ACLY_MOUSE
ID ACLY_MOUSE Reviewed; 1091 AA.
AC Q91V92;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=ATP-citrate synthase;
DE EC=2.3.3.8 {ECO:0000269|PubMed:25450640};
DE AltName: Full=ATP-citrate (pro-S-)-lyase;
DE AltName: Full=Citrate cleavage enzyme;
GN Name=Acly;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ILS, and ISS;
RX PubMed=11471062; DOI=10.1007/s00335-001-1001-x;
RA Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J.,
RA Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.;
RT "High-throughput sequence identification of gene coding variants within
RT alcohol-related QTLs.";
RL Mamm. Genome 12:657-663(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-672, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-672, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263; SER-653 AND SER-1090,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-968, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25450640; DOI=10.1016/j.jbiotec.2014.10.004;
RA Zhang H., Zhang L., Chen H., Chen Y.Q., Chen W., Song Y., Ratledge C.;
RT "Enhanced lipid accumulation in the yeast Yarrowia lipolytica by over-
RT expression of ATP:citrate lyase from Mus musculus.";
RL J. Biotechnol. 192:78-84(2014).
CC -!- FUNCTION: Catalyzes the cleavage of citrate into oxaloacetate and
CC acetyl-CoA, the latter serving as common substrate for de novo
CC cholesterol and fatty acid synthesis. {ECO:0000269|PubMed:25450640}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + ADP + oxaloacetate + phosphate = ATP + citrate +
CC CoA; Xref=Rhea:RHEA:21160, ChEBI:CHEBI:16452, ChEBI:CHEBI:16947,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:456216; EC=2.3.3.8;
CC Evidence={ECO:0000269|PubMed:25450640};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21162;
CC Evidence={ECO:0000305|PubMed:25450640};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P53396};
CC -!- ACTIVITY REGULATION: Phosphorylation results in activation of its
CC activity (By similarity). Glucose 6-phosphate, fructose 6-phosphate,
CC fructose 2,6-bisphosphate, ribulose 5-phosphate, and fructose 1,6-
CC bisphosphate also act as activators (By similarity).
CC {ECO:0000250|UniProtKB:P53396}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P53396}.
CC -!- INTERACTION:
CC Q91V92; Q8CFN5-4: Mef2c; NbExp=3; IntAct=EBI-644049, EBI-643822;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P53396}.
CC -!- PTM: Phosphorylated by PKA and GSK3 in a sequential manner;
CC phosphorylation results in activation of its activity (By similarity).
CC Phosphorylation on Thr-447 and Ser-451 depends on the phosphorylation
CC state of Ser-455 (By similarity). Phosphorylation on Ser-455 is
CC decreased by prior phosphorylation on the other 2 residues (By
CC similarity). {ECO:0000250|UniProtKB:P16638,
CC ECO:0000250|UniProtKB:P53396}.
CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}.
CC -!- PTM: Acetylated at Lys-530, Lys-536 and Lys-544 by KAT2B/PCAF (By
CC similarity). Acetylation is promoted by glucose and stabilizes the
CC protein, probably by preventing ubiquitination at the same sites (By
CC similarity). Acetylation promotes de novo lipid synthesis (By
CC similarity). Deacetylated by SIRT2 (By similarity).
CC {ECO:0000250|UniProtKB:P53396}.
CC -!- PTM: Ubiquitinated at Lys-530, Lys-536 and Lys-544 by UBR4, leading to
CC its degradation (By similarity). Ubiquitination is probably inhibited
CC by acetylation at same site (By similarity).
CC {ECO:0000250|UniProtKB:P53396}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the succinate/malate
CC CoA ligase beta subunit family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the succinate/malate
CC CoA ligase alpha subunit family. {ECO:0000305}.
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DR EMBL; AF332052; AAK56081.1; -; mRNA.
DR EMBL; AF332051; AAK56080.1; -; mRNA.
DR EMBL; BC056378; AAH56378.1; -; mRNA.
DR CCDS; CCDS25425.1; -.
DR RefSeq; NP_598798.1; NM_134037.3.
DR AlphaFoldDB; Q91V92; -.
DR SMR; Q91V92; -.
DR BioGRID; 222369; 19.
DR IntAct; Q91V92; 2.
DR MINT; Q91V92; -.
DR STRING; 10090.ENSMUSP00000103012; -.
DR ChEMBL; CHEMBL3264; -.
DR SwissLipids; SLP:000001386; -.
DR iPTMnet; Q91V92; -.
DR PhosphoSitePlus; Q91V92; -.
DR SwissPalm; Q91V92; -.
DR EPD; Q91V92; -.
DR jPOST; Q91V92; -.
DR MaxQB; Q91V92; -.
DR PaxDb; Q91V92; -.
DR PeptideAtlas; Q91V92; -.
DR PRIDE; Q91V92; -.
DR ProteomicsDB; 285643; -.
DR Antibodypedia; 3578; 565 antibodies from 37 providers.
DR DNASU; 104112; -.
DR Ensembl; ENSMUST00000007131; ENSMUSP00000007131; ENSMUSG00000020917.
DR Ensembl; ENSMUST00000165111; ENSMUSP00000127632; ENSMUSG00000020917.
DR GeneID; 104112; -.
DR KEGG; mmu:104112; -.
DR UCSC; uc007lll.2; mouse.
DR CTD; 47; -.
DR MGI; MGI:103251; Acly.
DR VEuPathDB; HostDB:ENSMUSG00000020917; -.
DR eggNOG; KOG1254; Eukaryota.
DR GeneTree; ENSGT00940000154881; -.
DR HOGENOM; CLU_006587_2_0_1; -.
DR InParanoid; Q91V92; -.
DR BRENDA; 2.3.3.8; 3474.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-75105; Fatty acyl-CoA biosynthesis.
DR BioGRID-ORCS; 104112; 20 hits in 77 CRISPR screens.
DR ChiTaRS; Acly; mouse.
DR PRO; PR:Q91V92; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q91V92; protein.
DR Bgee; ENSMUSG00000020917; Expressed in facial nucleus and 290 other tissues.
DR ExpressionAtlas; Q91V92; baseline and differential.
DR Genevisible; Q91V92; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003878; F:ATP citrate synthase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; ISO:MGI.
DR GO; GO:0006101; P:citrate metabolic process; ISS:BHF-UCL.
DR GO; GO:0006633; P:fatty acid biosynthetic process; ISO:MGI.
DR GO; GO:0008610; P:lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006107; P:oxaloacetate metabolic process; ISS:BHF-UCL.
DR Gene3D; 1.10.230.10; -; 1.
DR Gene3D; 1.10.580.10; -; 1.
DR Gene3D; 3.40.50.261; -; 2.
DR InterPro; IPR014608; ATP-citrate_synthase.
DR InterPro; IPR017440; Cit_synth/succinyl-CoA_lig_AS.
DR InterPro; IPR032263; Citrate-bd.
DR InterPro; IPR016142; Citrate_synth-like_lrg_a-sub.
DR InterPro; IPR016143; Citrate_synth-like_sm_a-sub.
DR InterPro; IPR002020; Citrate_synthase.
DR InterPro; IPR036969; Citrate_synthase_sf.
DR InterPro; IPR033847; Citrt_syn/SCS-alpha_CS.
DR InterPro; IPR003781; CoA-bd.
DR InterPro; IPR005811; CoA_ligase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR017866; Succ-CoA_synthase_bsu_CS.
DR InterPro; IPR016102; Succinyl-CoA_synth-like.
DR Pfam; PF16114; Citrate_bind; 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 SMART; SM00881; CoA_binding; 1.
DR SUPFAM; SSF48256; SSF48256; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52210; SSF52210; 1.
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 Acetylation; ATP-binding; Cytoplasm; Isopeptide bond; Lipid biosynthesis;
KW Lipid metabolism; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation.
FT CHAIN 1..1091
FT /note="ATP-citrate synthase"
FT /id="PRO_0000102782"
FT DOMAIN 4..265
FT /note="ATP-grasp"
FT REGION 442..478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 442..458
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 750
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000250"
FT BINDING 58
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 66..67
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 109..111
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 118
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 201
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 203
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 346
FT /ligand="citrate"
FT /ligand_id="ChEBI:CHEBI:16947"
FT /evidence="ECO:0000250"
FT BINDING 348
FT /ligand="citrate"
FT /ligand_id="ChEBI:CHEBI:16947"
FT /evidence="ECO:0000250"
FT BINDING 379
FT /ligand="citrate"
FT /ligand_id="ChEBI:CHEBI:16947"
FT /evidence="ECO:0000250"
FT BINDING 691..711
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 708
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 742..768
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 769..779
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255"
FT MOD_RES 131
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 447
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P16638"
FT MOD_RES 451
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16638"
FT MOD_RES 455
FT /note="Phosphoserine; by PKA and PKB/AKT1 or PKB/AKT2"
FT /evidence="ECO:0007744|PubMed:19131326"
FT MOD_RES 459
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 530
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 536
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 544
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 629
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 653
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 672
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455"
FT MOD_RES 829
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 938
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 958
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 968
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 1067
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 1090
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 530
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT CROSSLNK 536
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT CROSSLNK 544
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
SQ SEQUENCE 1091 AA; 119728 MW; 660293D027D797DD CRC64;
MSAKAISEQT GKELLYKYIC TTSAIQNRFK YARVTPDTDW AHLLQDHPWL LSQSLVVKPD
QLIKRRGKLG LVGVNLSLDG VKSWLKPRLG HEATVGKAKG FLKNFLIEPF VPHSQAEEFY
VCIYATREGD YVLFHHEGGV DVGDVDAKAQ KLLVGVDEKL NTEDIKRHLL VHAPEDKKEV
LASFISGLFN FYEDLYFTYL EINPLVVTKD GVYILDLAAK VDATADYICK VKWGDIEFPP
PFGREAYPEE AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE
LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPEGKILII GGSIANFTNV AATFKGIVRA
IRDYQGPLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI PIHVFGTETH MTAIVGMALG
HRPIPNQPPT AAHTANFLLN ASGSTSTPAP SRTASFSESR ADEVAPAKKA KPAMPQGKSA
TLFSRHTKAI VWGMQTRAVQ GMLDFDYVCS RDEPSVAAMV YPFTGDHKQK FYWGHKEILI
PVFKNMADAM KKHPEVDVLI NFASLRSAYD STMETMNYAQ IRTIAIIAEG IPEALTRKLI
KKADQKGVTI IGPATVGGIK PGCFKIGNTG GMLDNILASK LYRPGSVAYV SRSGGMSNEL
NNIISRTTDG VYEGVAIGGD RYPGSTFMDH VLRYQDTPGV KMIVVLGEIG GTEEYKICRG
IKEGRLTKPV VCWCIGTCAT MFSSEVQFGH AGACANQASE TAVAKNQALK EAGVFVPRSF
DELGEIIQSV YEDLVAKGAI VPAQEVPPPT VPMDYSWARE LGLIRKPASF MTSICDERGQ
ELIYAGMPIT EVFKEEMGIG GVLGLLWFQR RLPKYSCQFI EMCLMVTADH GPAVSGAHNT
IICARAGKDL VSSLTSGLLT IGDRFGGALD AAAKMFSKAF DSGIIPMEFV NKMKKEGKLI
MGIGHRVKSI NNPDMRVQIL KDFVKQHFPA TPLLDYALEV EKITTSKKPN LILNVDGFIG
VAFVDMLRNC GSFTREEADE YVDIGALNGI FVLGRSMGFI GHYLDQKRLK QGLYRHPWDD
ISYVLPEHMS M
