ACSS3_HUMAN
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 03-AUG-2022, entry version 156.
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}.
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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; 3.
DR IntAct; Q9H6R3; 2.
DR STRING; 9606.ENSP00000449535; -.
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; Q9H6R3; -.
DR PeptideAtlas; Q9H6R3; -.
DR PRIDE; Q9H6R3; -.
DR ProteomicsDB; 81014; -. [Q9H6R3-1]
DR ProteomicsDB; 81015; -. [Q9H6R3-2]
DR TopDownProteomics; Q9H6R3-1; -. [Q9H6R3-1]
DR Antibodypedia; 29817; 121 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 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; YVFVMGR; -.
DR OrthoDB; 288915at2759; -.
DR PhylomeDB; Q9H6R3; -.
DR TreeFam; TF354241; -.
DR PathwayCommons; Q9H6R3; -.
DR Reactome; R-HSA-77111; Synthesis of Ketone Bodies.
DR SignaLink; Q9H6R3; -.
DR BioGRID-ORCS; 79611; 12 hits in 1072 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 151 other tissues.
DR ExpressionAtlas; Q9H6R3; baseline and differential.
DR Genevisible; Q9H6R3; HS.
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 GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
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; 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
