ACSM2_RAT
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 03-AUG-2022, entry version 117.
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 STRING; 10116.ENSRNOP00000020587; -.
DR iPTMnet; O70490; -.
DR PhosphoSitePlus; O70490; -.
DR PaxDb; O70490; -.
DR PRIDE; O70490; -.
DR GeneID; 246263; -.
DR KEGG; rno:246263; -.
DR UCSC; RGD:708383; rat.
DR CTD; 233799; -.
DR RGD; 708383; Acsm2.
DR eggNOG; KOG1175; Eukaryota.
DR InParanoid; O70490; -.
DR OrthoDB; 683933at2759; -.
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; -; 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 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
