ACSA_MOUSE
ID ACSA_MOUSE Reviewed; 701 AA.
AC Q9QXG4; Q8BK97;
DT 03-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Acetyl-coenzyme A synthetase, cytoplasmic;
DE EC=6.2.1.1 {ECO:0000269|PubMed:11150295, ECO:0000269|PubMed:16790548};
DE AltName: Full=Acetate--CoA ligase;
DE AltName: Full=Acetyl-CoA synthetase;
DE Short=ACS;
DE Short=AceCS;
DE AltName: Full=Acetyl-CoA synthetase 1 {ECO:0000303|PubMed:11150295, ECO:0000303|PubMed:16790548};
DE Short=AceCS1 {ECO:0000303|PubMed:11150295, ECO:0000303|PubMed:16790548};
DE AltName: Full=Acyl-CoA synthetase short-chain family member 2;
DE AltName: Full=Acyl-activating enzyme;
DE AltName: Full=Propionate--CoA ligase;
DE EC=6.2.1.17 {ECO:0000269|PubMed:11150295};
GN Name=Acss2; Synonyms=Acas2, Acecs1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12049778; DOI=10.1016/s0925-4773(02)00097-7;
RA Loikkanen I., Haghighi S., Vainio S., Pajunen A.;
RT "Expression of cytosolic acetyl-CoA synthetase gene is developmentally
RT regulated.";
RL Mech. Dev. 115:139-141(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=11150295; DOI=10.1074/jbc.m008782200;
RA Fujino T., Kondo J., Ishikawa M., Morikawa K., Yamamoto T.T.;
RT "Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the
RT oxidation of acetate.";
RL J. Biol. Chem. 276:11420-11426(2001).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, ACETYLATION AT LYS-661,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16790548; DOI=10.1073/pnas.0604392103;
RA Hallows W.C., Lee S., Denu J.M.;
RT "Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10230-10235(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263 AND SER-267, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30; SER-263; SER-265 AND
RP SER-267, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the synthesis of acetyl-CoA from short-chain fatty
CC acids (PubMed:11150295, PubMed:16790548). Acetate is the preferred
CC substrate but can also utilize propionate with a much lower affinity
CC (PubMed:11150295). {ECO:0000269|PubMed:11150295,
CC ECO:0000269|PubMed:16790548}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate;
CC Xref=Rhea:RHEA:23176, ChEBI:CHEBI:30089, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:456215; EC=6.2.1.1;
CC Evidence={ECO:0000269|PubMed:11150295, ECO:0000269|PubMed:16790548};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23177;
CC Evidence={ECO:0000305|PubMed:11150295, ECO:0000305|PubMed:16790548};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + propanoate = AMP + diphosphate + propanoyl-CoA;
CC Xref=Rhea:RHEA:20373, ChEBI:CHEBI:17272, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57392,
CC ChEBI:CHEBI:456215; EC=6.2.1.17;
CC Evidence={ECO:0000269|PubMed:11150295};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20374;
CC Evidence={ECO:0000305|PubMed:11150295};
CC -!- ACTIVITY REGULATION: Inhibited by acetylation at Lys-661 and activated
CC by deacetylation mediated by the deacetylases SIRT1 and SIRT3.
CC {ECO:0000269|PubMed:16790548}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.11 mM for acetate {ECO:0000269|PubMed:11150295};
CC KM=3.4 mM for propionate {ECO:0000269|PubMed:11150295};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9NR19}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11150295}.
CC -!- PTM: Reversibly acetylated at Lys-661 (PubMed:16790548). The acetyl-CoA
CC synthase activity is inhibited by acetylation and activated by
CC deacetylation mediated by the deacetylases SIRT1 and SIRT3.
CC {ECO:0000269|PubMed:16790548}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AF216873; AAF24510.1; -; mRNA.
DR EMBL; AK053877; BAC35571.1; -; mRNA.
DR EMBL; AL844852; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC051432; AAH51432.1; -; mRNA.
DR CCDS; CCDS16950.1; -.
DR RefSeq; NP_062785.2; NM_019811.3.
DR AlphaFoldDB; Q9QXG4; -.
DR SMR; Q9QXG4; -.
DR BioGRID; 208597; 2.
DR DIP; DIP-61210N; -.
DR IntAct; Q9QXG4; 3.
DR STRING; 10090.ENSMUSP00000029135; -.
DR ChEMBL; CHEMBL2924; -.
DR iPTMnet; Q9QXG4; -.
DR PhosphoSitePlus; Q9QXG4; -.
DR SwissPalm; Q9QXG4; -.
DR EPD; Q9QXG4; -.
DR jPOST; Q9QXG4; -.
DR MaxQB; Q9QXG4; -.
DR PaxDb; Q9QXG4; -.
DR PRIDE; Q9QXG4; -.
DR ProteomicsDB; 285543; -.
DR Antibodypedia; 1332; 450 antibodies from 33 providers.
DR DNASU; 60525; -.
DR Ensembl; ENSMUST00000029135; ENSMUSP00000029135; ENSMUSG00000027605.
DR GeneID; 60525; -.
DR KEGG; mmu:60525; -.
DR UCSC; uc008nku.1; mouse.
DR CTD; 55902; -.
DR MGI; MGI:1890410; Acss2.
DR VEuPathDB; HostDB:ENSMUSG00000027605; -.
DR eggNOG; KOG1175; Eukaryota.
DR GeneTree; ENSGT00940000156358; -.
DR HOGENOM; CLU_000022_3_6_1; -.
DR InParanoid; Q9QXG4; -.
DR OMA; DHWWHDL; -.
DR OrthoDB; 288915at2759; -.
DR TreeFam; TF300417; -.
DR Reactome; R-MMU-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-MMU-71384; Ethanol oxidation.
DR BioGRID-ORCS; 60525; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Acss2; mouse.
DR PRO; PR:Q9QXG4; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9QXG4; protein.
DR Bgee; ENSMUSG00000027605; Expressed in aorta tunica adventitia and 249 other tissues.
DR ExpressionAtlas; Q9QXG4; baseline and differential.
DR Genevisible; Q9QXG4; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0003987; F:acetate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0050218; F:propionate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0019413; P:acetate biosynthetic process; ISO:MGI.
DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; IDA:MGI.
DR GO; GO:0008610; P:lipid biosynthetic process; ISO:MGI.
DR GO; GO:0019542; P:propionate biosynthetic process; ISO:MGI.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR032387; ACAS_N.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF16177; ACAS_N; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cytoplasm; Ligase; Lipid metabolism;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..701
FT /note="Acetyl-coenzyme A synthetase, cytoplasmic"
FT /id="PRO_0000208424"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..24
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 219..222
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT BINDING 363
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT BINDING 439..441
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 463..468
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 552
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 567
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 575
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT BINDING 636
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 418
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NR19"
FT MOD_RES 661
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:16790548"
FT CONFLICT 498..500
FT /note="PAI -> LQS (in Ref. 1; AAF24510)"
FT /evidence="ECO:0000305"
FT CONFLICT 655..657
FT /note="PKT -> LKP (in Ref. 1; AAF24510)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 701 AA; 78862 MW; D1EA6312CD4527D7 CRC64;
MGLPEERRKS GSGSRAREET GAEGRVRGWS PPPEVRRSAH VPSLQRYREL HRRSVEEPRE
FWGNIAKEFY WKTACPGPFL QYNFDVTKGK IFTEWMKGAT TNICYNVLDR NVHEKKLGDK
VAFYWEGNEP GETTKITYRE LLVQVCQFSN VLRKQGIQKG DRVAIYMPMI LELVVAMLAC
ARLGALHSIV FAGFSAESLC ERILDSSCCL LITTDAFYRG EKLVNLKELA DESLEKCREK
GFPVRCCIVV KHLGRAELGM NDSPSQSPPV KRPCPDVQIC WNEGVDLWWH ELMQQAGDEC
EPEWCDAEDP LFILYTSGST GKPKGVVHTI GGYMLYVATT FKYVFDFHPE DVFWCTADIG
WITGHSYVTY GPLANGATSV LFEGIPTYPD EGRLWSIVDK YKVTKFYTAP TAIRMLMKFG
DDPVTKHSRA SLQVLGTVGE PINPEAWLWY HRVVGSQRCP IVDTFWQTET GGHMLTPLPG
ATPMKPGSAS FPFFGVAPAI LNESGEELEG EAEGYLVFKQ PWPGIMRTVY GNHTRFETTY
FKKFPGYYVT GDGCRRDQDG YYWITGRIDD MLNVSGHLLS TAEVESALVE HEAVAEAAVV
GHPHPVKGEC LYCFVTLCDG HTFSPTLTEE LKKQIREKIG PIATPDYIQN APGLPKTRSG
KIMRRVLRKI AQNDHDLGDT STVADPSVIN HLFSHRCLTT Q
