ID ACSS3_MOUSE Reviewed; 682 AA.
AC Q14DH7; Q8BZX0;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 27-MAR-2024, entry version 124.
DE RecName: Full=Acyl-CoA synthetase short-chain family member 3, mitochondrial;
DE EC=6.2.1.1 {ECO:0000250|UniProtKB:A0A0G2K047};
DE AltName: Full=Acetate--CoA ligase 3;
DE AltName: Full=Propionate--CoA ligase;
DE EC=6.2.1.17 {ECO:0000250|UniProtKB:A0A0G2K047};
DE Flags: Precursor;
GN Name=Acss3;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Lung;
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, and Lung;
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).
RN [5]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-513, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-519, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Catalyzes the synthesis of acetyl-CoA from short-chain fatty
CC acids (By similarity). Propionate is the preferred substrate but can
CC also utilize acetate and butyrate with a much lower affinity (By
CC similarity). {ECO:0000250|UniProtKB:A0A0G2K047}.
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:0000250|UniProtKB:A0A0G2K047};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23177;
CC Evidence={ECO:0000250|UniProtKB:A0A0G2K047};
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:A0A0G2K047};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20374;
CC Evidence={ECO:0000250|UniProtKB:A0A0G2K047};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + butanoate + CoA = AMP + butanoyl-CoA + diphosphate;
CC Xref=Rhea:RHEA:46172, ChEBI:CHEBI:17968, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57371,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:A0A0G2K047};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46173;
CC Evidence={ECO:0000250|UniProtKB:A0A0G2K047};
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:A0A0G2K047}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14DH7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14DH7-2; Sequence=VSP_031693, VSP_031694;
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AK033376; BAC28254.1; -; mRNA.
DR EMBL; AC111014; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC121946; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC134457; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113198; AAI13199.1; -; mRNA.
DR CCDS; CCDS24159.1; -. [Q14DH7-2]
DR CCDS; CCDS48688.1; -. [Q14DH7-1]
DR RefSeq; NP_001136276.1; NM_001142804.1. [Q14DH7-1]
DR RefSeq; NP_941038.2; NM_198636.3. [Q14DH7-2]
DR AlphaFoldDB; Q14DH7; -.
DR SMR; Q14DH7; -.
DR STRING; 10090.ENSMUSP00000128209; -.
DR iPTMnet; Q14DH7; -.
DR PhosphoSitePlus; Q14DH7; -.
DR jPOST; Q14DH7; -.
DR MaxQB; Q14DH7; -.
DR PaxDb; 10090-ENSMUSP00000040823; -.
DR PeptideAtlas; Q14DH7; -.
DR ProteomicsDB; 285851; -. [Q14DH7-1]
DR ProteomicsDB; 285852; -. [Q14DH7-2]
DR Antibodypedia; 29817; 137 antibodies from 27 providers.
DR DNASU; 380660; -.
DR Ensembl; ENSMUST00000044668.5; ENSMUSP00000040823.5; ENSMUSG00000035948.14. [Q14DH7-2]
DR Ensembl; ENSMUST00000165067.9; ENSMUSP00000128209.2; ENSMUSG00000035948.14. [Q14DH7-1]
DR GeneID; 380660; -.
DR KEGG; mmu:380660; -.
DR UCSC; uc007gyv.2; mouse. [Q14DH7-2]
DR UCSC; uc011xna.1; mouse. [Q14DH7-1]
DR AGR; MGI:2685720; -.
DR CTD; 79611; -.
DR MGI; MGI:2685720; Acss3.
DR VEuPathDB; HostDB:ENSMUSG00000035948; -.
DR eggNOG; KOG1175; Eukaryota.
DR GeneTree; ENSGT00940000157479; -.
DR HOGENOM; CLU_000022_3_5_1; -.
DR InParanoid; Q14DH7; -.
DR OMA; FIMGRTD; -.
DR OrthoDB; 144557at2759; -.
DR PhylomeDB; Q14DH7; -.
DR TreeFam; TF354241; -.
DR Reactome; R-MMU-77111; Synthesis of Ketone Bodies.
DR BioGRID-ORCS; 380660; 2 hits in 78 CRISPR screens.
DR ChiTaRS; Acss3; mouse.
DR PRO; PR:Q14DH7; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q14DH7; Protein.
DR Bgee; ENSMUSG00000035948; Expressed in white adipose tissue and 156 other cell types or tissues.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0003987; F:acetate-CoA ligase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047760; F:butyrate-CoA ligase activity; ISS:UniProtKB.
DR GO; GO:0050218; F:propionate-CoA ligase activity; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0044281; P:small molecule metabolic process; IEA:UniProt.
DR CDD; cd05967; PrpE; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 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_com.
DR InterPro; IPR042099; ANL_N_sf.
DR PANTHER; PTHR43347; ACYL-COA SYNTHETASE; 1.
DR PANTHER; PTHR43347:SF3; ACYL-COA SYNTHETASE SHORT-CHAIN FAMILY MEMBER 3, MITOCHONDRIAL; 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.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Ligase; Lipid metabolism;
KW Mitochondrion; Nucleotide-binding; Reference proteome; Transit peptide.
FT TRANSIT 1..29
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 30..682
FT /note="Acyl-CoA synthetase short-chain family member 3,
FT mitochondrial"
FT /id="PRO_0000320625"
FT BINDING 222..225
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT BINDING 420..422
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 441..446
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 534
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 549
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 560
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 619
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250"
FT MOD_RES 513
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 519
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT VAR_SEQ 479
FT /note="V -> GRYLLHHSAESLTPPAMGK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_031693"
FT VAR_SEQ 480..682
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_031694"
FT CONFLICT 477
FT /note="Y -> N (in Ref. 1; BAC28254)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 682 AA; 74518 MW; B865D534C631D5D1 CRC64;
MKPSWLQCRK VTGAGTLGAP LPGSPSVRGA AVTRRALVAG FGGRGCRALT TGSGGEYKTH
FAASVADPER FWGKAAEQIS WYKPWTKTLE SRYPPSTSWF VEGMLNICYN AIDRHIENGQ
GDKIAIIYDS PVTDTKATIS YKEVLEQVSK LAGVLVKQGV KKGDTVVIYM PMIPQAIYTM
LACARIGAIH SLIFGGFASK ELSTRIDHAK PKVVVTASFG IEPGRKVEYI PLLEEALRIG
QHRPDRVLIY SRPNMEKVPL MSGRDLDWEE EMAKAQSHDC VPVLSEHPLY ILYTSGTTGL
PKGVVRPTGG YAVMLNWTMS SIYGLKPGEV WWAASDLGWV VGHSYICYGP LLHGNTTVLY
EGKPVGTPDA GAYFRVLAEH GVAALFTAPT AIRAIRQQDP GAALGKQYSL TRFKTLFVAG
ERCDVETLEW SKKVFRVPVL DHWWQTETGS PITASCIGLG NSKTPPPGQA GKCVPGYNVM
ILDDNMQKLK ARSLGNIVVK LPLPPGAFSG LWKNQEAFKH LYFEKFPGYY DTMDAGYMDE
EGYLYVMSRV DDVINVAGHR ISAGAIEESV LSHGTVADCA VVGKEDPLKG HVPLALCVLK
KDVNASEEQV LEEIVKHVRQ SIGPVAAFRN AVFVKQLPKT RSGKIPRSTL SALVNGKPYK
VTPTIEDPSI FGHIEEVLKQ AV
//
