ID ACLY_BOVIN Reviewed; 1091 AA. AC Q32PF2; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 06-DEC-2005, sequence version 1. DT 02-SEP-2026, entry version 132. DE RecName: Full=ATP-citrate synthase; DE EC=2.3.3.8 {ECO:0000250|UniProtKB:P53396}; DE AltName: Full=ATP-citrate (pro-S-)-lyase; DE AltName: Full=Citrate cleavage enzyme; GN Name=ACLY; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Ascending colon; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Catalyzes the cleavage of citrate into oxaloacetate and CC acetyl-CoA, the latter serving as common substrate in multiple CC biochemical reactions in protein, carbohydrate and lipid metabolism. CC {ECO:0000250|UniProtKB:P53396}. CC -!- CATALYTIC ACTIVITY: CC Reaction=oxaloacetate + acetyl-CoA + ADP + phosphate = citrate + ATP + 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:0000250|UniProtKB:P53396}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21162; CC Evidence={ECO:0000250|UniProtKB:P53396}; 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 -!- 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). Phosphorylated at Ser-455 by BCKDK and dephosphorylated by CC protein phosphatase PPM1K. {ECO:0000250|UniProtKB:P16638, CC ECO:0000250|UniProtKB:P53396}. CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P53396}. 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 the BCR(KLHL25) CC E3 ubiquitin ligase complex and UBR4, leading to its degradation (By CC similarity). Ubiquitination is probably inhibited by acetylation at CC same site (By similarity). BCR(KLHL25)-mediated degradation of ACLY CC promotes fatty acid oxidation and is required for differentiation of CC inducible regulatory T (iTreg) cells (By similarity). CC {ECO:0000250|UniProtKB:P53396, ECO:0000250|UniProtKB:Q91V92}. CC -!- PTM: Benzoylated at Lys-968. Debenzoylated by SIRT3; inhibiting the CC ATP-citrate synthase activity. {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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC108138; AAI08139.1; -; mRNA. DR RefSeq; NP_001032534.1; NM_001037457.1. DR AlphaFoldDB; Q32PF2; -. DR SMR; Q32PF2; -. DR FunCoup; Q32PF2; 3348. DR STRING; 9913.ENSBTAP00000059914; -. DR GlyGen; Q32PF2; 2 sites. DR PaxDb; 9913-ENSBTAP00000059914; -. DR Ensembl; ENSBTAT00000022258.5; ENSBTAP00000022258.4; ENSBTAG00000016740.7. DR Ensembl; ENSBTAT00085069317; ENSBTAP00085043262; ENSBTAG00085004066. DR Ensembl; ENSBTAT00090083147; ENSBTAP00090047115; ENSBTAG00090039118. DR GeneID; 511135; -. DR KEGG; bta:511135; -. DR CTD; 47; -. DR VEuPathDB; HostDB:ENSBTAG00000016740; -. DR VGNC; VGNC:25543; ACLY. DR eggNOG; KOG1254; Eukaryota. DR GeneTree; ENSGT00940000154881; -. DR HOGENOM; CLU_006587_2_0_1; -. DR InParanoid; Q32PF2; -. DR OrthoDB; 3261737at2759; -. DR Reactome; R-BTA-6798695; Neutrophil degranulation. DR Reactome; R-BTA-75105; Fatty acyl-CoA biosynthesis. DR Proteomes; UP000009136; Chromosome 19. DR Bgee; ENSBTAG00000016740; Expressed in diaphragm and 106 other cell types or tissues. DR ExpressionAtlas; Q32PF2; baseline. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0003878; F:ATP citrate synthase activity; ISS:UniProtKB. DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; IBA:GO_Central. DR GO; GO:0006101; P:citrate metabolic process; IEA:InterPro. DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central. DR GO; GO:0008610; P:lipid biosynthetic process; ISS:UniProtKB. DR CDD; cd06100; CCL_ACL-C; 1. DR FunFam; 1.10.230.10:FF:000004; ATP-citrate synthase; 1. DR FunFam; 3.30.470.110:FF:000001; ATP-citrate synthase; 1. DR FunFam; 3.40.50.261:FF:000003; ATP-citrate synthase subunit; 1. DR FunFam; 3.40.50.261:FF:000004; ATP-citrate synthase subunit; 1. DR FunFam; 3.40.50.720:FF:000024; Probable ATP-citrate synthase; 1. DR Gene3D; 3.30.470.110; -; 1. DR Gene3D; 1.10.580.10; Citrate Synthase, domain 1; 1. DR Gene3D; 1.10.230.10; Cytochrome P450-Terp, domain 2; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR Gene3D; 3.40.50.261; Succinyl-CoA synthetase domains; 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; IPR056749; Citrate_synth_N. 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; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR017866; Succ-CoA_synthase_bsu_CS. DR InterPro; IPR005811; SUCC_ACL_C. DR InterPro; IPR016102; Succinyl-CoA_synth-like. DR PANTHER; PTHR23118; ATP-CITRATE SYNTHASE; 1. DR PANTHER; PTHR23118:SF42; ATP-CITRATE SYNTHASE; 1. DR Pfam; PF16114; Citrate_bind; 1. DR Pfam; PF00285; Citrate_synt; 1. DR Pfam; PF24948; Citrate_synth_N; 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; Citrate synthase; 1. DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR SUPFAM; SSF52210; Succinyl-CoA synthetase domains; 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 2: Evidence at transcript 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_0000270815" FT DOMAIN 4..265 FT /note="ATP-grasp" FT REGION 442..471 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 442..457 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 750 FT /note="Tele-phosphohistidine intermediate" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 58 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 66 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 67 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 109 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 111 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 118 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 216 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 257 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 260 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 262 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 309 FT /ligand="citrate" FT /ligand_id="ChEBI:CHEBI:16947" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 346 FT /ligand="citrate" FT /ligand_id="ChEBI:CHEBI:16947" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 348 FT /ligand="citrate" FT /ligand_id="ChEBI:CHEBI:16947" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 364 FT /ligand="citrate" FT /ligand_id="ChEBI:CHEBI:16947" FT /evidence="ECO:0000250|UniProtKB:P53396" FT BINDING 379 FT /ligand="citrate" FT /ligand_id="ChEBI:CHEBI:16947" FT /evidence="ECO:0000250|UniProtKB:P53396" 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:0000250|UniProtKB:Q91V92" 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 or FT BCKDK" FT /evidence="ECO:0000250|UniProtKB:P53396" 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:0000250|UniProtKB:P53396" FT MOD_RES 672 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P53396" 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; alternate" FT /evidence="ECO:0000250|UniProtKB:Q91V92" FT MOD_RES 968 FT /note="N6-benzoyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P53396" FT MOD_RES 1067 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P53396" FT MOD_RES 1090 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P53396" 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; 119789 MW; CC88C4054C6568D3 CRC64; MSAKAISEQT GKELLYKYIC TTSAIQNRFK YARVTPDTDW ARLLQDHPWL LSQSLVVKPD QLIKRRGKLG LIGVNLTLDG VKSWLKPRLG QEATVGKATG FLKNFLIEPF VPHTQEEEFY 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 TDEVAPAKKA KPAMLQGKSA TLFSRHTKAI VWGMQTRAVQ GMLDFDYVCS RDEPSVAAMV YPFTGDHKQK FYWGHKEILI PVFKNMADAM KKHPEVDVLI NFASLRSAYD STMETMNYAQ IRTIAIIAEG IPEALTRKLI KKADQKGVTI IGPATVGGIK PGCFKIGNTG GMLDNILASK LYRPGSVAYV SRSGGMSNEL NNIISRTTDG VYEGVAIGGD RYPGSTFMDH VLRYQDTAGV KMIVVLGEIG GTEEYKICRG VTEGRITKPV VCWCIGTCAA MFSSEVQFGH AGACANQASE TAVAKNQALK EAGVFVPRSF DELGEIIQSV YEDLVARGVI VPAQEVPPPT VPMDYSWARE LGLIRKPASF MTSICDERGQ ELIYAGMPIT EVFKEEMGIG GVLGLLWFQK RLPKYSCQFI EMCLMVTADH GPAVSGAHNT IICARAGKDL VSSLTSGLLT IGDRFGGALD AAAKMFSKAF DSGIIPMEFV NKMKKEGKLI MGIGHRVKSI NNPDMRVQIL KDYVRQHFPA TPLLDYALEV EKITTSKKPN LILNVDGLIG VAFVDMLRHC GSFTREEADE YIDIGALNGI FVLGRSMGFI GHYLDQKRLK QGLYRHPWDD ISYVLPEHMS M //