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P16638 (ACLY_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ATP-citrate synthase

EC=2.3.3.8
Alternative name(s):
ATP-citrate (pro-S-)-lyase
Citrate cleavage enzyme
Gene names
Name:Acly
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1100 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

ATP citrate-lyase 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 activity

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

Cofactor

Magnesium By similarity.

Enzyme regulation

Major regulation of ATP citrate-lyase activity is probably not by phosphorylation/dephosphorylation but by altering the amount of enzyme.

Subunit structure

Homotetramer.

Subcellular location

Cytoplasm.

Tissue specificity

Expreesed in the brain, kidney, mammary gland, lung and liver. Ref.3

Post-translational modification

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. Ref.4 Ref.5

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.

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.

Sequence similarities

In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.

In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family.

Contains 1 ATP-grasp domain.

Ontologies

Keywords
   Biological processLipid biosynthesis
Lipid metabolism
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionTransferase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processacetyl-CoA biosynthetic process

Non-traceable author statement Ref.1. Source: RGD

acetyl-CoA metabolic process

Inferred from direct assay PubMed 18062843. Source: RGD

cellular carbohydrate metabolic process

Inferred from electronic annotation. Source: InterPro

citrate metabolic process

Inferred from direct assay PubMed 18062843. Source: RGD

fatty acid biosynthetic process

Inferred from direct assay PubMed 11735100. Source: RGD

lipid biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

lipid metabolic process

Inferred from expression pattern Ref.1. Source: RGD

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATP citrate synthase activity

Inferred from direct assay PubMed 11735100PubMed 18062843Ref.1. Source: RGD

cofactor binding

Inferred from electronic annotation. Source: InterPro

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

succinate-CoA ligase (ADP-forming) activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P16638-1)

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.
Isoform 2 (identifier: P16638-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11001100ATP-citrate synthase
PRO_0000102783

Regions

Domain4 – 265262ATP-grasp
Nucleotide binding66 – 672ATP By similarity
Nucleotide binding109 – 1113ATP By similarity
Nucleotide binding700 – 72021ATP By similarity
Nucleotide binding751 – 77727ATP By similarity
Region778 – 78811CoA-binding Potential

Sites

Active site7591Tele-phosphohistidine intermediate
Metal binding2011Magnesium By similarity
Metal binding2031Magnesium By similarity
Metal binding7171Magnesium By similarity
Binding site581ATP By similarity
Binding site1181ATP By similarity
Binding site3461Citrate; via amide nitrogen By similarity
Binding site3481Citrate By similarity
Binding site3791Citrate By similarity

Amino acid modifications

Modified residue1311Phosphotyrosine By similarity
Modified residue4461Phosphothreonine Ref.4
Modified residue4501Phosphoserine Ref.4
Modified residue4541Phosphoserine; by PKA and PKB/AKT1 or PKB/AKT2 Ref.5
Modified residue4801Phosphoserine By similarity
Modified residue5391N6-acetyllysine; alternate By similarity
Modified residue5451N6-acetyllysine; alternate By similarity
Modified residue5531N6-acetyllysine; alternate By similarity
Modified residue6381Phosphothreonine By similarity
Modified residue6621Phosphoserine By similarity
Modified residue6811Phosphotyrosine By similarity
Modified residue8381Phosphoserine By similarity
Modified residue9471N6-acetyllysine By similarity
Modified residue9671N6-acetyllysine By similarity
Modified residue9771N6-acetyllysine By similarity
Modified residue10761N6-acetyllysine By similarity
Modified residue10991Phosphoserine By similarity
Cross-link539Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
Cross-link545Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
Cross-link553Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity

Natural variations

Alternative sequence419 – 4224WAPA → LGHRP in isoform 2.
VSP_026273
Alternative sequence475 – 48410Missing in isoform 2.
VSP_026274

Experimental info

Sequence conflict1161A → V in AAI00619. Ref.2
Sequence conflict3671S → P in AAI00619. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 1, 1990. Version 1.
Checksum: 2C6BE4BC1F53BDD2

FASTA1,100120,636
        10         20         30         40         50         60 
MSAKAISEQT GKELLYKYIC TTSAIQNRFK YARVTPDTDW AHLLQDHPWL LSQSLVVKPD 

        70         80         90        100        110        120 
QLIKRRGKLG LVGVNLSLDG VKSWLKPRLG HEATVGKAKG FLKNFLIEPF VPHSQAEEFY 

       130        140        150        160        170        180 
VCIYATREGD YVLFHHEGGV DVGDVDTKAQ KLLVGVDEKL NAEDIKRHLL VHAPEDKKEI 

       190        200        210        220        230        240 
LASFISGLFN FYEDLYFTYL EINPLVVTKD GVYILDLAAK VDATADYICK VKWGDIEFPP 

       250        260        270        280        290        300 
PFGREAYPEE AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE 

       310        320        330        340        350        360 
LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV AATFKGIVRA 

       370        380        390        400        410        420 
IRDYQGSLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI PIHVFGTETH MTAIVGMAWA 

       430        440        450        460        470        480 
PAIPNQPPTA AHTANFLLNA SGSTSTPAPS RTASFSESRA DEVAPAKKAK PAMPQDSVPS 

       490        500        510        520        530        540 
PRSLQGKSAT LFSRHTKAIV WGMQTRAVQG MLDFDYVCSR DEPSVAAMVY PFTGDHKQKF 

       550        560        570        580        590        600 
YWGHKEILIP VFKNMADAMK KHPEVDVLIN FASLRSAYDS TMETMNYAQI RTIAIIAEGI 

       610        620        630        640        650        660 
PEALTRKLIK KADQKGVTII GPATVGGIKP GCFKIGNTGG MLDNILASKL YRPGSVAYVS 

       670        680        690        700        710        720 
RSGGMSNELN NIISRTTDGV YEGVAIGGDR YPGSTFMDHV LRYQDTPGVK MIVVLGEIGG 

       730        740        750        760        770        780 
TEEYKICRGI KEGRLTKPVV CWCIGTCATM FSSEVQFGHA GACANQASET AVAKNQALKE 

       790        800        810        820        830        840 
AGVFVPRSFD ELGEIIQSVY EDLVAKGAIV PAQEVPPPTV PMDYSWAREL GLIRKPASFM 

       850        860        870        880        890        900 
TSICDERGQE LIYAGMPITE VFKEEMGIGG VLGLLWFQRR LPKYSCQFIE MCLMVTADHG 

       910        920        930        940        950        960 
PAVSGAHNTI ICARAGKDLV SSLTSGLLTI GDRFGGALDA AAKMFSKAFD SGIIPMEFVN 

       970        980        990       1000       1010       1020 
KMKKEGKLIM GIGHRVKSIN NPDMRVQILK DFVKQHFPAT PLLDYALEVE KITTSKKPNL 

      1030       1040       1050       1060       1070       1080 
ILNVDGFIGV AFVDMLRNCG SFTREEADEY VDIGALNGVF VLGRSMGFIG HYLDQKRLKQ 

      1090       1100 
GLYRHPWDDI SYVLPEHMSM 

« Hide

Isoform 2 [UniParc].

Checksum: CC7A9B9F0C18E62E
Show »

FASTA1,091119,704

References

« Hide 'large scale' references
[1]"Rat ATP citrate-lyase. Molecular cloning and sequence analysis of a full-length cDNA and mRNA abundance as a function of diet, organ, and age."
Elshourbagy N.A., Near J.C., Kmetz P.J., Sathe G.M., Southan C., Strickler J.E., Gross M., Young J.F., Wells T.N.C., Groot P.H.E.
J. Biol. Chem. 265:1430-1435(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
Tissue: Liver.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Prostate.
[3]"Cloning and identification of exon-intron organization of the rat ATP-citrate lyase gene."
Moon Y.-A., Kim K.-S., Park S.-W., Kim Y.-S.
Biochim. Biophys. Acta 1307:280-284(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 250-1100, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[4]"Sequence of sites on ATP-citrate lyase and phosphatase inhibitor 2 phosphorylated by multifunctional protein kinase (a glycogen synthase kinase 3 like kinase)."
Ramakrishna S., D'Angelo G., Benjamin W.B.
Biochemistry 29:7617-7624(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 418-459, PHOSPHORYLATION AT THR-446 AND SER-450.
[5]"The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes."
Berwick D.C., Hers I., Heesom K.J., Moule S.K., Tavare J.M.
J. Biol. Chem. 277:33895-33900(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-454.
[6]"Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS."
Moser K., White F.M.
J. Proteome Res. 5:98-104(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J05210 mRNA. Translation: AAA74463.1.
BC100618 mRNA. Translation: AAI00619.1.
AH011205 Genomic DNA. Translation: AAL34316.1.
PIRA35007.
RefSeqNP_001104565.1. NM_001111095.1.
NP_058683.2. NM_016987.2.
UniGeneRn.29771.

3D structure databases

ProteinModelPortalP16638.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid246351. 2 interactions.
IntActP16638. 1 interaction.
MINTMINT-4568685.

Chemistry

BindingDBP16638.
ChEMBLCHEMBL2745.

PTM databases

PhosphoSiteP16638.

Proteomic databases

PaxDbP16638.
PRIDEP16638.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID24159.
KEGGrno:24159.

Organism-specific databases

CTD47.
RGD2018. Acly.

Phylogenomic databases

eggNOGCOG0372.
HOGENOMHOG000151479.
HOVERGENHBG003318.
InParanoidP16638.
KOK01648.
PhylomeDBP16638.

Gene expression databases

GenevestigatorP16638.

Family and domain databases

Gene3D1.10.230.10. 1 hit.
3.30.470.20. 1 hit.
3.40.50.261. 2 hits.
3.40.50.720. 1 hit.
InterProIPR014608. ATP-citrate_synthase.
IPR013650. ATP-grasp_succ-CoA_synth-type.
IPR013816. ATP_grasp_subdomain_2.
IPR017440. Cit_synth/succinyl-CoA_lig_AS.
IPR016143. Citrate_synth-like_sm_a-sub.
IPR002020. Citrate_synthase-like.
IPR016141. Citrate_synthase-like_core.
IPR003781. CoA-bd.
IPR005810. CoA_lig_alpha.
IPR005811. CoA_ligase.
IPR016040. NAD(P)-bd_dom.
IPR017866. Succ-CoA_synthase_bsu_CS.
IPR016102. Succinyl-CoA_synth-like.
[Graphical view]
PfamPF08442. ATP-grasp_2. 1 hit.
PF00285. Citrate_synt. 1 hit.
PF02629. CoA_binding. 1 hit.
PF00549. Ligase_CoA. 1 hit.
[Graphical view]
PIRSFPIRSF036511. ATP_citrt_syn. 1 hit.
SUPFAMSSF48256. SSF48256. 2 hits.
SSF52210. SSF52210. 1 hit.
PROSITEPS01216. SUCCINYL_COA_LIG_1. 1 hit.
PS00399. SUCCINYL_COA_LIG_2. 1 hit.
PS01217. SUCCINYL_COA_LIG_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio602453.
PROP16638.

Entry information

Entry nameACLY_RAT
AccessionPrimary (citable) accession number: P16638
Secondary accession number(s): Q497C7, Q8VIQ1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: April 16, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families