https://www.ncbi.nlm.nih.gov/pubmed/11150295
Näillä on nykyisin toiset nimetm joissa numero on päinvastoin siis ACSS2 sytosolinen (AceCS1 ennen) ja ACSS1 mitokondriaalinen ( AceCS2 ennen). Mitokondriaalista on eniten sydämessä ja maksasta se puuttuu.
AseCS1 on mitokondriaalinen asetyyli-CoA-syntetaasi. (Asetaatti-CoA ligaasi; etikkahapon CoA-ligaasi) , Sillä on ainakin hiirissä - (joilla ei liikuntafaktoristaole puutetta) tärkeä osuus sitruunahapposyklissä (CSC, TCA) , jossa se katalysoi asetaatit eli etikkahapon konversiota aktiiviksi etikkahapoksi , asetyyli CoA:ksi.( AsetyyliCoA taas on se perustava molekyyli, jolla on heti käyttöä monenmoisiin metabolisiin teihin! Pelkkä etikkahappo taas tuottaa harmia, jos se ei kykene aktivoitumaan). Geenistä pleissautuu vaihtoehtoisia transkriptejä, jotka koodaavat monia isoformeja. Tätä geeniä ilmentyy istukassa, pohjukaisisuolessa ja 24 muussa kudoksessa.
Geenin virallinen symboli nykyään on ACSS1, muita nimiä ovat ACAS2L, ACECS1, AceCS2L
ACSS1 (20p11.21) . acyl-CoA synthetase short chain family member 1 [ Homo sapiens (human)
]
https://www.ncbi.nlm.nih.gov/gene/84532
https://www.ncbi.nlm.nih.gov/gene/84532
- Official Symbol ACSS1
- Official Full Name acyl-CoA synthetase short chain family member 1
- Also known as ACAS2L; ACECS1; AceCS2L
- Summary: This gene encodes a mitochondrial acetyl-CoA synthetase enzyme. A similar protein in mice plays an important role in the tricarboxylic acid cycle by catalyzing the conversion of acetate to acetyl CoA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]
- Expression Broad expression in placenta (RPKM 70.4), duodenum (RPKM 23.0) and 24 other tissues See more Orthologs mouse all
- Preferred Names: acetyl-coenzyme A synthetase 2-like, mitochondrial
- Names: acetate--CoA ligase 2
- Features: NM_001252675.1 → NP_001239604.1 acetyl-coenzyme A synthetase 2-like, mitochondrial isoform 2 precursor ( Plenty of isoforms!)
FEATURES Location/Qualifiers source 1..687 /organism="Homo sapiens" /db_xref="taxon:9606" /chromosome="20" /map="20p11.21" Protein 1..687 /product="acetyl-coenzyme A synthetase 2-like, mitochondrial isoform 2 precursor" /EC_number="6.2.1.1" /note="acetyl-coenzyme A synthetase 2-like, mitochondrial; acetate--CoA ligase 2" /calculated_mol_wt=70901 transit_peptide 1..37 /experiment="experimental evidence, no additional details recorded" /note="Mitochondrion. {ECO:0000269|PubMed:16788062}; propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)" /calculated_mol_wt=3743 Region 54..674 /region_name="Ac_CoA_lig_AcsA" /note="acetate--CoA ligase; TIGR02188" /db_xref="CDD:274022" Region 64..665 /region_name="ACS" /note="Acetyl-CoA synthetase (also known as acetate-CoA ligase and acetyl-activating enzyme); cd05966" /db_xref="CDD:213313"Acetyl-CoA synthetase (also known as acetate-CoA ligase and acetyl-activating enzyme)Acetyl-CoA synthetase (ACS) catalyzes the formation of acetyl-CoA from acetate, CoA, and ATP. Synthesis of acetyl-CoA is carried out in a two-step reaction. In the first step, the enzyme catalyzes the synthesis of acetyl-AMP intermediate from acetate and ATP. In the second step, acetyl-AMP reacts with CoA to produce acetyl-CoA. This enzyme is widely present in all living organisms. The activity of this enzyme is crucial for maintaining the required levels of acetyl-CoA, a key intermediate in many important biosynthetic and catabolic processes. Acetyl-CoA is used in the biosynthesis of glucose, fatty acids, and cholesterol. It can also be used in the production of energy in the citric acid cycle. Eukaryotes typically have two isoforms of acetyl-CoA synthetase, a cytosolic form involved in biosynthetic processes and a mitochondrial form primarily involved in energy generation. Site order(196..198,224,227,229,335,340..341,363..365,389..390, 393,416..419,441..446,531,543,546,554..557,615,620..621) /site_type="active" /db_xref="CDD:213313" Site order(196..198,224,227,229,335,341,363..365,389..390,393, 554..556,615,620) /site_type="other" /note="CoA binding site [chemical binding]" /db_xref="CDD:213313" Region 224..227 (RGGR) /region_name="Coenzyme A binding. {ECO:0000250}" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)" Site order(291,294..299,301..302) /site_type="other" /note="acyl-activating enzyme (AAE) consensus motif" /db_xref="CDD:213313" Site order(340..341,416..419,441..446,531,543,546,557) /site_type="other" /note="AMP binding site [chemical binding]" /db_xref="CDD:213313" Site order(340..341,416..417,444) /site_type="other" /note="acetate binding site [chemical binding]" /db_xref="CDD:213313" Site 396 K /site_type="acetylation" /experiment="experimental evidence, no additional details recorded" /note="N6-acetyllysine. {ECO:0000244|PubMed:19608861}; propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)" Site 640 K /site_type="acetylation" /experiment="experimental evidence, no additional details recorded" /note="N6-acetyllysine. {ECO:0000269|PubMed:16788062}; propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)" CDS 1..687 /gene="ACSS1" /gene_synonym="ACAS2L; ACECS1; AceCS2L" /coded_by="NM_001252675.1:81..2144" /note="isoform 2 precursor is encoded by transcript variant 2" /db_xref="GeneID:84532" /db_xref="HGNC:HGNC:16091" /db_xref="MIM:614355" ORIGIN 1 maartlgrgv grllgslrgl sgqparppcg vsaprraasg psgsapavaa aaaqpgsypa 61 lsaqaarepa afwgplardt lvwdtpyhtv wdcdfstgki gwflggqlnv svncldqhvr 121 kspesvaliw erdepgtevr ityrellett crlantlkrh gvhrgdrvai ympvsplava 181 amlacariga vhtvifagfs aeslagrind akckvvitfn qglrggrvve lkkivdeavk 241 hcptvqhvlv ahrtdnkvhm gdldvpleqe makedpvcap esmgsedmlf mlytsgstgm 301 pkgivhtqag yllyaalthk lvfdhqpgdi fgcvadigwi tghsyvvygp lcngatsvlf 361 estpvypnag rywetverlk inqfygapta vrlllKygda wvkkydrssl rtlgsvgepi 421 nceawewlhr vvgdsrctlv dtwwqtggic iaprpseega eilpamamrp ffgivpvlmd 481 ekgsvvegsn vsgalcisqa wpgmartiyg dhqrfvdayf kaypgyyftg dgayrteggy 541 yqitgrmddv inisghrlgt aeiedaiadh pavpesavig yphdikgeaa fafivvkdsa 601 gdsdvvvqel ksmvatkiak yavpdeilvv krlpktrsgK vmrrllrkii tseaqelgdt 661 ttledpsiia eilsvyqkck dkqaaak //
- Mitä tutkimuksia tästä geenituotteesta on saatavilla? Huomaa SIRT3:n osuus mitokondriassa!
- Gene network analysis reveals a novel 22-gene signature of carbon metabolism in hepatocellular carcinoma. Zhang J, et al. Oncotarget, 2016 Aug 2. PMID 27363021, Free PMC Article
- A novel Acetyl-CoA synthetase short-chain subfamily member 1 (Acss1) gene indicates a dynamic history of paralogue retention and loss in vertebrates. Castro LF, et al. Gene, 2012 Apr 15. PMID 22313524
- The importance of acetyl coenzyme A synthetase for 11C-acetate uptake and cell survival in hepatocellular carcinoma. Yun M, et al. J Nucl Med, 2009 Aug. PMID 19617323
-
Crystal structures of human SIRT3 displaying substrate-induced conformational changes.
Jin L, et al. J Biol Chem, 2009 Sep 4. PMID 19535340, Free PMC ArticleAbstractSIRT3 is a major mitochondrial NAD(+)-dependent protein deacetylase playing important roles in regulating mitochondrial metabolism and energy production and has been linked to the beneficial effects of exercise and caloric restriction. SIRT3 is emerging as a potential therapeutic target to treat metabolic and neurological diseases. We report the first sets of crystal structures of human SIRT3, an apo-structure with no substrate, a structure with a peptide containing acetyl lysine of its natural substrate acetyl-CoA synthetase 2 (ACSS1) , a reaction intermediate structure trapped by a thioacetyl peptide, and a structure with the dethioacetylated peptide bound. These structures provide insights into the conformational changes induced by the two substrates required for the reaction, the acetylated substrate peptide and NAD(+). In addition, the binding study by isothermal titration calorimetry suggests that the acetylated peptide is the first substrate to bind to SIRT3, before NAD(+). These structures and biophysical studies provide key insight into the structural and functional relationship of the SIRT3 deacetylation activity. DOI:10.1074/jbc.M109.014928[Indexed for MEDLINE]
- Glucose-independent Acetate Metabolism Promotes Melanoma Cell Survival and Tumor Growth. Lakhter AJ, et al. J Biol Chem, 2016 Oct 14. PMID 27539851, Free PMC ArticleTumors rely on multiple nutrients to meet cellular bioenergetics and macromolecular synthesis demands of rapidly dividing cells. Although the role of glucose and glutamine in cancer metabolism is well understood, the relative contribution of acetate metabolism remains to be clarified. We show that glutamine supplementation is not sufficient to prevent loss of cell viability in a subset of glucose-deprived melanoma cells, but synergizes with acetate to support cell survival. Glucose-deprived melanoma cells depend on both oxidative phosphorylation and acetate metabolism for cell survival. Acetate supplementation significantly contributed to maintenance of ATP levels in glucose-starved cells. Unlike acetate, short chain fatty acids such as butyrate and propionate failed to prevent loss of cell viability from glucose deprivation. In vivo studies revealed that in addition to nucleo-cytoplasmic acetate assimilating enzyme ACSS2, mitochondrial ACSS1 was critical for melanoma tumor growth in mice. Our data indicate that acetate metabolism may be a potential therapeutic target for BRAF mutant melanoma.
GeneRIFs: Gene References Into Functions
- citrate synthase and ACSS1 have tumorigenic functions in hepatocellular carcinoma
- ACSS1 is essential for glucose-independent acetate-mediated cell survival and tumor growth.
- Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
- Observational study of gene-disease association. (HuGE Navigator)
Inga kommentarer:
Skicka en kommentar