ID ACSM1_BOVIN Reviewed; 577 AA.
AC Q9BEA2; Q32LF8; Q9TVB5; Q9XT43;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 2.
DT 08-NOV-2023, entry version 104.
DE RecName: Full=Acyl-coenzyme A synthetase ACSM1, mitochondrial;
DE EC=6.2.1.2 {ECO:0000269|PubMed:11382754};
DE AltName: Full=Acyl-CoA synthetase medium-chain family member 1;
DE AltName: Full=Benzoate--CoA ligase;
DE EC=6.2.1.25 {ECO:0000269|PubMed:10561077};
DE AltName: Full=Butyrate--CoA ligase 1;
DE AltName: Full=Butyryl-coenzyme A synthetase 1;
DE AltName: Full=Lipoate-activating enzyme {ECO:0000303|PubMed:11382754};
DE AltName: Full=Middle-chain acyl-CoA synthetase 1;
DE AltName: Full=XL-III;
DE AltName: Full=Xenobiotic/medium-chain fatty acid:CoA ligase XL-3;
DE Short=XM-ligase 3;
DE Flags: Precursor;
GN Name=ACSM1; Synonyms=BUCS1, LAE {ECO:0000303|PubMed:11382754}, MACS1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 35-53 AND 324-333,
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, SUBUNIT, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=10561077;
RX DOI=10.1002/(sici)1099-0461(2000)14:1<11::aid-jbt2>3.0.co;2-e;
RA Vessey D.A., Lau E., Kelley M.;
RT "Isolation and sequencing of cDNAs for the XL-I and XL-III forms of bovine
RT liver xenobiotic-metabolizing medium-chain fatty acid:CoA ligase.";
RL J. Biochem. Mol. Toxicol. 14:11-19(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 32-35, VARIANT ALA-372,
RP FUNCTION, COFACTOR, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=11382754; DOI=10.1074/jbc.m101748200;
RA Fujiwara K., Takeuchi S., Okamura-Ikeda K., Motokawa Y.;
RT "Purification, characterization, and cDNA cloning of lipoate-activating
RT enzyme from bovine liver.";
RL J. Biol. Chem. 276:28819-28823(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-372.
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16378734; DOI=10.1016/j.pep.2005.11.006;
RA Kasuya F., Tatsuki T., Ohta M., Kawai Y., Igarashi K.;
RT "Purification, characterization, and mass spectrometric sequencing of a
RT medium chain acyl-CoA synthetase from mouse liver mitochondria and
RT comparisons with the homologues of rat and bovine.";
RL Protein Expr. Purif. 47:405-414(2006).
CC -!- FUNCTION: Catalyzes the activation of fatty acids by CoA to produce an
CC acyl-CoA, the first step in fatty acid metabolism (PubMed:11382754,
CC PubMed:10561077). Capable of activating medium-chain fatty acids (e.g.
CC butyric (C4) to decanoic (C10) acids), and certain carboxylate-
CC containing xenobiotics, e.g. benzoate (PubMed:10561077,
CC PubMed:11382754). Also catalyzes the activation of lipoate to lipoyl-
CC nucleoside monophosphate (PubMed:11382754). Activates lipoate with GTP
CC at a 1000-fold higher rate than with ATP and activates both (R)- and
CC (S)-lipoate to the respective lipoyl-GMP, with a preference for (R)-
CC lipoate (PubMed:11382754). {ECO:0000269|PubMed:10561077,
CC ECO:0000269|PubMed:11382754}.
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:11382754};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48341;
CC Evidence={ECO:0000305|PubMed:11382754};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + benzoate + CoA = AMP + benzoyl-CoA + diphosphate;
CC Xref=Rhea:RHEA:10132, ChEBI:CHEBI:16150, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57369,
CC ChEBI:CHEBI:456215; EC=6.2.1.25;
CC Evidence={ECO:0000269|PubMed:10561077};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10133;
CC Evidence={ECO:0000305|PubMed:10561077};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-lipoate + GTP + H(+) = (R)-lipoyl-GMP + diphosphate;
CC Xref=Rhea:RHEA:46700, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:83088, ChEBI:CHEBI:86460;
CC Evidence={ECO:0000269|PubMed:11382754};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46701;
CC Evidence={ECO:0000305|PubMed:11382754};
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:11382754};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33632;
CC Evidence={ECO:0000305|PubMed:11382754};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + decanoate = AMP + decanoyl-CoA + diphosphate;
CC Xref=Rhea:RHEA:33627, ChEBI:CHEBI:27689, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:61430,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:11382754};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33628;
CC Evidence={ECO:0000250|UniProtKB:Q91VA0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + dodecanoate = AMP + diphosphate + dodecanoyl-CoA;
CC Xref=Rhea:RHEA:33623, ChEBI:CHEBI:18262, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57375,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:11382754};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33624;
CC Evidence={ECO:0000305|PubMed:11382754};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + tetradecanoate = AMP + diphosphate +
CC tetradecanoyl-CoA; Xref=Rhea:RHEA:33619, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57385, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000250|UniProtKB:Q91VA0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33620;
CC Evidence={ECO:0000250|UniProtKB:Q91VA0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + hexanoate = AMP + diphosphate + hexanoyl-CoA;
CC Xref=Rhea:RHEA:43740, ChEBI:CHEBI:17120, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:62620,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:11382754};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43741;
CC Evidence={ECO:0000305|PubMed:11382754};
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:0000269|PubMed:11382754};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46173;
CC Evidence={ECO:0000305|PubMed:11382754};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + hexadecanoate = AMP + diphosphate + hexadecanoyl-
CC CoA; Xref=Rhea:RHEA:30751, ChEBI:CHEBI:7896, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:Q91VA0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30752;
CC Evidence={ECO:0000250|UniProtKB:Q91VA0};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11382754};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q08AH1};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.0047 mM for (R)-lipoate with ATP as phosphate donor
CC {ECO:0000269|PubMed:11382754};
CC KM=0.041 mM for (R)-lipoate with GTP as phosphate donor
CC {ECO:0000269|PubMed:11382754};
CC KM=0.039 mM for (R)-lipoate with CTP as phosphate donor
CC {ECO:0000269|PubMed:11382754};
CC KM=0.18 mM for (R)-lipoate with UTP as phosphate donor
CC {ECO:0000269|PubMed:11382754};
CC KM=1.3 mM for ATP (with (R)-lipoate as substrate)
CC {ECO:0000269|PubMed:11382754};
CC KM=0.37 mM for GTP (with (R)-lipoate as substrate)
CC {ECO:0000269|PubMed:11382754};
CC KM=1.2 mM for CTP (with (R)-lipoate as substrate)
CC {ECO:0000269|PubMed:11382754};
CC KM=8.8 mM for UTP (with (R)-lipoate as substrate)
CC {ECO:0000269|PubMed:11382754};
CC KM=3.9 uM for hexanoate {ECO:0000269|PubMed:11382754};
CC KM=0.32 uM for ATP (with hexanoate as substrate)
CC {ECO:0000269|PubMed:11382754};
CC Vmax=14.3 nmol/h/mg enzyme for (R)-lipoate with ATP as phosphate
CC donor {ECO:0000269|PubMed:11382754};
CC Vmax=15300 nmol/h/mg enzyme for (R)-lipoate with GTP as phosphate
CC donor {ECO:0000269|PubMed:11382754};
CC Vmax=12700 nmol/h/mg enzyme for (R)-lipoate with CTP as phosphate
CC donor {ECO:0000269|PubMed:11382754};
CC Vmax=13000 nmol/h/mg enzyme for (R)-lipoate with UTP as phosphate
CC donor {ECO:0000269|PubMed:11382754};
CC Vmax=14.4 nmol/h/mg enzyme for ATP (with (R)-lipoate as substrate)
CC {ECO:0000269|PubMed:11382754};
CC Vmax=13800 nmol/h/mg enzyme for GTP (with (R)-lipoate as substrate)
CC {ECO:0000269|PubMed:11382754};
CC Vmax=13500 nmol/h/mg enzyme for CTP (with (R)-lipoate as substrate)
CC {ECO:0000269|PubMed:11382754};
CC Vmax=14100 nmol/h/mg enzyme for UTP (with (R)-lipoate as substrate)
CC {ECO:0000269|PubMed:11382754};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:10561077}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q91VA0}. Mitochondrion
CC {ECO:0000269|PubMed:10561077, ECO:0000269|PubMed:11382754}.
CC -!- TISSUE SPECIFICITY: Detected in liver. {ECO:0000269|PubMed:10561077}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AF126145; AAD39140.1; -; mRNA.
DR EMBL; AJ132751; CAB44431.1; -; mRNA.
DR EMBL; AB048289; BAB40420.1; -; mRNA.
DR EMBL; BC109602; AAI09603.1; -; mRNA.
DR RefSeq; NP_777107.1; NM_174682.2.
DR AlphaFoldDB; Q9BEA2; -.
DR SMR; Q9BEA2; -.
DR STRING; 9913.ENSBTAP00000001859; -.
DR PaxDb; 9913-ENSBTAP00000001859; -.
DR PeptideAtlas; Q9BEA2; -.
DR GeneID; 282576; -.
DR KEGG; bta:282576; -.
DR CTD; 116285; -.
DR eggNOG; KOG1175; Eukaryota.
DR InParanoid; Q9BEA2; -.
DR OrthoDB; 5474118at2759; -.
DR Proteomes; UP000009136; Unplaced.
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:0018858; F:benzoate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0047760; F:butyrate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0102391; F:decanoate-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0015645; F:fatty acid ligase activity; ISS:AgBase.
DR GO; GO:0004321; F:fatty-acyl-CoA synthase activity; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; ISS:AgBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006637; P:acyl-CoA metabolic process; IBA:GO_Central.
DR GO; GO:0006633; P:fatty acid biosynthetic process; ISS:AgBase.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 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_com.
DR InterPro; IPR042099; ANL_N_sf.
DR PANTHER; PTHR43605; ACYL-COENZYME A SYNTHETASE; 1.
DR PANTHER; PTHR43605:SF5; ACYL-COENZYME A SYNTHETASE ACSM1, MITOCHONDRIAL; 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; ATP-binding; Direct protein sequencing; Fatty acid metabolism;
KW GTP-binding; Ligase; Lipid metabolism; Magnesium; Metal-binding;
KW Mitochondrion; Nucleotide-binding; Reference proteome; Transit peptide.
FT TRANSIT 1..31
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:11382754"
FT CHAIN 32..577
FT /note="Acyl-coenzyme A synthetase ACSM1, mitochondrial"
FT /id="PRO_5000049630"
FT BINDING 226..234
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 452
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 467
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 563
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 85
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 146
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 146
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 183
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 204
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 204
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 214
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 237
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 356
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 356
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 391
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 391
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 531
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 538
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 538
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT MOD_RES 549
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VA0"
FT VARIANT 372
FT /note="T -> A"
FT /evidence="ECO:0000269|PubMed:11382754, ECO:0000269|Ref.3"
FT CONFLICT 186
FT /note="L -> H (in Ref. 3; AAI09603)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 577 AA; 64923 MW; 33C3DA651E461BE4 CRC64;
MQRLMKFRVL WGIHMSCPGF HHAPQHLRCR SLSGAGTLRW NDYDRPEEFN FASDVLDHWT
QMEKEGKRSP NPALWWVNDQ GDEVKWSFRE MTDLTCRTAN VLTQTCGLQT GDRLALILPR
VPEWWLVCVG CIRTGIIFMP GTTQMKAKDI LYRLQVSGAK AIVTTDTLAP EVESVAPECP
SLKTKLLVSD HSREGWLDFR SLVKSASPDH ICIKSKTLDP MAIFFTSGTT GFPKMAKHSH
GFALRSYFPA CRKLLQLKMS DVFWCLSDTG WILAALGSLL EPWTAGSTVF AHHLPQFDPK
VIIETFFKYP ITQCLAAPSV YRMILQQNYT SLRFPTLEHC CTGGEALLPE EQEQWKRQTG
VLLYQAYGQS ETGISCGTLR GMKIKPGSMG KAIPPFDIQI IDDKGNIQPP NTEGNIGIRI
KPTRPIGLFM YYENNPEKTA EVECGDFYNT GDRATIDEEG YFWFLGRSDD VINASGYRVG
PAEVENALAE HPAVAESAVV SSPDPVRGEV VKAFIVLNPE FSSRDPGELT KELQQHVKSV
TAPYKYPRKV EFVSELPKTI TGKIKRSELR KKEFGQK
//
