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UniProtKB - P16638 (ACLY_RAT)
Protein
ATP-citrate synthase
Gene
Acly
Organism
Rattus norvegicus (Rat)
Status
Functioni
Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis.
1 PublicationCatalytic activityi
Cofactori
Mg2+By similarity
Activity regulationi
Phosphorylation results in activation of its activity (By similarity). Glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate, ribulose 5-phosphate, and fructose 1,6-bisphosphate also act as activators (By similarity).By similarity
Kineticsi
- KM=155.0 µM for citrate1 Publication
- KM=103.0 µM for ATP1 Publication
- KM=15.0 µM for CoA1 Publication
- Vmax=1.9 µmol/h/µg enzyme1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 58 | ATPBy similarity | 1 | |
Binding sitei | 118 | ATPBy similarity | 1 | |
Metal bindingi | 201 | MagnesiumBy similarity | 1 | |
Metal bindingi | 203 | MagnesiumBy similarity | 1 | |
Binding sitei | 346 | Citrate; via amide nitrogenBy similarity | 1 | |
Binding sitei | 348 | CitrateBy similarity | 1 | |
Binding sitei | 379 | CitrateBy similarity | 1 | |
Metal bindingi | 717 | MagnesiumBy similarity | 1 | |
Active sitei | 759 | Tele-phosphohistidine intermediate | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 66 – 67 | ATPBy similarity | 2 | |
Nucleotide bindingi | 109 – 111 | ATPBy similarity | 3 | |
Nucleotide bindingi | 700 – 720 | ATPBy similarityAdd BLAST | 21 | |
Nucleotide bindingi | 751 – 777 | ATPBy similarityAdd BLAST | 27 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- ATP citrate synthase activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- acetyl-CoA biosynthetic process Source: RGD
- acetyl-CoA metabolic process Source: RGD
- citrate metabolic process Source: RGD
- fatty acid biosynthetic process Source: RGD
- lipid biosynthetic process Source: UniProtKB
- lipid metabolic process Source: RGD
- oxaloacetate metabolic process Source: RGD
Keywordsi
Molecular function | Transferase |
Biological process | Lipid biosynthesis, Lipid metabolism |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-RNO-6798695, Neutrophil degranulation R-RNO-75105, Fatty acyl-CoA biosynthesis |
Names & Taxonomyi
Protein namesi | Recommended name: ATP-citrate synthase (EC:2.3.3.81 Publication)Alternative name(s): ATP-citrate (pro-S-)-lyase Citrate cleavage enzyme |
Gene namesi | Name:Acly |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 2018, Acly |
Subcellular locationi
Cytoplasm and Cytosol
- cytosol By similarity
Cytosol
- cytosol Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000102783 | 1 – 1100 | ATP-citrate synthaseAdd BLAST | 1100 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 131 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 263 | PhosphoserineBy similarity | 1 | |
Modified residuei | 446 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 450 | Phosphoserine1 Publication | 1 | |
Modified residuei | 454 | Phosphoserine; by PKA and PKB/AKT1 or PKB/AKT2Combined sources1 Publication | 1 | |
Modified residuei | 458 | PhosphoserineBy similarity | 1 | |
Modified residuei | 480 | PhosphoserineCombined sources | 1 | |
Modified residuei | 539 | N6-acetyllysine; alternateBy similarity | 1 | |
Cross-linki | 539 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity | ||
Modified residuei | 545 | N6-acetyllysine; alternateBy similarity | 1 | |
Cross-linki | 545 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity | ||
Modified residuei | 553 | N6-acetyllysine; alternateBy similarity | 1 | |
Cross-linki | 553 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity | ||
Modified residuei | 638 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 662 | PhosphoserineCombined sources | 1 | |
Modified residuei | 681 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 838 | PhosphoserineBy similarity | 1 | |
Modified residuei | 947 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 967 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 977 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 1076 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 1099 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Phosphorylated by PKA and GSK3 in a sequential manner; phosphorylation results in activation of its activity (By similarity). Phosphorylation on Thr-446 and Ser-450 depends on the phosphorylation state of Ser-454 (PubMed:12107176, PubMed:2176822). Phosphorylation on Ser-454 is decreased by prior phosphorylation on the other 2 residues (PubMed:12107176, PubMed:2176822).By similarity2 Publications
The N-terminus is blocked.1 Publication
ISGylated.By similarity
Acetylated at Lys-539, Lys-545 and Lys-553 by KAT2B/PCAF (By similarity). Acetylation is promoted by glucose and stabilizes the protein, probably by preventing ubiquitination at the same sites (By similarity). Acetylation promotes de novo lipid synthesis (By similarity). Deacetylated by SIRT2 (By similarity).By similarity
Ubiquitinated at Lys-539, Lys-545 and Lys-553 by UBR4, leading to its degradation (By similarity). Ubiquitination is probably inhibited by acetylation at same site (By similarity).By similarity
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | P16638 |
PaxDbi | P16638 |
PeptideAtlasi | P16638 |
PRIDEi | P16638 |
PTM databases
iPTMneti | P16638 |
PhosphoSitePlusi | P16638 |
Expressioni
Tissue specificityi
Expressed in the brain, kidney, mammary gland, lung and liver.1 Publication
Interactioni
Subunit structurei
Homotetramer.
By similarityProtein-protein interaction databases
BioGRIDi | 246351, 6 interactors |
IntActi | P16638, 3 interactors |
MINTi | P16638 |
STRINGi | 10116.ENSRNOP00000023447 |
Chemistry databases
BindingDBi | P16638 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 4 – 265 | ATP-graspAdd BLAST | 262 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 442 – 485 | DisorderedSequence analysisAdd BLAST | 44 | |
Regioni | 778 – 788 | CoA-bindingSequence analysisAdd BLAST | 11 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 442 – 457 | Polar residuesSequence analysisAdd BLAST | 16 |
Sequence similaritiesi
In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.Curated
In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family.Curated
Phylogenomic databases
eggNOGi | KOG1254, Eukaryota |
InParanoidi | P16638 |
OrthoDBi | 349367at2759 |
PhylomeDBi | P16638 |
Family and domain databases
Gene3Di | 1.10.230.10, 1 hit 1.10.580.10, 1 hit 3.40.50.261, 2 hits |
InterProi | View protein in InterPro IPR014608, ATP-citrate_synthase IPR017440, Cit_synth/succinyl-CoA_lig_AS IPR032263, Citrate-bd IPR016142, Citrate_synth-like_lrg_a-sub IPR016143, Citrate_synth-like_sm_a-sub IPR002020, Citrate_synthase IPR036969, Citrate_synthase_sf IPR033847, Citrt_syn/SCS-alpha_CS IPR003781, CoA-bd IPR005811, CoA_ligase IPR036291, NAD(P)-bd_dom_sf IPR017866, Succ-CoA_synthase_bsu_CS IPR016102, Succinyl-CoA_synth-like |
Pfami | View protein in Pfam PF16114, Citrate_bind, 1 hit PF00285, Citrate_synt, 1 hit PF02629, CoA_binding, 1 hit PF00549, Ligase_CoA, 1 hit |
PIRSFi | PIRSF036511, ATP_citrt_syn, 1 hit |
SMARTi | View protein in SMART SM00881, CoA_binding, 1 hit |
SUPFAMi | SSF48256, SSF48256, 1 hit SSF51735, SSF51735, 1 hit SSF52210, SSF52210, 1 hit |
PROSITEi | View protein in PROSITE PS01216, SUCCINYL_COA_LIG_1, 1 hit PS00399, SUCCINYL_COA_LIG_2, 1 hit PS01217, SUCCINYL_COA_LIG_3, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P16638-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSAKAISEQT GKELLYKYIC TTSAIQNRFK YARVTPDTDW AHLLQDHPWL
60 70 80 90 100
LSQSLVVKPD QLIKRRGKLG LVGVNLSLDG VKSWLKPRLG HEATVGKAKG
110 120 130 140 150
FLKNFLIEPF VPHSQAEEFY VCIYATREGD YVLFHHEGGV DVGDVDTKAQ
160 170 180 190 200
KLLVGVDEKL NAEDIKRHLL VHAPEDKKEI LASFISGLFN FYEDLYFTYL
210 220 230 240 250
EINPLVVTKD GVYILDLAAK VDATADYICK VKWGDIEFPP PFGREAYPEE
260 270 280 290 300
AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE
310 320 330 340 350
LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV
360 370 380 390 400
AATFKGIVRA IRDYQGSLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI
410 420 430 440 450
PIHVFGTETH MTAIVGMAWA PAIPNQPPTA AHTANFLLNA SGSTSTPAPS
460 470 480 490 500
RTASFSESRA DEVAPAKKAK PAMPQDSVPS PRSLQGKSAT LFSRHTKAIV
510 520 530 540 550
WGMQTRAVQG MLDFDYVCSR DEPSVAAMVY PFTGDHKQKF YWGHKEILIP
560 570 580 590 600
VFKNMADAMK KHPEVDVLIN FASLRSAYDS TMETMNYAQI RTIAIIAEGI
610 620 630 640 650
PEALTRKLIK KADQKGVTII GPATVGGIKP GCFKIGNTGG MLDNILASKL
660 670 680 690 700
YRPGSVAYVS RSGGMSNELN NIISRTTDGV YEGVAIGGDR YPGSTFMDHV
710 720 730 740 750
LRYQDTPGVK MIVVLGEIGG TEEYKICRGI KEGRLTKPVV CWCIGTCATM
760 770 780 790 800
FSSEVQFGHA GACANQASET AVAKNQALKE AGVFVPRSFD ELGEIIQSVY
810 820 830 840 850
EDLVAKGAIV PAQEVPPPTV PMDYSWAREL GLIRKPASFM TSICDERGQE
860 870 880 890 900
LIYAGMPITE VFKEEMGIGG VLGLLWFQRR LPKYSCQFIE MCLMVTADHG
910 920 930 940 950
PAVSGAHNTI ICARAGKDLV SSLTSGLLTI GDRFGGALDA AAKMFSKAFD
960 970 980 990 1000
SGIIPMEFVN KMKKEGKLIM GIGHRVKSIN NPDMRVQILK DFVKQHFPAT
1010 1020 1030 1040 1050
PLLDYALEVE KITTSKKPNL ILNVDGFIGV AFVDMLRNCG SFTREEADEY
1060 1070 1080 1090 1100
VDIGALNGVF VLGRSMGFIG HYLDQKRLKQ GLYRHPWDDI SYVLPEHMSM
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG3V888 | G3V888_RAT | ATP-citrate synthase | Acly rCG_33241 | 1,101 | Annotation score: | ||
G3V9G4 | G3V9G4_RAT | ATP-citrate synthase | Acly rCG_33241 | 1,091 | Annotation score: | ||
A0A0G2K5E7 | A0A0G2K5E7_RAT | ATP-citrate synthase | Acly | 1,070 | Annotation score: | ||
A0A8I6AM81 | A0A8I6AM81_RAT | ATP-citrate synthase | Acly | 1,085 | Annotation score: | ||
A0A8I6GAT1 | A0A8I6GAT1_RAT | ATP-citrate synthase | Acly | 491 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 116 | A → V in AAI00619 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 367 | S → P in AAI00619 (PubMed:15489334).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_026273 | 419 – 422 | WAPA → LGHRP in isoform 2. 1 Publication | 4 | |
Alternative sequenceiVSP_026274 | 475 – 484 | Missing in isoform 2. 1 Publication | 10 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J05210 mRNA Translation: AAA74463.1 BC100618 mRNA Translation: AAI00619.1 AH011205 Genomic DNA Translation: AAL34316.1 |
PIRi | A35007 |
RefSeqi | NP_001104565.1, NM_001111095.1 NP_058683.2, NM_016987.2 |
Genome annotation databases
GeneIDi | 24159 |
KEGGi | rno:24159 |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J05210 mRNA Translation: AAA74463.1 BC100618 mRNA Translation: AAI00619.1 AH011205 Genomic DNA Translation: AAL34316.1 |
PIRi | A35007 |
RefSeqi | NP_001104565.1, NM_001111095.1 NP_058683.2, NM_016987.2 |
3D structure databases
AlphaFoldDBi | P16638 |
SMRi | P16638 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 246351, 6 interactors |
IntActi | P16638, 3 interactors |
MINTi | P16638 |
STRINGi | 10116.ENSRNOP00000023447 |
Chemistry databases
BindingDBi | P16638 |
ChEMBLi | CHEMBL2745 |
PTM databases
iPTMneti | P16638 |
PhosphoSitePlusi | P16638 |
Proteomic databases
jPOSTi | P16638 |
PaxDbi | P16638 |
PeptideAtlasi | P16638 |
PRIDEi | P16638 |
Genome annotation databases
GeneIDi | 24159 |
KEGGi | rno:24159 |
Organism-specific databases
CTDi | 47 |
RGDi | 2018, Acly |
Phylogenomic databases
eggNOGi | KOG1254, Eukaryota |
InParanoidi | P16638 |
OrthoDBi | 349367at2759 |
PhylomeDBi | P16638 |
Enzyme and pathway databases
Reactomei | R-RNO-6798695, Neutrophil degranulation R-RNO-75105, Fatty acyl-CoA biosynthesis |
Miscellaneous databases
PROi | PR:P16638 |
Family and domain databases
Gene3Di | 1.10.230.10, 1 hit 1.10.580.10, 1 hit 3.40.50.261, 2 hits |
InterProi | View protein in InterPro IPR014608, ATP-citrate_synthase IPR017440, Cit_synth/succinyl-CoA_lig_AS IPR032263, Citrate-bd IPR016142, Citrate_synth-like_lrg_a-sub IPR016143, Citrate_synth-like_sm_a-sub IPR002020, Citrate_synthase IPR036969, Citrate_synthase_sf IPR033847, Citrt_syn/SCS-alpha_CS IPR003781, CoA-bd IPR005811, CoA_ligase IPR036291, NAD(P)-bd_dom_sf IPR017866, Succ-CoA_synthase_bsu_CS IPR016102, Succinyl-CoA_synth-like |
Pfami | View protein in Pfam PF16114, Citrate_bind, 1 hit PF00285, Citrate_synt, 1 hit PF02629, CoA_binding, 1 hit PF00549, Ligase_CoA, 1 hit |
PIRSFi | PIRSF036511, ATP_citrt_syn, 1 hit |
SMARTi | View protein in SMART SM00881, CoA_binding, 1 hit |
SUPFAMi | SSF48256, SSF48256, 1 hit SSF51735, SSF51735, 1 hit SSF52210, SSF52210, 1 hit |
PROSITEi | View protein in PROSITE PS01216, SUCCINYL_COA_LIG_1, 1 hit PS00399, SUCCINYL_COA_LIG_2, 1 hit PS01217, SUCCINYL_COA_LIG_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ACLY_RAT | |
Accessioni | P16638Primary (citable) accession number: P16638 Secondary accession number(s): Q497C7, Q8VIQ1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | August 1, 1990 | |
Last modified: | May 25, 2022 | |
This is version 182 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families