ACSM5_HUMAN
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 03-AUG-2022, entry version 136.
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 iPTMnet; Q6NUN0; -.
DR PhosphoSitePlus; Q6NUN0; -.
DR BioMuta; ACSM5; -.
DR DMDM; 269849538; -.
DR MassIVE; Q6NUN0; -.
DR PaxDb; Q6NUN0; -.
DR PeptideAtlas; Q6NUN0; -.
DR PRIDE; Q6NUN0; -.
DR ProteomicsDB; 66692; -. [Q6NUN0-1]
DR ProteomicsDB; 66693; -. [Q6NUN0-2]
DR Antibodypedia; 25526; 111 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 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; TTFYDGP; -.
DR OrthoDB; 683933at2759; -.
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 1072 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 136 other tissues.
DR ExpressionAtlas; Q6NUN0; baseline and differential.
DR Genevisible; Q6NUN0; HS.
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 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 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
