RAS p21 proteinski aktivator 1

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RAS p21 proteinski aktivator (Protein aktivacije GTPaze) 1

PDB rendering based on 1wer.
Dostupne strukture
1WER, 1WQ1, 2GQI, 2GSB, 2J05, 2J06, 2M51, 4FSS
Identifikatori
SimboliRASA1; CM-AVM; CMAVM; GAP; PKWS; RASA; RASGAP; p120GAP; p120RASGAP
Vanjski IDOMIM139150 MGI97860 HomoloGene2168 GeneCards: RASA1 Gene
Pregled RNK izražavanja
PBB GE RASA1 210621 s at tn.png
PBB GE RASA1 202677 at tn.png
podaci
Ortolozi
VrstaČovekMiš
Entrez5921218397
EnsemblENSG00000145715ENSMUSG00000021549
UniProtP20936E9PYG6
Ref. Sekv. (iRNK)NM_002890NM_145452
Ref. Sekv. (protein)NP_002881NP_663427
Lokacija (UCSC)Chr 5:
86.56 - 86.69 Mb
Chr 13:
85.21 - 85.29 Mb
PubMed pretraga[1][2]

RAS p21 proteinski aktivator 1 ili RasGAP (aktivirajući protein Ras GTPaze), takođe poznat kao RASA1, je 120-kDa citosolni ljudski protein koji ima dve glavne aktivnosti:

  • Inakctivacija Ras proteina iz njegove aktivne GTP-vezane forme do njegove neaktivne GDP-vezane forme pojačavanjem endogene GTPazne Ras aktivnosti, preko njegovog C-terminalnog GAP domena
  • Mitogena transmisija signala u smeru daljih interakcionih partnera putemn njegovih N-terminalnih SH2-SH3-SH2 domena

Protein kodiran ovim genom je lociran u citoplazmi i deo je GAP1 familije GTPazno-aktiviranih proteina. Ovaj genski produkt stimuliše GTPaznu aktivnost normalnog RAS p21, ali ne i njegovog onkogenog pandana. Delujući kao supresor RAS funkcije, ovaj protein pojačava slabu unutrašnju GTPaznu aktivnost RAS proteina, što dovodi do inaktiviranje GDP-vezane forme RAS-a, čime pospešuje kontrolu ćelijske proliferacije i diferencijacije. Mutacije koje dovode do promena u mestima vezivanja ovog proteina su vezane za bazalne ćelijske kacinome. Alternativnim splajsovanjem se formiraju dve izoforme, pri čemu kraća izoforma, kojoj nedostaje N-terminusni hidrofobni region zadržava aktivnost. Ona je izobilno izražena u materičnim, ali ne i odraslim tkivima.[1]

Domeni[uredi - уреди | uredi izvor]

RasGAP sadrži jedan SH3 domen i dva SH2 domena, PH domen, i GAP domen.

Interakcije[uredi - уреди | uredi izvor]

RAS p21 proteinski aktivator 1 formira interakcije sa:

iRNK može da formira interakcije sa Mir-132 mikroRNK. Ovaj protein učestvuje u angiogenezi.[28]

Baza podataka bolesti[uredi - уреди | uredi izvor]

Reference[uredi - уреди | uredi izvor]

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  13. 13,0 13,1 Giglione C, Gonfloni S, Parmeggiani A (June 2001). "Differential actions of p60c-Src and Lck kinases on the Ras regulators p120-GAP and GDP/GTP exchange factor CDC25Mm". Eur. J. Biochem. 268 (11): 3275–83. PMID 11389730. doi:10.1046/j.1432-1327.2001.02230.x. 
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  19. Jabado N, Jauliac S, Pallier A, Bernard F, Fischer A, Hivroz C (September 1998). "Sam68 association with p120GAP in CD4+ T cells is dependent on CD4 molecule expression". J. Immunol. 161 (6): 2798–803. PMID 9743338. 
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  28. Anand S, Majeti BK, Acevedo LM, Murphy EA, Mukthavaram R, Scheppke L, Huang M, Shields DJ, Lindquist JN, Lapinski PE, King PD, Weis SM, Cheresh DA (2010). "MicroRNA-132–mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis". Nat Med 16 (8): 909–14. PMC 3094020. PMID 20676106. doi:10.1038/nm.2186. 

Literatura[uredi - уреди | uredi izvor]

  • Tocque B, Delumeau I, Parker F et al. (1997). "Ras-GTPase activating protein (GAP): a putative effector for Ras". Cell. Signal. 9 (2): 153–8. PMID 9113414. doi:10.1016/S0898-6568(96)00135-0. 
  • Boon LM, Mulliken JB, Vikkula M (2005). "RASA1: variable phenotype with capillary and arteriovenous malformations". Curr. Opin. Genet. Dev. 15 (3): 265–9. PMID 15917201. doi:10.1016/j.gde.2005.03.004. 

Vanjske veze[uredi - уреди | uredi izvor]