AACS_HUMAN
ID AACS_HUMAN Reviewed; 672 AA.
AC Q86V21; Q49AB9; Q49AC3; Q658Q8; Q8IWD2; Q8NEW5; Q9BSJ9; Q9H829; Q9HA19;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Acetoacetyl-CoA synthetase;
DE EC=6.2.1.16 {ECO:0000250|UniProtKB:Q9JMI1};
DE AltName: Full=Acyl-CoA synthetase family member 1;
DE AltName: Full=Protein sur-5 homolog;
GN Name=AACS; Synonyms=ACSF1;
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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=12623130; DOI=10.1016/s0006-2952(02)01656-8;
RA Ohgami M., Takahashi N., Yamasaki M., Fukui T.;
RT "Expression of acetoacetyl-CoA synthetase, a novel cytosolic ketone body-
RT utilizing enzyme, in human brain.";
RL Biochem. Pharmacol. 65:989-994(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland, and Retinoblastoma;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP VAL-118.
RC TISSUE=Brain, Kidney, and Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-672 (ISOFORM 1).
RX PubMed=9671465; DOI=10.1128/mcb.18.8.4556;
RA Gu T., Orita S., Han M.;
RT "Caenorhabditis elegans SUR-5, a novel but conserved protein, negatively
RT regulates LET-60 Ras activity during vulval induction.";
RL Mol. Cell. Biol. 18:4556-4564(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 48-672 (ISOFORM 1).
RC TISSUE=Stomach;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Converts acetoacetate to acetoacetyl-CoA in the cytosol (By
CC similarity). Ketone body-utilizing enzyme, responsible for the
CC synthesis of cholesterol and fatty acids (By similarity).
CC {ECO:0000250|UniProtKB:Q9D2R0, ECO:0000250|UniProtKB:Q9JMI1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetoacetate + ATP + CoA = acetoacetyl-CoA + AMP +
CC diphosphate; Xref=Rhea:RHEA:16117, ChEBI:CHEBI:13705,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57286,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:456215; EC=6.2.1.16;
CC Evidence={ECO:0000250|UniProtKB:Q9JMI1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16118;
CC Evidence={ECO:0000250|UniProtKB:Q9JMI1};
CC -!- INTERACTION:
CC Q86V21; Q96DZ9: CMTM5; NbExp=3; IntAct=EBI-10259474, EBI-2548702;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9JMI1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q86V21-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86V21-2; Sequence=VSP_030702;
CC Name=3;
CC IsoId=Q86V21-3; Sequence=VSP_030701;
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney, heart and brain, but
CC low in liver. {ECO:0000269|PubMed:12623130}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH41000.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB14793.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB054121; BAD22560.1; -; mRNA.
DR EMBL; AK022451; BAB14040.1; -; mRNA.
DR EMBL; AK024036; BAB14793.1; ALT_FRAME; mRNA.
DR EMBL; CH471054; EAW98474.1; -; Genomic_DNA.
DR EMBL; BC004997; AAH04997.1; -; mRNA.
DR EMBL; BC040490; AAH40490.2; -; mRNA.
DR EMBL; BC040574; AAH40574.1; -; mRNA.
DR EMBL; BC041000; AAH41000.1; ALT_FRAME; mRNA.
DR EMBL; BC051862; AAH51862.1; -; mRNA.
DR EMBL; AY091468; AAM44124.1; -; mRNA.
DR EMBL; AL833047; CAH56309.1; -; mRNA.
DR CCDS; CCDS9263.1; -. [Q86V21-1]
DR RefSeq; NP_001306768.1; NM_001319839.1. [Q86V21-2]
DR RefSeq; NP_076417.2; NM_023928.4. [Q86V21-1]
DR AlphaFoldDB; Q86V21; -.
DR SMR; Q86V21; -.
DR BioGRID; 122434; 17.
DR IntAct; Q86V21; 1.
DR STRING; 9606.ENSP00000324842; -.
DR GlyGen; Q86V21; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86V21; -.
DR MetOSite; Q86V21; -.
DR PhosphoSitePlus; Q86V21; -.
DR BioMuta; AACS; -.
DR DMDM; 74750446; -.
DR EPD; Q86V21; -.
DR jPOST; Q86V21; -.
DR MassIVE; Q86V21; -.
DR MaxQB; Q86V21; -.
DR PaxDb; Q86V21; -.
DR PeptideAtlas; Q86V21; -.
DR PRIDE; Q86V21; -.
DR ProteomicsDB; 69950; -. [Q86V21-1]
DR ProteomicsDB; 69951; -. [Q86V21-2]
DR ProteomicsDB; 69952; -. [Q86V21-3]
DR Antibodypedia; 31900; 147 antibodies from 19 providers.
DR DNASU; 65985; -.
DR Ensembl; ENST00000316519.11; ENSP00000324842.6; ENSG00000081760.17. [Q86V21-1]
DR GeneID; 65985; -.
DR KEGG; hsa:65985; -.
DR MANE-Select; ENST00000316519.11; ENSP00000324842.6; NM_023928.5; NP_076417.2.
DR UCSC; uc001uhc.4; human. [Q86V21-1]
DR CTD; 65985; -.
DR DisGeNET; 65985; -.
DR GeneCards; AACS; -.
DR HGNC; HGNC:21298; AACS.
DR HPA; ENSG00000081760; Low tissue specificity.
DR MIM; 614364; gene.
DR neXtProt; NX_Q86V21; -.
DR OpenTargets; ENSG00000081760; -.
DR PharmGKB; PA134940696; -.
DR VEuPathDB; HostDB:ENSG00000081760; -.
DR eggNOG; KOG1175; Eukaryota.
DR GeneTree; ENSGT00940000156044; -.
DR HOGENOM; CLU_000022_3_3_1; -.
DR InParanoid; Q86V21; -.
DR OMA; WYSSTGW; -.
DR PhylomeDB; Q86V21; -.
DR TreeFam; TF354241; -.
DR PathwayCommons; Q86V21; -.
DR Reactome; R-HSA-77111; Synthesis of Ketone Bodies.
DR SignaLink; Q86V21; -.
DR BioGRID-ORCS; 65985; 14 hits in 1075 CRISPR screens.
DR ChiTaRS; AACS; human.
DR GenomeRNAi; 65985; -.
DR Pharos; Q86V21; Tbio.
DR PRO; PR:Q86V21; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q86V21; protein.
DR Bgee; ENSG00000081760; Expressed in parotid gland and 194 other tissues.
DR ExpressionAtlas; Q86V21; baseline and differential.
DR Genevisible; Q86V21; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030729; F:acetoacetate-CoA ligase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046951; P:ketone body biosynthetic process; TAS:Reactome.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IBA:GO_Central.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR005914; Acac_CoA_synth.
DR InterPro; IPR032387; ACAS_N.
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; PF16177; ACAS_N; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR TIGRFAMs; TIGR01217; ac_ac_CoA_syn; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Fatty acid metabolism;
KW Ligase; Lipid metabolism; Nucleotide-binding; Reference proteome.
FT CHAIN 1..672
FT /note="Acetoacetyl-CoA synthetase"
FT /id="PRO_0000315784"
FT VAR_SEQ 1..402
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030701"
FT VAR_SEQ 561..672
FT /note="ESFEEVEDSLCVPQYNKYREERVILFLKMASGHAFQPDLVKRIRDAIRMGLS
FT ARHVPSLILETKGIPYTLNGKKVEVAVKQIIAGKAVEQGGAFSNPETLDLYRDIPELQG
FT F -> YAQRQESGSCRQTDHRWKSRGARRCFLEPRDPGSVPGHP (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030702"
FT VARIANT 118
FT /note="I -> V (in dbSNP:rs11549081)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_038303"
FT VARIANT 470
FT /note="A -> V (in dbSNP:rs59883951)"
FT /id="VAR_060997"
FT CONFLICT 70
FT /note="G -> E (in Ref. 2; BAB14793)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="A -> V (in Ref. 2; BAB14040)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="K -> E (in Ref. 2; BAB14793)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="E -> G (in Ref. 2; BAB14040)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="V -> A (in Ref. 2; BAB14040)"
FT /evidence="ECO:0000305"
FT CONFLICT 391
FT /note="K -> E (in Ref. 4; AAH41000)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 672 AA; 75144 MW; 36006739EE4857D9 CRC64;
MSKEERPGRE EILECQVMWE PDSKKNTQMD RFRAAVGAAC GLALESYDDL YHWSVESYSD
FWAEFWKFSG IVFSRVYDEV VDTSKGIADV PEWFKGSRLN YAENLLRHKE NDRVALYIAR
EGKEEIVKVT FEELRQEVAL FAAAMRKMGV KKGDRVVGYL PNSEHAVEAM LAAASIGAIW
SSTSPDFGVN GVLDRFSQIQ PKLIFSVEAV VYNGKEHNHM EKLQQVVKGL PDLKKVVVIP
YVSSRENIDL SKIPNSVFLD DFLATGTSEQ APQLEFEQLP FSHPLFIMFS SGTTGAPKCM
VHSAGGTLIQ HLKEHLLHGN MTSSDILLCY TTVGWMMWNW MVSLLATGAA MVLYDGSPLV
PTPNVLWDLV DRIGITVLVT GAKWLSVLEE KAMKPVETHS LQMLHTILST GSPLKAQSYE
YVYRCIKSSI LLGSISGGTD IISCFMGHNF SLPVYKGEIQ ARNLGMAVEA WNEEGKAVWG
ESGELVCTKP IPCQPTHFWN DENGNKYRKA YFSKFPGIWA HGDYCRINPK TGGIVMLGRS
DGTLNPNGVR FGSSEIYNIV ESFEEVEDSL CVPQYNKYRE ERVILFLKMA SGHAFQPDLV
KRIRDAIRMG LSARHVPSLI LETKGIPYTL NGKKVEVAVK QIIAGKAVEQ GGAFSNPETL
DLYRDIPELQ GF
