Q2TCH3 · ACLY_SHEEP
- ProteinATP-citrate synthase
- GeneACLY
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1101 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
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
- acetyl-CoA + ADP + oxaloacetate + phosphate = ATP + citrate + CoAThis reaction proceeds in the backward direction.
Cofactor
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 58 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 66 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 67 | ATP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 109 | ATP (UniProtKB | ChEBI) | ||||
Sequence: P | ||||||
Binding site | 111 | ATP (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 118 | ATP (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 216 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 257 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 260 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 262 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 309 | citrate (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 346 | citrate (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 348 | citrate (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 364 | citrate (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 379 | citrate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Active site | 760 | Tele-phosphohistidine intermediate | ||||
Sequence: H | ||||||
Binding site | 779-789 | CoA (UniProtKB | ChEBI) | ||||
Sequence: LKEAGVFVPRS |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | ATP binding | |
Molecular Function | ATP citrate synthase activity | |
Molecular Function | metal ion binding | |
Biological Process | acetyl-CoA biosynthetic process | |
Biological Process | citrate metabolic process | |
Biological Process | lipid biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameATP-citrate synthase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Caprinae > Ovis
Accessions
- Primary accessionQ2TCH3
Proteomes
Subcellular Location
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000270816 | 1-1101 | ATP-citrate synthase | |||
Sequence: MSAKAISEQTGKELLYKYICTTSAIQNRFKYARVTPDTDWARLLQDHPWLLSQSLVVKPDQLIKRRGKLGLVGVNLTLDGVKSWLKPRLGQEATVGKATGFLKNFLIEPFVPHTQEEEFYVCIYATREGDYVLFHHEGGVDVGDVDAKAQKLLVAVDEKLNPEDIKKHLLVHAPEDKKEILASFISGLFNFYEDLYFTYLEINPLVVTKDGVYILDLAAKVDATADYICKVKWGDIEFPPPFGREAYPEEAYIADLDAKSGASLKLTLLNPKGRIWTMVAGGGASVVYSDTICDLGGVNELANYGEYSGAPSEQQTYDYAKTILSLMTREKHPDGKILIIGGSIANFTNVAATFKGIVRAIRDYQGPLKEHEVTIFVRRGGPNYQEGLRVMGEVGKTTGIPIHVFGTETHMTAIVGMALGHRPIPNQPPTAAHTANFLLNASGSTSTPAPSRTASFSESRTDEVAPAKKAKPAMPQDSVPSPRPLQGKSATLFSRHTKAIVWGMQTRAVQGMLDFDYVCSRDEPSVAAMVYPFTGDHKQKFYWGHKEILIPVFKNMADAMKKHPEVDVLINFASLRSAYDSTMETMNYTQIRTIAIIAEGIPEALTRKLIKKAEQKGVTIIGPATVGGIKPGCFKIGNTGGMLDNILASKLYRPGSVAYVSRSGGMSNELNNIISRTTDGVYEGVAIGGDRYPGSTFMDHVLRYQDTPGVKMIVVLGEIGGTEEYKICRGVTEGRITKPVVCWCIGTCAAMFSSEVQFGHAGACANQASETAVAKNQALKEAGVFVPRSFDELGEIIQSVYEDLVARGVIVPAQEVPPPTVPMDYSWARELGLIRKPASFMTSICDERGQELIYAGMPITEVFKEEMGIGGVLGLLWFQKRLPKYSCQFIEMCLMVTADHGPAVSGAHNTIICARAGKDLVSSLTSGLLTIGDRFGGALDAAAKMFSKAFDSGIIPMEFVNKMKKEGKLIMGIGHRVKSINNPDMRVQILKDYVRQHFPATPLLDYALEVEKITTSKKPNLILNVDGLIGVAFVDMLRHCGSFTREEADEYIDIGALNGIFVLGRSMGFIGHYLDQKRLKQGLYRHPWDDISYVLPEHMSM | ||||||
Modified residue | 131 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 263 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 447 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 451 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 455 | Phosphoserine; by PKA or BCKDK | ||||
Sequence: S | ||||||
Modified residue | 459 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 481 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 540 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Cross-link | 540 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate | ||||
Sequence: K | ||||||
Modified residue | 546 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Cross-link | 546 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate | ||||
Sequence: K | ||||||
Modified residue | 554 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Cross-link | 554 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate | ||||
Sequence: K | ||||||
Modified residue | 639 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 663 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 682 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 839 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 948 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 968 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 978 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 1077 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 1100 | Phosphoserine | ||||
Sequence: S |
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
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).
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).
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
- PTM
Proteomic databases
Interaction
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 4-265 | ATP-grasp | ||||
Sequence: KAISEQTGKELLYKYICTTSAIQNRFKYARVTPDTDWARLLQDHPWLLSQSLVVKPDQLIKRRGKLGLVGVNLTLDGVKSWLKPRLGQEATVGKATGFLKNFLIEPFVPHTQEEEFYVCIYATREGDYVLFHHEGGVDVGDVDAKAQKLLVAVDEKLNPEDIKKHLLVHAPEDKKEILASFISGLFNFYEDLYFTYLEINPLVVTKDGVYILDLAAKVDATADYICKVKWGDIEFPPPFGREAYPEEAYIADLDAKSGASLK | ||||||
Compositional bias | 440-460 | Polar residues | ||||
Sequence: NASGSTSTPAPSRTASFSESR | ||||||
Region | 440-485 | Disordered | ||||
Sequence: NASGSTSTPAPSRTASFSESRTDEVAPAKKAKPAMPQDSVPSPRPL |
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 statusComplete
- Length1,101
- Mass (Da)120,934
- Last updated2006-01-24 v1
- Checksum92D0F0DCB0E2D445
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 440-460 | Polar residues | ||||
Sequence: NASGSTSTPAPSRTASFSESR |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY971952 EMBL· GenBank· DDBJ | AAY40742.1 EMBL· GenBank· DDBJ | mRNA |