ID   Q4LE36_HUMAN            Unreviewed;      1137 AA.
AC   Q4LE36;
DT   02-AUG-2005, integrated into UniProtKB/TrEMBL.
DT   02-AUG-2005, sequence version 1.
DT   02-SEP-2026, entry version 110.
DE   RecName: Full=ATP-citrate synthase {ECO:0000256|ARBA:ARBA00015259};
DE            EC=2.3.3.8 {ECO:0000256|ARBA:ARBA00012639};
DE   AltName: Full=ATP-citrate (pro-S-)-lyase {ECO:0000256|ARBA:ARBA00030151};
DE   AltName: Full=Citrate cleavage enzyme {ECO:0000256|ARBA:ARBA00030982};
DE   Flags: Fragment;
GN   Name=ACLY variant protein {ECO:0000313|EMBL:BAE06117.1};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606 {ECO:0000313|EMBL:BAE06117.1};
RN   [1] {ECO:0000313|EMBL:BAE06117.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Brain {ECO:0000313|EMBL:BAE06117.1};
RA   Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R.,
RA   Okazaki N., Koga H., Nagase T., Ohara O.;
RT   "Preparation of a set of expression-ready clones of mammalian long cDNAs
RT   encoding large proteins by the ORF trap cloning method.";
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 in multiple
CC       biochemical reactions in protein, carbohydrate and lipid metabolism.
CC       {ECO:0000256|ARBA:ARBA00093367}.
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:0000256|ARBA:ARBA00048669};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21162;
CC         Evidence={ECO:0000256|ARBA:ARBA00048669};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000256|ARBA:ARBA00001946};
CC   -!- SUBUNIT: Homotetramer. {ECO:0000256|ARBA:ARBA00011881}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000256|ARBA:ARBA00004514}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the succinate/malate
CC       CoA ligase alpha subunit family. {ECO:0000256|ARBA:ARBA00005899}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the succinate/malate
CC       CoA ligase beta subunit family. {ECO:0000256|ARBA:ARBA00010719}.
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DR   EMBL; AB210035; BAE06117.1; -; mRNA.
DR   AlphaFoldDB; Q4LE36; -.
DR   IntAct; Q4LE36; 2.
DR   DNASU; 47; -.
DR   DisGeNET; 47; -.
DR   OrthoDB; 3261737at2759; -.
DR   BioGRID-ORCS; 47; 321 hits in 1165 CRISPR screens.
DR   ChiTaRS; ACLY; human.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0003878; F:ATP citrate synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006085; P:acetyl-CoA biosynthetic process; IEA:InterPro.
DR   GO; GO:0006101; P:citrate metabolic process; IEA:InterPro.
DR   CDD; cd06100; CCL_ACL-C; 1.
DR   FunFam; 1.10.230.10:FF:000004; ATP-citrate synthase; 1.
DR   FunFam; 1.10.580.10:FF:000009; 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; 1.10.230.10; 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; 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 {ECO:0000256|ARBA:ARBA00022990};
KW   ATP-binding {ECO:0000256|ARBA:ARBA00022840};
KW   Cytoplasm {ECO:0000256|ARBA:ARBA00022490};
KW   Isopeptide bond {ECO:0000256|ARBA:ARBA00022499};
KW   Lipid biosynthesis {ECO:0000256|ARBA:ARBA00022516};
KW   Lipid metabolism {ECO:0000256|ARBA:ARBA00023098};
KW   Magnesium {ECO:0000256|ARBA:ARBA00022842};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW   Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741};
KW   Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW   Transferase {ECO:0000256|ARBA:ARBA00022679};
KW   Ubl conjugation {ECO:0000256|ARBA:ARBA00022843}.
FT   DOMAIN          528..637
FT                   /note="CoA-binding"
FT                   /evidence="ECO:0000259|SMART:SM00881"
FT   REGION          477..523
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        477..493
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        514..523
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        796
FT                   /note="Tele-phosphohistidine intermediate"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR036511-1"
FT   NON_TER         1
FT                   /evidence="ECO:0000313|EMBL:BAE06117.1"
SQ   SEQUENCE   1137 AA;  124557 MW;  E634EE8F9AEDB882 CRC64;
     LPAAGVLRIL RGSSGLWKKR RARTSAETGR AGLSAAMSAK AISEQTGKEL LYKFICTTSA
     IQNRFKYARV TPDTDWARLL QDHPWLLSQN LVVKPDQLIK RRGKLGLVGV NLTLDGVKSW
     LKPRLGQEAT VGKATGFLKN FLIEPFVPHS QAEEFYVCIY ATREGDYVLF HHEGGVDVGD
     VDAKAQKLLV GVDEKLNPED IKKHLLVHAP EDKKEILASF ISGLFNFYED LYFTYLEINP
     LVVTKDGVYV LDLAAKVDAT ADYICKVKWG DIEFPPPFGR EAYPEEAYIA DLDAKSGASL
     KLTLLNPKGR IWTMVAGGGA SVVYSDTICD LGGVNELANY GEYSGAPSEQ QTYDYAKTIL
     SLMTREKHPD GKILIIGGSI ANFTNVAATF KGIVRAIRDY QGPLKEHEVT IFVRRGGPNY
     QEGLRVMGEV GKTTGIPIHV FGTETHMTAI VGMALGHRPI PNQPPTAAHT ANFLLNASGS
     TSTPAPSRTA SFSESRADEV APAKKAKPAM PQDSVPSPRS LQGKSTTLFS RHTKAIVWGM
     QTRAVQGMLD FDYVCSRDEP SVAAMVYPFT GDHKQKFYWG HKEILIPVFK NMADAMRKHP
     EVDVLINFAS LRSAYDSTME TMNYAQIRTI AIIAEGIPEA LTRKLIKKAD QKGVTIIGPA
     TVGGIKPGCF KIGNTGGMLD NILASKLYRP GSVAYVSRSG GMSNELNNII SRTTDGVYEG
     VAIGGDRYPG STFMDHVLRY QDTPGVKMIV VLGEIGGTEE YKICRGIKEG RLTKPIVCWC
     IGTCATMFSS EVQFGHAGAC ANQASETAVA KNQALKEAGV FVPRSFDELG EIIQSVYEDL
     VANGVIVPAQ EVPPPTVPMD YSWARELGLI RKPASFMTSI CDERGQELIY AGMPITEVFK
     EEMGIGGVLG LLWFQKRLPK YSCQFIEMCL MVTADHGPAV SGAHNTIICA RAGKDLVSSL
     TSGLLTIGDR FGGALDAAAK MFSKAFDSGI IPMEFVNKMK KEGKLIMGIG HRVKSINNPD
     MRVQILKDYV RQHFPATPLL DYALEVEKIT TSKKPNLILN VDGLIGVAFV DMLRNCGSFT
     REEADEYIDI GALNGIFVLG RSMGFIGHYL DQKRLKQGLY RHPWDDISYV LPEHMSM
//