ACLY_SHEEP
ID ACLY_SHEEP Reviewed; 1101 AA.
AC Q2TCH3;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 85.
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 Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pineal gland;
RA Morin F., Moller M., Mukda S., Benjamin W.B., Shi Q., Jaffe H., Malpaux B.,
RA Klein D.C.;
RT "Pineal ATP-citrate lyase: function and regulation.";
RL Submitted (MAR-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-540, Lys-546 and Lys-554 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-540, Lys-546 and Lys-554 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; AY971952; AAY40742.1; -; mRNA.
DR RefSeq; NP_001033711.1; NM_001038622.1.
DR RefSeq; XP_012040508.1; XM_012185118.2.
DR RefSeq; XP_012040509.1; XM_012185119.2.
DR AlphaFoldDB; Q2TCH3; -.
DR SMR; Q2TCH3; -.
DR STRING; 9940.ENSOARP00000019140; -.
DR PRIDE; Q2TCH3; -.
DR GeneID; 654404; -.
DR KEGG; oas:654404; -.
DR CTD; 47; -.
DR eggNOG; KOG1254; Eukaryota.
DR OrthoDB; 349367at2759; -.
DR Proteomes; UP000002356; Unplaced.
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; IEA:InterPro.
DR GO; GO:0006101; P:citrate metabolic process; IEA:InterPro.
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..1101
FT /note="ATP-citrate synthase"
FT /id="PRO_0000270816"
FT DOMAIN 4..265
FT /note="ATP-grasp"
FT REGION 440..485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 440..460
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 760
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 701..721
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 718
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 752..778
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 779..789
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"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 459
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 481
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 540
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 546
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 554
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 639
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 663
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 682
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 839
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 948
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 968
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 978
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91V92"
FT MOD_RES 1077
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT MOD_RES 1100
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT CROSSLNK 540
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT CROSSLNK 546
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
FT CROSSLNK 554
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P53396"
SQ SEQUENCE 1101 AA; 120934 MW; 92D0F0DCB0E2D445 CRC64;
MSAKAISEQT GKELLYKYIC TTSAIQNRFK YARVTPDTDW ARLLQDHPWL LSQSLVVKPD
QLIKRRGKLG LVGVNLTLDG VKSWLKPRLG QEATVGKATG FLKNFLIEPF VPHTQEEEFY
VCIYATREGD YVLFHHEGGV DVGDVDAKAQ KLLVAVDEKL NPEDIKKHLL VHAPEDKKEI
LASFISGLFN FYEDLYFTYL EINPLVVTKD GVYILDLAAK 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 KPAMPQDSVP
SPRPLQGKSA TLFSRHTKAI VWGMQTRAVQ GMLDFDYVCS RDEPSVAAMV YPFTGDHKQK
FYWGHKEILI PVFKNMADAM KKHPEVDVLI NFASLRSAYD STMETMNYTQ IRTIAIIAEG
IPEALTRKLI KKAEQKGVTI IGPATVGGIK PGCFKIGNTG GMLDNILASK LYRPGSVAYV
SRSGGMSNEL NNIISRTTDG VYEGVAIGGD RYPGSTFMDH VLRYQDTPGV 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
