Fibroblast Growth Factor-basic
Human Recombinant FGFR1
Reference ID:KB-2041
Western Blot
Gene of Interest
Gene Synonyms:FGFR1;BFGFR;CEK;FGFBR;FLG;FLT2;HBGFR
Protein Names:Fibroblast growth factor receptor 1 (FGFR-1) (EC 2.7.10.1) (Basic fibroblast growth factor receptor 1) (BFGFR) (bFGF-R-1) (Fms-like tyrosine kinase 2) (FLT-2) (N-sam) (Proto-oncogene c-Fgr) (CD antigen CD331)
Accession Data
Organism:Homo sapiens (Human)
Mass (kDa):918.68
Length (aa):822
Sequence:MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRLRDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYFSVNVSDALPSSEDDDDDDDSSSEEKETDNTKPNRMPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPSSGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTCIVENEYGSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQPHIQWLKHIEVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLEALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKMKSGTKKSDFHSQMAVHKLAKSIPLRRQVTVSADSSASMNSGVLLVRPSRLSSSGTPMLAGVSEYELPEDPRWELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLQARRPPGLEYCYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQYSPSFPDTRSSTCSSGEDSVFSHEPLPEEPCLPRHPAQLANGGLKRR
Proteomics (Proteome ID):UP000005640
Proteomics (Chromosome): Chromosome 8
Active Site:ACT_SITE 623 623 Proton acceptor. {ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:19224897}.
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. {ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:21454610, ECO:0000269|PubMed:8622701}.
Binding Site:BINDING 514 514 ATP.; BINDING 568 568 ATP.; BINDING 627 627 ATP.; BINDING 641 641 ATP.
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, ECO:0000269|PubMed:1379697, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:19665973, ECO:0000269|PubMed:20133753, ECO:0000269|PubMed:8622701};
Function [CC]: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. {ECO:0000250|UniProtKB:P16092, ECO:0000269|PubMed:10830168, ECO:0000269|PubMed:11353842, ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:1379697, ECO:0000269|PubMed:1379698, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:19261810, ECO:0000269|PubMed:19665973, ECO:0000269|PubMed:20133753, ECO:0000269|PubMed:20139426, ECO:0000269|PubMed:21765395, ECO:0000269|PubMed:8622701, ECO:0000269|PubMed:8663044}.
Nucleotide Binding:NP_BIND 484 490 ATP.; NP_BIND 562 564 ATP.
Site:SITE 428 429 Breakpoint for translocation to form CNTRL-FGFR1 OR FGFR1-CNTRL fusion proteins. {ECO:0000269|PubMed:10688839}.; SITE 428 429 Breakpoint for translocation to form FGFR1OP-FGFR1 or FGFR1-FGFR1OP fusion proteins. {ECO:0000269|PubMed:9949182}.; SITE 428 429 Breakpoint for translocation to form FGFR1OP2-FGFR1. {ECO:0000269|PubMed:15034873, ECO:0000269|PubMed:16946300, ECO:0000269|PubMed:17389761}.; SITE 766 766 Mediates interaction with PLCG1 and SHB.
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. {ECO:0000269|PubMed:1652059}.
Chemical Profile | ChEBI:H(+) [CHEBI:15378]; ATP [CHEBI:30616]; L-tyrosine residue [CHEBI:46858]; L-tyrosine-phosphate residue [CHEBI:82620]; ADP [CHEBI:456216]
ChEBI (Catalytic Activity):H(+) [CHEBI:15378]; ATP [CHEBI:30616]; L-tyrosine residue [CHEBI:46858]; L-tyrosine-phosphate residue [CHEBI:82620]; ADP [CHEBI:456216]
Disease:Pfeiffer syndrome (PS) [MIM:101600]: A syndrome characterized by the association of craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly of the fingers and toes. Three subtypes are known: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3). {ECO:0000269|PubMed:7874169}. Note=The disease is caused by mutations affecting the gene represented in this entry.; Hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:147950]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:12627230, ECO:0000269|PubMed:15001591, ECO:0000269|PubMed:15605412, ECO:0000269|PubMed:15845591, ECO:0000269|PubMed:16606836, ECO:0000269|PubMed:16757108, ECO:0000269|PubMed:16764984, ECO:0000269|PubMed:16882753, ECO:0000269|PubMed:17154279, ECO:0000269|PubMed:19820032, ECO:0000269|PubMed:21700882, ECO:0000269|PubMed:22927827, ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900, ECO:0000269|PubMed:26277103}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FGFR1 also have a mutation other HH-associated genes including DUSP6, FGF8, FGF17, FLRT3, GNRH1, GNRHR, HS6ST1, IL17RD, ANOS1, KISS1R, NSMF, PROKR2, SPRY4 and TACR3 (PubMed:23643382). {ECO:0000269|PubMed:23643382}.; Osteoglophonic dysplasia (OGD) [MIM:166250]: Characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant. {ECO:0000269|PubMed:15625620, ECO:0000269|PubMed:16470795}. Note=The disease is caused by mutations affecting the gene represented in this entry.; Hartsfield syndrome (HRTFDS) [MIM:615465]: A syndrome characterized by the triad of holoprosencephaly, ectrodactyly, and cleft/lip palate. Profound mental retardation is also present. Multiple other congenital anomalies usually occur. {ECO:0000269|PubMed:23812909, ECO:0000269|PubMed:24888332}. Note=The disease is caused by mutations affecting the gene represented in this entry.; Trigonocephaly 1 (TRIGNO1) [MIM:190440]: A keel-shaped deformation of the forehead, caused by premature fusion of the metopic sutures. It results in a triangular shape of the head. {ECO:0000269|PubMed:11173846}. Note=The disease is caused by mutations affecting the gene represented in this entry.; Note=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. {ECO:0000269|PubMed:9716603}.; Note=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. {ECO:0000269|PubMed:10688839, ECO:0000269|PubMed:15034873, ECO:0000269|PubMed:16946300, ECO:0000269|PubMed:17389761, ECO:0000269|PubMed:9949182}.; Note=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.; Encephalocraniocutaneous lipomatosis (ECCL) [MIM:613001]: A sporadically occurring, neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system anomalies. Clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, intracranial and intraspinal lipomas, and congenital abnormalities of the meninges. Seizures, spasticity, and intellectual disability can be present. {ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:26942290}. Note=The disease is caused by mutations affecting the gene represented in this entry.; Jackson-Weiss syndrome (JWS) [MIM:123150]: An autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence. {ECO:0000269|PubMed:10861678}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Mutagenesis:MUTAGEN 514 514 K->A: Loss of kinase activity. {ECO:0000269|PubMed:15117958}.; MUTAGEN 577 577 R->E: Strongly reduced autophosphorylation in response to FGF signaling. No effect on in vitro kinase activity. {ECO:0000269|PubMed:20133753}.; MUTAGEN 609 609 R->V: Abolishes interaction with PLCG1.; MUTAGEN 623 623 D->A: Loss of kinase activity. {ECO:0000269|PubMed:19224897}.; MUTAGEN 653 653 Y->F: No effect on kinase activity. Loss of autophosphorylation and kinase activity; when associated with F-654. {ECO:0000269|PubMed:8622701}.; MUTAGEN 654 654 Y->F: Reduced kinase activity. Loss of autophosphorylation and kinase activity; when associated with F-653. {ECO:0000269|PubMed:8622701}.; MUTAGEN 755 755 D->V: Abolishes interaction with PLCG1.; MUTAGEN 766 766 Y->F: Abolishes interaction with PLCG1 and SHB. Decreases phosphorylation of FRS2, activation of RAS and MAP kinase signaling and stimulation of cell proliferation. {ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:1379697, ECO:0000269|PubMed:1379698, ECO:0000269|PubMed:7516330}.
Reagent Data
Name:Fibroblast Growth Factor-basic
Class:Growth Factor
Subcategory:Protein
Molecular Weight:17.353
Source:E.Coli
Species:Human
Tag:
Extinction:0.8511
Bioactivity
Measured:1-10 ng/ml
Determined By:Assay (Variable)
Assay Profile:LOT-Specific (Check COA)
Format:Lyophilized
Purification System:Chromatography
Formulation:Sterile-filtered colorless solution
Formulation Concentration:1 mg/ml
Buffer Volume:Standard
Buffer Solution:PBS
pH:7.4-7.5
Toxicity
Endotoxin Level:< 1%
Aggregate Tested By:SDS-PAGE
Endotoxin Screened:< 0.1 ng/ug
Purity:> 98%
Determined: SDS-PAGE
Stain:Silver
Chromotography:Anion-exchange
Validated: RP-HPLC
Sample Handling
Storage:4°C
Stability:This bioreagent is stable at 4°C (short-term) and -70°C(long-term). After reconstitution, sample may be stored at 4°C for 2-7 days and below -18°C for future use.
Preparation:Reconstitute in sterile distilled H2O to no less than 100 ug/ml; dilute reconstituted stock further in other aqueous solutions if needed. Please review COA for lot-specific instructions. Final measurements should be determined by the end-user for optimal performance.