ACS2L_MOUSE
ID ACS2L_MOUSE Reviewed; 682 AA.
AC Q99NB1; Q8K0M6;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Acetyl-coenzyme A synthetase 2-like, mitochondrial;
DE EC=6.2.1.1 {ECO:0000269|PubMed:11150295, ECO:0000269|PubMed:16790548};
DE AltName: Full=Acetate--CoA ligase 2;
DE AltName: Full=Acetyl-CoA synthetase 2 {ECO:0000303|PubMed:11150295, ECO:0000303|PubMed:16790548};
DE Short=AceCS2 {ECO:0000303|PubMed:11150295, ECO:0000303|PubMed:16790548};
DE AltName: Full=Acyl-CoA synthetase short-chain family member 1;
DE AltName: Full=Propionate--CoA ligase;
DE EC=6.2.1.17 {ECO:0000269|PubMed:11150295};
DE Flags: Precursor;
GN Name=Acss1; Synonyms=Acas2, Acas2l;
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], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, AND INDUCTION.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Thymus;
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 MRNA] OF 262-682.
RC TISSUE=Salivary gland;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, ACETYLATION AT LYS-635,
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 [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19187775; DOI=10.1016/j.cmet.2008.12.008;
RA Sakakibara I., Fujino T., Ishii M., Tanaka T., Shimosawa T., Miura S.,
RA Zhang W., Tokutake Y., Yamamoto J., Awano M., Iwasaki S., Motoike T.,
RA Okamura M., Inagaki T., Kita K., Ezaki O., Naito M., Kuwaki T., Chohnan S.,
RA Yamamoto T.T., Hammer R.E., Kodama T., Yanagisawa M., Sakai J.;
RT "Fasting-induced hypothermia and reduced energy production in mice lacking
RT acetyl-CoA synthetase 2.";
RL Cell Metab. 9:191-202(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, 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 (PubMed:11150295, PubMed:16790548). Can also utilize
CC propionate with a much lower affinity (PubMed:11150295). Provides
CC acetyl-CoA that is utilized mainly for oxidation under ketogenic
CC conditions (PubMed:11150295). Involved in thermogenesis under ketogenic
CC conditions, using acetate as a vital fuel when carbohydrate
CC availability is insufficient (PubMed:19187775).
CC {ECO:0000269|PubMed:11150295, ECO:0000269|PubMed:16790548,
CC ECO:0000269|PubMed:19187775}.
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-635 and activated
CC by deacetylation mediated by the deacetylase SIRT3.
CC {ECO:0000269|PubMed:16790548}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.06 mM for acetate {ECO:0000269|PubMed:11150295};
CC KM=4.1 mM for propionate {ECO:0000269|PubMed:11150295};
CC -!- SUBUNIT: Interacts with SIRT3. {ECO:0000250|UniProtKB:Q9NUB1}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:11150295}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, testis, kidney, skeletal
CC muscle, lung and spleen. Detected at low levels in brain.
CC {ECO:0000269|PubMed:11150295}.
CC -!- INDUCTION: By fasting. {ECO:0000269|PubMed:11150295}.
CC -!- PTM: Reversibly acetylated at Lys-635 (PubMed:16790548). The acetyl-CoA
CC synthase activity is inhibited by acetylation and activated by
CC deacetylation mediated by the deacetylase SIRT3.
CC {ECO:0000269|PubMed:16790548}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype at birth, but exhibit
CC significant growth retardation at the time of weaning. Attain normal
CC size and weight when fed normally. Exhibit hypothermia and hypoglycemia
CC when fed high-fat, low-carbohydrate diet, leading to 50% mortality.
CC Display strongly reduced whole-body acetate oxidation when fasting.
CC Fasting adults exhibit hypothermia, reduced capacity to sustain running
CC and low ATP levels. {ECO:0000269|PubMed:19187775}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH30930.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB046742; BAB21612.1; -; mRNA.
DR EMBL; AK088244; BAC40232.1; -; mRNA.
DR EMBL; BC030930; AAH30930.1; ALT_INIT; mRNA.
DR CCDS; CCDS16859.1; -.
DR RefSeq; NP_542142.1; NM_080575.2.
DR AlphaFoldDB; Q99NB1; -.
DR SMR; Q99NB1; -.
DR BioGRID; 213026; 2.
DR DIP; DIP-61209N; -.
DR IntAct; Q99NB1; 6.
DR MINT; Q99NB1; -.
DR STRING; 10090.ENSMUSP00000028944; -.
DR iPTMnet; Q99NB1; -.
DR PhosphoSitePlus; Q99NB1; -.
DR EPD; Q99NB1; -.
DR jPOST; Q99NB1; -.
DR MaxQB; Q99NB1; -.
DR PaxDb; Q99NB1; -.
DR PRIDE; Q99NB1; -.
DR ProteomicsDB; 285542; -.
DR Antibodypedia; 24959; 141 antibodies from 24 providers.
DR DNASU; 68738; -.
DR Ensembl; ENSMUST00000028944; ENSMUSP00000028944; ENSMUSG00000027452.
DR GeneID; 68738; -.
DR KEGG; mmu:68738; -.
DR UCSC; uc008muf.2; mouse.
DR CTD; 84532; -.
DR MGI; MGI:1915988; Acss1.
DR VEuPathDB; HostDB:ENSMUSG00000027452; -.
DR eggNOG; KOG1175; Eukaryota.
DR GeneTree; ENSGT00940000158550; -.
DR HOGENOM; CLU_000022_3_6_1; -.
DR InParanoid; Q99NB1; -.
DR OMA; AIKASWP; -.
DR OrthoDB; 288915at2759; -.
DR PhylomeDB; Q99NB1; -.
DR TreeFam; TF354241; -.
DR BRENDA; 6.2.1.1; 3474.
DR Reactome; R-MMU-71384; Ethanol oxidation.
DR BioGRID-ORCS; 68738; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Acss1; mouse.
DR PRO; PR:Q99NB1; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q99NB1; protein.
DR Bgee; ENSMUSG00000027452; Expressed in submandibular gland and 257 other tissues.
DR ExpressionAtlas; Q99NB1; baseline and differential.
DR Genevisible; Q99NB1; MM.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0003987; F:acetate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0016208; F:AMP binding; IEA:InterPro.
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:0019427; P:acetyl-CoA biosynthetic process from acetate; IEA:InterPro.
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; 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.
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 TIGRFAMs; TIGR02188; Ac_CoA_lig_AcsA; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Ligase; Lipid metabolism; Mitochondrion;
KW Nucleotide-binding; Reference proteome; Transit peptide.
FT TRANSIT 1..38
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 39..682
FT /note="Acetyl-coenzyme A synthetase 2-like, mitochondrial"
FT /id="PRO_0000000597"
FT BINDING 217..220
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT BINDING 334
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT BINDING 410..412
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 434..439
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 526
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 541
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 549
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT BINDING 552
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 389
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUB1"
FT MOD_RES 635
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:16790548"
FT CONFLICT 332
FT /note="W -> C (in Ref. 3; AAH30930)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 682 AA; 74623 MW; 1B21981D29F9C8E7 CRC64;
MAARSLGSGV GRLLRGLQGR SGQSGWSLSV SRSTATRLPG CVPAAAQPGS YPALSAQAAQ
EPAAFWGPLA RDTLVWDTPY HTVWDCDFRT GKIGWFLGGQ LNVSVNCLDQ HVQKSPETIA
LIWERDEPGT EVRITYRELL ETTCRLANTL KRHGVHRGDR VAIYMPVSPL AVAAMLACAR
IGAIHTVVFA GFSAESLAGR INDAKCKAVI TFNQGLRGGR VVELKKIVDE AVKSCPTVQH
VLVAHRTDTK VPMGSLDIPL EQEMAKEAPV CTPESMSSED MLFMLYTSGS TGTPKGLVHT
QAGYLLYAAM THKLVFDYQP GDVFGCVADI GWITGHSYVV YGPLCNGATT VLFESTPVYP
DAGRYWETVQ RLKINQFYGA PTAVRLLLKY GDAWVKKYDR SSLRTLGSVG EPINHEAWEW
LHKVVGDGRC TLVDTWWQTE TGGICIAPRP SEDGAEILPG MAMRPFFGIV PVLMDEKGNV
LEGGDVSGAL CISQAWPGMA RTIYGDHQRF VDAYFRAYPG YYFTGDGAHR TEGGYYQITG
RMDDVINISG HRLGTAEIED AMADHPAVPE TAVIGYPHDI KGEAAFAFIV LKDNISDENM
VVNELKLSVA TKIAKYAVPD QILVVKRLPK TRSGKVMRRL LRKIITSRGQ DLGDTTTLED
PSVITEILSA FQKYEEQRAA TN
