ID   ACSM2_RAT               Reviewed;         572 AA.
AC   O70490; Q6AZ63;
DT   02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   02-OCT-2007, sequence version 2.
DT   24-JAN-2024, entry version 123.
DE   RecName: Full=Acyl-coenzyme A synthetase ACSM2, mitochondrial;
DE            EC=6.2.1.2 {ECO:0000250|UniProtKB:Q68CK6};
DE   AltName: Full=Acyl-CoA synthetase medium-chain family member 2;
DE   AltName: Full=Benzoate--CoA ligase;
DE            EC=6.2.1.25 {ECO:0000250|UniProtKB:Q68CK6};
DE   AltName: Full=Butyrate--CoA ligase 2;
DE   AltName: Full=Butyryl-coenzyme A synthetase 2;
DE   AltName: Full=Kidney-specific protein KS;
DE   AltName: Full=Middle-chain acyl-CoA synthetase 2;
DE   Flags: Precursor;
GN   Name=Acsm2; Synonyms=Ks;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, INDUCTION, AND TISSUE
RP   SPECIFICITY.
RC   STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX   PubMed=9844120; DOI=10.1046/j.1523-1755.1998.00143.x;
RA   Hilgers K.F., Nagaraj S.K., Karginova E.A., Kazakova I.G., Chevalier R.L.,
RA   Carey R.M., Pentz E.S., Gomez R.A.;
RT   "Molecular cloning of KS, a novel rat gene expressed exclusively in the
RT   kidney.";
RL   Kidney Int. 54:1444-1454(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
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).
CC   -!- FUNCTION: Catalyzes the activation of fatty acids by CoA to produce an
CC       acyl-CoA, the first step in fatty acid metabolism (By similarity).
CC       Capable of activating medium-chain fatty acids (e.g. butyric (C4) to
CC       decanoic (C10) acids), and certain carboxylate-containing xenobiotics,
CC       e.g. benzoate (By similarity). {ECO:0000250|UniProtKB:Q68CK6}.
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:0000250|UniProtKB:Q68CK6};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48341;
CC         Evidence={ECO:0000250|UniProtKB:Q68CK6};
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:0000250|UniProtKB:Q68CK6};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10133;
CC         Evidence={ECO:0000250|UniProtKB:Q68CK6};
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:0000250|UniProtKB:Q68CK6};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43741;
CC         Evidence={ECO:0000250|UniProtKB:Q68CK6};
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:Q68CK6};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46173;
CC         Evidence={ECO:0000250|UniProtKB:Q68CK6};
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:0000250|UniProtKB:Q68CK6};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33632;
CC         Evidence={ECO:0000250|UniProtKB:Q68CK6};
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:0000250|UniProtKB:Q68CK6};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33628;
CC         Evidence={ECO:0000250|UniProtKB:Q68CK6};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q68CK6};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:Q68CK6};
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q68CK6}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q68CK6}.
CC   -!- TISSUE SPECIFICITY: Detected in kidney, in proximal tubules.
CC       {ECO:0000269|PubMed:9844120}.
CC   -!- DEVELOPMENTAL STAGE: First detected in kidney from 1 week old rats. Not
CC       detectable in fetal kidney and in kidney from newborn rats.
CC       {ECO:0000269|PubMed:9844120}.
CC   -!- INDUCTION: Down-regulated in kidneys from a strain of spontaneously
CC       hypertensive rats (SHR). Down-regulated after unilateral ureteral
CC       obstruction or unilateral nephrectomy. {ECO:0000269|PubMed:9844120}.
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000305}.
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DR   EMBL; AF062389; AAD05209.1; -; mRNA.
DR   EMBL; BC078721; AAH78721.1; -; mRNA.
DR   RefSeq; NP_653349.1; NM_144748.1.
DR   AlphaFoldDB; O70490; -.
DR   SMR; O70490; -.
DR   iPTMnet; O70490; -.
DR   PhosphoSitePlus; O70490; -.
DR   PaxDb; 10116-ENSRNOP00000020587; -.
DR   GeneID; 246263; -.
DR   KEGG; rno:246263; -.
DR   UCSC; RGD:708383; rat.
DR   AGR; RGD:708383; -.
DR   CTD; 233799; -.
DR   RGD; 708383; Acsm2.
DR   eggNOG; KOG1175; Eukaryota.
DR   InParanoid; O70490; -.
DR   OrthoDB; 5474118at2759; -.
DR   PhylomeDB; O70490; -.
DR   TreeFam; TF354287; -.
DR   Reactome; R-RNO-177128; Conjugation of salicylate with glycine.
DR   Reactome; R-RNO-177135; Conjugation of benzoate with glycine.
DR   Reactome; R-RNO-177162; Conjugation of phenylacetate with glutamine.
DR   Reactome; R-RNO-9749641; Aspirin ADME.
DR   PRO; PR:O70490; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0018858; F:benzoate-CoA ligase activity; ISS:UniProtKB.
DR   GO; GO:0047760; F:butyrate-CoA ligase activity; ISO:RGD.
DR   GO; GO:0102391; F:decanoate-CoA ligase activity; IEA:RHEA.
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:0006637; P:acyl-CoA metabolic process; IBA:GO_Central.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR   GO; GO:0036112; P:medium-chain fatty-acyl-CoA metabolic process; ISO:RGD.
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:SF3; ACYL-COENZYME A SYNTHETASE ACSM2B, 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   2: Evidence at transcript level;
KW   ATP-binding; Fatty acid metabolism; Ligase; Lipid metabolism; Magnesium;
KW   Metal-binding; Mitochondrion; Nucleotide-binding; Reference proteome;
KW   Transit peptide.
FT   TRANSIT         1..46
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           47..572
FT                   /note="Acyl-coenzyme A synthetase ACSM2, mitochondrial"
FT                   /id="PRO_0000306096"
FT   BINDING         139
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250"
FT   BINDING         221..229
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         359..364
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         364
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         446
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         469..471
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250"
FT   BINDING         472
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         501
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250"
FT   BINDING         532
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250"
FT   BINDING         540..542
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250"
FT   BINDING         557
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        22
FT                   /note="T -> S (in Ref. 1; AAD05209)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        99
FT                   /note="G -> R (in Ref. 2; AAH78721)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   572 AA;  64145 MW;  34BB5FB87A43958C CRC64;
     MHWLWKIPRL CTFWGTEMFH RTFHMNIKKL MPIQWGHQEV PAKFNFASDV IDHWASLEKA
     GKRSPGPALW WMNGSGEELK WNFRELSEIS KQTANVLTGA CGLQRGDRVA VVLPRVPEWW
     LVTLGCMRSG LVFMPGTTQM KSTDILYRLQ SSKARAIVAG DEVVQEVDAV APDCSFLKIK
     LLVSEKNREG WLNFKALLKD ASPIHQCVET VSQESAAIYF TSGTSGPPKM AEHSHCSLGL
     KAKMDAGWTG LGPSDTMWTI SDTGWILNIL GSFLEPWVLG TCIFVHLLPK FDPQTVLKVL
     SSYPINTLLG APLIYRMLLQ QDLSSYKFPH LHSCFSGGET LLPETLESWK AKTGLEIREI
     YGQTETGITC RVSRTMKVKP GYLGTAIVPY DVQVIDEQGN VLPPGKEGDM ALRVKPIRPI
     GMFSGYVDNP KKTQANIRGD FWLLGDRGIK DTEGYFHFMG RTDDIINSSG YRIGPSEVEN
     ALMEHPAVVE TAVISSPDPI RREVVKAFVV LAPEFLSHDQ DQLTKVLQEH VKSVTAPYKY
     PRKVEFVLDL PKTITGKIER AKLRAKEWKT SG
//