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Details on Person UniProt:P53396 ACLY
| Class:Id | ReferenceGeneProduct:49538 |
|---|---|
| _chainChangeLog | chain:1-1101 added on Fri February 6 2015 |
| _displayName | UniProt:P53396 ACLY |
| _timestamp | 2026-02-20 21:46:32 |
| chain | chain:1-1101 |
| checksum | 12BB4416A30DC30C |
| comment | FUNCTION Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate in multiple biochemical reactions in protein, carbohydrate and lipid metabolism.CATALYTIC ACTIVITY oxaloacetate + acetyl-CoA + ADP + phosphate = citrate + ATP + CoACOFACTOR Phosphorylation results in activation of its activity (PubMed:10653665). Glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate, ribulose 5-phosphate, and fructose 1,6-bisphosphate also act as activators (PubMed:10653665).BIOPHYSICOCHEMICAL PROPERTIES Homotetramer.SUBCELLULAR LOCATION Phosphorylated by PKA and GSK3 in a sequential manner; phosphorylation results in activation of its activity (PubMed:10653665). 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.PTM ISGylated.PTM Acetylated at Lys-540, Lys-546 and Lys-554 by KAT2B/PCAF (PubMed:23932781). Acetylation is promoted by glucose and stabilizes the protein, probably by preventing ubiquitination at the same sites (PubMed:23932781). Acetylation promotes de novo lipid synthesis (PubMed:23932781). Deacetylated by SIRT2.PTM Benzoylated at Lys-978 (PubMed:39524354). Debenzoylated by SIRT3; inhibiting the ATP-citrate synthase activity (PubMed:39524354).PTM Ubiquitinated at Lys-540, Lys-546 and Lys-554 by the BCR(KLHL25) E3 ubiquitin ligase complex and UBR4, leading to its degradation (PubMed:23932781, PubMed:27664236, PubMed:34491895). Ubiquitination is probably inhibited by acetylation at same site (PubMed:23932781). BCR(KLHL25)-mediated degradation of ACLY promotes fatty acid oxidation and is required for differentiation of inducible regulatory T (iTreg) cells (PubMed:34491895).SIMILARITY In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.SIMILARITY In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family. |
| description | recommendedName: ATP-citrate synthase ecNumber evidence="5 6 9 12 18"2.3.3.8 alternativeName: ATP-citrate (pro-S-)-lyase shortName: ACL alternativeName: Citrate cleavage enzyme |
| geneName | ACLY |
| identifier | P53396 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing ATP-binding Cytoplasm Isopeptide bond Lipid biosynthesis Lipid metabolism Magnesium Metal-binding Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome Transferase Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | ACLY |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8998138] ENSEMBL:ENSG00000131473 ACLY [Homo sapiens] |
| secondaryIdentifier | ACLY_HUMAN B4DIM0 B4E3P0 Q13037 Q9BRL0 |
| sequenceLength | 1101 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8969066] UniProt:P53396-1 ACLY [Homo sapiens] [ReferenceIsoform:8969067] UniProt:P53396-2 ACLY [Homo sapiens] [ReferenceIsoform:8969068] UniProt:P53396-3 ACLY [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:76187] ACLY [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:6798765] ACLY [azurophil granule lumen] [Homo sapiens] [EntityWithAccessionedSequence:6801031] ACLY [ficolin-1-rich granule lumen] [Homo sapiens] [EntityWithAccessionedSequence:6806218] ACLY [extracellular region] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P53396 ACLY (49538)
