Full text data of ACLY
ACLY
[Confidence: high (present in two of the MS resources)]
ATP-citrate synthase; 2.3.3.8 (ATP-citrate (pro-S-)-lyase; ACL; Citrate cleavage enzyme)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
ATP-citrate synthase; 2.3.3.8 (ATP-citrate (pro-S-)-lyase; ACL; Citrate cleavage enzyme)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00021290
IPI00021290 ATP-citrate synthase ATP-citrate synthase membrane n/a 5 n/a n/a 2 n/a 1 n/a 1 n/a n/a n/a 2 n/a n/a n/a n/a 6 8 5 cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00021290 ATP-citrate synthase ATP-citrate synthase membrane n/a 5 n/a n/a 2 n/a 1 n/a 1 n/a n/a n/a 2 n/a n/a n/a n/a 6 8 5 cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P53396
ID ACLY_HUMAN Reviewed; 1101 AA.
AC P53396; B4DIM0; Q13037; Q9BRL0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=ATP-citrate synthase;
DE EC=2.3.3.8;
DE AltName: Full=ATP-citrate (pro-S-)-lyase;
DE Short=ACL;
DE AltName: Full=Citrate cleavage enzyme;
GN Name=ACLY;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASP-175.
RC TISSUE=Liver;
RX PubMed=1371749; DOI=10.1111/j.1432-1033.1992.tb16659.x;
RA Elshourbagy N.A., Near J.C., Kmetz P.J., Wells T.N.C., Groot P.H.E.,
RA Saxty B.A., Hughes S.A., Franklin M., Gloger I.S.;
RT "Cloning and expression of a human ATP-citrate lyase cDNA.";
RL Eur. J. Biochem. 204:491-499(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASP-175.
RC TISSUE=Liver;
RX PubMed=9116495; DOI=10.1006/prep.1996.0668;
RA Lord K.A., Wang X.M., Simmons S.J., Bruckner R.C., Loscig J.,
RA O'Connor B., Bentley R., Smallwood A., Chadwick C.C., Stevis P.E.,
RA Ciccarelli R.B.;
RT "Variant cDNA sequences of human ATP:citrate lyase: cloning,
RT expression, and purification from baculovirus-infected insect cells.";
RL Protein Expr. Purif. 9:133-141(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP ASP-175.
RC TISSUE=Hippocampus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-131 AND TYR-682, AND
RP MASS SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455; SER-481 AND
RP SER-1100, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481; THR-639; SER-663;
RP TYR-682; SER-839 AND SER-1100, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-546; LYS-554; LYS-948;
RP LYS-968 AND LYS-1077, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455 AND SER-481, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455 AND SER-481, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP FUNCTION, ACETYLATION AT LYS-540; LYS-546 AND LYS-554, UBIQUITINATION
RP AT LYS-540; LYS-546 AND LYS-554, AND MUTAGENESIS OF LYS-540; LYS-546
RP AND LYS-554.
RX PubMed=23932781; DOI=10.1016/j.molcel.2013.07.002;
RA Lin R., Tao R., Gao X., Li T., Zhou X., Guan K.L., Xiong Y., Lei Q.Y.;
RT "Acetylation stabilizes ATP-citrate lyase to promote lipid
RT biosynthesis and tumor growth.";
RL Mol. Cell 51:506-518(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-425 AND 487-820 IN COMPLEX
RP WITH CITRATE, AND CITRATE-BINDING SITES.
RX PubMed=20558738; DOI=10.1074/jbc.M109.078667;
RA Sun T., Hayakawa K., Bateman K.S., Fraser M.E.;
RT "Identification of the citrate-binding site of human ATP-citrate lyase
RT using X-ray crystallography.";
RL J. Biol. Chem. 285:27418-27428(2010).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-817 IN COMPLEX WITH ADP.
RX PubMed=22102020; DOI=10.1107/S1744309111028363;
RA Sun T., Hayakawa K., Fraser M.E.;
RT "ADP-Mg2+ bound to the ATP-grasp domain of ATP-citrate lyase.";
RL Acta Crystallogr. F 67:1168-1172(2011).
CC -!- FUNCTION: ATP citrate-lyase is the primary enzyme responsible for
CC the synthesis of cytosolic acetyl-CoA in many tissues. Has a
CC central role in de novo lipid synthesis. In nervous tissue it may
CC be involved in the biosynthesis of acetylcholine.
CC -!- CATALYTIC ACTIVITY: ADP + phosphate + acetyl-CoA + oxaloacetate =
CC ATP + citrate + CoA.
CC -!- COFACTOR: Magnesium.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P53396-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P53396-2; Sequence=VSP_042201;
CC -!- PTM: ISGylated.
CC -!- PTM: Acetylated at Lys-540, Lys-546 and Lys-554 by KAT2B/PCAF.
CC Acetylation is promoted by glucose and stabilizes the protein,
CC probably by preventing ubiquitination at the same sites.
CC Acetylation promotes de novo lipid synthesis. Deacetylated by
CC SIRT2.
CC -!- PTM: Ubiquitinated at Lys-540, Lys-546 and Lys-554 by UBR4,
CC leading to its degradation. Ubiquitination is probably inhibited
CC by acetylation at same site (Probable).
CC -!- SIMILARITY: In the N-terminal section; belongs to the
CC succinate/malate CoA ligase beta subunit family.
CC -!- SIMILARITY: In the C-terminal section; belongs to the
CC succinate/malate CoA ligase alpha subunit family.
CC -!- SIMILARITY: Contains 1 ATP-grasp domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ACLYID50486ch17q21.html";
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DR EMBL; X64330; CAA45614.1; -; mRNA.
DR EMBL; U18197; AAB60340.1; -; mRNA.
DR EMBL; AK295675; BAG58532.1; -; mRNA.
DR EMBL; AC091172; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006195; AAH06195.1; -; mRNA.
DR PIR; S21173; S21173.
DR RefSeq; NP_001087.2; NM_001096.2.
DR RefSeq; NP_942127.1; NM_198830.1.
DR RefSeq; XP_005257452.1; XM_005257395.1.
DR RefSeq; XP_005277082.1; XM_005277025.1.
DR UniGene; Hs.387567; -.
DR PDB; 3MWD; X-ray; 2.10 A; A=1-425, B=487-820.
DR PDB; 3MWE; X-ray; 2.20 A; A=1-425, B=487-821.
DR PDB; 3PFF; X-ray; 2.30 A; A=1-817.
DR PDBsum; 3MWD; -.
DR PDBsum; 3MWE; -.
DR PDBsum; 3PFF; -.
DR ProteinModelPortal; P53396; -.
DR SMR; P53396; 2-425, 487-820, 911-1075.
DR IntAct; P53396; 5.
DR MINT; MINT-3019895; -.
DR STRING; 9606.ENSP00000253792; -.
DR BindingDB; P53396; -.
DR ChEMBL; CHEMBL3720; -.
DR PhosphoSite; P53396; -.
DR DMDM; 116241237; -.
DR PaxDb; P53396; -.
DR PeptideAtlas; P53396; -.
DR PRIDE; P53396; -.
DR DNASU; 47; -.
DR Ensembl; ENST00000352035; ENSP00000253792; ENSG00000131473.
DR Ensembl; ENST00000353196; ENSP00000345398; ENSG00000131473.
DR Ensembl; ENST00000393896; ENSP00000377474; ENSG00000131473.
DR Ensembl; ENST00000564506; ENSP00000455275; ENSG00000260245.
DR Ensembl; ENST00000567793; ENSP00000456811; ENSG00000260245.
DR Ensembl; ENST00000590151; ENSP00000466259; ENSG00000131473.
DR GeneID; 47; -.
DR KEGG; hsa:47; -.
DR UCSC; uc002hyg.3; human.
DR CTD; 47; -.
DR GeneCards; GC17M040023; -.
DR HGNC; HGNC:115; ACLY.
DR HPA; CAB007783; -.
DR HPA; HPA022434; -.
DR HPA; HPA022953; -.
DR HPA; HPA022959; -.
DR HPA; HPA028758; -.
DR MIM; 108728; gene.
DR neXtProt; NX_P53396; -.
DR PharmGKB; PA24441; -.
DR eggNOG; COG0372; -.
DR HOGENOM; HOG000151479; -.
DR HOVERGEN; HBG003318; -.
DR InParanoid; P53396; -.
DR KO; K01648; -.
DR OMA; RLPKYAC; -.
DR PhylomeDB; P53396; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P53396; -.
DR ChiTaRS; ACLY; human.
DR EvolutionaryTrace; P53396; -.
DR GenomeRNAi; 47; -.
DR NextBio; 181; -.
DR PRO; PR:P53396; -.
DR ArrayExpress; P53396; -.
DR Bgee; P53396; -.
DR CleanEx; HS_ACLY; -.
DR Genevestigator; P53396; -.
DR GO; GO:0009346; C:citrate lyase complex; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003878; F:ATP citrate synthase activity; TAS:UniProtKB.
DR GO; GO:0048037; F:cofactor binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004775; F:succinate-CoA ligase (ADP-forming) activity; IEA:InterPro.
DR GO; GO:0006200; P:ATP catabolic process; TAS:ProtInc.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0006101; P:citrate metabolic process; TAS:ProtInc.
DR GO; GO:0015936; P:coenzyme A metabolic process; TAS:ProtInc.
DR GO; GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome.
DR GO; GO:0031325; P:positive regulation of cellular metabolic process; TAS:Reactome.
DR GO; GO:0019432; P:triglyceride biosynthetic process; TAS:Reactome.
DR Gene3D; 1.10.230.10; -; 1.
DR Gene3D; 3.30.470.20; -; 1.
DR Gene3D; 3.40.50.261; -; 2.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR014608; ATP-citrate_synthase.
DR InterPro; IPR013650; ATP-grasp_succ-CoA_synth-type.
DR InterPro; IPR013816; ATP_grasp_subdomain_2.
DR InterPro; IPR017440; Cit_synth/succinyl-CoA_lig_AS.
DR InterPro; IPR016143; Citrate_synth-like_sm_a-sub.
DR InterPro; IPR002020; Citrate_synthase-like.
DR InterPro; IPR016141; Citrate_synthase-like_core.
DR InterPro; IPR003781; CoA-bd.
DR InterPro; IPR005810; CoA_lig_alpha.
DR InterPro; IPR005811; CoA_ligase.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR017866; Succ-CoA_synthase_bsu_CS.
DR InterPro; IPR016102; Succinyl-CoA_synth-like.
DR Pfam; PF08442; ATP-grasp_2; 1.
DR Pfam; PF00285; Citrate_synt; 1.
DR Pfam; PF02629; CoA_binding; 1.
DR Pfam; PF00549; Ligase_CoA; 1.
DR PIRSF; PIRSF036511; ATP_citrt_syn; 1.
DR SUPFAM; SSF48256; SSF48256; 2.
DR SUPFAM; SSF52210; SSF52210; 1.
DR PROSITE; PS50975; ATP_GRASP; FALSE_NEG.
DR PROSITE; PS01216; SUCCINYL_COA_LIG_1; 1.
DR PROSITE; PS00399; SUCCINYL_COA_LIG_2; 1.
DR PROSITE; PS01217; SUCCINYL_COA_LIG_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Complete proteome; Cytoplasm; Isopeptide bond; Lipid biosynthesis;
KW Lipid metabolism; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome; Transferase;
KW Ubl conjugation.
FT CHAIN 1 1101 ATP-citrate synthase.
FT /FTId=PRO_0000102781.
FT DOMAIN 4 265 ATP-grasp.
FT NP_BIND 66 67 ATP.
FT NP_BIND 109 111 ATP.
FT NP_BIND 701 721 ATP (By similarity).
FT NP_BIND 752 778 ATP (By similarity).
FT REGION 779 789 CoA-binding (Potential).
FT ACT_SITE 760 760 Tele-phosphohistidine intermediate (By
FT similarity).
FT METAL 201 201 Magnesium (By similarity).
FT METAL 203 203 Magnesium (By similarity).
FT METAL 718 718 Magnesium (By similarity).
FT BINDING 58 58 ATP.
FT BINDING 118 118 ATP.
FT BINDING 346 346 Citrate; via amide nitrogen.
FT BINDING 348 348 Citrate.
FT BINDING 379 379 Citrate.
FT MOD_RES 131 131 Phosphotyrosine.
FT MOD_RES 447 447 Phosphothreonine (By similarity).
FT MOD_RES 451 451 Phosphoserine (By similarity).
FT MOD_RES 455 455 Phosphoserine; by PKA and PKB/AKT1 or
FT PKB/AKT2.
FT MOD_RES 481 481 Phosphoserine.
FT MOD_RES 540 540 N6-acetyllysine; alternate.
FT MOD_RES 546 546 N6-acetyllysine; alternate.
FT MOD_RES 554 554 N6-acetyllysine; alternate.
FT MOD_RES 639 639 Phosphothreonine.
FT MOD_RES 663 663 Phosphoserine.
FT MOD_RES 682 682 Phosphotyrosine.
FT MOD_RES 839 839 Phosphoserine.
FT MOD_RES 948 948 N6-acetyllysine.
FT MOD_RES 968 968 N6-acetyllysine.
FT MOD_RES 1077 1077 N6-acetyllysine.
FT MOD_RES 1100 1100 Phosphoserine.
FT CROSSLNK 540 540 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate (Probable).
FT CROSSLNK 546 546 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate (Probable).
FT CROSSLNK 554 554 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate (Probable).
FT VAR_SEQ 476 485 Missing (in isoform 2).
FT /FTId=VSP_042201.
FT VARIANT 175 175 E -> D (in dbSNP:rs2304497).
FT /FTId=VAR_028230.
FT MUTAGEN 540 540 K->R,Q: Decreased acetylation and
FT increased de novo lipid synthesis; when
FT associated with R,Q-546 and R,Q-554.
FT MUTAGEN 546 546 K->R,Q: Decreased acetylation and
FT increased de novo lipid synthesis; when
FT associated with R,Q-540 and R,Q-554.
FT MUTAGEN 554 554 K->R,Q: Decreased acetylation and
FT increased de novo lipid synthesis; when
FT associated with R,Q-540 and R,Q-546.
FT CONFLICT 75 75 N -> D (in Ref. 1; CAA45614).
FT CONFLICT 111 111 V -> A (in Ref. 1; CAA45614).
FT CONFLICT 245 245 E -> V (in Ref. 1; CAA45614).
FT CONFLICT 419 423 LGHRP -> WAPA (in Ref. 1; CAA45614).
FT CONFLICT 442 444 SGS -> QRE (in Ref. 1; CAA45614).
FT CONFLICT 457 459 SES -> YESMVDEV (in Ref. 1; CAA45614).
FT CONFLICT 653 656 RPGS -> PQAA (in Ref. 1; CAA45614).
FT CONFLICT 728 728 C -> S (in Ref. 1; CAA45614).
FT CONFLICT 872 872 V -> A (in Ref. 1; CAA45614).
FT CONFLICT 916 919 AGKD -> TAVE (in Ref. 1; CAA45614).
FT STRAND 3 6
FT HELIX 8 18
FT STRAND 32 34
FT HELIX 40 46
FT HELIX 48 51
FT STRAND 55 59
FT TURN 66 70
FT STRAND 73 76
FT HELIX 78 85
FT TURN 86 90
FT STRAND 92 95
FT STRAND 98 101
FT STRAND 105 109
FT HELIX 115 117
FT STRAND 118 126
FT STRAND 129 137
FT HELIX 140 142
FT HELIX 145 148
FT STRAND 149 155
FT HELIX 162 167
FT TURN 168 172
FT TURN 175 177
FT HELIX 178 194
FT STRAND 197 208
FT STRAND 211 214
FT STRAND 217 222
FT HELIX 223 225
FT HELIX 226 233
FT STRAND 242 244
FT HELIX 248 258
FT STRAND 260 269
FT STRAND 274 277
FT HELIX 282 294
FT HELIX 298 300
FT STRAND 303 309
FT HELIX 313 326
FT STRAND 336 340
FT STRAND 346 348
FT HELIX 350 363
FT HELIX 365 370
FT STRAND 373 378
FT HELIX 384 398
FT STRAND 402 405
FT HELIX 413 418
FT STRAND 499 503
FT HELIX 506 518
FT STRAND 525 530
FT STRAND 536 543
FT STRAND 546 555
FT HELIX 556 562
FT STRAND 568 571
FT TURN 575 577
FT HELIX 578 585
FT STRAND 593 596
FT HELIX 603 616
FT STRAND 619 621
FT STRAND 628 630
FT TURN 631 633
FT TURN 637 640
FT HELIX 643 648
FT TURN 649 652
FT STRAND 656 662
FT HELIX 664 677
FT STRAND 681 686
FT STRAND 689 692
FT HELIX 697 705
FT STRAND 712 722
FT HELIX 723 732
FT STRAND 740 745
FT HELIX 768 770
FT HELIX 772 781
FT HELIX 790 792
FT HELIX 793 806
SQ SEQUENCE 1101 AA; 120839 MW; 12BB4416A30DC30C CRC64;
MSAKAISEQT GKELLYKFIC TTSAIQNRFK YARVTPDTDW ARLLQDHPWL LSQNLVVKPD
QLIKRRGKLG LVGVNLTLDG VKSWLKPRLG QEATVGKATG FLKNFLIEPF VPHSQAEEFY
VCIYATREGD YVLFHHEGGV DVGDVDAKAQ KLLVGVDEKL NPEDIKKHLL VHAPEDKKEI
LASFISGLFN FYEDLYFTYL EINPLVVTKD GVYVLDLAAK VDATADYICK VKWGDIEFPP
PFGREAYPEE AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE
LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV AATFKGIVRA
IRDYQGPLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI PIHVFGTETH MTAIVGMALG
HRPIPNQPPT AAHTANFLLN ASGSTSTPAP SRTASFSESR ADEVAPAKKA KPAMPQDSVP
SPRSLQGKST TLFSRHTKAI VWGMQTRAVQ GMLDFDYVCS RDEPSVAAMV YPFTGDHKQK
FYWGHKEILI PVFKNMADAM RKHPEVDVLI NFASLRSAYD STMETMNYAQ IRTIAIIAEG
IPEALTRKLI KKADQKGVTI IGPATVGGIK PGCFKIGNTG GMLDNILASK LYRPGSVAYV
SRSGGMSNEL NNIISRTTDG VYEGVAIGGD RYPGSTFMDH VLRYQDTPGV KMIVVLGEIG
GTEEYKICRG IKEGRLTKPI VCWCIGTCAT MFSSEVQFGH AGACANQASE TAVAKNQALK
EAGVFVPRSF DELGEIIQSV YEDLVANGVI VPAQEVPPPT VPMDYSWARE LGLIRKPASF
MTSICDERGQ ELIYAGMPIT EVFKEEMGIG GVLGLLWFQK RLPKYSCQFI EMCLMVTADH
GPAVSGAHNT IICARAGKDL VSSLTSGLLT IGDRFGGALD AAAKMFSKAF DSGIIPMEFV
NKMKKEGKLI MGIGHRVKSI NNPDMRVQIL KDYVRQHFPA TPLLDYALEV EKITTSKKPN
LILNVDGLIG VAFVDMLRNC GSFTREEADE YIDIGALNGI FVLGRSMGFI GHYLDQKRLK
QGLYRHPWDD ISYVLPEHMS M
//
ID ACLY_HUMAN Reviewed; 1101 AA.
AC P53396; B4DIM0; Q13037; Q9BRL0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 3.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=ATP-citrate synthase;
DE EC=2.3.3.8;
DE AltName: Full=ATP-citrate (pro-S-)-lyase;
DE Short=ACL;
DE AltName: Full=Citrate cleavage enzyme;
GN Name=ACLY;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASP-175.
RC TISSUE=Liver;
RX PubMed=1371749; DOI=10.1111/j.1432-1033.1992.tb16659.x;
RA Elshourbagy N.A., Near J.C., Kmetz P.J., Wells T.N.C., Groot P.H.E.,
RA Saxty B.A., Hughes S.A., Franklin M., Gloger I.S.;
RT "Cloning and expression of a human ATP-citrate lyase cDNA.";
RL Eur. J. Biochem. 204:491-499(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASP-175.
RC TISSUE=Liver;
RX PubMed=9116495; DOI=10.1006/prep.1996.0668;
RA Lord K.A., Wang X.M., Simmons S.J., Bruckner R.C., Loscig J.,
RA O'Connor B., Bentley R., Smallwood A., Chadwick C.C., Stevis P.E.,
RA Ciccarelli R.B.;
RT "Variant cDNA sequences of human ATP:citrate lyase: cloning,
RT expression, and purification from baculovirus-infected insect cells.";
RL Protein Expr. Purif. 9:133-141(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP ASP-175.
RC TISSUE=Hippocampus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-131 AND TYR-682, AND
RP MASS SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455; SER-481 AND
RP SER-1100, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481; THR-639; SER-663;
RP TYR-682; SER-839 AND SER-1100, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-546; LYS-554; LYS-948;
RP LYS-968 AND LYS-1077, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455 AND SER-481, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455 AND SER-481, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP FUNCTION, ACETYLATION AT LYS-540; LYS-546 AND LYS-554, UBIQUITINATION
RP AT LYS-540; LYS-546 AND LYS-554, AND MUTAGENESIS OF LYS-540; LYS-546
RP AND LYS-554.
RX PubMed=23932781; DOI=10.1016/j.molcel.2013.07.002;
RA Lin R., Tao R., Gao X., Li T., Zhou X., Guan K.L., Xiong Y., Lei Q.Y.;
RT "Acetylation stabilizes ATP-citrate lyase to promote lipid
RT biosynthesis and tumor growth.";
RL Mol. Cell 51:506-518(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-425 AND 487-820 IN COMPLEX
RP WITH CITRATE, AND CITRATE-BINDING SITES.
RX PubMed=20558738; DOI=10.1074/jbc.M109.078667;
RA Sun T., Hayakawa K., Bateman K.S., Fraser M.E.;
RT "Identification of the citrate-binding site of human ATP-citrate lyase
RT using X-ray crystallography.";
RL J. Biol. Chem. 285:27418-27428(2010).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-817 IN COMPLEX WITH ADP.
RX PubMed=22102020; DOI=10.1107/S1744309111028363;
RA Sun T., Hayakawa K., Fraser M.E.;
RT "ADP-Mg2+ bound to the ATP-grasp domain of ATP-citrate lyase.";
RL Acta Crystallogr. F 67:1168-1172(2011).
CC -!- FUNCTION: ATP citrate-lyase is the primary enzyme responsible for
CC the synthesis of cytosolic acetyl-CoA in many tissues. Has a
CC central role in de novo lipid synthesis. In nervous tissue it may
CC be involved in the biosynthesis of acetylcholine.
CC -!- CATALYTIC ACTIVITY: ADP + phosphate + acetyl-CoA + oxaloacetate =
CC ATP + citrate + CoA.
CC -!- COFACTOR: Magnesium.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P53396-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P53396-2; Sequence=VSP_042201;
CC -!- PTM: ISGylated.
CC -!- PTM: Acetylated at Lys-540, Lys-546 and Lys-554 by KAT2B/PCAF.
CC Acetylation is promoted by glucose and stabilizes the protein,
CC probably by preventing ubiquitination at the same sites.
CC Acetylation promotes de novo lipid synthesis. Deacetylated by
CC SIRT2.
CC -!- PTM: Ubiquitinated at Lys-540, Lys-546 and Lys-554 by UBR4,
CC leading to its degradation. Ubiquitination is probably inhibited
CC by acetylation at same site (Probable).
CC -!- SIMILARITY: In the N-terminal section; belongs to the
CC succinate/malate CoA ligase beta subunit family.
CC -!- SIMILARITY: In the C-terminal section; belongs to the
CC succinate/malate CoA ligase alpha subunit family.
CC -!- SIMILARITY: Contains 1 ATP-grasp domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ACLYID50486ch17q21.html";
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DR EMBL; X64330; CAA45614.1; -; mRNA.
DR EMBL; U18197; AAB60340.1; -; mRNA.
DR EMBL; AK295675; BAG58532.1; -; mRNA.
DR EMBL; AC091172; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006195; AAH06195.1; -; mRNA.
DR PIR; S21173; S21173.
DR RefSeq; NP_001087.2; NM_001096.2.
DR RefSeq; NP_942127.1; NM_198830.1.
DR RefSeq; XP_005257452.1; XM_005257395.1.
DR RefSeq; XP_005277082.1; XM_005277025.1.
DR UniGene; Hs.387567; -.
DR PDB; 3MWD; X-ray; 2.10 A; A=1-425, B=487-820.
DR PDB; 3MWE; X-ray; 2.20 A; A=1-425, B=487-821.
DR PDB; 3PFF; X-ray; 2.30 A; A=1-817.
DR PDBsum; 3MWD; -.
DR PDBsum; 3MWE; -.
DR PDBsum; 3PFF; -.
DR ProteinModelPortal; P53396; -.
DR SMR; P53396; 2-425, 487-820, 911-1075.
DR IntAct; P53396; 5.
DR MINT; MINT-3019895; -.
DR STRING; 9606.ENSP00000253792; -.
DR BindingDB; P53396; -.
DR ChEMBL; CHEMBL3720; -.
DR PhosphoSite; P53396; -.
DR DMDM; 116241237; -.
DR PaxDb; P53396; -.
DR PeptideAtlas; P53396; -.
DR PRIDE; P53396; -.
DR DNASU; 47; -.
DR Ensembl; ENST00000352035; ENSP00000253792; ENSG00000131473.
DR Ensembl; ENST00000353196; ENSP00000345398; ENSG00000131473.
DR Ensembl; ENST00000393896; ENSP00000377474; ENSG00000131473.
DR Ensembl; ENST00000564506; ENSP00000455275; ENSG00000260245.
DR Ensembl; ENST00000567793; ENSP00000456811; ENSG00000260245.
DR Ensembl; ENST00000590151; ENSP00000466259; ENSG00000131473.
DR GeneID; 47; -.
DR KEGG; hsa:47; -.
DR UCSC; uc002hyg.3; human.
DR CTD; 47; -.
DR GeneCards; GC17M040023; -.
DR HGNC; HGNC:115; ACLY.
DR HPA; CAB007783; -.
DR HPA; HPA022434; -.
DR HPA; HPA022953; -.
DR HPA; HPA022959; -.
DR HPA; HPA028758; -.
DR MIM; 108728; gene.
DR neXtProt; NX_P53396; -.
DR PharmGKB; PA24441; -.
DR eggNOG; COG0372; -.
DR HOGENOM; HOG000151479; -.
DR HOVERGEN; HBG003318; -.
DR InParanoid; P53396; -.
DR KO; K01648; -.
DR OMA; RLPKYAC; -.
DR PhylomeDB; P53396; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P53396; -.
DR ChiTaRS; ACLY; human.
DR EvolutionaryTrace; P53396; -.
DR GenomeRNAi; 47; -.
DR NextBio; 181; -.
DR PRO; PR:P53396; -.
DR ArrayExpress; P53396; -.
DR Bgee; P53396; -.
DR CleanEx; HS_ACLY; -.
DR Genevestigator; P53396; -.
DR GO; GO:0009346; C:citrate lyase complex; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003878; F:ATP citrate synthase activity; TAS:UniProtKB.
DR GO; GO:0048037; F:cofactor binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004775; F:succinate-CoA ligase (ADP-forming) activity; IEA:InterPro.
DR GO; GO:0006200; P:ATP catabolic process; TAS:ProtInc.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0006101; P:citrate metabolic process; TAS:ProtInc.
DR GO; GO:0015936; P:coenzyme A metabolic process; TAS:ProtInc.
DR GO; GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome.
DR GO; GO:0031325; P:positive regulation of cellular metabolic process; TAS:Reactome.
DR GO; GO:0019432; P:triglyceride biosynthetic process; TAS:Reactome.
DR Gene3D; 1.10.230.10; -; 1.
DR Gene3D; 3.30.470.20; -; 1.
DR Gene3D; 3.40.50.261; -; 2.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR014608; ATP-citrate_synthase.
DR InterPro; IPR013650; ATP-grasp_succ-CoA_synth-type.
DR InterPro; IPR013816; ATP_grasp_subdomain_2.
DR InterPro; IPR017440; Cit_synth/succinyl-CoA_lig_AS.
DR InterPro; IPR016143; Citrate_synth-like_sm_a-sub.
DR InterPro; IPR002020; Citrate_synthase-like.
DR InterPro; IPR016141; Citrate_synthase-like_core.
DR InterPro; IPR003781; CoA-bd.
DR InterPro; IPR005810; CoA_lig_alpha.
DR InterPro; IPR005811; CoA_ligase.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR017866; Succ-CoA_synthase_bsu_CS.
DR InterPro; IPR016102; Succinyl-CoA_synth-like.
DR Pfam; PF08442; ATP-grasp_2; 1.
DR Pfam; PF00285; Citrate_synt; 1.
DR Pfam; PF02629; CoA_binding; 1.
DR Pfam; PF00549; Ligase_CoA; 1.
DR PIRSF; PIRSF036511; ATP_citrt_syn; 1.
DR SUPFAM; SSF48256; SSF48256; 2.
DR SUPFAM; SSF52210; SSF52210; 1.
DR PROSITE; PS50975; ATP_GRASP; FALSE_NEG.
DR PROSITE; PS01216; SUCCINYL_COA_LIG_1; 1.
DR PROSITE; PS00399; SUCCINYL_COA_LIG_2; 1.
DR PROSITE; PS01217; SUCCINYL_COA_LIG_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Complete proteome; Cytoplasm; Isopeptide bond; Lipid biosynthesis;
KW Lipid metabolism; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome; Transferase;
KW Ubl conjugation.
FT CHAIN 1 1101 ATP-citrate synthase.
FT /FTId=PRO_0000102781.
FT DOMAIN 4 265 ATP-grasp.
FT NP_BIND 66 67 ATP.
FT NP_BIND 109 111 ATP.
FT NP_BIND 701 721 ATP (By similarity).
FT NP_BIND 752 778 ATP (By similarity).
FT REGION 779 789 CoA-binding (Potential).
FT ACT_SITE 760 760 Tele-phosphohistidine intermediate (By
FT similarity).
FT METAL 201 201 Magnesium (By similarity).
FT METAL 203 203 Magnesium (By similarity).
FT METAL 718 718 Magnesium (By similarity).
FT BINDING 58 58 ATP.
FT BINDING 118 118 ATP.
FT BINDING 346 346 Citrate; via amide nitrogen.
FT BINDING 348 348 Citrate.
FT BINDING 379 379 Citrate.
FT MOD_RES 131 131 Phosphotyrosine.
FT MOD_RES 447 447 Phosphothreonine (By similarity).
FT MOD_RES 451 451 Phosphoserine (By similarity).
FT MOD_RES 455 455 Phosphoserine; by PKA and PKB/AKT1 or
FT PKB/AKT2.
FT MOD_RES 481 481 Phosphoserine.
FT MOD_RES 540 540 N6-acetyllysine; alternate.
FT MOD_RES 546 546 N6-acetyllysine; alternate.
FT MOD_RES 554 554 N6-acetyllysine; alternate.
FT MOD_RES 639 639 Phosphothreonine.
FT MOD_RES 663 663 Phosphoserine.
FT MOD_RES 682 682 Phosphotyrosine.
FT MOD_RES 839 839 Phosphoserine.
FT MOD_RES 948 948 N6-acetyllysine.
FT MOD_RES 968 968 N6-acetyllysine.
FT MOD_RES 1077 1077 N6-acetyllysine.
FT MOD_RES 1100 1100 Phosphoserine.
FT CROSSLNK 540 540 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate (Probable).
FT CROSSLNK 546 546 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate (Probable).
FT CROSSLNK 554 554 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate (Probable).
FT VAR_SEQ 476 485 Missing (in isoform 2).
FT /FTId=VSP_042201.
FT VARIANT 175 175 E -> D (in dbSNP:rs2304497).
FT /FTId=VAR_028230.
FT MUTAGEN 540 540 K->R,Q: Decreased acetylation and
FT increased de novo lipid synthesis; when
FT associated with R,Q-546 and R,Q-554.
FT MUTAGEN 546 546 K->R,Q: Decreased acetylation and
FT increased de novo lipid synthesis; when
FT associated with R,Q-540 and R,Q-554.
FT MUTAGEN 554 554 K->R,Q: Decreased acetylation and
FT increased de novo lipid synthesis; when
FT associated with R,Q-540 and R,Q-546.
FT CONFLICT 75 75 N -> D (in Ref. 1; CAA45614).
FT CONFLICT 111 111 V -> A (in Ref. 1; CAA45614).
FT CONFLICT 245 245 E -> V (in Ref. 1; CAA45614).
FT CONFLICT 419 423 LGHRP -> WAPA (in Ref. 1; CAA45614).
FT CONFLICT 442 444 SGS -> QRE (in Ref. 1; CAA45614).
FT CONFLICT 457 459 SES -> YESMVDEV (in Ref. 1; CAA45614).
FT CONFLICT 653 656 RPGS -> PQAA (in Ref. 1; CAA45614).
FT CONFLICT 728 728 C -> S (in Ref. 1; CAA45614).
FT CONFLICT 872 872 V -> A (in Ref. 1; CAA45614).
FT CONFLICT 916 919 AGKD -> TAVE (in Ref. 1; CAA45614).
FT STRAND 3 6
FT HELIX 8 18
FT STRAND 32 34
FT HELIX 40 46
FT HELIX 48 51
FT STRAND 55 59
FT TURN 66 70
FT STRAND 73 76
FT HELIX 78 85
FT TURN 86 90
FT STRAND 92 95
FT STRAND 98 101
FT STRAND 105 109
FT HELIX 115 117
FT STRAND 118 126
FT STRAND 129 137
FT HELIX 140 142
FT HELIX 145 148
FT STRAND 149 155
FT HELIX 162 167
FT TURN 168 172
FT TURN 175 177
FT HELIX 178 194
FT STRAND 197 208
FT STRAND 211 214
FT STRAND 217 222
FT HELIX 223 225
FT HELIX 226 233
FT STRAND 242 244
FT HELIX 248 258
FT STRAND 260 269
FT STRAND 274 277
FT HELIX 282 294
FT HELIX 298 300
FT STRAND 303 309
FT HELIX 313 326
FT STRAND 336 340
FT STRAND 346 348
FT HELIX 350 363
FT HELIX 365 370
FT STRAND 373 378
FT HELIX 384 398
FT STRAND 402 405
FT HELIX 413 418
FT STRAND 499 503
FT HELIX 506 518
FT STRAND 525 530
FT STRAND 536 543
FT STRAND 546 555
FT HELIX 556 562
FT STRAND 568 571
FT TURN 575 577
FT HELIX 578 585
FT STRAND 593 596
FT HELIX 603 616
FT STRAND 619 621
FT STRAND 628 630
FT TURN 631 633
FT TURN 637 640
FT HELIX 643 648
FT TURN 649 652
FT STRAND 656 662
FT HELIX 664 677
FT STRAND 681 686
FT STRAND 689 692
FT HELIX 697 705
FT STRAND 712 722
FT HELIX 723 732
FT STRAND 740 745
FT HELIX 768 770
FT HELIX 772 781
FT HELIX 790 792
FT HELIX 793 806
SQ SEQUENCE 1101 AA; 120839 MW; 12BB4416A30DC30C CRC64;
MSAKAISEQT GKELLYKFIC TTSAIQNRFK YARVTPDTDW ARLLQDHPWL LSQNLVVKPD
QLIKRRGKLG LVGVNLTLDG VKSWLKPRLG QEATVGKATG FLKNFLIEPF VPHSQAEEFY
VCIYATREGD YVLFHHEGGV DVGDVDAKAQ KLLVGVDEKL NPEDIKKHLL VHAPEDKKEI
LASFISGLFN FYEDLYFTYL EINPLVVTKD GVYVLDLAAK VDATADYICK VKWGDIEFPP
PFGREAYPEE AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE
LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV AATFKGIVRA
IRDYQGPLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI PIHVFGTETH MTAIVGMALG
HRPIPNQPPT AAHTANFLLN ASGSTSTPAP SRTASFSESR ADEVAPAKKA KPAMPQDSVP
SPRSLQGKST TLFSRHTKAI VWGMQTRAVQ GMLDFDYVCS RDEPSVAAMV YPFTGDHKQK
FYWGHKEILI PVFKNMADAM RKHPEVDVLI NFASLRSAYD STMETMNYAQ IRTIAIIAEG
IPEALTRKLI KKADQKGVTI IGPATVGGIK PGCFKIGNTG GMLDNILASK LYRPGSVAYV
SRSGGMSNEL NNIISRTTDG VYEGVAIGGD RYPGSTFMDH VLRYQDTPGV KMIVVLGEIG
GTEEYKICRG IKEGRLTKPI VCWCIGTCAT MFSSEVQFGH AGACANQASE TAVAKNQALK
EAGVFVPRSF DELGEIIQSV YEDLVANGVI VPAQEVPPPT VPMDYSWARE LGLIRKPASF
MTSICDERGQ ELIYAGMPIT EVFKEEMGIG GVLGLLWFQK RLPKYSCQFI EMCLMVTADH
GPAVSGAHNT IICARAGKDL VSSLTSGLLT IGDRFGGALD AAAKMFSKAF DSGIIPMEFV
NKMKKEGKLI MGIGHRVKSI NNPDMRVQIL KDYVRQHFPA TPLLDYALEV EKITTSKKPN
LILNVDGLIG VAFVDMLRNC GSFTREEADE YIDIGALNGI FVLGRSMGFI GHYLDQKRLK
QGLYRHPWDD ISYVLPEHMS M
//
MIM
108728
*RECORD*
*FIELD* NO
108728
*FIELD* TI
*108728 ATP CITRATE LYASE; ACLY
;;CLATP;;
ATPCL;;
ACL
*FIELD* TX
DESCRIPTION
ATP citrate lyase is the primary enzyme responsible for the synthesis of
read morecytosolic acetyl-CoA in many tissues. The enzyme is a tetramer (relative
molecular weight approximately 440,000) of apparently identical
subunits. It catalyzes the formation of acetyl-CoA and oxaloacetate from
citrate and CoA with a concomitant hydrolysis of ATP to ADP and
phosphate. The product, acetyl-CoA, serves several important
biosynthetic pathways, including lipogenesis and cholesterogenesis. In
nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of
acetylcholine.
CLONING
Cloning of cDNAs has been reported for murine (Sul et al., 1984), rat
(Elshourbagy et al., 1990), and human (Elshourbagy et al., 1992) ATP
citrate lyase. Elshourbagy et al. (1992) found that the subunits of the
enzyme have 1,105 amino acids and a calculated molecular mass of 121,419
Da. The human and rat ATPCL cDNAs showed 96.3% amino acid identity.
GENE FUNCTION
Wellen et al. (2009) showed that histone acetylation in mammalian cells
is dependent on ATP-citrate lyase (ACL), the enzyme that converts
glucose-derived citrate into acetyl-CoA. They found that ACL is required
for increases in histone acetylation in response to growth factor
stimulation and during differentiation, and that glucose availability
can affect histone acetylation in an ACL-dependent manner. Wellen et al.
(2009) concluded that ACL activity is required to link growth
factor-induced increases in nutrient metabolism to the regulation of
histone acetylation and gene expression.
MAPPING
Remmers et al. (1992) found that the genes for growth hormone (139250),
pancreatic polypeptide (167780), ERBB2 (164870), sex hormone binding
globulin (182205), embryonic skeletal myosin heavy chain (160720), and
asialoglycoprotein receptor (108360) map to human chromosome 17 and rat
chromosome 10. Many of the same genes are known to be located on mouse
chromosome 11. Furthermore, Remmers et al. (1992) showed that in the rat
the gene for ATP citrate lyase is closely linked to the gene for PPY,
which in turn is close to the GH gene, on chromosome 10. They predicted,
therefore, that the homologous gene in the human would be located on
chromosome 17, probably close to PPY which is situated at 17q22-q24.
Couch et al. (1994) mapped the ACLY gene to 17q12-q21 by PCR analysis of
a panel of human/rodent somatic cell hybrids and localized it to 17q21.1
by PCR on a panel of radiation hybrids. The radiation hybrid panel
indicated that the most likely position of ACLY on 17q21.1 is between
gastrin (137250) and D17S856 at a distance of 170 to 290 kb from the GAS
locus.
*FIELD* RF
1. Couch, F. J.; Abel, K. J.; Brody, L. C.; Boehnke, M.; Collins,
F. S.; Weber, B. L.: Localization of the gene for ATP citrate lyase
(ACLY) distal to gastrin (GAS) and proximal to D17S856 on chromosome
17q12-q21. Genomics 21: 444-446, 1994.
2. Elshourbagy, N. A.; Near, J. C.; Kmetz, P. J.; Sathe, G. M.; Southan,
C.; Strickler, J. E.; Gross, M.; Young, J. F.; Wells, T. N. C.; Groot,
P. H. E.: Rat ATP citrate-lyase: molecular cloning and sequence analysis
of a full-length cDNA and mRNA abundance as a function of diet, organ,
and age. J. Biol. Chem. 265: 1430-1435, 1990.
3. Elshourbagy, N. A.; Near, J. C.; Kmetz, P. J.; Wells, T. N. C.;
Groot, P. H. E.; Saxty, B. A.; Hughes, S. A.; Franklin, M.; Gloger,
I. S.: Cloning and expression of a human ATP-citrate lyase cDNA. Europ.
J. Biochem. 204: 491-499, 1992.
4. Remmers, E. F.; Goldmuntz, E. A.; Cash, J. M.; Crofford, L. J.;
Misiewicz-Poltorak, B.; Zha, H.; Wilder, R. L.: Genetic map of nine
polymorphic loci comprising a single linkage group on rat chromosome
10: evidence for linkage conservation with human chromosome 17 and
mouse chromosome 11. Genomics 14: 618-623, 1992.
5. Sul, H. S.; Wise, L. S.; Brown, M. L.; Rubin, C. S.: Cloning of
cDNA sequences for murine ATP-citrate lyase: construction of recombinant
plasmids using an immunopurified mRNA template and evidence for the
nutritional regulation of ATP-citrate lyase mRNA content in mouse
liver. J. Biol. Chem. 259: 1201-1205, 1984.
6. Wellen, K. E.; Hatzivassiliou, G.; Sachdeva, U. M.; Bui, T. V.;
Cross, J. R.; Thompson, C. B.: ATP-citrate lyase links cellular metabolism
to histone acetylation. Science 324: 1076-1080, 2009.
*FIELD* CN
Ada Hamosh - updated: 6/17/2009
*FIELD* CD
Victor A. McKusick: 11/4/1992
*FIELD* ED
alopez: 06/23/2009
alopez: 6/23/2009
terry: 6/17/2009
mark: 5/20/1996
jason: 6/9/1994
carol: 4/9/1994
carol: 12/31/1992
carol: 12/16/1992
carol: 11/12/1992
carol: 11/4/1992
*RECORD*
*FIELD* NO
108728
*FIELD* TI
*108728 ATP CITRATE LYASE; ACLY
;;CLATP;;
ATPCL;;
ACL
*FIELD* TX
DESCRIPTION
ATP citrate lyase is the primary enzyme responsible for the synthesis of
read morecytosolic acetyl-CoA in many tissues. The enzyme is a tetramer (relative
molecular weight approximately 440,000) of apparently identical
subunits. It catalyzes the formation of acetyl-CoA and oxaloacetate from
citrate and CoA with a concomitant hydrolysis of ATP to ADP and
phosphate. The product, acetyl-CoA, serves several important
biosynthetic pathways, including lipogenesis and cholesterogenesis. In
nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of
acetylcholine.
CLONING
Cloning of cDNAs has been reported for murine (Sul et al., 1984), rat
(Elshourbagy et al., 1990), and human (Elshourbagy et al., 1992) ATP
citrate lyase. Elshourbagy et al. (1992) found that the subunits of the
enzyme have 1,105 amino acids and a calculated molecular mass of 121,419
Da. The human and rat ATPCL cDNAs showed 96.3% amino acid identity.
GENE FUNCTION
Wellen et al. (2009) showed that histone acetylation in mammalian cells
is dependent on ATP-citrate lyase (ACL), the enzyme that converts
glucose-derived citrate into acetyl-CoA. They found that ACL is required
for increases in histone acetylation in response to growth factor
stimulation and during differentiation, and that glucose availability
can affect histone acetylation in an ACL-dependent manner. Wellen et al.
(2009) concluded that ACL activity is required to link growth
factor-induced increases in nutrient metabolism to the regulation of
histone acetylation and gene expression.
MAPPING
Remmers et al. (1992) found that the genes for growth hormone (139250),
pancreatic polypeptide (167780), ERBB2 (164870), sex hormone binding
globulin (182205), embryonic skeletal myosin heavy chain (160720), and
asialoglycoprotein receptor (108360) map to human chromosome 17 and rat
chromosome 10. Many of the same genes are known to be located on mouse
chromosome 11. Furthermore, Remmers et al. (1992) showed that in the rat
the gene for ATP citrate lyase is closely linked to the gene for PPY,
which in turn is close to the GH gene, on chromosome 10. They predicted,
therefore, that the homologous gene in the human would be located on
chromosome 17, probably close to PPY which is situated at 17q22-q24.
Couch et al. (1994) mapped the ACLY gene to 17q12-q21 by PCR analysis of
a panel of human/rodent somatic cell hybrids and localized it to 17q21.1
by PCR on a panel of radiation hybrids. The radiation hybrid panel
indicated that the most likely position of ACLY on 17q21.1 is between
gastrin (137250) and D17S856 at a distance of 170 to 290 kb from the GAS
locus.
*FIELD* RF
1. Couch, F. J.; Abel, K. J.; Brody, L. C.; Boehnke, M.; Collins,
F. S.; Weber, B. L.: Localization of the gene for ATP citrate lyase
(ACLY) distal to gastrin (GAS) and proximal to D17S856 on chromosome
17q12-q21. Genomics 21: 444-446, 1994.
2. Elshourbagy, N. A.; Near, J. C.; Kmetz, P. J.; Sathe, G. M.; Southan,
C.; Strickler, J. E.; Gross, M.; Young, J. F.; Wells, T. N. C.; Groot,
P. H. E.: Rat ATP citrate-lyase: molecular cloning and sequence analysis
of a full-length cDNA and mRNA abundance as a function of diet, organ,
and age. J. Biol. Chem. 265: 1430-1435, 1990.
3. Elshourbagy, N. A.; Near, J. C.; Kmetz, P. J.; Wells, T. N. C.;
Groot, P. H. E.; Saxty, B. A.; Hughes, S. A.; Franklin, M.; Gloger,
I. S.: Cloning and expression of a human ATP-citrate lyase cDNA. Europ.
J. Biochem. 204: 491-499, 1992.
4. Remmers, E. F.; Goldmuntz, E. A.; Cash, J. M.; Crofford, L. J.;
Misiewicz-Poltorak, B.; Zha, H.; Wilder, R. L.: Genetic map of nine
polymorphic loci comprising a single linkage group on rat chromosome
10: evidence for linkage conservation with human chromosome 17 and
mouse chromosome 11. Genomics 14: 618-623, 1992.
5. Sul, H. S.; Wise, L. S.; Brown, M. L.; Rubin, C. S.: Cloning of
cDNA sequences for murine ATP-citrate lyase: construction of recombinant
plasmids using an immunopurified mRNA template and evidence for the
nutritional regulation of ATP-citrate lyase mRNA content in mouse
liver. J. Biol. Chem. 259: 1201-1205, 1984.
6. Wellen, K. E.; Hatzivassiliou, G.; Sachdeva, U. M.; Bui, T. V.;
Cross, J. R.; Thompson, C. B.: ATP-citrate lyase links cellular metabolism
to histone acetylation. Science 324: 1076-1080, 2009.
*FIELD* CN
Ada Hamosh - updated: 6/17/2009
*FIELD* CD
Victor A. McKusick: 11/4/1992
*FIELD* ED
alopez: 06/23/2009
alopez: 6/23/2009
terry: 6/17/2009
mark: 5/20/1996
jason: 6/9/1994
carol: 4/9/1994
carol: 12/31/1992
carol: 12/16/1992
carol: 11/12/1992
carol: 11/4/1992