ihmisen sytosolisesta AcetylCoa syntetaasista ACSS2 (20q11.22)

 (Mainitsen että aiemmin sain eräästä lähteestä tietää, että vain sirtuiini SIRT1 pystyy deasetyloimaan tätä sytosolista asetyyliCoA-syntaasia, kun taas mitokondriaalista deasetyloi SIRT3. )


 ACSS2 ( 20q11.22), sytosolinen asetyyliCoA syntetaasi, etikkahapon aktivoija.
https://www.ncbi.nlm.nih.gov/gene/55902
Tämä geeni koodaa sytosolista etnsyymiä, joka  katalysoi etikkahapon aktivoitumista   ja  tämä aktivoitunut etikkahappo  voi käyttyä lipidisynteesiin tai energian generoimiseen. Proteiini toimii monomeerina ja  tuottaa asetyyli-CoA:n etikkahaposta reaktiossa, joka vaatii ATP:tä.
 Tämän geenin ilmentymää säätelee SREB- proteiinit, transkriptiotekijät, jotka aktivoivat geenejä, mitä vaaditaan  kolesterolin ja tyydyttymättömien rasvahappojen synteesin. Vaihtoehtoispleissauksista tulee useita  transkriptivariantteja. Geeniä ilmentyy laajasti rasvakudoksessa, pohjukaissuolesas ja 24 muussa kudoksessa. 

Official Symbol ACSS2

Official Full Name acyl-CoA synthetase short chain family member 2

Also known as ACS; ACSA; ACAS2; ACECS; dJ1161H23.1

Summary: This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP.

 Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

Expression: Broad expression in fat (RPKM 49.2), duodenum (RPKM 47.1) and 24 other tissues See more. Orthologs. mouse all.

Preferred Names

acetyl-coenzyme A synthetase, cytoplasmic

Names

acetate thiokinase

acetate-CoA ligase

acetyl-Coenzyme A synthetase 2 (ADP forming)

acyl-activating enzyme

cytoplasmic acetyl-coenzyme A synthetase

 

( Millä tavalla sytosolinen ja mitokondriaalinen ACSS eroavat  toisistaan rakenteellisesti? Mm. vaikuttaa olevan kuusi seriinifosforylaatiota ja vain yksi N-lysiiniasetylaatio tässä sytosolisessa. Tämä geeni sijaitsee saman kromosomin q päädyssä, kun mitokondrinen  ACSS taas sijaitsee p-päädyssä).

  

Features. 

NM_001076552.2 → NP_001070020.2  acetyl-coenzyme A synthetase, cytoplasmic isoform 2

 

FEATURES             Location/Qualifiers
     source          1..714
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20q11.22"
     Protein         1..714
                     /product="acetyl-coenzyme A synthetase, cytoplasmic
                     isoform 2"
                     /EC_number="6.2.1.1"
                     /note="acetyl-Coenzyme A synthetase 2 (ADP forming);
                     cytoplasmic acetyl-coenzyme A synthetase; acetate-CoA
                     ligase; acyl-activating enzyme; acetate thiokinase;
                     acetyl-coenzyme A synthetase, cytoplasmic"
                     /calculated_mol_wt=79957
     Site            28
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163,
                     ECO:0000244|PubMed:24275569}; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            30
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:23186163, ECO:0000244|PubMed:24275569};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Region          31..705
                     /region_name="PRK00174"
                     /note="acetyl-CoA synthetase; Provisional"
                     /db_xref="CDD:234677"
     Site            36
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:24275569};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Region          51..698
                     /region_name="ACS"
                     /note="Acetyl-CoA synthetase (also known as acetate-CoA
                     ligase and acetyl-activating enzyme); cd05966"
                     /db_xref="CDD:213313"
     Site            order(191..193,219,222,224,370,375..376,398..400,424..425,
                     428,451..454,476..481,565,577,580,588..591,649,654..655)
                     /site_type="active"
                     /db_xref="CDD:213313"
     Site            order(191..193,219,222,224,370,376,398..400,424..425,428,
                     588..590,649,654)
                     /site_type="other"
                     /note="CoA binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Region          219..222
                     /region_name="Coenzyme A binding. {ECO:0000250}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            263
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:Q9QXG4};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            265
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:Q9QXG4};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            267
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:23186163,
                     ECO:0000244|PubMed:24275569}; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            order(326,329..334,336..337)
                     /site_type="other"
                     /note="acyl-activating enzyme (AAE) consensus motif"
                     /db_xref="CDD:213313"
     Site            order(375..376,451..454,476..481,565,577,580,591)
                     /site_type="other"
                     /note="AMP binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Site            order(375..376,451..452,479)
                     /site_type="other"
                     /note="acetate binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Site            431
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000244|PubMed:19608861};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     CDS             1..714
                     /gene="ACSS2"
                     /gene_synonym="ACAS2; ACECS; ACS; ACSA; dJ1161H23.1"
                     /coded_by="NM_001076552.2:122..2266"
                     /note="isoform 2 is encoded by transcript variant 2"
                     /db_xref="CCDS:CCDS42868.2"
                     /db_xref="GeneID:55902"
                     /db_xref="HGNC:HGNC:15814"
                     /db_xref="MIM:605832"
ORIGIN      
        1 mglpeervrs gsgsrgqeea gaggrarsws pppevsrsah vpslqryrel hrrsveepre
       61 fwgdiakefy wktpcpgpfl rynfdvtkgk ifiewmkgat tnicynvldr nvhekklgdk
      121 vafywegnep gettqityhq llvqvcqfsn vlrkqgiqkg drvaiympmi pelvvamlac
      181 arigalhsiv fagfsseslc erildsscsl littdafyrg eklvnlkela dealqkcqek
      241 gfpvrccivv khlgraelgm gdstsqsppi krscpdvqgk lkekskrvqp qiswnqgidl
      301 wwhelmqeag decepewcda edplfilyts gstgkpkgvv htvggymlyv attfkyvfdf
      361 haedvfwcta digwitghsy vtygplanga tsvlfegipt ypdvnrlwsi vdkykvtkfy
      421 taptairllm Kfgdepvtkh sraslqvlgt vgepinpeaw lwyhrvvgaq rcpivdtfwq
      481 tetgghmltp lpgatpmkpg satfpffgva pailnesgee legeaegylv fkqpwpgimr
      541 tvygnherfe ttyfkkfpgy yvtgdgcqrd qdgyywitgr iddmlnvsgh llstaevesa
      601 lveheavaea avvghphpvk geclycfvtl cdghtfspkl teelkkqire kigpiatpdy
      661 iqnapglpkt rsgkimrrvl rkiaqndhdl gdmstvadps vishlfshrc ltiq
//

(Mitä tietoja on tästä proteiinista saatu tähän mennessä?)

 

Related articles in PubMed

1. Acetyl-CoA synthetase 2 enhances tumorigenesis and is indicative of a poor prognosis for patients with renal cell carcinoma. Zhang S, et al. Urol Oncol, 2018 May. PMID 29503142
2. Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression. Yao L, et al. Cell Physiol Biochem, 2018. PMID 29444517
3. Local histone acetylation by ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy. Li X, et al. Autophagy, 2017 Oct 3. PMID 28820290, Free PMC Article
4. Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy. Li X, et al. Mol Cell, 2017 Jun 1. PMID 28552616, Free PMC Article
5. Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. Bulusu V, et al. Cell Rep, 2017 Jan 17. PMID 28099844, Free PMC Article

See all (32) citations in PubMed

GeneRIFs: Gene References Into Functions

1. High ACSS2 expression is associated with renal cell carcinoma.
2. A novel biologic role for ACSS2 in recycling of nuclear acetate for histone acetylation to promote lysosomal and autophagy-related gene expression and counteract nutritional stress, highlighting the importance of ACSS2 in maintaining autophagy and lysosome-mediated cellular energy homeostasis during tumor development.
3. ACLY and ACSS2 are both activated to produce cytosolic Ac-CoA from glucose carbon for lipogenesis during human cytomegalovirus infection.
4. ACSS2 is an important factor for promoting RCC development and is essential for cell migration and invasion, which it promotes by increasing the expression of LAMP1.
5. these findings suggest that downregulation of acetyl-CoA synthetase-2 expression is a metabolic hallmark of tumor progression and aggressive behavior in colorectal carcinoma.
6. Exogenous acetate augments Acss2/HIF-2 dependent cancer growth and metastasis in cell culture and mouse models
7. The nuclear-cytosolic acetyl-CoA synthetase 2 recaptures acetate released from histone deacetylation for recycling by histone acetyltransferases.
8. In a Honduran population, the odds of having nonsyndromic cleft lip/palate (NSCLP) among carriers of the ACSS2 variant was 4.0 with a carrier frequency of 7.1% in unrelated affected and 1.9% in unrelated unaffected individuals. In a Colombian population, the odds of having NSCLP among carriers of the ACSS2 variant was 2.6 with a carrier frequency of 10.0% in unrelated affected and 4.1% in unrelated unaffected individuals.
9. In the nucleus, ACSS2 binds to transcription factor EB and translocates to lysosomal and autophagy gene promoter regions, where ACSS2 incorporates acetate generated from histone acetylation turnover to locally produce acetyl-CoA for histone H3 acetylation in these regions and promote lysosomal biogenesis, autophagy, cell survival, and brain tumorigenesis.
10. ACSS2 is essential for glucose-independent acetate-mediated cell survival and tumor growth.

Submit: New GeneRIF Correction See all GeneRIFs (21)

https://www.ncbi.nlm.nih.gov/pubmed/?term=ACSS2%2C+Sirtuins 
https://www.ncbi.nlm.nih.gov/pubmed/?term=ACSS2%2C++hypercholesterolemia 
(Joku toinenkin on kiinnittänyt huomion ACSS- geenien  sijaintiin ja ominaisuuksiin ja  ei koodaavan pitkän RNA:n mahdolliseen  osuuteen. Otan aivan  tuoreen artikkelin pohdittavaksi. ACSS1 ja ACSS2  pitävät lyhyistä ja keskipitkistä rasvahapoista C2-C5  ensisijaisena kohteena C2 etikkahappoa.)  
https://www.ncbi.nlm.nih.gov/pubmed/31281828 

Int J Genomics. 2019 Jun 2;2019:5070975. doi: 10.1155/2019/5070975. eCollection 2019.

Identification of lncRNAs and Genes Responsible for Fatness and Fatty Acid Composition Traits between the Tibetan and Yorkshire Pigs.

Shang P¹, Li W², Liu G³, Zhang J¹, Li M¹, Wu L¹, Wang K², Chamba Y¹.

Abstract

Tibetan pigs from the Tibetan Plateau are characterized with a significant phenotypic difference relative to lowland pigs. In this study, a significant difference of the fatness and fatty acid composition traits was observed between the Tibetan and Yorkshire pigs. To uncover the involved mechanism, the expression profile of long noncoding RNAs (lncRNAs) and genes was compared between them. After serial filtered steps, 1,964 lncRNAs were obtained through our computational pipeline. In total, 63 and 715 lncRNAs and genes were identified to be differentially expressed. Evidence from cis- and trans-targeting analysis of lncRNAs demonstrated that some lncRNAs, such as MSTRG.14097 and MSTRG.8034, played important roles in the fatness and fatty acid composition traits. Bioinformatics analysis revealed that many candidate genes were responsible for the two traits. Of these, FASN, ACACA, SCD, ME3, PDHB, ACSS1, ACSS2, and ACLY were identified, which functioned in regulating the level of hexadecanoic acid, hexadecenoic acid, octadecenoic acid, and monounsaturated fatty acid. And LPGAT1, PDK4, ACAA1, and ADIPOQ were associated with the content of stearic acid, octadecadienoic acid, and polyunsaturated fatty acid. Candidate genes, which were responsible for fatness trait, consisted of FGF2, PLAG1, ADIPOQ, IRX3, MIF, IL-34, ADAM8, HMOX1, Vav1, and TLR8. In addition, association analysis also revealed that 34 and 57 genes significantly correlated to the fatness and fatty acid composition trait, respectively. Working out the mechanism caused by these lncRNAs and candidate genes is proven to be complicated but is invaluable to our understanding of fatness and fatty acid composition traits.