ID ACSS3_HUMAN Reviewed; 686 AA. AC Q9H6R3; Q8NC66; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 27-MAR-2024, entry version 165. 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=Acyl-CoA synthetase short-chain family member 3; DE AltName: Full=Propionate--CoA ligase; DE EC=6.2.1.17 {ECO:0000269|PubMed:28003429}; DE Flags: Precursor; GN Name=ACSS3; 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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Hepatoma, and Teratocarcinoma; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle; 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, AND NOMENCLATURE. RX PubMed=17762044; DOI=10.1194/jlr.m700378-jlr200; RA Watkins P.A., Maiguel D., Jia Z., Pevsner J.; RT "Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human RT genome."; RL J. Lipid Res. 48:2736-2750(2007). RN [5] 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 [6] RP 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 [7] 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). CC -!- FUNCTION: Catalyzes the synthesis of acetyl-CoA from short-chain fatty CC acids (PubMed:28003429). Propionate is the preferred substrate CC (PubMed:28003429). Can utilize acetate and butyrate with a much lower CC affinity (By similarity). {ECO:0000250|UniProtKB:A0A0G2K047, CC ECO:0000269|PubMed:28003429}. 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:0000269|PubMed:28003429}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20374; CC Evidence={ECO:0000305|PubMed:28003429}; 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 -!- INTERACTION: CC Q9H6R3; Q96CV9: OPTN; NbExp=3; IntAct=EBI-3921478, EBI-748974; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:28003429}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9H6R3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H6R3-2; Sequence=VSP_031692; 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; AK025616; BAB15190.1; -; mRNA. DR EMBL; AK074938; BAC11304.1; -; mRNA. DR EMBL; CH471054; EAW97372.1; -; Genomic_DNA. DR EMBL; BC009317; AAH09317.1; -; mRNA. DR EMBL; BC015769; AAH15769.1; -; mRNA. DR CCDS; CCDS9022.1; -. [Q9H6R3-1] DR RefSeq; NP_001317171.1; NM_001330242.1. DR RefSeq; NP_001317172.1; NM_001330243.1. [Q9H6R3-2] DR RefSeq; NP_078836.1; NM_024560.3. [Q9H6R3-1] DR AlphaFoldDB; Q9H6R3; -. DR SMR; Q9H6R3; -. DR BioGRID; 122745; 7. DR IntAct; Q9H6R3; 2. DR STRING; 9606.ENSP00000449535; -. DR GlyGen; Q9H6R3; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9H6R3; -. DR PhosphoSitePlus; Q9H6R3; -. DR BioMuta; ACSS3; -. DR DMDM; 74752698; -. DR EPD; Q9H6R3; -. DR jPOST; Q9H6R3; -. DR MassIVE; Q9H6R3; -. DR MaxQB; Q9H6R3; -. DR PaxDb; 9606-ENSP00000449535; -. DR PeptideAtlas; Q9H6R3; -. DR ProteomicsDB; 81014; -. [Q9H6R3-1] DR ProteomicsDB; 81015; -. [Q9H6R3-2] DR Pumba; Q9H6R3; -. DR TopDownProteomics; Q9H6R3-1; -. [Q9H6R3-1] DR Antibodypedia; 29817; 137 antibodies from 27 providers. DR DNASU; 79611; -. DR Ensembl; ENST00000548058.6; ENSP00000449535.1; ENSG00000111058.8. [Q9H6R3-1] DR GeneID; 79611; -. DR KEGG; hsa:79611; -. DR MANE-Select; ENST00000548058.6; ENSP00000449535.1; NM_024560.4; NP_078836.1. DR UCSC; uc001szl.2; human. [Q9H6R3-1] DR AGR; HGNC:24723; -. DR CTD; 79611; -. DR DisGeNET; 79611; -. DR GeneCards; ACSS3; -. DR HGNC; HGNC:24723; ACSS3. DR HPA; ENSG00000111058; Tissue enhanced (liver). DR MIM; 614356; gene. DR neXtProt; NX_Q9H6R3; -. DR OpenTargets; ENSG00000111058; -. DR PharmGKB; PA162375534; -. DR VEuPathDB; HostDB:ENSG00000111058; -. DR eggNOG; KOG1175; Eukaryota. DR GeneTree; ENSGT00940000157479; -. DR HOGENOM; CLU_000022_3_5_1; -. DR InParanoid; Q9H6R3; -. DR OMA; FIMGRTD; -. DR OrthoDB; 144557at2759; -. DR PhylomeDB; Q9H6R3; -. DR TreeFam; TF354241; -. DR PathwayCommons; Q9H6R3; -. DR Reactome; R-HSA-77111; Synthesis of Ketone Bodies. DR SignaLink; Q9H6R3; -. DR SIGNOR; Q9H6R3; -. DR BioGRID-ORCS; 79611; 12 hits in 1153 CRISPR screens. DR ChiTaRS; ACSS3; human. DR GenomeRNAi; 79611; -. DR Pharos; Q9H6R3; Tbio. DR PRO; PR:Q9H6R3; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q9H6R3; Protein. DR Bgee; ENSG00000111058; Expressed in germinal epithelium of ovary and 153 other cell types or tissues. DR ExpressionAtlas; Q9H6R3; baseline and differential. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. 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; IDA:UniProtKB. DR GO; GO:0046951; P:ketone body biosynthetic process; TAS:Reactome. 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. DR Genevisible; Q9H6R3; HS. 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..686 FT /note="Acyl-CoA synthetase short-chain family member 3, FT mitochondrial" FT /id="PRO_0000320624" FT BINDING 227..230 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250" FT BINDING 425..427 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 446..451 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 539 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 554 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 565 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 624 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250" FT MOD_RES 518 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q14DH7" FT MOD_RES 524 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q14DH7" FT VAR_SEQ 1..318 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_031692" FT CONFLICT 428 FT /note="C -> S (in Ref. 1; BAC11304)" FT /evidence="ECO:0000305" SQ SEQUENCE 686 AA; 74778 MW; 3386338C6FFFD7E8 CRC64; MKPSWLQCRK VTSAGGLGGP LPGSSPARGA GAALRALVVP GPRGGLGGRG CRALSSGSGS EYKTHFAASV TDPERFWGKA AEQISWYKPW TKTLENKHSP STRWFVEGML NICYNAVDRH IENGKGDKIA IIYDSPVTNT KATFTYKEVL EQVSKLAGVL VKHGIKKGDT VVIYMPMIPQ AMYTMLACAR IGAIHSLIFG GFASKELSSR IDHVKPKVVV TASFGIEPGR RVEYVPLVEE ALKIGQHKPD KILIYNRPNM EAVPLAPGRD LDWDEEMAKA QSHDCVPVLS EHPLYILYTS GTTGLPKGVI RPTGGYAVML HWSMSSIYGL QPGEVWWAAS DLGWVVGHSY ICYGPLLHGN TTVLYEGKPV GTPDAGAYFR VLAEHGVAAL FTAPTAIRAI RQQDPGAALG KQYSLTRFKT LFVAGERCDV ETLEWSKNVF RVPVLDHWWQ TETGSPITAS CVGLGNSKTP PPGQAGKSVP GYNVMILDDN MQKLKARCLG NIVVKLPLPP GAFSGLWKNQ EAFKHLYFEK FPGYYDTMDA GYMDEEGYLY VMSRVDDVIN VAGHRISAGA IEESILSHGT VADCAVVGKE DPLKGHVPLA LCVLRKDINA TEEQVLEEIV KHVRQNIGPV AAFRNAVFVK QLPKTRSGKI PRSALSAIVN GKPYKITSTI EDPSIFGHVE EMLKQA //