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Protein

ATP-citrate synthase

Gene

Acly

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

ATP-citrate synthase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Has a central role in de novo lipid synthesis. In nervous tissue it may be involved in the biosynthesis of acetylcholine.

Catalytic activityi

ADP + phosphate + acetyl-CoA + oxaloacetate = ATP + citrate + CoA.

Cofactori

Mg2+By similarity

Enzyme regulationi

Phosphorylation results in a 6-fold increase in V(max) and the conversion of citrate dependence from sigmoidal to hyperbolic. Fructose 6-phosphate (F6P) is also a potent activator.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei58ATPBy similarity1
Binding sitei118ATPBy similarity1
Metal bindingi201MagnesiumBy similarity1
Metal bindingi203MagnesiumBy similarity1
Binding sitei346Citrate; via amide nitrogenBy similarity1
Binding sitei348CitrateBy similarity1
Binding sitei379CitrateBy similarity1
Metal bindingi717MagnesiumBy similarity1
Active sitei759Tele-phosphohistidine intermediate1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi66 – 67ATPBy similarity2
Nucleotide bindingi109 – 111ATPBy similarity3
Nucleotide bindingi700 – 720ATPBy similarityAdd BLAST21
Nucleotide bindingi751 – 777ATPBy similarityAdd BLAST27

GO - Molecular functioni

GO - Biological processi

  • acetyl-CoA biosynthetic process Source: GO_Central
  • 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

Keywordsi

Molecular functionTransferase
Biological processLipid biosynthesis, Lipid metabolism
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-citrate synthase (EC:2.3.3.8)
Alternative name(s):
ATP-citrate (pro-S-)-lyase
Citrate cleavage enzyme
Gene namesi
Name:Acly
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2018 Acly

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2745

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001027831 – 1100ATP-citrate synthaseAdd BLAST1100

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei131PhosphotyrosineBy similarity1
Modified residuei263PhosphoserineBy similarity1
Modified residuei446Phosphothreonine1 Publication1
Modified residuei450Phosphoserine1 Publication1
Modified residuei454Phosphoserine; by PKA and PKB/AKT1 or PKB/AKT2Combined sources1 Publication1
Modified residuei458PhosphoserineBy similarity1
Modified residuei480PhosphoserineCombined sources1
Modified residuei539N6-acetyllysine; alternateBy similarity1
Cross-linki539Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei545N6-acetyllysine; alternateBy similarity1
Cross-linki545Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei553N6-acetyllysine; alternateBy similarity1
Cross-linki553Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei638PhosphothreonineBy similarity1
Modified residuei662PhosphoserineCombined sources1
Modified residuei681PhosphotyrosineBy similarity1
Modified residuei838PhosphoserineBy similarity1
Modified residuei947N6-acetyllysineBy similarity1
Modified residuei967N6-acetyllysineBy similarity1
Modified residuei977N6-acetyllysineBy similarity1
Modified residuei1076N6-acetyllysineBy similarity1
Modified residuei1099PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on two serines and one threonine. Phosphorylation on Thr-446 and Ser-450 depends on the phosphorylation state of Ser-454. Phosphorylation on Ser-454 is decreased by prior phosphorylation on the other 2 residues.2 Publications
The N-terminus is blocked.
ISGylated.By similarity
Acetylated at Lys-539, Lys-545 and Lys-553 by KAT2B/PCAF. Acetylation is promoted by glucose and stabilizes the protein, probably by preventing ubiquitination at the same sites. Acetylation promotes de novo lipid synthesis. Deacetylated by SIRT2 (By similarity).By similarity
Ubiquitinated at Lys-539, Lys-545 and Lys-553 by UBR4, leading to its degradation. Ubiquitination is probably inhibited by acetylation at same site (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP16638
PeptideAtlasiP16638
PRIDEiP16638

PTM databases

iPTMnetiP16638
PhosphoSitePlusiP16638

Expressioni

Tissue specificityi

Expreesed in the brain, kidney, mammary gland, lung and liver.1 Publication

Interactioni

Subunit structurei

Homotetramer.

Protein-protein interaction databases

BioGridi246351, 3 interactors
IntActiP16638, 1 interactor
STRINGi10116.ENSRNOP00000023447

Chemistry databases

BindingDBiP16638

Structurei

3D structure databases

ProteinModelPortaliP16638
SMRiP16638
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 265ATP-graspAdd BLAST262

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni778 – 788CoA-bindingSequence analysisAdd BLAST11

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

eggNOGiKOG1254 Eukaryota
COG0045 LUCA
COG0074 LUCA
COG0372 LUCA
HOGENOMiHOG000151479
HOVERGENiHBG003318
InParanoidiP16638
KOiK01648
PhylomeDBiP16638

Family and domain databases

Gene3Di1.10.230.10, 1 hit
1.10.580.10, 1 hit
3.30.1490.20, 1 hit
3.40.50.261, 2 hits
InterProiView protein in InterPro
IPR014608 ATP-citrate_synthase
IPR013815 ATP_grasp_subdomain_1
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
PfamiView protein in Pfam
PF16114 Citrate_bind, 1 hit
PF00285 Citrate_synt, 1 hit
PF02629 CoA_binding, 1 hit
PF00549 Ligase_CoA, 1 hit
PIRSFiPIRSF036511 ATP_citrt_syn, 1 hit
SMARTiView protein in SMART
SM00881 CoA_binding, 1 hit
SUPFAMiSSF48256 SSF48256, 2 hits
SSF51735 SSF51735, 1 hit
SSF52210 SSF52210, 1 hit
PROSITEiView protein in PROSITE
PS01216 SUCCINYL_COA_LIG_1, 1 hit
PS00399 SUCCINYL_COA_LIG_2, 1 hit
PS01217 SUCCINYL_COA_LIG_3, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P16638-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:1,100
Mass (Da):120,636
Last modified:August 1, 1990 - v1
Checksum:i2C6BE4BC1F53BDD2
GO
Isoform 2 (identifier: P16638-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     419-422: WAPA → LGHRP
     475-484: Missing.

Show »
Length:1,091
Mass (Da):119,704
Checksum:iCC7A9B9F0C18E62E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti116A → V in AAI00619 (PubMed:15489334).Curated1
Sequence conflicti367S → P in AAI00619 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_026273419 – 422WAPA → LGHRP in isoform 2. 1 Publication4
Alternative sequenceiVSP_026274475 – 484Missing in isoform 2. 1 Publication10

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
PIRiA35007
RefSeqiNP_001104565.1, NM_001111095.1
NP_058683.2, NM_016987.2
UniGeneiRn.29771

Genome annotation databases

GeneIDi24159
KEGGirno:24159

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiACLY_RAT
AccessioniPrimary (citable) accession number: P16638
Secondary accession number(s): Q497C7, Q8VIQ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: May 23, 2018
This is version 160 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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