ACSM3_HUMAN
ID ACSM3_HUMAN Reviewed; 586 AA.
AC Q53FZ2; O60363; Q13732; Q15425; Q7KYM6; Q9BUA2;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Acyl-coenzyme A synthetase ACSM3, mitochondrial;
DE EC=6.2.1.2 {ECO:0000269|PubMed:11772874};
DE AltName: Full=Acyl-CoA synthetase medium-chain family member 3;
DE AltName: Full=Butyrate--CoA ligase 3;
DE AltName: Full=Butyryl-coenzyme A synthetase 3;
DE AltName: Full=Middle-chain acyl-CoA synthetase 3;
DE AltName: Full=Propionate--CoA ligase;
DE EC=6.2.1.17 {ECO:0000250|UniProtKB:Q3UNX5};
DE AltName: Full=Protein SA homolog;
DE Flags: Precursor;
GN Name=ACSM3; Synonyms=SAH;
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).
RC TISSUE=Liver;
RX PubMed=7907320; DOI=10.1161/01.hyp.23.3.375;
RA Iwai N., Ohmichi N., Hanai K., Nakamura Y., Kinoshita M.;
RT "Human SA gene locus as a candidate locus for essential hypertension.";
RL Hypertension 23:375-380(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND LACK OF INVOLVEMENT IN
RP HEREDITARY HYPERTENSION.
RX PubMed=7843754; DOI=10.1161/01.hyp.25.1.6;
RA Nabika T., Bonnardeaux A., James M., Julier C., Jeunemaitre X., Corvol P.,
RA Lathrop M., Soubrier F.;
RT "Evaluation of the SA locus in human hypertension.";
RL Hypertension 25:6-13(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J.,
RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X.,
RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C.,
RA Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from human
RT chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASN-367.
RC TISSUE=Kidney;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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].
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 [7]
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 [8]
RP REVIEW.
RX PubMed=27351777; DOI=10.1080/17425255.2016.1206888;
RA van der Sluis R., Erasmus E.;
RT "Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its
RT role in fatty acid metabolism and the detoxification of benzoic acid and
RT aspirin.";
RL Expert Opin. Drug Metab. Toxicol. 12:1169-1179(2016).
RN [9]
RP VARIANT ASN-367, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11772874; DOI=10.1161/hc0102.101780;
RA Iwai N., Katsuya T., Mannami T., Higaki J., Ogihara T., Kokame K.,
RA Ogata J., Baba S.;
RT "Association between SAH, an acyl-CoA synthetase gene, and
RT hypertriglyceridemia, obesity, and hypertension.";
RL Circulation 105:41-47(2002).
RN [10]
RP VARIANT ASN-367.
RX PubMed=17278971; DOI=10.1097/hjh.0b013e3280144779;
RA Telgmann R., Brand E., Nicaud V., Hagedorn C., Beining K., Schoenfelder J.,
RA Brink-Spalink V., Schmidt-Petersen K., Matanis T., Vischer P., Nofer J.-R.,
RA Hasenkamp S., Plouin P.-F., Drouet L., Cambien F., Paul M., Tiret L.,
RA Brand-Herrmann S.-M.;
RT "SAH gene variants are associated with obesity-related hypertension in
RT Caucasians: the PEGASE Study.";
RL J. Hypertens. 25:557-564(2007).
CC -!- FUNCTION: Catalyzes the activation of fatty acids by CoA to produce an
CC acyl-CoA, the first step in fatty acid metabolism (PubMed:11772874).
CC Capable of activating medium-chain fatty acids with a preference for
CC isobutyrate among fatty acids with 2-6 carbon atoms (By similarity).
CC {ECO:0000250|UniProtKB:Q3UNX5, ECO:0000269|PubMed:11772874}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a medium chain fatty acid + ATP + CoA = a medium-chain fatty
CC acyl-CoA + AMP + diphosphate; Xref=Rhea:RHEA:48340,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:59558, ChEBI:CHEBI:90546, ChEBI:CHEBI:456215; EC=6.2.1.2;
CC Evidence={ECO:0000269|PubMed:11772874};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48341;
CC Evidence={ECO:0000305|PubMed:11772874};
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:Q3UNX5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20374;
CC Evidence={ECO:0000250|UniProtKB:Q3UNX5};
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:Q3UNX5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46173;
CC Evidence={ECO:0000250|UniProtKB:Q3UNX5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylpropanoate + ATP + CoA = 2-methylpropanoyl-CoA + AMP +
CC diphosphate; Xref=Rhea:RHEA:46176, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:48944, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57338, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000250|UniProtKB:Q3UNX5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46177;
CC Evidence={ECO:0000250|UniProtKB:Q3UNX5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylbutanoate + ATP + CoA = 2-methylbutanoyl-CoA + AMP +
CC diphosphate; Xref=Rhea:RHEA:46180, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:48946, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57336, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000250|UniProtKB:Q3UNX5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46181;
CC Evidence={ECO:0000250|UniProtKB:Q3UNX5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + octanoate = AMP + diphosphate + octanoyl-CoA;
CC Xref=Rhea:RHEA:33631, ChEBI:CHEBI:25646, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57386,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:11772874};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33632;
CC Evidence={ECO:0000305|PubMed:11772874};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q08AH1};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q08AH1};
CC -!- INTERACTION:
CC Q53FZ2-2; Q92876: KLK6; NbExp=3; IntAct=EBI-25887341, EBI-2432309;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:11772874}.
CC Mitochondrion matrix {ECO:0000250|UniProtKB:Q3UNX5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q53FZ2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q53FZ2-2; Sequence=VSP_028395, VSP_028396;
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-9 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC31667.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA03853.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA56369.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D16350; BAA03853.1; ALT_INIT; mRNA.
DR EMBL; X80062; CAA56369.1; ALT_INIT; mRNA.
DR EMBL; AC004381; AAC31667.1; ALT_INIT; Genomic_DNA.
DR EMBL; AK223139; BAD96859.1; -; mRNA.
DR EMBL; BC002790; AAH02790.3; -; mRNA.
DR CCDS; CCDS10589.1; -. [Q53FZ2-1]
DR CCDS; CCDS45435.1; -. [Q53FZ2-2]
DR PIR; I54401; I54401.
DR PIR; S69913; S69913.
DR RefSeq; NP_005613.2; NM_005622.3. [Q53FZ2-1]
DR RefSeq; NP_973729.1; NM_202000.2. [Q53FZ2-2]
DR AlphaFoldDB; Q53FZ2; -.
DR SMR; Q53FZ2; -.
DR BioGRID; 112203; 16.
DR IntAct; Q53FZ2; 2.
DR STRING; 9606.ENSP00000289416; -.
DR SwissLipids; SLP:000001189; -.
DR iPTMnet; Q53FZ2; -.
DR PhosphoSitePlus; Q53FZ2; -.
DR BioMuta; ACSM3; -.
DR DMDM; 158706483; -.
DR EPD; Q53FZ2; -.
DR jPOST; Q53FZ2; -.
DR MassIVE; Q53FZ2; -.
DR MaxQB; Q53FZ2; -.
DR PaxDb; Q53FZ2; -.
DR PeptideAtlas; Q53FZ2; -.
DR PRIDE; Q53FZ2; -.
DR ProteomicsDB; 62470; -. [Q53FZ2-1]
DR ProteomicsDB; 62471; -. [Q53FZ2-2]
DR Antibodypedia; 25607; 159 antibodies from 24 providers.
DR DNASU; 6296; -.
DR Ensembl; ENST00000289416.10; ENSP00000289416.5; ENSG00000005187.12. [Q53FZ2-1]
DR Ensembl; ENST00000440284.6; ENSP00000394565.2; ENSG00000005187.12. [Q53FZ2-2]
DR GeneID; 6296; -.
DR KEGG; hsa:6296; -.
DR MANE-Select; ENST00000289416.10; ENSP00000289416.5; NM_005622.4; NP_005613.2.
DR UCSC; uc002dhq.4; human. [Q53FZ2-1]
DR CTD; 6296; -.
DR DisGeNET; 6296; -.
DR GeneCards; ACSM3; -.
DR HGNC; HGNC:10522; ACSM3.
DR HPA; ENSG00000005187; Tissue enhanced (kidney, liver).
DR MIM; 145505; gene.
DR neXtProt; NX_Q53FZ2; -.
DR OpenTargets; ENSG00000005187; -.
DR PharmGKB; PA34930; -.
DR VEuPathDB; HostDB:ENSG00000005187; -.
DR eggNOG; KOG1175; Eukaryota.
DR GeneTree; ENSGT00940000157930; -.
DR InParanoid; Q53FZ2; -.
DR OMA; HAWSNLF; -.
DR OrthoDB; 683933at2759; -.
DR PhylomeDB; Q53FZ2; -.
DR TreeFam; TF354287; -.
DR PathwayCommons; Q53FZ2; -.
DR Reactome; R-HSA-77352; Beta oxidation of butanoyl-CoA to acetyl-CoA.
DR SignaLink; Q53FZ2; -.
DR BioGRID-ORCS; 6296; 7 hits in 1072 CRISPR screens.
DR ChiTaRS; ACSM3; human.
DR GeneWiki; ACSM3; -.
DR GenomeRNAi; 6296; -.
DR Pharos; Q53FZ2; Tbio.
DR PRO; PR:Q53FZ2; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q53FZ2; protein.
DR Bgee; ENSG00000005187; Expressed in left ovary and 120 other tissues.
DR ExpressionAtlas; Q53FZ2; baseline and differential.
DR Genevisible; Q53FZ2; HS.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047760; F:butyrate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0015645; F:fatty acid ligase activity; IBA:GO_Central.
DR GO; GO:0004321; F:fatty-acyl-CoA synthase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043759; F:methylbutanoate-CoA ligase activity; IEA:RHEA.
DR GO; GO:0018729; F:propionate CoA-transferase activity; IEA:Ensembl.
DR GO; GO:0050218; F:propionate-CoA ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0006637; P:acyl-CoA metabolic process; IBA:GO_Central.
DR GO; GO:0042632; P:cholesterol homeostasis; NAS:BHF-UCL.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0008217; P:regulation of blood pressure; TAS:ProtInc.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
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; 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; Fatty acid metabolism;
KW Ligase; Lipid metabolism; Magnesium; Metal-binding; Mitochondrion;
KW Nucleotide-binding; Reference proteome; Transit peptide.
FT TRANSIT 1..27
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 28..586
FT /note="Acyl-coenzyme A synthetase ACSM3, mitochondrial"
FT /id="PRO_0000306097"
FT BINDING 235..243
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 374..379
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 461
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 476
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 572
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 73
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UNX5"
FT MOD_RES 106
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UNX5"
FT MOD_RES 157
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3UNX5"
FT VAR_SEQ 409..438
FT /note="IVDVNGNVLPPGQEGDIGIQVLPNRPFGLF -> VCTSPSRRMFNNPICTLP
FT TYRLPPYKLSLL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7843754"
FT /id="VSP_028395"
FT VAR_SEQ 439..586
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7843754"
FT /id="VSP_028396"
FT VARIANT 100
FT /note="L -> P (in dbSNP:rs5713)"
FT /id="VAR_035249"
FT VARIANT 270
FT /note="D -> H (in dbSNP:rs13306603)"
FT /id="VAR_048239"
FT VARIANT 308
FT /note="P -> T (in dbSNP:rs7196188)"
FT /id="VAR_035250"
FT VARIANT 367
FT /note="K -> N (in dbSNP:rs5716)"
FT /evidence="ECO:0000269|PubMed:11772874,
FT ECO:0000269|PubMed:17278971, ECO:0000269|Ref.4"
FT /id="VAR_035251"
FT CONFLICT 132
FT /note="E -> R (in Ref. 1; BAA03853)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="G -> A (in Ref. 1; BAA03853)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="T -> S (in Ref. 1; BAA03853)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="V -> D (in Ref. 4; BAD96859)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="G -> A (in Ref. 1; BAA03853)"
FT /evidence="ECO:0000305"
FT CONFLICT 569
FT /note="I -> V (in Ref. 1; BAA03853)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 586 AA; 66153 MW; 329967C751F11F1D CRC64;
MLARVTRKML RHAKCFQRLA IFGSVRALHK DNRTATPQNF SNYESMKQDF KLGIPEYFNF
AKDVLDQWTD KEKAGKKPSN PAFWWINRNG EEMRWSFEEL GSLSRKFANI LSEACSLQRG
DRVILILPRV PEWWLANVAC LRTGTVLIPG TTQLTQKDIL YRLQSSKANC IITNDVLAPA
VDAVASKCEN LHSKLIVSEN SREGWGNLKE LMKHASDSHT CVKTKHNEIM AIFFTSGTSG
YPKMTAHTHS SFGLGLSVNG RFWLDLTPSD VMWNTSDTGW AKSAWSSVFS PWIQGACVFT
HHLPRFEPTS ILQTLSKYPI TVFCSAPTVY RMLVQNDITS YKFKSLKHCV SAGEPITPDV
TEKWRNKTGL DIYEGYGQTE TVLICGNFKG MKIKPGSMGK PSPAFDVKIV DVNGNVLPPG
QEGDIGIQVL PNRPFGLFTH YVDNPSKTAS TLRGNFYITG DRGYMDKDGY FWFVARADDV
ILSSGYRIGP FEVENALNEH PSVAESAVVS SPDPIRGEVV KAFVVLNPDY KSHDQEQLIK
EIQEHVKKTT APYKYPRKVE FIQELPKTIS GKTKRNELRK KEWKTI
