ID ACSA_HUMAN Reviewed; 701 AA. AC Q9NR19; A6NE90; Q5QPH2; Q5QPH3; Q8N238; Q96EL0; Q9NQP7; Q9UJ15; DT 03-APR-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 27-MAR-2024, entry version 181. DE RecName: Full=Acetyl-coenzyme A synthetase, cytoplasmic; DE EC=6.2.1.1 {ECO:0000269|PubMed:10843999, ECO:0000269|PubMed:28003429, ECO:0000269|PubMed:28552616}; 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:0000250|UniProtKB:Q9QXG4}; DE Short=AceCS1 {ECO:0000250|UniProtKB:Q9QXG4}; 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:0000250|UniProtKB:Q9QXG4}; GN Name=ACSS2; Synonyms=ACAS2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=10843999; DOI=10.1074/jbc.m004160200; RA Luong A., Hannah V.C., Brown M.S., Goldstein J.L.; RT "Molecular characterization of human acetyl-CoA synthetase, an enzyme RT regulated by sterol regulatory element-binding proteins."; RL J. Biol. Chem. 275:26458-26466(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Skin; 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 [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30 AND SER-267, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-418, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-267, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28; SER-30 AND SER-267, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28; SER-30; SER-36 AND RP SER-267, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=28003429; DOI=10.1093/jb/mvw067; RA Yoshimura Y., Araki A., Maruta H., Takahashi Y., Yamashita H.; RT "Molecular cloning of rat acss3 and characterization of mammalian RT propionyl-CoA synthetase in the liver mitochondrial matrix."; RL J. Biochem. 161:279-289(2017). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-659, MUTAGENESIS OF RP THR-363; SER-659 AND 664-ARG--ARG-665, SUBCELLULAR LOCATION, NUCLEOLAR RP LOCALIZATION SIGNAL, AND INTERACTION WITH PRKAA2; TFEB AND KPAN1. RX PubMed=28552616; DOI=10.1016/j.molcel.2017.04.026; RA Li X., Yu W., Qian X., Xia Y., Zheng Y., Lee J.H., Li W., Lyu J., Rao G., RA Zhang X., Qian C.N., Rozen S.G., Jiang T., Lu Z.; RT "Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal RT Biogenesis and Autophagy."; RL Mol. Cell 66:684-697(2017). CC -!- FUNCTION: Catalyzes the synthesis of acetyl-CoA from short-chain fatty CC acids (PubMed:10843999, PubMed:28003429, PubMed:28552616). Acetate is CC the preferred substrate (PubMed:10843999, PubMed:28003429). Can also CC utilize propionate with a much lower affinity (By similarity). Nuclear CC ACSS2 promotes glucose deprivation-induced lysosomal biogenesis and CC autophagy, tumor cell survival and brain tumorigenesis CC (PubMed:28552616). Glucose deprivation results in AMPK-mediated CC phosphorylation of ACSS2 leading to its translocation to the nucleus CC where it binds to TFEB and locally produces acetyl-CoA for histone CC acetylation in the promoter regions of TFEB target genes thereby CC activating their transcription (PubMed:28552616). The regulation of CC genes associated with autophagy and lysosomal activity through ACSS2 is CC important for brain tumorigenesis and tumor survival (PubMed:28552616). CC Acts as a chromatin-bound transcriptional coactivator that up-regulates CC histone acetylation and expression of neuronal genes (By similarity). CC Can be recruited to the loci of memory-related neuronal genes to CC maintain a local acetyl-CoA pool, providing the substrate for histone CC acetylation and promoting the expression of specific genes, which is CC essential for maintaining long-term spatial memory (By similarity). CC {ECO:0000250|UniProtKB:Q9QXG4, ECO:0000269|PubMed:10843999, CC ECO:0000269|PubMed:28003429, ECO:0000269|PubMed:28552616}. 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:10843999, ECO:0000269|PubMed:28003429, CC ECO:0000269|PubMed:28552616}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23177; CC Evidence={ECO:0000305|PubMed:10843999, ECO:0000305|PubMed:28003429}; 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:0000250|UniProtKB:Q9QXG4}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20374; CC Evidence={ECO:0000250|UniProtKB:Q9QXG4}; CC -!- ACTIVITY REGULATION: Inhibited by acetylation at Lys-661 and activated CC by deacetylation mediated by the deacetylases SIRT1 and SIRT3. CC {ECO:0000250|UniProtKB:Q9QXG4}. CC -!- SUBUNIT: Monomer (PubMed:10843999). Interacts with TFEB CC (PubMed:28552616). AMPK-mediated phosphorylated form at Ser-659 CC interacts with KPNA1; this interaction results in nuclear translocation CC of ACSS2 (PubMed:28552616). Interacts with the 'Thr-172' phosphorylated CC form of PRKAA2 (PubMed:28552616). Interacts with CREBBP (By CC similarity). {ECO:0000250|UniProtKB:Q9QXG4, CC ECO:0000269|PubMed:10843999, ECO:0000269|PubMed:28552616}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10843999, CC ECO:0000269|PubMed:28003429, ECO:0000269|PubMed:28552616}. Cytoplasm CC {ECO:0000250|UniProtKB:Q9QXG4}. Nucleus {ECO:0000269|PubMed:28552616}. CC Note=Glucose deprivation results in its AMPK-dependent phosphorylation CC and subsequent nuclear translocation (PubMed:28552616). Phosphorylation CC at Ser-659, leads to exposure of its nuclear localization signal which CC is required for its interaction with KPNA1 and subsequent translocation CC to the nucleus (PubMed:28552616). Found in the cytoplasm in CC undifferentiated neurons and upon differentiation, translocates to CC nucleus (By similarity). {ECO:0000250|UniProtKB:Q9QXG4, CC ECO:0000269|PubMed:28552616}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NR19-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NR19-2; Sequence=VSP_046376; CC -!- PTM: Reversibly acetylated at Lys-661 (By similarity). The acetyl-CoA CC synthase activity is inhibited by acetylation and activated by CC deacetylation mediated by the deacetylases SIRT1 and SIRT3 (By CC similarity). {ECO:0000250|UniProtKB:Q9QXG4}. CC -!- PTM: Glucose deprivation results in its AMPK-dependent phosphorylation CC at Ser-659, which leads to exposure of its nuclear localization signal, CC required for its interaction with KPNA1 and subsequent translocation to CC the nucleus. {ECO:0000269|PubMed:28552616}. CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF263614; AAF75064.1; -; mRNA. DR EMBL; AK092281; BAC03849.1; -; mRNA. DR EMBL; AL133324; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL049709; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471077; EAW76248.1; -; Genomic_DNA. DR EMBL; BC012172; AAH12172.1; -; mRNA. DR CCDS; CCDS13243.1; -. [Q9NR19-1] DR CCDS; CCDS42868.2; -. [Q9NR19-2] DR RefSeq; NP_001070020.2; NM_001076552.2. [Q9NR19-2] DR RefSeq; NP_061147.1; NM_018677.3. [Q9NR19-1] DR AlphaFoldDB; Q9NR19; -. DR SMR; Q9NR19; -. DR BioGRID; 120989; 14. DR IntAct; Q9NR19; 5. DR STRING; 9606.ENSP00000253382; -. DR BindingDB; Q9NR19; -. DR ChEMBL; CHEMBL4523467; -. DR DrugBank; DB00131; Adenosine phosphate. DR DrugBank; DB00171; ATP. DR DrugBank; DB09395; Sodium acetate. DR GuidetoPHARMACOLOGY; 3128; -. DR SwissLipids; SLP:000001167; -. DR GlyGen; Q9NR19; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NR19; -. DR PhosphoSitePlus; Q9NR19; -. DR SwissPalm; Q9NR19; -. DR BioMuta; ACSS2; -. DR DMDM; 20137525; -. DR EPD; Q9NR19; -. DR jPOST; Q9NR19; -. DR MassIVE; Q9NR19; -. DR MaxQB; Q9NR19; -. DR PaxDb; 9606-ENSP00000253382; -. DR PeptideAtlas; Q9NR19; -. DR ProteomicsDB; 63659; -. DR ProteomicsDB; 82253; -. [Q9NR19-1] DR Pumba; Q9NR19; -. DR Antibodypedia; 1332; 515 antibodies from 33 providers. DR DNASU; 55902; -. DR Ensembl; ENST00000253382.5; ENSP00000253382.5; ENSG00000131069.20. [Q9NR19-2] DR Ensembl; ENST00000360596.7; ENSP00000353804.2; ENSG00000131069.20. [Q9NR19-1] DR GeneID; 55902; -. DR KEGG; hsa:55902; -. DR MANE-Select; ENST00000360596.7; ENSP00000353804.2; NM_018677.4; NP_061147.1. DR UCSC; uc002xbd.3; human. [Q9NR19-1] DR AGR; HGNC:15814; -. DR CTD; 55902; -. DR DisGeNET; 55902; -. DR GeneCards; ACSS2; -. DR HGNC; HGNC:15814; ACSS2. DR HPA; ENSG00000131069; Tissue enhanced (skeletal). DR MalaCards; ACSS2; -. DR MIM; 605832; gene. DR neXtProt; NX_Q9NR19; -. DR OpenTargets; ENSG00000131069; -. DR PharmGKB; PA24429; -. DR VEuPathDB; HostDB:ENSG00000131069; -. DR eggNOG; KOG1175; Eukaryota. DR GeneTree; ENSGT00940000156358; -. DR HOGENOM; CLU_000022_3_6_1; -. DR InParanoid; Q9NR19; -. DR OMA; INVSYNC; -. DR OrthoDB; 144557at2759; -. DR PhylomeDB; Q9NR19; -. DR TreeFam; TF300417; -. DR BioCyc; MetaCyc:HS05484-MONOMER; -. DR BRENDA; 6.2.1.1; 2681. DR PathwayCommons; Q9NR19; -. DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis. DR Reactome; R-HSA-71384; Ethanol oxidation. DR SignaLink; Q9NR19; -. DR SIGNOR; Q9NR19; -. DR BioGRID-ORCS; 55902; 8 hits in 1163 CRISPR screens. DR ChiTaRS; ACSS2; human. DR GeneWiki; ACSS2; -. DR GenomeRNAi; 55902; -. DR Pharos; Q9NR19; Tchem. DR PRO; PR:Q9NR19; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q9NR19; Protein. DR Bgee; ENSG00000131069; Expressed in ileal mucosa and 180 other cell types or tissues. DR ExpressionAtlas; Q9NR19; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003987; F:acetate-CoA ligase activity; IDA:UniProtKB. DR GO; GO:0016208; F:AMP binding; IC:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0050218; F:propionate-CoA ligase activity; ISS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB. DR GO; GO:0019413; P:acetate biosynthetic process; IEA:Ensembl. DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; IBA:GO_Central. DR GO; GO:0019427; P:acetyl-CoA biosynthetic process from acetate; IEA:InterPro. DR GO; GO:0006069; P:ethanol oxidation; TAS:Reactome. DR GO; GO:0008610; P:lipid biosynthetic process; IMP:UniProtKB. DR GO; GO:0007616; P:long-term memory; ISS:UniProtKB. DR GO; GO:0035066; P:positive regulation of histone acetylation; ISS:UniProtKB. DR GO; GO:0019542; P:propionate biosynthetic process; IEA:Ensembl. DR CDD; cd05966; ACS; 1. DR Gene3D; 3.30.300.30; -; 1. DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1. DR InterPro; IPR011904; Ac_CoA_lig. 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_com. DR InterPro; IPR042099; ANL_N_sf. DR NCBIfam; TIGR02188; Ac_CoA_lig_AcsA; 1. DR PANTHER; PTHR24095; ACETYL-COENZYME A SYNTHETASE; 1. DR PANTHER; PTHR24095:SF126; ACETYL-COENZYME A SYNTHETASE, CYTOPLASMIC; 1. DR Pfam; PF16177; ACAS_N; 1. DR Pfam; PF00501; AMP-binding; 1. DR Pfam; PF13193; AMP-binding_C; 1. DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1. DR PROSITE; PS00455; AMP_BINDING; 1. DR Genevisible; Q9NR19; HS. PE 1: Evidence at protein level; KW Acetylation; Activator; Alternative splicing; ATP-binding; Cytoplasm; KW Ligase; Lipid metabolism; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation. FT CHAIN 1..701 FT /note="Acetyl-coenzyme A synthetase, cytoplasmic" FT /id="PRO_0000208423" FT REGION 1..107 FT /note="Interaction with TFEB" FT /evidence="ECO:0000269|PubMed:28552616" FT REGION 1..41 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 656..668 FT /note="Nuclear localization signal" FT /evidence="ECO:0000269|PubMed:28552616" 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 28 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 30 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 36 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 263 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QXG4" FT MOD_RES 265 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QXG4" FT MOD_RES 267 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 418 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 659 FT /note="Phosphoserine; by AMPK" FT /evidence="ECO:0000269|PubMed:28552616" FT MOD_RES 661 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9QXG4" FT VAR_SEQ 277 FT /note="V -> VQGKLKEKSKRVQP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046376" FT MUTAGEN 363 FT /note="T->A: Loss of catalytic activity but no effect on FT its nuclear translocation upon glucose deprivation. Loss of FT ability to promote gene transcription for lysosomal FT biogenesis and autophagy." FT /evidence="ECO:0000269|PubMed:28552616" FT MUTAGEN 659 FT /note="S->A: No effect on catalytic activity. Loss of FT AMPK-mediated phosphorylation, interaction with KPNA1 and FT nuclear translocation upon glucose deprivation. Loss of FT ability to promote gene transcription for lysosomal FT biogenesis and autophagy." FT /evidence="ECO:0000269|PubMed:28552616" FT MUTAGEN 664..665 FT /note="RR->AA: No effect on catalytic activity. Loss of FT interaction with KPNA1 and nuclear translocation upon FT glucose deprivation. Loss of ability to promote gene FT transcription for lysosomal biogenesis and autophagy." FT /evidence="ECO:0000269|PubMed:28552616" FT CONFLICT 79 FT /note="F -> L (in Ref. 2; BAC03849)" FT /evidence="ECO:0000305" FT CONFLICT 615 FT /note="V -> F (in Ref. 5; AAH12172)" FT /evidence="ECO:0000305" FT CONFLICT 680 FT /note="M -> L (in Ref. 2; BAC03849)" FT /evidence="ECO:0000305" SQ SEQUENCE 701 AA; 78580 MW; 833580B41B73A8B4 CRC64; MGLPEERVRS GSGSRGQEEA GAGGRARSWS PPPEVSRSAH VPSLQRYREL HRRSVEEPRE FWGDIAKEFY WKTPCPGPFL RYNFDVTKGK IFIEWMKGAT TNICYNVLDR NVHEKKLGDK VAFYWEGNEP GETTQITYHQ LLVQVCQFSN VLRKQGIQKG DRVAIYMPMI PELVVAMLAC ARIGALHSIV FAGFSSESLC ERILDSSCSL LITTDAFYRG EKLVNLKELA DEALQKCQEK GFPVRCCIVV KHLGRAELGM GDSTSQSPPI KRSCPDVQIS WNQGIDLWWH ELMQEAGDEC EPEWCDAEDP LFILYTSGST GKPKGVVHTV GGYMLYVATT FKYVFDFHAE DVFWCTADIG WITGHSYVTY GPLANGATSV LFEGIPTYPD VNRLWSIVDK YKVTKFYTAP TAIRLLMKFG DEPVTKHSRA SLQVLGTVGE PINPEAWLWY HRVVGAQRCP IVDTFWQTET GGHMLTPLPG ATPMKPGSAT FPFFGVAPAI LNESGEELEG EAEGYLVFKQ PWPGIMRTVY GNHERFETTY FKKFPGYYVT GDGCQRDQDG YYWITGRIDD MLNVSGHLLS TAEVESALVE HEAVAEAAVV GHPHPVKGEC LYCFVTLCDG HTFSPKLTEE LKKQIREKIG PIATPDYIQN APGLPKTRSG KIMRRVLRKI AQNDHDLGDM STVADPSVIS HLFSHRCLTI Q //