ALAS1
Delta-aminolevulinat sintaza 1 znana i kao ALAS1 jest enzim koji je kod ljudi kodiran genom ALAS1 sa hromosoma 3.[5][6] ALAS1 je aminolevulinska kisela sintaza.
Aminokiselinska sekvenca[uredi | uredi izvor]
Dužina polipeptidnog lanca je 640 aminokiselina, а molekulska težina 70.581 Da.[7]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MESVVRRCPF | LSRVPQAFLQ | KAGKSLLFYA | QNCPKMMEVG | AKPAPRALST | ||||
| AAVHYQQIKE | TPPASEKDKT | AKAKVQQTPD | GSQQSPDGTQ | LPSGHPLPAT | ||||
| SQGTASKCPF | LAAQMNQRGS | SVFCKASLEL | QEDVQEMNAV | RKEVAETSAG | ||||
| PSVVSVKTDG | GDPSGLLKNF | QDIMQKQRPE | RVSHLLQDNL | PKSVSTFQYD | ||||
| RFFEKKIDEK | KNDHTYRVFK | TVNRRAHIFP | MADDYSDSLI | TKKQVSVWCS | ||||
| NDYLGMSRHP | RVCGAVMDTL | KQHGAGAGGT | RNISGTSKFH | VDLERELADL | ||||
| HGKDAALLFS | SCFVANDSTL | FTLAKMMPGC | EIYSDSGNHA | SMIQGIRNSR | ||||
| VPKYIFRHND | VSHLRELLQR | SDPSVPKIVA | FETVHSMDGA | VCPLEELCDV | ||||
| AHEFGAITFV | DEVHAVGLYG | ARGGGIGDRD | GVMPKMDIIS | GTLGKAFGCV | ||||
| GGYIASTSSL | IDTVRSYAAG | FIFTTSLPPM | LLAGALESVR | ILKSAEGRVL | ||||
| RRQHQRNVKL | MRQMLMDAGL | PVVHCPSHII | PVRVADAAKN | TEVCDELMSR | ||||
| HNIYVQAINY | PTVPRGEELL | RIAPTPHHTP | QMMNYFLENL | LVTWKQVGLE | ||||
| LKPHSSAECN | FCRRPLHFEV | MSEREKSYFS | GLSKLVSAQA |
Funkcija[uredi | uredi izvor]
Delta-aminolevulinat sintaza katalizira kondenzaciju glicina putem sukcinil-CoA da bi se formirala delta-aminolevulinska kiselina. Ovaj jedarno kodirani mitohondrijski enzim je prvi enzim koji ograničava brzinu u biosintetskom putu sisarskoh hema. Postoje dva tkivno specifična izozima: domaćinski enzim kodiran genom ALAS1 i enzim specifičan za eritroidno tkivo, kodiran genom ALAS2.[6]
Miševi kojima nedostaje ovaj gen pokazuju smrtnost na stupnju embriona, što ukazuje da je ALAS neophodan za ranu embriogenezu.[8]
Reference[uredi | uredi izvor]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000023330 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032786 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Bishop DF, Henderson AS, Astrin KH (juni 1990). "Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome". Genomics. 7 (2): 207–14. doi:10.1016/0888-7543(90)90542-3. PMID 2347585.
- ^ a b "Entrez Gene: Delta-aminolevulinate synthase 1".
- ^ "UniProt, P13196" (jezik: engleski). Pristupljeno 31. 10. 2021.
- ^ Okano, S; Zhou, L; Kusaka, T; Shibata, K; Shimizu, K; Gao, X; Kikuchi, Y; Togashi, Y; Hosoya, T; Takahashi, S; Nakajima, O; Yamamoto, M (januar 2010). "Indispensable function for embryogenesis, expression and regulation of the nonspecific form of the 5-aminolevulinate synthase gene in mouse". Genes to Cells. 15 (1): 77–89. doi:10.1111/j.1365-2443.2009.01366.x. PMID 20015225. S2CID 25018156.
Dopunska literatura[uredi | uredi izvor]
- Goodfellow BJ, Dias JS, Ferreira GC, et al. (2001). "The solution structure and heme binding of the presequence of murine 5-aminolevulinate synthase". FEBS Lett. 505 (2): 325–31. doi:10.1016/S0014-5793(01)02818-6. PMID 11566198. S2CID 34879759.
- Cortesão E, Vidan J, Pereira J, et al. (2004). "Onset of X-linked sideroblastic anemia in the fourth decade". Haematologica. 89 (10): 1261–3. PMID 15477213.
- May BK, Bhasker CR, Bawden MJ, Cox TC (1990). "Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis". Mol. Biol. Med. 7 (5): 405–21. PMID 2095458.
- Dwyer BE, Smith MA, Richardson SL, et al. (2009). "Down-Regulation of Aminolevulinate Synthase, the Rate-Limiting Enzyme for Heme Biosynthesis in Alzheimer's Disease". Neurosci. Lett. 460 (2): 180–4. doi:10.1016/j.neulet.2009.05.058. PMC 2743886. PMID 19477221.
- Furuyama K, Sassa S (2002). "Multiple mechanisms for hereditary sideroblastic anemia". Cell. Mol. Biol. (Noisy-le-grand). 48 (1): 5–10. PMID 11929048.
- Guberman AS, Scassa ME, Cánepa ET (2005). "Repression of 5-aminolevulinate synthase gene by the potent tumor promoter, TPA, involves multiple signal transduction pathways". Arch. Biochem. Biophys. 436 (2): 285–96. doi:10.1016/j.abb.2005.02.011. PMID 15797241.
- Roberts AG, Elder GH (2001). "Alternative splicing and tissue-specific transcription of human and rodent ubiquitous 5-aminolevulinate synthase (ALAS1) genes". Biochim. Biophys. Acta. 1518 (1–2): 95–105. doi:10.1016/s0167-4781(01)00187-7. PMID 11267664.
- Szafranski K, Schindler S, Taudien S, et al. (2007). "Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns". Genome Biol. 8 (8): R154. doi:10.1186/gb-2007-8-8-r154. PMC 2374985. PMID 17672918.
- Scassa ME, Guberman AS, Ceruti JM, Cánepa ET (2004). "Hepatic nuclear factor 3 and nuclear factor 1 regulate 5-aminolevulinate synthase gene expression and are involved in insulin repression". J. Biol. Chem. 279 (27): 28082–92. doi:10.1074/jbc.M401792200. PMID 15123725.
- Imabayashi H, Mori T, Gojo S, et al. (2003). "Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis". Exp. Cell Res. 288 (1): 35–50. doi:10.1016/S0014-4827(03)00130-7. PMID 12878157.
- Fujii H, Takahashi T, Matsumi M, et al. (2004). "Increased heme oxygenase-1 and decreased delta-aminolevulinate synthase expression in the liver of patients with acute liver failure". Int. J. Mol. Med. 14 (6): 1001–5. doi:10.3892/ijmm.14.6.1001. PMID 15547665.
- Zheng J, Shan Y, Lambrecht RW, et al. (2008). "Differential regulation of human ALAS1 mRNA and protein levels by heme and cobalt protoporphyrin". Mol. Cell. Biochem. 319 (1–2): 153–61. doi:10.1007/s11010-008-9888-0. PMID 18719978. S2CID 33770538.
- Roberts AG, Redding SJ, Llewellyn DH (2005). "An alternatively-spliced exon in the 5'-UTR of human ALAS1 mRNA inhibits translation and renders it resistant to haem-mediated decay". FEBS Lett. 579 (5): 1061–6. doi:10.1016/j.febslet.2004.12.080. PMID 15710391. S2CID 32462861.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Jung M, Ohl F, Stephan C, et al. (2007). "[Quantifying gene expression in prostate carcinoma. Which endogenous reference genes are suitable?]". Urologe A. 46 (9): 1083–4. doi:10.1007/s00120-007-1436-0. PMID 17628775. S2CID 11640176.
- Guberman AS, Scassa ME, Giono LE, et al. (2003). "Inhibitory effect of AP-1 complex on 5-aminolevulinate synthase gene expression through sequestration of cAMP-response element protein (CRE)-binding protein (CBP) coactivator". J. Biol. Chem. 278 (4): 2317–26. doi:10.1074/jbc.M205057200. PMID 12433930.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Ferreira GC, Cheltsov AV (2002). "Circular permutation of 5-aminolevulinate synthase as a tool to evaluate folding, structure and function". Cell. Mol. Biol. (Noisy-le-grand). 48 (1): 11–6. PMID 11929042.
- Tsang HT, Connell JW, Brown SE, et al. (2006). "A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex". Genomics. 88 (3): 333–46. doi:10.1016/j.ygeno.2006.04.003. PMID 16730941.
Vanjski linkovi[uredi | uredi izvor]
Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.
- Lokacija ljudskog genoma ALAS1 i stranica sa detaljima o genu ALAS1 u UCSC Genome Browseru.