LOCUS       NP_061147                701 aa            linear   PRI 27-APR-2025
DEFINITION  acetyl-coenzyme A synthetase, cytoplasmic isoform 1 [Homo sapiens].
ACCESSION   NP_061147
VERSION     NP_061147.1
DBSOURCE    REFSEQ: accession NM_018677.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 701)
  AUTHORS   Mochmann,L.H., Treue,D., Bockmayr,M., Silva,P., Zasada,C.,
            Mastrobuoni,G., Bayram,S., Forbes,M., Jurmeister,P., Liebig,S.,
            Blau,O., Schleich,K., Splettstoesser,B., Nordmann,T.M., von der
            Heide,E.K., Isaakidis,K., Schulze,V., Busch,C., Siddiq,H.,
            Schlee,C., Hester,S., Fransecky,L., Neumann,M., Kempa,S.,
            Klauschen,F. and Baldus,C.D.
  TITLE     Proteomic profiling reveals ACSS2 facilitating metabolic support in
            acute myeloid leukemia
  JOURNAL   Cancer Gene Ther 31 (9), 1344-1356 (2024)
   PUBMED   38851813
  REMARK    GeneRIF: Proteomic profiling reveals ACSS2 facilitating metabolic
            support in acute myeloid leukemia.
REFERENCE   2  (residues 1 to 701)
  AUTHORS   Mukhi,D., Li,L., Liu,H., Doke,T., Kolligundla,L.P., Ha,E.,
            Kloetzer,K., Abedini,A., Mukherjee,S., Wu,J., Dhillon,P., Hu,H.,
            Guan,D., Funai,K., Uehara,K., Titchenell,P.M., Baur,J.A.,
            Wellen,K.E. and Susztak,K.
  TITLE     ACSS2 gene variants determine kidney disease risk by controlling de
            novo lipogenesis in kidney tubules
  JOURNAL   J Clin Invest 134 (4), e172963 (2023)
   PUBMED   38051585
  REMARK    GeneRIF: ACSS2 gene variants determine kidney disease risk by
            controlling de novo lipogenesis in kidney tubules.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 701)
  AUTHORS   Que,D., Kuang,F., Kang,R., Tang,D. and Liu,J.
  TITLE     ACSS2-mediated NF-kappaB activation promotes alkaliptosis in human
            pancreatic cancer cells
  JOURNAL   Sci Rep 13 (1), 1483 (2023)
   PUBMED   36707625
  REMARK    GeneRIF: ACSS2-mediated NF-kappaB activation promotes alkaliptosis
            in human pancreatic cancer cells.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 701)
  AUTHORS   Zhou,Z., Ren,Y., Yang,J., Liu,M., Shi,X., Luo,W., Fung,K.M., Xu,C.,
            Bronze,M.S., Zhang,Y., Houchen,C.W. and Li,M.
  TITLE     Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis and
            Muscle Wasting Through Metabolic Reprogramming in Pancreatic Cancer
  JOURNAL   Gastroenterology 163 (5), 1281-1293 (2022)
   PUBMED   35777482
  REMARK    GeneRIF: Acetyl-Coenzyme A Synthetase 2 Potentiates
            Macropinocytosis and Muscle Wasting Through Metabolic Reprogramming
            in Pancreatic Cancer.
REFERENCE   5  (residues 1 to 701)
  AUTHORS   Ciraku,L., Bacigalupa,Z.A., Ju,J., Moeller,R.A., Le Minh,G.,
            Lee,R.H., Smith,M.D., Ferrer,C.M., Trefely,S., Izzo,L.T.,
            Doan,M.T., Gocal,W.A., D'Agostino,L., Shi,W., Jackson,J.G.,
            Katsetos,C.D., Wellen,K.E., Snyder,N.W. and Reginato,M.J.
  TITLE     O-GlcNAc transferase regulates glioblastoma acetate metabolism via
            regulation of CDK5-dependent ACSS2 phosphorylation
  JOURNAL   Oncogene 41 (14), 2122-2136 (2022)
   PUBMED   35190642
  REMARK    GeneRIF: O-GlcNAc transferase regulates glioblastoma acetate
            metabolism via regulation of CDK5-dependent ACSS2 phosphorylation.
REFERENCE   6  (residues 1 to 701)
  AUTHORS   Talmud,P.J., Drenos,F., Shah,S., Shah,T., Palmen,J., Verzilli,C.,
            Gaunt,T.R., Pallas,J., Lovering,R., Li,K., Casas,J.P., Sofat,R.,
            Kumari,M., Rodriguez,S., Johnson,T., Newhouse,S.J., Dominiczak,A.,
            Samani,N.J., Caulfield,M., Sever,P., Stanton,A., Shields,D.C.,
            Padmanabhan,S., Melander,O., Hastie,C., Delles,C., Ebrahim,S.,
            Marmot,M.G., Smith,G.D., Lawlor,D.A., Munroe,P.B., Day,I.N.,
            Kivimaki,M., Whittaker,J., Humphries,S.E. and Hingorani,A.D.
  CONSRTM   ASCOT investigators; NORDIL investigators; BRIGHT Consortium
  TITLE     Gene-centric association signals for lipids and apolipoproteins
            identified via the HumanCVD BeadChip
  JOURNAL   Am J Hum Genet 85 (5), 628-642 (2009)
   PUBMED   19913121
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   7  (residues 1 to 701)
  AUTHORS   Yun,M., Bang,S.H., Kim,J.W., Park,J.Y., Kim,K.S. and Lee,J.D.
  TITLE     The importance of acetyl coenzyme A synthetase for 11C-acetate
            uptake and cell survival in hepatocellular carcinoma
  JOURNAL   J Nucl Med 50 (8), 1222-1228 (2009)
   PUBMED   19617323
  REMARK    GeneRIF: The patterns of (18)F-FDG and (11)C-acetate uptake seemed
            to complement each other in both human HCC and HCC cell lines.
REFERENCE   8  (residues 1 to 701)
  AUTHORS   Lu,Y., Dolle,M.E., Imholz,S., van 't Slot,R., Verschuren,W.M.,
            Wijmenga,C., Feskens,E.J. and Boer,J.M.
  TITLE     Multiple genetic variants along candidate pathways influence plasma
            high-density lipoprotein cholesterol concentrations
  JOURNAL   J Lipid Res 49 (12), 2582-2589 (2008)
   PUBMED   18660489
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   9  (residues 1 to 701)
  AUTHORS   Schwer,B., Bunkenborg,J., Verdin,R.O., Andersen,J.S. and Verdin,E.
  TITLE     Reversible lysine acetylation controls the activity of the
            mitochondrial enzyme acetyl-CoA synthetase 2
  JOURNAL   Proc Natl Acad Sci U S A 103 (27), 10224-10229 (2006)
   PUBMED   16788062
  REMARK    GeneRIF: Because the activity of a bacterial ortholog of AceCS2,
            called ACS, is controlled via deacetylation by a bacterial sirtuin
            protein, our observation highlights the conservation of a metabolic
            regulatory pathway from bacteria to humans
REFERENCE   10 (residues 1 to 701)
  AUTHORS   Luong,A., Hannah,V.C., Brown,M.S. and Goldstein,J.L.
  TITLE     Molecular characterization of human acetyl-CoA synthetase, an
            enzyme regulated by sterol regulatory element-binding proteins
  JOURNAL   J Biol Chem 275 (34), 26458-26466 (2000)
   PUBMED   10843999
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA411343.1 and BC073846.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            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].
            
            Transcript Variant: This variant (1) encodes the predominant
            isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK025990.1, BC012172.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000360596.7/ ENSP00000353804.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..701
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20q11.22"
     Protein         1..701
                     /product="acetyl-coenzyme A synthetase, cytoplasmic
                     isoform 1"
                     /EC_number="6.2.1.1"
                     /EC_number="6.2.1.17"
                     /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; propionate--CoA
                     ligase; acetyl-CoA synthetase 1"
                     /calculated_mol_wt=78449
     Region          1..107
                     /region_name="Interaction with TFEB.
                     /evidence=ECO:0000269|PubMed:28552616"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Region          1..41
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            28
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163,
                     ECO:0007744|PubMed:24275569; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            30
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648,
                     ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569;
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            36
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:24275569; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Region          45..685
                     /region_name="ACS"
                     /note="Acetyl-CoA synthetase (also known as acetate-CoA
                     ligase and acetyl-activating enzyme); cd05966"
                     /db_xref="CDD:341270"
     Site            order(191..193,219,222,224,357,362..363,385..387,411..412,
                     415,438..441,463..468,552,564,567,575..578,636,641..642)
                     /site_type="active"
                     /db_xref="CDD:341270"
     Site            order(191..193,219,222,224,357,363,385..387,411..412,415,
                     575..577,636,641)
                     /site_type="other"
                     /note="CoA binding site [chemical binding]"
                     /db_xref="CDD:341270"
     Site            263
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9QXG4; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            265
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9QXG4; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            267
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648,
                     ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
                     ECO:0007744|PubMed:24275569; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            order(313,316..321,323..324)
                     /site_type="other"
                     /note="acyl-activating enzyme (AAE) consensus motif"
                     /db_xref="CDD:341270"
     Site            order(362..363,438..441,463..468,552,564,567,578)
                     /site_type="other"
                     /note="AMP binding site [chemical binding]"
                     /db_xref="CDD:341270"
     Site            order(362..363,438..439,466)
                     /site_type="other"
                     /note="acetate binding site [chemical binding]"
                     /db_xref="CDD:341270"
     Site            418
                     /site_type="acetylation"
                     /note="N6-acetyllysine.
                     /evidence=ECO:0007744|PubMed:19608861; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Region          656..668
                     /region_name="Nuclear localization signal.
                     /evidence=ECO:0000269|PubMed:28552616"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            659
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by AMPK.
                     /evidence=ECO:0000269|PubMed:28552616; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            661
                     /site_type="acetylation"
                     /note="N6-acetyllysine.
                     /evidence=ECO:0000250|UniProtKB:Q9QXG4; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     CDS             1..701
                     /gene="ACSS2"
                     /gene_synonym="ACAS2; ACECS; AceCS1; ACS; ACSA;
                     dJ1161H23.1"
                     /coded_by="NM_018677.4:35..2140"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS13243.1"
                     /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 krscpdvqis wnqgidlwwh elmqeagdec
      301 epewcdaedp lfilytsgst gkpkgvvhtv ggymlyvatt fkyvfdfhae dvfwctadig
      361 witghsyvty gplangatsv lfegiptypd vnrlwsivdk ykvtkfytap tairllmkfg
      421 depvtkhsra slqvlgtvge pinpeawlwy hrvvgaqrcp ivdtfwqtet gghmltplpg
      481 atpmkpgsat fpffgvapai lnesgeeleg eaegylvfkq pwpgimrtvy gnherfetty
      541 fkkfpgyyvt gdgcqrdqdg yywitgridd mlnvsghlls taevesalve heavaeaavv
      601 ghphpvkgec lycfvtlcdg htfspkltee lkkqirekig piatpdyiqn apglpktrsg
      661 kimrrvlrki aqndhdlgdm stvadpsvis hlfshrclti q
//
