Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Phosphorylation of recombinant human ATP:citrate lyase by cAMP-dependent protein kinase abolishes homotropic allosteric regulation of the enzyme by citrate and increases the enzyme activity. Allosteric activation of ATP:citrate lyase by phosphorylated sugars.
-
Recombinant human ATP:citrate lyase was purified and its kinetics characterized; PKA phosphorylation increases Vmax 6-fold and abolishes homotropic allosteric regulation by citrate, and phosphorylated sugars (e.g. fructose 6-phosphate) allosterically activate it.
"Recombinantly expressed human ATP:citrate lyase was purified from E. coli, and its kinetic behavior was characterized before and after phosphorylation"
Cloning and expression of a human ATP-citrate lyase cDNA.
-
Cloning and expression of the human ACLY cDNA yielded an enzymatically active protein; His->Ala mutagenesis of the catalytic histidine (His765 in the paper's numbering; UniProt His-760) diminished activity, consistent with a phosphohistidine catalytic intermediate.
"Site-specific mutagenesis of His765----Ala diminishes the catalytic activity of the expressed ATP-citrate lyase protein"
Large-scale proteomics and phosphoproteomics of urinary exosomes.
A novel direct homogeneous assay for ATP citrate lyase.
-
Describes ACLY as a cytosolic enzyme catalyzing synthesis of acetyl-CoA and oxaloacetate from citrate, CoA and ATP with Mg2+ as cofactor, and frames acetyl-CoA production as the essential step for de novo fatty acid and cholesterol synthesis.
"ATP citrate lyase (ACL) is a cytosolic enzyme that catalyzes the synthesis of acetyl-CoA and oxaloacetate using citrate, CoA, and ATP as substrates"
Defining the membrane proteome of NK cells.
MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth.
-
ACLY is acetylated at Lys-540/546/554 by PCAF under high glucose, which blocks its ubiquitylation and degradation, stabilizes the protein, and promotes de novo lipid synthesis, proliferation and tumor growth; SIRT2 deacetylates and destabilizes ACLY.
"Substitution of 3K abolishes ACLY ubiquitylation and promotes de novo lipid synthesis, cell proliferation, and tumor growth"
Molecular basis for acetyl-CoA production by ATP-citrate lyase.
-
Cryo-EM of human ACLY shows it is the predominant source of nucleocytosolic acetyl-CoA and forms a homotetramer (a rigid citrate synthase homology module flanked by four flexible acetyl-CoA synthetase homology domains) that uses citrate, Mg-ATP and CoA to produce acetyl-CoA and oxaloacetate.
"ATP-citrate lyase (ACLY) is the predominant source of nucleocytosolic acetyl-CoA"
SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation.
-
In the cytosol ACLY converts citrate into oxaloacetate and acetyl-CoA; this acetyl-CoA supply sustains FSP1 acetylation and stability, so ACLY knockdown/inhibition sensitizes cancer cells to RSL3- and erastin-induced ferroptosis.
"ACLY knockdown heightened cell susceptibility to RSL3- and erastin-induced ferroptosis"
Variant cDNA sequences of human ATP:citrate lyase: cloning, expression, and purification from baculovirus-infected insect cells.
-
Human ACL was cloned, expressed and purified to homogeneity as an active tetramer; ACL is described as a major generator of cytosolic acetyl-CoA required for both fatty acid and cholesterol biosynthesis.
"ATP:citrate lyase (ACL) is a major generator of cytosolic acetyl-coenzymeA"
Transcriptional activation of Citrate lyase monomer gene by ChREBP:MLX
Exocytosis of azurophil granule lumen proteins
Exocytosis of ficolin-rich granule lumen proteins
ACLY tetramer transforms CIT to Ac-CoA
ACLY tetramer binds ETC-1002-CoA