ALAS1

ALAS1
Identifikatori
Aliasi	ALAS1
Vanjski ID-jevi	OMIM: 125290 MGI: 87989 HomoloGene: 55478 GeneCards: ALAS1
Lokacija gena (čovjek)
Hrom.	Hromosom 3 (čovjek)
Kraj	52,214,327 bp
Lokacija gena (miš)
Hrom.	Hromosom 9 (miš)
Kraj	106,125,853 bp
Ontologija gena
Molekularna funkcija	• aktivnost sa transferazom; • pyridoxal phosphate binding; • acyltransferase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • catalytic activity; • 5-aminolevulinate synthase activity; • vezivanje identičnih proteina;
Ćelijska komponenta	• mitochondrial matrix; • mitohondrija; • nukleoplazma; • citosol;
Biološki proces	• heme biosynthetic process; • mitochondrion organization; • metabolizam; • protoporphyrinogen IX biosynthetic process; • Biosinteza; • tetrapyrrole biosynthetic process; • porphyrin-containing compound metabolic process; • regulation of lipid metabolic process;
	Izvori:Amigo / QuickGO
Ortolozi
	211
	11655
	ENSG00000023330
	ENSMUSG00000032786
	P13196
	Q8VC19
	NM_000688; NM_001304443; NM_001304444; NM_199166
	NM_001291835; NM_020559
	NP_000679; NP_001291372; NP_001291373; NP_954635
	NP_001278764; NP_065584
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

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

Dužina polipeptidnog lanca je 640 aminokiselina, а molekulska težina 70.581 Da.^[7]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

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

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

^ ^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

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

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.

Šablon:Enzimi porfirinskog metabolizma

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000023330 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000032786 - 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.

[pmid2347585-5] 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.

[entrez-6] "Entrez Gene: Delta-aminolevulinate synthase 1".

[UniProt-7] "UniProt, P13196" (jezik: engleski). Pristupljeno 31. 10. 2021.

[Okano_et_al.,_Genes_to_Cells_2010-8] 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.

[5]