ID   ACSM5_HUMAN             Reviewed;         579 AA.
AC   Q6NUN0; Q96AV1; Q96CX8; Q9NWV3;
DT   02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   24-NOV-2009, sequence version 2.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=Acyl-coenzyme A synthetase ACSM5, mitochondrial;
DE            EC=6.2.1.2 {ECO:0000250|UniProtKB:Q08AH1};
DE   AltName: Full=Acyl-CoA synthetase medium-chain family member 5;
DE   Flags: Precursor;
GN   Name=ACSM5; Synonyms=MACS3;
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 MRNA] (ISOFORM 1).
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15616553; DOI=10.1038/nature03187;
RA   Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA   Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA   Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA   Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA   Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA   Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA   Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA   Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA   Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA   Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA   Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA   Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA   Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA   Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA   Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA   Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA   Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA   Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA   Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA   DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA   Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA   Myers R.M., Rubin E.M., Pennacchio L.A.;
RT   "The sequence and analysis of duplication-rich human chromosome 16.";
RL   Nature 432:988-994(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain, and 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).
RN   [4]
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   [5]
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   [6]
RP   VARIANTS HIS-159; ARG-352; ARG-360 AND MET-533, AND TISSUE SPECIFICITY.
RX   PubMed=12654705; DOI=10.1161/01.hyp.0000064944.60569.87;
RA   Iwai N., Mannami T., Tomoike H., Ono K., Iwanaga Y.;
RT   "An acyl-CoA synthetase gene family in chromosome 16p12 may contribute to
RT   multiple risk factors.";
RL   Hypertension 41:1041-1046(2003).
CC   -!- FUNCTION: Catalyzes the activation of fatty acids by CoA to produce an
CC       acyl-CoA, the first step in fatty acid metabolism.
CC       {ECO:0000250|UniProtKB:Q08AH1}.
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       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48341;
CC         Evidence={ECO:0000250|UniProtKB:Q08AH1};
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 matrix
CC       {ECO:0000250|UniProtKB:Q91VA0}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q6NUN0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6NUN0-2; Sequence=VSP_028398;
CC   -!- TISSUE SPECIFICITY: Detected in kidney and liver.
CC       {ECO:0000269|PubMed:12654705}.
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA91273.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AK000588; BAA91273.1; ALT_FRAME; mRNA.
DR   EMBL; AC137056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC013753; AAH13753.1; -; mRNA.
DR   EMBL; BC016703; AAH16703.1; -; mRNA.
DR   EMBL; BC068516; AAH68516.1; -; mRNA.
DR   CCDS; CCDS10585.1; -. [Q6NUN0-1]
DR   CCDS; CCDS81954.1; -. [Q6NUN0-2]
DR   RefSeq; NP_001311300.1; NM_001324371.1. [Q6NUN0-1]
DR   RefSeq; NP_001311302.1; NM_001324373.1. [Q6NUN0-2]
DR   RefSeq; NP_060358.2; NM_017888.2. [Q6NUN0-1]
DR   AlphaFoldDB; Q6NUN0; -.
DR   SMR; Q6NUN0; -.
DR   BioGRID; 120323; 58.
DR   IntAct; Q6NUN0; 16.
DR   STRING; 9606.ENSP00000327916; -.
DR   GlyGen; Q6NUN0; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q6NUN0; -.
DR   PhosphoSitePlus; Q6NUN0; -.
DR   BioMuta; ACSM5; -.
DR   DMDM; 269849538; -.
DR   MassIVE; Q6NUN0; -.
DR   PaxDb; 9606-ENSP00000327916; -.
DR   PeptideAtlas; Q6NUN0; -.
DR   ProteomicsDB; 66692; -. [Q6NUN0-1]
DR   ProteomicsDB; 66693; -. [Q6NUN0-2]
DR   Antibodypedia; 25526; 131 antibodies from 18 providers.
DR   DNASU; 54988; -.
DR   Ensembl; ENST00000331849.8; ENSP00000327916.4; ENSG00000183549.10. [Q6NUN0-1]
DR   Ensembl; ENST00000575584.5; ENSP00000460112.1; ENSG00000183549.10. [Q6NUN0-2]
DR   GeneID; 54988; -.
DR   KEGG; hsa:54988; -.
DR   MANE-Select; ENST00000331849.8; ENSP00000327916.4; NM_017888.3; NP_060358.2.
DR   UCSC; uc002dhd.1; human. [Q6NUN0-1]
DR   AGR; HGNC:26060; -.
DR   CTD; 54988; -.
DR   GeneCards; ACSM5; -.
DR   HGNC; HGNC:26060; ACSM5.
DR   HPA; ENSG00000183549; Tissue enriched (liver).
DR   MIM; 614361; gene.
DR   neXtProt; NX_Q6NUN0; -.
DR   OpenTargets; ENSG00000183549; -.
DR   PharmGKB; PA162375501; -.
DR   VEuPathDB; HostDB:ENSG00000183549; -.
DR   eggNOG; KOG1175; Eukaryota.
DR   GeneTree; ENSGT00940000161148; -.
DR   HOGENOM; CLU_088808_0_0_1; -.
DR   InParanoid; Q6NUN0; -.
DR   OMA; PFNWALD; -.
DR   OrthoDB; 5474118at2759; -.
DR   PhylomeDB; Q6NUN0; -.
DR   TreeFam; TF354287; -.
DR   PathwayCommons; Q6NUN0; -.
DR   Reactome; R-HSA-177128; Conjugation of salicylate with glycine.
DR   Reactome; R-HSA-9749641; Aspirin ADME.
DR   SignaLink; Q6NUN0; -.
DR   BioGRID-ORCS; 54988; 10 hits in 1151 CRISPR screens.
DR   ChiTaRS; ACSM5; human.
DR   GenomeRNAi; 54988; -.
DR   Pharos; Q6NUN0; Tbio.
DR   PRO; PR:Q6NUN0; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q6NUN0; Protein.
DR   Bgee; ENSG00000183549; Expressed in right lobe of liver and 137 other cell types or tissues.
DR   ExpressionAtlas; Q6NUN0; baseline and differential.
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: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:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0031956; F:medium-chain fatty acid-CoA ligase activity; IEA:UniProtKB-EC.
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   CDD; cd05928; MACS_euk; 1.
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:SF6; ACYL-COENZYME A SYNTHETASE ACSM5, 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.
DR   Genevisible; Q6NUN0; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; ATP-binding; Fatty acid metabolism;
KW   GTP-binding; Ligase; Lipid metabolism; Magnesium; Metal-binding;
KW   Mitochondrion; Nucleotide-binding; Reference proteome; Transit peptide.
FT   TRANSIT         1..26
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           27..579
FT                   /note="Acyl-coenzyme A synthetase ACSM5, mitochondrial"
FT                   /id="PRO_0000306101"
FT   BINDING         230..238
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   MOD_RES         97
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BGA8"
FT   MOD_RES         97
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BGA8"
FT   MOD_RES         152
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BGA8"
FT   MOD_RES         303
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BGA8"
FT   MOD_RES         303
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BGA8"
FT   VAR_SEQ         209..579
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_028398"
FT   VARIANT         65
FT                   /note="R -> Q (in dbSNP:rs9928053)"
FT                   /id="VAR_055495"
FT   VARIANT         159
FT                   /note="Q -> H (in dbSNP:rs559741756)"
FT                   /evidence="ECO:0000269|PubMed:12654705"
FT                   /id="VAR_035252"
FT   VARIANT         182
FT                   /note="E -> K (in dbSNP:rs7192210)"
FT                   /id="VAR_055496"
FT   VARIANT         217
FT                   /note="M -> V (in dbSNP:rs59025904)"
FT                   /id="VAR_061011"
FT   VARIANT         352
FT                   /note="P -> R (in dbSNP:rs8062344)"
FT                   /evidence="ECO:0000269|PubMed:12654705"
FT                   /id="VAR_035253"
FT   VARIANT         360
FT                   /note="H -> R (in dbSNP:rs12931877)"
FT                   /evidence="ECO:0000269|PubMed:12654705"
FT                   /id="VAR_035254"
FT   VARIANT         533
FT                   /note="T -> M (in dbSNP:rs554734865)"
FT                   /evidence="ECO:0000269|PubMed:12654705"
FT                   /id="VAR_035255"
FT   CONFLICT        142
FT                   /note="M -> V (in Ref. 3; AAH16703)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        231..234
FT                   /note="SGTT -> KREPP (in Ref. 1; BAA91273)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        502
FT                   /note="V -> A (in Ref. 3; AAH68516)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   579 AA;  64760 MW;  9493CB853CE29CB1 CRC64;
     MRPWLRHLVL QALRNSRAFC GSHGKPAPLP VPQKIVATWE AISLGRQLVP EYFNFAHDVL
     DVWSRLEEAG HRPPNPAFWW VNGTGAEIKW SFEELGKQSR KAANVLGGAC GLQPGDRMML
     VLPRLPEWWL VSVACMRTGT VMIPGVTQLT EKDLKYRLQA SRAKSIITSD SLAPRVDAIS
     AECPSLQTKL LVSDSSRPGW LNFRELLREA STEHNCMRTK SRDPLAIYFT SGTTGAPKMV
     EHSQSSYGLG FVASGRRWVA LTESDIFWNT TDTGWVKAAW TLFSAWPNGS CIFVHELPRV
     DAKVILNTLS KFPITTLCCV PTIFRLLVQE DLTRYQFQSL RHCLTGGEAL NPDVREKWKH
     QTGVELYEGY GQSETVVICA NPKGMKIKSG SMGKASPPYD VQIVDDEGNV LPPGEEGNVA
     VRIRPTRPFC FFNCYLDNPE KTAASEQGDF YITGDRARMD KDGYFWFMGR NDDVINSSSY
     RIGPVEVESA LAEHPAVLES AVVSSPDPIR GEVVKAFIVL TPAYSSHDPE ALTRELQEHV
     KRVTAPYKYP RKVAFVSELP KTVSGKIQRS KLRSQEWGK
//