Q2TCH3 · ACLY_SHEEP

  • Protein
    ATP-citrate synthase
  • Gene
    ACLY
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at transcript level
  • Annotation score
    5/5

Function

function

Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis.

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Activity regulation

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).

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site58ATP (UniProtKB | ChEBI)
Binding site66ATP (UniProtKB | ChEBI)
Binding site67ATP (UniProtKB | ChEBI)
Binding site109ATP (UniProtKB | ChEBI)
Binding site111ATP (UniProtKB | ChEBI)
Binding site118ATP (UniProtKB | ChEBI)
Binding site216ATP (UniProtKB | ChEBI)
Binding site257Mg2+ (UniProtKB | ChEBI)
Binding site260Mg2+ (UniProtKB | ChEBI)
Binding site262Mg2+ (UniProtKB | ChEBI)
Binding site309citrate (UniProtKB | ChEBI)
Binding site346citrate (UniProtKB | ChEBI)
Binding site348citrate (UniProtKB | ChEBI)
Binding site364citrate (UniProtKB | ChEBI)
Binding site379citrate (UniProtKB | ChEBI)
Active site760Tele-phosphohistidine intermediate
Binding site779-789CoA (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytosol
Molecular FunctionATP binding
Molecular FunctionATP citrate synthase activity
Molecular Functionmetal ion binding
Biological Processacetyl-CoA biosynthetic process
Biological Processcitrate metabolic process
Biological Processlipid biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    ATP-citrate synthase
  • EC number
  • Alternative names
    • ATP-citrate (pro-S-)-lyase
    • Citrate cleavage enzyme

Gene names

    • Name
      ACLY

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Caprinae > Ovis

Accessions

  • Primary accession
    Q2TCH3

Proteomes

Subcellular Location

Keywords

PTM/Processing

Features

Showing features for chain, modified residue, cross-link.

TypeIDPosition(s)Description
ChainPRO_00002708161-1101ATP-citrate synthase
Modified residue131Phosphotyrosine
Modified residue263Phosphoserine
Modified residue447Phosphothreonine
Modified residue451Phosphoserine
Modified residue455Phosphoserine; by PKA or BCKDK
Modified residue459Phosphoserine
Modified residue481Phosphoserine
Modified residue540N6-acetyllysine; alternate
Cross-link540Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Modified residue546N6-acetyllysine; alternate
Cross-link546Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Modified residue554N6-acetyllysine; alternate
Cross-link554Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Modified residue639Phosphothreonine
Modified residue663Phosphoserine
Modified residue682Phosphotyrosine
Modified residue839Phosphoserine
Modified residue948N6-acetyllysine
Modified residue968N6-acetyllysine
Modified residue978N6-acetyllysine
Modified residue1077N6-acetyllysine
Modified residue1100Phosphoserine

Post-translational modification

Phosphorylated by PKA and GSK3 in a sequential manner; phosphorylation results in activation of its activity (By similarity).
Phosphorylation on Thr-447 and Ser-451 depends on the phosphorylation state of Ser-455 (By similarity).
Phosphorylation on Ser-455 is decreased by prior phosphorylation on the other 2 residues (By similarity).
Phosphorylated at Ser-455 by BCKDK and dephosphorylated by protein phosphatase PPM1K
ISGylated.
Acetylated at Lys-540, Lys-546 and Lys-554 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).
Ubiquitinated at Lys-540, Lys-546 and Lys-554 by the BCR(KLHL25) E3 ubiquitin ligase complex and UBR4, leading to its degradation (By similarity).
Ubiquitination is probably inhibited by acetylation at same site (By similarity).
BCR(KLHL25)-mediated degradation of ACLY promotes fatty acid oxidation and is required for differentiation of inducible regulatory T (iTreg) cells (By similarity).

Keywords

Proteomic databases

Interaction

Subunit

Homotetramer.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for domain, compositional bias, region.

TypeIDPosition(s)Description
Domain4-265ATP-grasp
Compositional bias440-460Polar residues
Region440-485Disordered

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.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,101
  • Mass (Da)
    120,934
  • Last updated
    2006-01-24 v1
  • Checksum
    92D0F0DCB0E2D445
MSAKAISEQTGKELLYKYICTTSAIQNRFKYARVTPDTDWARLLQDHPWLLSQSLVVKPDQLIKRRGKLGLVGVNLTLDGVKSWLKPRLGQEATVGKATGFLKNFLIEPFVPHTQEEEFYVCIYATREGDYVLFHHEGGVDVGDVDAKAQKLLVAVDEKLNPEDIKKHLLVHAPEDKKEILASFISGLFNFYEDLYFTYLEINPLVVTKDGVYILDLAAKVDATADYICKVKWGDIEFPPPFGREAYPEEAYIADLDAKSGASLKLTLLNPKGRIWTMVAGGGASVVYSDTICDLGGVNELANYGEYSGAPSEQQTYDYAKTILSLMTREKHPDGKILIIGGSIANFTNVAATFKGIVRAIRDYQGPLKEHEVTIFVRRGGPNYQEGLRVMGEVGKTTGIPIHVFGTETHMTAIVGMALGHRPIPNQPPTAAHTANFLLNASGSTSTPAPSRTASFSESRTDEVAPAKKAKPAMPQDSVPSPRPLQGKSATLFSRHTKAIVWGMQTRAVQGMLDFDYVCSRDEPSVAAMVYPFTGDHKQKFYWGHKEILIPVFKNMADAMKKHPEVDVLINFASLRSAYDSTMETMNYTQIRTIAIIAEGIPEALTRKLIKKAEQKGVTIIGPATVGGIKPGCFKIGNTGGMLDNILASKLYRPGSVAYVSRSGGMSNELNNIISRTTDGVYEGVAIGGDRYPGSTFMDHVLRYQDTPGVKMIVVLGEIGGTEEYKICRGVTEGRITKPVVCWCIGTCAAMFSSEVQFGHAGACANQASETAVAKNQALKEAGVFVPRSFDELGEIIQSVYEDLVARGVIVPAQEVPPPTVPMDYSWARELGLIRKPASFMTSICDERGQELIYAGMPITEVFKEEMGIGGVLGLLWFQKRLPKYSCQFIEMCLMVTADHGPAVSGAHNTIICARAGKDLVSSLTSGLLTIGDRFGGALDAAAKMFSKAFDSGIIPMEFVNKMKKEGKLIMGIGHRVKSINNPDMRVQILKDYVRQHFPATPLLDYALEVEKITTSKKPNLILNVDGLIGVAFVDMLRHCGSFTREEADEYIDIGALNGIFVLGRSMGFIGHYLDQKRLKQGLYRHPWDDISYVLPEHMSM

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias440-460Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY971952
EMBL· GenBank· DDBJ
AAY40742.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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