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   03-AUG-2022, entry version 115.
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 for de novo
CC       cholesterol and fatty acid synthesis. {ECO:0000250|UniProtKB:P53396}.
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: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). {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 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; BC108138; AAI08139.1; -; mRNA.
DR   RefSeq; NP_001032534.1; NM_001037457.1.
DR   AlphaFoldDB; Q32PF2; -.
DR   SMR; Q32PF2; -.
DR   STRING; 9913.ENSBTAP00000022258; -.
DR   PaxDb; Q32PF2; -.
DR   PRIDE; Q32PF2; -.
DR   Ensembl; ENSBTAT00000022258; ENSBTAP00000022258; ENSBTAG00000016740.
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; 349367at2759; -.
DR   TreeFam; TF300560; -.
DR   Proteomes; UP000009136; Chromosome 19.
DR   Bgee; ENSBTAG00000016740; Expressed in diaphragm and 106 other tissues.
DR   ExpressionAtlas; Q32PF2; baseline and differential.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003878; F:ATP citrate synthase activity; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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   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   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..460
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: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"
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"
FT                   /evidence="ECO:0000250|UniProtKB:Q91V92"
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