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FGF1

S Wikipedije, slobodne enciklopedije
FGF1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

4QO3, 1AXM, 1DJS, 1DZC, 1DZD, 1E0O, 1EVT, 1HKN, 1JQZ, 1JT3, 1JT4, 1JT5, 1JT7, 1JTC, 1JY0, 1K5U, 1K5V, 1M16, 1NZK, 1P63, 1PZZ, 1Q03, 1Q04, 1RG8, 1RML, 1RY7, 1YTO, 1Z2V, 1Z4S, 2AFG, 2AQZ, 2AXM, 2ERM, 2HW9, 2HWA, 2HWM, 2HZ9, 2K43, 2K4A, 2K8R, 2KI4, 2KI6, 2NTD, 2Q9X, 2RQ9, 3B9U, 3BA4, 3BA5, 3BA7, 3BAD, 3BAG, 3BAH, 3BAO, 3BAQ, 3BAU, 3BAV, 3BB2, 3CQA, 3CRG, 3CRH, 3CRI, 3CU1, 3FGM, 3FJ8, 3FJ9, 3FJA, 3FJB, 3FJC, 3FJD, 3FJE, 3FJF, 3FJH, 3FJI, 3FJJ, 3FJK, 3HOM, 3JUT, 3K1X, 3O3Q, 3OJ2, 3OJM, 3OJV, 3UD7, 3UD8, 3UD9, 3UDA, 4J23, 4Q91, 4Q9G, 4Q9P, 4QAL, 4QBC, 4QBV, 4QC4, 4XKI, 4YOL

Identifikatori
AliasiFGF1
Vanjski ID-jeviOMIM: 131220 MGI: 95515 HomoloGene: 625 GeneCards: FGF1
Lokacija gena (čovjek)
Hromosom 5 (čovjek)
Hrom.Hromosom 5 (čovjek)[1]
Hromosom 5 (čovjek)
Genomska lokacija za FGF1
Genomska lokacija za FGF1
Bend5q31.3Početak142,592,178 bp[1]
Kraj142,698,070 bp[1]
Lokacija gena (miš)
Hromosom 18 (miš)
Hrom.Hromosom 18 (miš)[2]
Hromosom 18 (miš)
Genomska lokacija za FGF1
Genomska lokacija za FGF1
Bend18 B3|18 20.74 cMPočetak38,971,726 bp[2]
Kraj39,062,525 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija S100 protein binding
GO:0001948, GO:0016582 vezivanje za proteine
growth factor activity
protein tyrosine kinase activity
phosphatidylinositol-4,5-bisphosphate 3-kinase activity
fibroblast growth factor receptor binding
integrin binding
1-phosphatidylinositol-3-kinase activity
heparin binding
Hsp70 protein binding
Ćelijska komponenta citoplazma
citosol
extracellular region
cell cortex
Jedarce
jedro
Vanćelijsko
GO:0005578 Vanćelijski matriks
Biološki proces Ćelijska diferencijacija
cellular response to heat
positive regulation of protein phosphorylation
positive regulation of MAP kinase activity
organ induction
lung development
positive regulation of epithelial cell proliferation
anatomical structure morphogenesis
GO:0010740 positive regulation of intracellular signal transduction
branch elongation involved in ureteric bud branching
positive regulation of angiogenesis
MAPK cascade
multicellular organism development
mesonephric epithelium development
Angiogeneza
regulation of endothelial cell chemotaxis to fibroblast growth factor
positive regulation of cholesterol biosynthetic process
Ćelijska proliferacija
positive regulation of cell division
GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
GO:0072468 Transdukcija signala
phosphatidylinositol phosphate biosynthetic process
peptidyl-tyrosine phosphorylation
positive regulation of sprouting angiogenesis
fibroblast growth factor receptor signaling pathway
positive regulation of cell population proliferation
phosphatidylinositol-3-phosphate biosynthetic process
regulation of endothelial tube morphogenesis
positive regulation of cell migration
positive regulation of endothelial cell migration
activation of protein kinase B activity
regulation of signaling receptor activity
positive regulation of protein kinase B signaling
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)
NM_000800
NM_001144892
NM_001144934
NM_001144935
NM_001257205

NM_001257206
NM_001257207
NM_001257208
NM_001257209
NM_001257210
NM_001257211
NM_001257212
NM_033136
NM_033137
NM_001354955
NM_001354956
NM_001354957
NM_001354958
NM_001354959
NM_001354961
NM_001354963
NM_001354964
NM_001354951
NM_001354952
NM_001354953
NM_001354954
NM_001354962

NM_010197

RefSeq (bjelančevina)
NP_000791
NP_001138364
NP_001138406
NP_001138407
NP_001244134

NP_001244135
NP_001244136
NP_001244137
NP_001244138
NP_001244139
NP_001244140
NP_001244141
NP_149127
NP_149128
NP_001341884
NP_001341885
NP_001341886
NP_001341887
NP_001341888
NP_001341890
NP_001341892
NP_001341893
NP_001341880
NP_001341881
NP_001341882
NP_001341883
NP_001341891

NP_034327

Lokacija (UCSC)Chr 5: 142.59 – 142.7 MbChr 18: 38.97 – 39.06 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

FGF1, znan i kao kiseli faktor rasta fibroblasta (aFGF), jest faktor rasta i signalni protein koji je kod ljudi kodiran genom FGF1 sa hromosoma 5.[5][6]

Sintetizira se kao polipeptid od 155 aminokiselina, čiji je zreli oblik neglikoziliran protein od 17-18 kDa. Protein faktora rasta fibroblasta je prvi put prečišćen 1975. godine, ali su ubrzo nakon toga drugi, koristeći različite uvjete, izolirali kiseli FGF, faktor rasta koji veže heparin-1 i faktor rasta endotelnih ćelija-1.[7] Sekvenciranje gena otkrilo je da je ova grupa zapravo isti faktor rasta i da je FGF1 bio član proteina porodice FGF.

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 155 aminokiselina, а molekulska težina 17.460 Da.[8]

1020304050
MAEGEITTFTALTEKFNLPPGNYKKPKLLYCSNGGHFLRILPDGTVDGTR
DRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLF
LERLEENHYNTYISKKHAEKNWFVGLKKNGSCKRGPRTHYGQKAILFLPL
PVSSD

Funkcija

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Članovi porodice FGF imaju široku mitogenu i aktivnost preživljavanja ćelija i uključeni su u različite biološke procese, uključujući embrionsk i razvoj, rast ćelija, morfogenezu, popravak tkiva, rast i invaziju tumora. Ovaj protein funkcionira kao modifikator migracije i proliferacije endotelnih ćelija, kao i angiogeni faktor. Djeluje kao mitogen za različite mezodermno izvedene ćelije i iz neuroektoderm in vitro, pa se smatra da je uključen u organogenezu. Opisane su tri alternativno prerađene varijante transkripta, koje kodiraju različite izoforme.[9]

FGF1 je multifunkcionalan sa mnogo prijavljenih efekata. Naprimjer, kod miševa s dijabetesom uzrokovanim ishranom, koji je eksperimentalni ekvivalent dijabetesa tipa 2 kod ljudi, jedna injekcija proteina FGF1 dovoljna je za vraćanje razine šećera u krvi u zdravi raspon za > 2 dana.[10]

FGF-1 nema definitivnu signalnu sekvencu pa se stoga ne izlučuje klasičnim putevima, ali čini se da tvori disulfidom povezan dimer unutar ćelija koji se povezuje sa kompleksom proteina na ćelijskoj membrani (uključujući S100A13 i Syt1) koji ga zatim pomažu prebaciti kroz membranu do vanjske strane ćelije.[11][12] U redukcijskim uvjetima okolnog tkiva, dimer se disocira na monomerni FGF1 koji može ući u sistemsku cirkulaciju ili se sekvestrirati u tkivima, gdje se vezuju za heparan sulfatni proteoglikan iz vanćelijskog matriksa . FGF1 se tada može vezati i djelovati putem specifičnih receptora faktora rasta fibroblasta (FGFR), proteina koji sami čine porodicu blisko povezanih molekula.[13]

Osim vanćelijske aktivnosti, FGF1 može djelovati i unutar ćelija. Protein ima jedarnu sekvencu (NLS), ali put kojim FGF1 prolazi do jedra nije jasan i čini se da je potreban neki tip vezanja receptora na površini ćdlije, nakon čega slijedi njegova internalizacija i translokacija u jedro pri čemu može stupiti u interakciju s jedarnim izoformama FGFR-a.[13] Ovo se razlikuje od FGF2 koji također može aktivirati jedarne FGFR-e, ali ima varijante transkripta proteina koje nikada ne napuštaju ćeliju i odlaze direktno do jedra.

Interakcije

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Pokazalo se da FGF1 stupa u interakcije sa:

Također pogledajte

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000113578 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036585 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Dionne CA, Crumley G, Bellot F, Kaplow JM, Searfoss G, Ruta M, Burgess WH, Jaye M, Schlessinger J (septembar 1990). "Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors". The EMBO Journal. 9 (9): 2685–92. doi:10.1002/j.1460-2075.1990.tb07454.x. PMC 551973. PMID 1697263.
  6. ^ Jaye M, Howk R, Burgess W, Ricca GA, Chiu IM, Ravera MW, O'Brien SJ, Modi WS, Maciag T, Drohan WN (august 1986). "Human endothelial cell growth factor: cloning, nucleotide sequence, and chromosome localization". Science. 233 (4763): 541–5. Bibcode:1986Sci...233..541J. doi:10.1126/science.3523756. PMID 3523756.
  7. ^ Burgess WH, Maciag T (1989). "The heparin-binding (fibroblast) growth factor family of proteins". Annual Review of Biochemistry. 58: 575–606. doi:10.1146/annurev.bi.58.070189.003043. PMID 2549857.
  8. ^ "UniProt, P05230" (jezik: engleski). Pristupljeno 15. 10. 2021.
  9. ^ "Entrez Gene: FGF1 fibroblast growth factor 1 (acidic)".
  10. ^ Suh JM, Jonker JW, Ahmadian M, Goetz R, Lackey D, Osborn O, Huang Z, Liu W, Yoshihara E, van Dijk TH, Havinga R, Fan W, Yin YQ, Yu RT, Liddle C, Atkins AR, Olefsky JM, Mohammadi M, Downes M, Evans RM (septembar 2014). "Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer". Nature. 513 (7518): 436–9. Bibcode:2014Natur.513..436S. doi:10.1038/nature13540. PMC 4184286. PMID 25043058. SažetakSalk Institute.
  11. ^ Tarantini F, Gamble S, Jackson A, Maciag T (decembar 1995). "The cysteine residue responsible for the release of fibroblast growth factor-1 residues in a domain independent of the domain for phosphatidylserine binding". The Journal of Biological Chemistry. 270 (49): 29039–42. doi:10.1074/jbc.270.49.29039. PMID 7493920.
  12. ^ a b c Prudovsky I, Bagala C, Tarantini F, Mandinova A, Soldi R, Bellum S, Maciag T (juli 2002). "The intracellular translocation of the components of the fibroblast growth factor 1 release complex precedes their assembly prior to export". The Journal of Cell Biology. 158 (2): 201–8. doi:10.1083/jcb.200203084. PMC 2173119. PMID 12135982.
  13. ^ a b Coleman SJ, Bruce C, Chioni AM, Kocher HM, Grose RP (august 2014). "The ins and outs of fibroblast growth factor receptor signalling". Clinical Science. 127 (4): 217–31. doi:10.1042/CS20140100. PMID 24780002.
  14. ^ a b c Skjerpen CS, Nilsen T, Wesche J, Olsnes S (august 2002). "Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity". The EMBO Journal. 21 (15): 4058–69. doi:10.1093/emboj/cdf402. PMC 126148. PMID 12145206.
  15. ^ Kolpakova E, Wiedłocha A, Stenmark H, Klingenberg O, Falnes PO, Olsnes S (novembar 1998). "Cloning of an intracellular protein that binds selectively to mitogenic acidic fibroblast growth factor". The Biochemical Journal. 336 (1): 213–22. doi:10.1042/bj3360213. PMC 1219860. PMID 9806903.
  16. ^ Schlessinger J, Plotnikov AN, Ibrahimi OA, Eliseenkova AV, Yeh BK, Yayon A, Linhardt RJ, Mohammadi M (septembar 2000). "Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization". Molecular Cell. 6 (3): 743–50. doi:10.1016/s1097-2765(00)00073-3. PMID 11030354.
  17. ^ a b c Santos-Ocampo S, Colvin JS, Chellaiah A, Ornitz DM (januar 1996). "Expression and biological activity of mouse fibroblast growth factor-9". The Journal of Biological Chemistry. 271 (3): 1726–31. doi:10.1074/jbc.271.3.1726. PMID 8576175.
  18. ^ Stauber DJ, DiGabriele AD, Hendrickson WA (januar 2000). "Structural interactions of fibroblast growth factor receptor with its ligands". Proceedings of the National Academy of Sciences of the United States of America. 97 (1): 49–54. Bibcode:2000PNAS...97...49S. doi:10.1073/pnas.97.1.49. PMC 26614. PMID 10618369.
  19. ^ Pellegrini L, Burke DF, von Delft F, Mulloy B, Blundell TL (oktobar 2000). "Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin". Nature. 407 (6807): 1029–34. Bibcode:2000Natur.407.1029P. doi:10.1038/35039551. PMID 11069186. S2CID 4418272.
  20. ^ Chellaiah A, Yuan W, Chellaiah M, Ornitz DM (decembar 1999). "Mapping ligand binding domains in chimeric fibroblast growth factor receptor molecules. Multiple regions determine ligand binding specificity". The Journal of Biological Chemistry. 274 (49): 34785–94. doi:10.1074/jbc.274.49.34785. PMID 10574949.
  21. ^ Loo BB, Darwish KK, Vainikka SS, Saarikettu JJ, Vihko PP, Hermonen JJ, Goldman AA, Alitalo KK, Jalkanen MM (maj 2000). "Production and characterization of the extracellular domain of recombinant human fibroblast growth factor receptor 4". The International Journal of Biochemistry & Cell Biology. 32 (5): 489–97. doi:10.1016/S1357-2725(99)00145-4. PMID 10736564.
  22. ^ Kan M, Wu X, Wang F, McKeehan WL (maj 1999). "Specificity for fibroblast growth factors determined by heparan sulfate in a binary complex with the receptor kinase". The Journal of Biological Chemistry. 274 (22): 15947–52. doi:10.1074/jbc.274.22.15947. PMID 10336501.
  23. ^ Mizukoshi E, Suzuki M, Loupatov A, Uruno T, Hayashi H, Misono T, Kaul SC, Wadhwa R, Imamura T (oktobar 1999). "Fibroblast growth factor-1 interacts with the glucose-regulated protein GRP75/mortalin". The Biochemical Journal. 343 (2): 461–6. doi:10.1042/0264-6021:3430461. PMC 1220575. PMID 10510314.
  24. ^ a b Mouta Carreira C, LaVallee TM, Tarantini F, Jackson A, Lathrop JT, Hampton B, Burgess WH, Maciag T (august 1998). "S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro". The Journal of Biological Chemistry. 273 (35): 22224–31. doi:10.1074/jbc.273.35.22224. PMID 9712836.
  25. ^ Landriscina M, Bagalá C, Mandinova A, Soldi R, Micucci I, Bellum S, Prudovsky I, Maciag T (juli 2001). "Copper induces the assembly of a multiprotein aggregate implicated in the release of fibroblast growth factor 1 in response to stress". The Journal of Biological Chemistry. 276 (27): 25549–57. doi:10.1074/jbc.M102925200. PMID 11432880.

Dopunska literatura

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Vanjski linkovi

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Šablon:Proteini i peptidi međučelijske signalizacije