ACSM4_HUMAN
ID ACSM4_HUMAN Reviewed; 580 AA.
AC P0C7M7; A8MTI6;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Acyl-coenzyme A synthetase ACSM4, mitochondrial;
DE EC=6.2.1.2 {ECO:0000250|UniProtKB:Q7TN78};
DE AltName: Full=Acyl-CoA synthetase medium-chain family member 4;
DE Flags: Precursor;
GN Name=ACSM4;
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 GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 330-474.
RA Stevens M., Wei C., Gross S.S., McPherson J., Brent M.R.;
RT "Exhaustive RT-PCR and sequencing of all novel TWINSCAN predictions in
RT human.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP IDENTIFICATION.
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 [4]
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).
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 with a preference for
CC C6-12 fatty acids (By similarity). {ECO:0000250|UniProtKB:Q7TN78}.
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:Q7TN78};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48341;
CC Evidence={ECO:0000250|UniProtKB:Q7TN78};
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:Q7TN78};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43741;
CC Evidence={ECO:0000250|UniProtKB:Q7TN78};
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:Q7TN78};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33632;
CC Evidence={ECO:0000250|UniProtKB:Q7TN78};
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:Q7TN78};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33628;
CC Evidence={ECO:0000250|UniProtKB:Q7TN78};
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:0000250|UniProtKB:Q7TN78};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33624;
CC Evidence={ECO:0000250|UniProtKB:Q7TN78};
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 -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q7TN78}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AC131205; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DY654856; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS44825.1; -.
DR RefSeq; NP_001073923.1; NM_001080454.1.
DR AlphaFoldDB; P0C7M7; -.
DR SMR; P0C7M7; -.
DR BioGRID; 131135; 2.
DR STRING; 9606.ENSP00000382349; -.
DR iPTMnet; P0C7M7; -.
DR PhosphoSitePlus; P0C7M7; -.
DR BioMuta; ACSM4; -.
DR DMDM; 190358135; -.
DR MassIVE; P0C7M7; -.
DR PaxDb; P0C7M7; -.
DR PeptideAtlas; P0C7M7; -.
DR PRIDE; P0C7M7; -.
DR ProteomicsDB; 52346; -.
DR Antibodypedia; 59210; 57 antibodies from 13 providers.
DR DNASU; 341392; -.
DR Ensembl; ENST00000399422.5; ENSP00000382349.4; ENSG00000215009.6.
DR GeneID; 341392; -.
DR KEGG; hsa:341392; -.
DR MANE-Select; ENST00000399422.5; ENSP00000382349.4; NM_001080454.2; NP_001073923.1.
DR UCSC; uc001qsx.2; human.
DR CTD; 341392; -.
DR GeneCards; ACSM4; -.
DR HGNC; HGNC:32016; ACSM4.
DR HPA; ENSG00000215009; Not detected.
DR MIM; 614360; gene.
DR neXtProt; NX_P0C7M7; -.
DR OpenTargets; ENSG00000215009; -.
DR PharmGKB; PA162375472; -.
DR VEuPathDB; HostDB:ENSG00000215009; -.
DR eggNOG; KOG1175; Eukaryota.
DR GeneTree; ENSGT00940000162316; -.
DR HOGENOM; CLU_000022_59_10_1; -.
DR InParanoid; P0C7M7; -.
DR OMA; GPVGCRY; -.
DR OrthoDB; 683933at2759; -.
DR PhylomeDB; P0C7M7; -.
DR TreeFam; TF354287; -.
DR PathwayCommons; P0C7M7; -.
DR Reactome; R-HSA-177128; Conjugation of salicylate with glycine.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR BioGRID-ORCS; 341392; 12 hits in 1066 CRISPR screens.
DR ChiTaRS; ACSM4; human.
DR GenomeRNAi; 341392; -.
DR Pharos; P0C7M7; Tdark.
DR PRO; PR:P0C7M7; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P0C7M7; protein.
DR Bgee; ENSG00000215009; Expressed in right ovary and 57 other tissues.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047760; F:butyrate-CoA ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0102391; F:decanoate-CoA ligase activity; ISS:UniProtKB.
DR GO; GO:0015645; F:fatty acid ligase activity; ISS:UniProtKB.
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 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..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 23..580
FT /note="Acyl-coenzyme A synthetase ACSM4, mitochondrial"
FT /id="PRO_0000339384"
FT BINDING 229..237
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 368..373
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 455
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 470
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 566
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT VARIANT 481
FT /note="R -> H (in dbSNP:rs61584783)"
FT /id="VAR_061010"
SQ SEQUENCE 580 AA; 65703 MW; 217EF355B93BACC0 CRC64;
MKIFFRYQTF RFIWLTKPPG RRLHKDHQLW TPLTLADFEA INRCNRPLPK NFNFAADVLD
QWSQKEKTGE RPANPALWWV NGKGDEVKWS FRELGSLSRK AANVLTKPCG LQRGDRLAVI
LPRIPEWWLV NVACIRTGII FMPGTIQLTA KDILYRLRAS KAKCIVASEE VAPAVESIVL
ECPDLKTKLL VSPQSWNGWL SFQELFQFAS EEHSCVETGS QEPMTIYFTS GTTGFPKMAQ
HSQSSLGIGF TLCGRYWLDL KSSDIIWNMS DTGWVKAAIG SVFSSWLCGA CVFVHRMAQF
DTDTFLDTLT TYPITTLCSP PTVYRMLVQK DLKRYKFKSL RHCLTGGEPL NPEVLEQWRV
QTGLELYEGY GQTEVGMICA NQKGQEIKPG SMGKGMLPYD VQIIDENGNV LPPGKEGEIA
LRLKPTRPFC FFSKYVDNPQ KTAATIRGDF YVTGDRGVMD SDGYFWFVGR ADDVIISSGY
RIGPFEVESA LIEHPAVVES AVVSSPDQIR GEVVKAFVVL AAPFKSYNPE KLTLELQDHV
KKSTAPYKYP RKVEFVQELP KTITGKIKRN VLRDQEWRGR
