BioPAX pathway converted from "Autocatalytic phosphorylation of FGFR1c P252X mutant dimers" in the Reactome database.LEFT-TO-RIGHT2.7.10Autocatalytic phosphorylation of FGFR1c P252X mutant dimersFGFR1 gain-of-function mutations at P252 that result in increased binding affinity to ligand are presumed to be phosphorylated on the same sites as the wild-type receptor, although this has not been demonstrated (Ibrahimi, 2004a).<br><br>Authored: Rothfels, K, 2012-02-09Reviewed: Ezzat, S, 2012-05-15Edited: Rothfels, K, 2012-05-16ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 113592cytosolGENE ONTOLOGYGO:0005829ATP(4-) [ChEBI:30616]ATP(4-)ATPatpAdenosine 5'-triphosphateChEBICHEBI:30616Reactome Database ID Release 71113592Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592ReactomeR-ALL-1135924Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113592.4Reactomehttp://www.reactome.org16FGFR1c P252X mutant dimers bound to FGFsReactome DB_ID: 2050638plasma membraneGENE ONTOLOGYGO:0005886HSHeparan Sulphateheparan sulfateReactome DB_ID: 190915extracellular regionGENE ONTOLOGYGO:0005576heparan sulfate [ChEBI:28815]heparan sulfateN-Acetylheparan sulfateHeparin monosulfateHeparatan sulfateHeparitin monosulfateHeparan sulphateHeparan N-sulfateHeparitin sulfateHeparin sulfateChEBICHEBI:28815Reactome Database ID Release 71190915Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=190915ReactomeR-ALL-1909153Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-190915.31Converted from EntitySet in ReactomeFGFR1c P252X mutant dimersReactome DB_ID: 2050635FGFR1c P252S mutant dimerReactome DB_ID: 2011924FGFR1c P252SReactome DB_ID: 1614383UniProt:P11362-1 FGFR1FGFR1BFGFRCEKFGFBRFLGFLT2HBGFRFUNCTION Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. 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 phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.ACTIVITY REGULATION Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues. Inhibited by ARQ 069; this compound maintains the kinase in an inactive conformation and inhibits autophosphorylation. Inhibited by PD173074.SUBUNIT Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF5, FGF6, FGF8, FGF10, FGF19, FGF21, FGF22 and FGF23 (in vitro) (PubMed:1697263, PubMed:1722683, PubMed:8663044, PubMed:9655399, PubMed:12181353, PubMed:16597617, PubMed:17623664). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19, FGF21 and FGF23 (PubMed:19966287). Interacts (phosphorylated on Tyr-766) with PLCG1 (via SH2 domains) (PubMed:1656221, PubMed:1379697, PubMed:21765395). Interacts with FRS2 (PubMed:21765395). Interacts with RPS6KA1 (PubMed:15117958). Interacts (via C-terminus) with NEDD4 (via WW3 domain) (PubMed:21765395). Interacts with KL (By similarity). Interacts with SHB (via SH2 domain) (PubMed:12181353). Interacts with GRB10 (PubMed:10454568). Interacts with ANOS1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2 (PubMed:19696444). Interacts with SOX2 and SOX3. Interacts with FLRT1, FLRT2 and FLRT3 (By similarity). Found in a ternary complex with FGF1 and ITGAV:ITGB3 (PubMed:20422052, PubMed:18441324).TISSUE SPECIFICITY Detected in astrocytoma, neuroblastoma and adrenal cortex cell lines. Some isoforms are detected in foreskin fibroblast cell lines, however isoform 17, isoform 18 and isoform 19 are not detected in these cells.DOMAIN The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains.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 and proceeds in a highly ordered manner. Initial autophosphorylation at Tyr-653 increases the kinase activity by a factor of 50 to 100. After this, Tyr-583 becomes phosphorylated, followed by phosphorylation of Tyr-463, Tyr-766, Tyr-583 and Tyr-585. In a third stage, Tyr-654 is autophosphorylated, resulting in a further tenfold increase of kinase activity. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation.PTM Ubiquitinated. FGFR1 is rapidly ubiquitinated by NEDD4 after autophosphorylation, leading to internalization and lysosomal degradation. CBL is recruited to activated FGFR1 via FRS2 and GRB2, and mediates ubiquitination and subsequent degradation of FGFR1.PTM N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.DISEASE A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.DISEASE A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity.DISEASE A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CNTRL. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CNTRL-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.Homo sapiensNCBI Taxonomy9606UniProt IsoformP11362-1252EQUALL-proline removalMODMOD:0164522EQUAL822EQUALReactome Database ID Release 711614383Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1614383ReactomeR-HSA-16143833Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1614383.32Reactome Database ID Release 712011924Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2011924ReactomeR-HSA-20119243Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2011924.3FGFR1c S252T mutant dimerReactome DB_ID: 2011926FGFR1c P252TReactome DB_ID: 1614386252EQUAL22EQUAL822EQUALReactome Database ID Release 711614386Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1614386ReactomeR-HSA-16143863Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1614386.32Reactome Database ID Release 712011926Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2011926ReactomeR-HSA-20119263Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2011926.3FGFR1c P252R mutant dimerReactome DB_ID: 2011923FGFR1c P252RFGFR1-1 P252RReactome DB_ID: 2011838252EQUAL22EQUAL822EQUALReactome Database ID Release 712011838Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2011838ReactomeR-HSA-20118381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2011838.12Reactome Database ID Release 712011923Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2011923ReactomeR-HSA-20119231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2011923.1Reactome Database ID Release 712050635Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2050635ReactomeR-HSA-20506352Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2050635.21Converted from EntitySet in ReactomeFGFR1c-binding FGFsReactome DB_ID: 189953FGF1Fibroblast growth factor-1Heparin-binding growth factor 1FGF1_HUMANReactome DB_ID: 189856UniProt:P05230 FGF1FGF1FGFAFUNCTION Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:18441324, PubMed:20422052). Can induce angiogenesis (PubMed:23469107).SUBUNIT Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Found in a complex with FGFBP1, FGF1 and FGF2. Interacts with FGFBP1. Part of a Cu(2+)-dependent multiprotein aggregate containing FGF1, S100A13 and SYT1. Interacts with SYT1. Interacts with S100A13. Interacts with LRRC59. Interacts with CSNKA, CSNKB and FIBP. While binding with LRRC59, CSNKA and FIBP seem mutually exclusive, CSNKB and FIBP may cooperatively interact with FGF1. Forms a ternary complex with FGFR1 and ITGAV:ITGB3 and induces the recruitment of PTPN11 to the complex (PubMed:20422052).TISSUE SPECIFICITY Predominantly expressed in kidney and brain. Detected at much lower levels in heart and skeletal muscle.PTM In the nucleus, phosphorylated by PKC/PRKCD.SIMILARITY Belongs to the heparin-binding growth factors family.UniProtP0523016EQUAL155EQUALReactome Database ID Release 71189856Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=189856ReactomeR-HSA-1898561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-189856.1FGF2FGF2(10-155)Fibroblast growth factor-2Heparin-binding growth factor 2FGF2_HUMANBasic fibroblast growth factorbFGFReactome DB_ID: 189898UniProt:P09038 FGF2FGF2FGFBFUNCTION Acts as a ligand for FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:8663044). Also acts as an integrin ligand which is required for FGF2 signaling (PubMed:28302677). Binds to integrin ITGAV:ITGB3 (PubMed:28302677). Plays an important role in the regulation of cell survival, cell division, cell differentiation and cell migration (PubMed:8663044, PubMed:28302677). Functions as a potent mitogen in vitro (PubMed:3732516, PubMed:3964259). Can induce angiogenesis (PubMed:23469107, PubMed:28302677).SUBUNIT Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Interacts with CSPG4, FGFBP1 and TEC. Found in a complex with FGFBP1, FGF1 and FGF2. Interacts with FGFBP3 (PubMed:18669637). Interacts with integrin ITGAV:ITGB3; the interaction is required for FGF2 signaling (PubMed:28302677). Interacts with SNORC (via the extracellular domain) (By similarity). Interacts with glypican GPC3 (By similarity).TISSUE SPECIFICITY Expressed in granulosa and cumulus cells. Expressed in hepatocellular carcinoma cells, but not in non-cancerous liver tissue.PTM Phosphorylation at Tyr-215 regulates FGF2 unconventional secretion.PTM Several N-termini starting at positions 94, 125, 126, 132, 143 and 162 have been identified by direct sequencing.MISCELLANEOUS This protein binds heparin more strongly than does aFGF.SIMILARITY Belongs to the heparin-binding growth factors family.UniProtP0903810EQUAL155EQUALReactome Database ID Release 71189898Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=189898ReactomeR-HSA-1898981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-189898.1FGF4Fibroblast growth factor-4FGF4_HUMANReactome DB_ID: 189907UniProt:P08620 FGF4FGF4HSTHSTF1KS3FUNCTION Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Required for normal limb and cardiac valve development during embryogenesis.SUBUNIT Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.SIMILARITY Belongs to the heparin-binding growth factors family.UniProtP0862031EQUAL206EQUALReactome Database ID Release 71189907Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=189907ReactomeR-HSA-1899071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-189907.1FGF5-1Fibroblast growth factor-5 isoform 1FGF5_HUMANReactome DB_ID: 189903UniProt:P12034-1 FGF5FGF5FUNCTION Plays an important role in the regulation of cell proliferation and cell differentiation. Required for normal regulation of the hair growth cycle. Functions as an inhibitor of hair elongation by promoting progression from anagen, the growth phase of the hair follicle, into catagen the apoptosis-induced regression phase (By similarity).SUBUNIT Interacts with FGFR1 and FGFR2. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.TISSUE SPECIFICITY Expressed in neonatal brain.DEVELOPMENTAL STAGE Can transform NIH 3T3 cells.SIMILARITY Belongs to the heparin-binding growth factors family.UniProt IsoformP12034-118EQUAL268EQUALReactome Database ID Release 71189903Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=189903ReactomeR-HSA-1899031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-189903.1FGF6Fibroblast growth factor-6FGF6_HUMANReactome DB_ID: 189881UniProt:P10767 FGF6FGF6HST2HSTF2FUNCTION Plays an important role in the regulation of cell proliferation, cell differentiation, angiogenesis and myogenesis, and is required for normal muscle regeneration.SUBUNIT Interacts with FGFR1, FGFR2 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.TISSUE SPECIFICITY Leukemia cell lines with platelet/ megakaryocytic differentiation potential.SIMILARITY Belongs to the heparin-binding growth factors family.UniProtP1076738EQUAL208EQUALReactome Database ID Release 71189881Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=189881ReactomeR-HSA-1898811Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-189881.1FGF8-1Fibroblast growth factor-8FGF8_HUMANFGF8 isoform 1Reactome DB_ID: 189892UniProt:P55075-1 FGF8FGF8AIGFFUNCTION Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. Required for normal brain, eye, ear and limb development during embryogenesis. Required for normal development of the gonadotropin-releasing hormone (GnRH) neuronal system (PubMed:16384934, PubMed:16597617, PubMed:8663044). Plays a role in neurite outgrowth in hippocampal cells (PubMed:21576111).SUBUNIT Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.DEVELOPMENTAL STAGE In adults expression is restricted to the gonads.SIMILARITY Belongs to the heparin-binding growth factors family.UniProt IsoformP55075-123EQUAL233EQUALReactome Database ID Release 71189892Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=189892ReactomeR-HSA-1898921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-189892.1FGF9Fibroblast growth factor-9Glia-activating factorFGF9_HUMANReactome DB_ID: 189870UniProt:P31371 FGF9FGF9FUNCTION Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. May have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors.SUBUNIT Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.TISSUE SPECIFICITY Glial cells.PTM Three molecular species were found (30 kDa, 29 kDa and 25 kDa), cleaved at Leu-4, Val-13 and Ser-34 respectively. The smaller ones might be products of proteolytic digestion. Furthermore, there may be a functional signal sequence in the 30 kDa species which is uncleavable in the secretion step.PTM N-glycosylated.MISCELLANEOUS Biochemical analysis of the Asn-99 mutation reveals a significantly impaired FGF signaling, as evidenced by diminished activity of the MAPK1/MAPK2 pathway and decreases CTNNB1 and MYC expression when compared with wild-type protein. Binding of mutant protein to the receptor FGFR3 is severely impaired, although homodimerization of mutant to itself or wild-type is not detectably affected, providing a basis for the observed defective FGF9 signaling.SIMILARITY Belongs to the heparin-binding growth factors family.UniProtP313714EQUAL208EQUALReactome Database ID Release 71189870Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=189870ReactomeR-HSA-1898701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-189870.1FGF17-1Fibroblast growth factor-17FGFH_HUMANFGF17 isoform 1Reactome DB_ID: 189914UniProt:O60258-1 FGF17FGF17UNQ161/PRO187FUNCTION Plays an important role in the regulation of embryonic development and as signaling molecule in the induction and patterning of the embryonic brain. Required for normal brain development.SUBUNIT Interacts with FGFR3 and FGFR4.TISSUE SPECIFICITY Preferentially expressed in the embryonic brain.DEVELOPMENTAL STAGE Detected in embryos at E14.5, but not at E10.5 and E19.5. Preferentially expressed in the neuroepithelia of the isthmus and septum of the embryonic brain at E14.5.SIMILARITY Belongs to the heparin-binding growth factors family.UniProt IsoformO60258-123EQUAL216EQUALReactome Database ID Release 71189914Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=189914ReactomeR-HSA-1899141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-189914.1FGF20Fibroblast growth factor-20FGFK_HUMANReactome DB_ID: 189862UniProt:Q9NP95 FGF20FGF20FUNCTION Neurotrophic factor that regulates central nervous development and function.SUBUNIT Homodimer. Interacts with FGFR2 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.TISSUE SPECIFICITY Predominantly expressed in the cerebellum.SIMILARITY Belongs to the heparin-binding growth factors family.CAUTION It is uncertain whether variants in this gene are associated with Parkinson disease. Some authors mention association with the disease (PubMed:18252210). In contrast, some others do not observe any association (PubMed:19133659).UniProtQ9NP951EQUAL211EQUALReactome Database ID Release 71189862Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=189862ReactomeR-HSA-1898621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-189862.1FGF23GalNAc-T178-FGF23(25-251)Fibroblast growth factor-23FGFN_HUMANReactome DB_ID: 8851633UniProt:Q9GZV9 FGF23FGF23HYPFUNQ3027/PRO9828FUNCTION Regulator of phosphate homeostasis. Inhibits renal tubular phosphate transport by reducing SLC34A1 levels. Upregulates EGR1 expression in the presence of KL (By similarity). Acts directly on the parathyroid to decrease PTH secretion (By similarity). Regulator of vitamin-D metabolism. Negatively regulates osteoblast differentiation and matrix mineralization.SUBUNIT Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by KL and heparan sulfate glycosaminoglycans that function as coreceptors (By similarity).TISSUE SPECIFICITY Expressed in osteogenic cells particularly during phases of active bone remodeling. In adult trabecular bone, expressed in osteocytes and flattened bone-lining cells (inactive osteoblasts).PTM Following secretion this protein is inactivated by cleavage into a N-terminal fragment and a C-terminal fragment. The processing is effected by proprotein convertases.PTM O-glycosylated by GALT3. Glycosylation is necessary for secretion; it blocks processing by proprotein convertases when the O-glycan is alpha 2,6-sialylated. Competition between proprotein convertase cleavage and block of cleavage by O-glycosylation determines the level of secreted active FGF23.SIMILARITY Belongs to the heparin-binding growth factors family.UniProtQ9GZV9178EQUALO-(N-acetylamino)galactosyl-L-threonineMODMOD:0016425EQUAL251EQUALReactome Database ID Release 718851633Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8851633ReactomeR-HSA-88516331Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8851633.1Reactome Database ID Release 71189953Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=189953ReactomeR-HSA-1899532Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-189953.22Reactome Database ID Release 712050638Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2050638ReactomeR-HSA-20506382Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2050638.2Activated FGFR1c P252X mutantsReactome DB_ID: 2050642Converted from EntitySet in Reactomep-8Y-FGFR1c P252X dimersReactome DB_ID: 2050627p-8Y-FGFR1c P252S dimerphosphorylated FGFR1c P252S dimerReactome DB_ID: 2011961p-8Y-FGFR1c P252SReactome DB_ID: 2011861463EQUALO4'-phospho-L-tyrosineMODMOD:00048583EQUAL585EQUAL653EQUAL654EQUAL730EQUAL766EQUAL776EQUAL22EQUAL822EQUALReactome Database ID Release 712011861Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2011861ReactomeR-HSA-20118612Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2011861.22Reactome Database ID Release 712011961Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2011961ReactomeR-HSA-20119613Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2011961.3p-8Y-FGFR1c P252T dimerphosphorylated FGFR1 P252T dimerReactome DB_ID: 2018773p-8Y-FGFR1c P252TReactome DB_ID: 201186822EQUAL822EQUALReactome Database ID Release 712011868Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2011868ReactomeR-HSA-20118682Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2011868.22Reactome Database ID Release 712018773Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2018773ReactomeR-HSA-20187732Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2018773.2p-8Y-FGFR1c P252R dimerphosphorylated FGFR1c P252R dimerReactome DB_ID: 2011960p-8Y-FGFR1c P252Rp-8Y-FGFR1-1 P252RReactome DB_ID: 2011858463EQUAL583EQUAL585EQUAL653EQUAL654EQUAL730EQUAL766EQUAL776EQUAL22EQUAL822EQUALReactome Database ID Release 712011858Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2011858ReactomeR-HSA-20118581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2011858.12Reactome Database ID Release 712011960Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2011960ReactomeR-HSA-20119601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2011960.1Reactome Database ID Release 712050627Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2050627ReactomeR-HSA-20506272Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2050627.2112Reactome Database ID Release 712050642Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2050642ReactomeR-HSA-20506422Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2050642.2ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 29370ADP(3-) [ChEBI:456216]ADP(3-)ADP5&apos;-O-[(phosphonatooxy)phosphinato]adenosineADP trianionChEBICHEBI:456216Reactome Database ID Release 7129370Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29370ReactomeR-ALL-293704Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29370.416ACTIVATIONGENE ONTOLOGYGO:0004713gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 712023453Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2023453Reactome Database ID Release 712023455Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2023455ReactomeR-HSA-20234552Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2023455.214613973Pubmed2004Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinityIbrahimi, OAZhang, FEliseenkova, AVLinhardt, RJMohammadi, MHum Mol Genet 13:69-78