protein {ECO:0000269|PubMed:18186042}. Endosome {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Note=Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane. {ECO:0000250}. |
| Modified Residue | MOD_RES 570; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P22455; MOD_RES 639; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P22455; MOD_RES 640; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P22455; MOD_RES 751; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P22455 |
| Post Translational Modification | PTM: N-glycosylated. Isoform 1 and isoform 2 are glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF19 (By similarity). {ECO:0000250}.; PTM: Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated (By similarity). {ECO:0000250}.; PTM: 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. Isoform 1 and isoform 2 are phosphorylated on tyrosine residues (By similarity). {ECO:0000250}. |
| Signal Peptide | SIGNAL 1..16; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10572038; 10704889; 10751173; 11027503; 11071758; 11114734; 11165488; 11335076; 11566361; 11731698; 11829488; 12141439; 12421715; 12460940; 12466116; 12466851; 12644244; 12666204; 12769260; 1326315; 14517998; 14681479; 14964469; 15201220; 15229180; 15340846; 15467729; 15470137; 15564323; 15576401; 15750181; 15788460; 15830353; 15963767; 15987787; 16049112; 16123981; 16213224; 16267055; 16284190; 16291796; 16436388; 16537572; 16602821; 16617195; 16772167; 16929488; 16989989; 17164422; 17196193; 17304337; 17623664; 17868131; 17957151; 18187602; 18524904; 18593883; 18625063; 18753255; 18776942; 19009564; 19232523; 19272164; 19515808; 19544582; 19706524; 19923290; 19966287; 20018231; 20018895; 20068154; 20093646; 20131355; 20348033; 20657013; 20833365; 20844967; 20934536; 21139072; 21223962; 21267068; 21437243; 21440680; 21633168; 21641554; 2165484; 21655085; 21677750; 21731673; 21876757; 21882254; 22076636; 22110055; 22174695; 22438570; 22442730; 22467244; 22615798; 22632802; 22874919; 23747249; 23747250; 24026051; 24194600; 24198358; 24259513; 24381197; 24470103; 24625004; 24859004; 24952961; 24983448; 25056539; 25204652; 25302779; 26074812; 26416771; 26437603; 26595272; 26764350; 26906157; 27078042; 27206683; 27626380; 28094278; 28169396; 28336912; 28465335; 28512310; 28919046; 28938467; 29122839; 29342370; 29360039; 29402970; 29438108; 29468415; 29532565; 29720668; 29869452; 30541128; 31575945; 31613912; 31758962; 32094117; 33897880; 33929896; 7873877; 7893599; 7959747; 8083748; 8223280; 8521822; 8883961; 8901049; 8938453; 8959336; 9010207; 9013630; 9056643; 9324058; 9337397; 9385055; 9664689; 9690623; 9771645; |
| Motif | |
| Gene Encoded By | |
| Mass | 88,661 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:10596 |
| Cross Reference Brenda | 2.7.10.1; |