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 27-MAR-2024, entry version 122.
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). 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 -!- 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.ENSBTAP00000059914; -.
DR PaxDb; 9913-ENSBTAP00000022258; -.
DR Ensembl; ENSBTAT00000022258.5; ENSBTAP00000022258.4; ENSBTAG00000016740.6.
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 TreeFam; TF300560; -.
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: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 GO; GO:0006099; P:tricarboxylic acid cycle; IEA:InterPro.
DR CDD; cd06100; CCL_ACL-C; 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; 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; 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..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|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"
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
//
