UniProt functional annotation for P53396



	UniProt functional annotation for P53396

UniProt code: P53396.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:10653665, ECO:0000269|PubMed:1371749, ECO:0000269|PubMed:19286649, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:9116495}.

Catalytic activity: Reaction=acetyl-CoA + ADP + oxaloacetate + phosphate = ATP + citrate + CoA; Xref=Rhea:RHEA:21160, ChEBI:CHEBI:16452, ChEBI:CHEBI:16947, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:456216; EC=2.3.3.8; Evidence={ECO:0000269|PubMed:10653665, ECO:0000269|PubMed:1371749, ECO:0000269|PubMed:19286649, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:9116495}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21162; Evidence={ECO:0000305|PubMed:10653665, ECO:0000305|PubMed:1371749, ECO:0000305|PubMed:19286649, ECO:0000305|PubMed:23932781, ECO:0000305|PubMed:9116495};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:19286649};

Activity regulation: 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). {ECO:0000269|PubMed:10653665}.

Biophysicochemical properties: Kinetic parameters: KM=98.0 uM for citrate {ECO:0000269|PubMed:9116495}; KM=73.8 uM for citrate {ECO:0000269|PubMed:19286649}; KM=127 uM for citrate (phosphorylated form by PKA) {ECO:0000269|PubMed:10653665}; KM=149 uM for citrate (phosphorylated form by both PKA and GSK3) {ECO:0000269|PubMed:10653665}; KM=14.0 uM for CoA {ECO:0000269|PubMed:9116495}; KM=4.0 uM for CoA {ECO:0000269|PubMed:19286649}; KM=2.59 uM for CoA (unphosphorylated form) {ECO:0000269|PubMed:10653665}; KM=2.32 uM for CoA (unphosphorylated form in the presence of fructose 6-phosphate) {ECO:0000269|PubMed:10653665}; KM=2.01 uM for CoA (phosphorylated form by PKA) {ECO:0000269|PubMed:10653665}; KM=2.35 uM for CoA (phosphorylated form by PKA in the presence of fructose 6-phosphate) {ECO:0000269|PubMed:10653665}; KM=2.28 uM for CoA (phosphorylated form by both PKA and GSK3) {ECO:0000269|PubMed:10653665}; KM=2.09 uM for CoA (phosphorylated form by both PKA and GSK3 in the presence of fructose 6-phosphate) {ECO:0000269|PubMed:10653665}; KM=120.0 uM for ATP {ECO:0000269|PubMed:9116495}; KM=47.0 uM for ATP {ECO:0000269|PubMed:19286649}; KM=41.0 uM for ATP (unphosphorylated form) {ECO:0000269|PubMed:10653665}; KM=2.89 uM for ATP ((unphosphorylated form in the presence of fructose 6-phosphate) {ECO:0000269|PubMed:10653665}; KM=41.15 uM for ATP (phosphorylated form by PKA) {ECO:0000269|PubMed:10653665}; KM=4.79 uM for ATP (phosphorylated form by PKA in the presence of fructose 6-phosphate) {ECO:0000269|PubMed:10653665}; KM=37.28 uM for ATP (phosphorylated form by both PKA and GSK3) {ECO:0000269|PubMed:10653665}; KM=4.01 uM for ATP (phosphorylated form by both PKA and GSK3 in the presence of fructose 6-phosphate) {ECO:0000269|PubMed:10653665}; Vmax=1.9 umol/h/ug enzyme {ECO:0000269|PubMed:9116495};

Subunit: Homotetramer. {ECO:0000269|PubMed:20558738, ECO:0000269|PubMed:22102020, ECO:0000269|PubMed:9116495}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:9116495}.

Ptm: 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). {ECO:0000250|UniProtKB:P16638, ECO:0000269|PubMed:10653665}.

Ptm: ISGylated. {ECO:0000269|PubMed:16139798}.

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. {ECO:0000269|PubMed:23932781}.

Ptm: Ubiquitinated at Lys-540, Lys-546 and Lys-554 by UBR4, leading to its degradation. Ubiquitination is probably inhibited by acetylation at same site (Probable). {ECO:0000305|PubMed:23932781}.

Similarity: In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family. {ECO:0000305}.

Similarity: In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:10653665, ECO:0000269\|PubMed:1371749, ECO:0000269\|PubMed:19286649, ECO:0000269\|PubMed:23932781, ECO:0000269\|PubMed:9116495}.


Catalytic activity:		Reaction=acetyl-CoA + ADP + oxaloacetate + phosphate = ATP + citrate + CoA; Xref=Rhea:RHEA:21160, ChEBI:CHEBI:16452, ChEBI:CHEBI:16947, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:456216; EC=2.3.3.8; Evidence={ECO:0000269\|PubMed:10653665, ECO:0000269\|PubMed:1371749, ECO:0000269\|PubMed:19286649, ECO:0000269\|PubMed:23932781, ECO:0000269\|PubMed:9116495}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21162; Evidence={ECO:0000305\|PubMed:10653665, ECO:0000305\|PubMed:1371749, ECO:0000305\|PubMed:19286649, ECO:0000305\|PubMed:23932781, ECO:0000305\|PubMed:9116495};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:19286649};
Activity regulation:		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). {ECO:0000269\|PubMed:10653665}.
Biophysicochemical properties:		Kinetic parameters: KM=98.0 uM for citrate {ECO:0000269\|PubMed:9116495}; KM=73.8 uM for citrate {ECO:0000269\|PubMed:19286649}; KM=127 uM for citrate (phosphorylated form by PKA) {ECO:0000269\|PubMed:10653665}; KM=149 uM for citrate (phosphorylated form by both PKA and GSK3) {ECO:0000269\|PubMed:10653665}; KM=14.0 uM for CoA {ECO:0000269\|PubMed:9116495}; KM=4.0 uM for CoA {ECO:0000269\|PubMed:19286649}; KM=2.59 uM for CoA (unphosphorylated form) {ECO:0000269\|PubMed:10653665}; KM=2.32 uM for CoA (unphosphorylated form in the presence of fructose 6-phosphate) {ECO:0000269\|PubMed:10653665}; KM=2.01 uM for CoA (phosphorylated form by PKA) {ECO:0000269\|PubMed:10653665}; KM=2.35 uM for CoA (phosphorylated form by PKA in the presence of fructose 6-phosphate) {ECO:0000269\|PubMed:10653665}; KM=2.28 uM for CoA (phosphorylated form by both PKA and GSK3) {ECO:0000269\|PubMed:10653665}; KM=2.09 uM for CoA (phosphorylated form by both PKA and GSK3 in the presence of fructose 6-phosphate) {ECO:0000269\|PubMed:10653665}; KM=120.0 uM for ATP {ECO:0000269\|PubMed:9116495}; KM=47.0 uM for ATP {ECO:0000269\|PubMed:19286649}; KM=41.0 uM for ATP (unphosphorylated form) {ECO:0000269\|PubMed:10653665}; KM=2.89 uM for ATP ((unphosphorylated form in the presence of fructose 6-phosphate) {ECO:0000269\|PubMed:10653665}; KM=41.15 uM for ATP (phosphorylated form by PKA) {ECO:0000269\|PubMed:10653665}; KM=4.79 uM for ATP (phosphorylated form by PKA in the presence of fructose 6-phosphate) {ECO:0000269\|PubMed:10653665}; KM=37.28 uM for ATP (phosphorylated form by both PKA and GSK3) {ECO:0000269\|PubMed:10653665}; KM=4.01 uM for ATP (phosphorylated form by both PKA and GSK3 in the presence of fructose 6-phosphate) {ECO:0000269\|PubMed:10653665}; Vmax=1.9 umol/h/ug enzyme {ECO:0000269\|PubMed:9116495};
Subunit:		Homotetramer. {ECO:0000269\|PubMed:20558738, ECO:0000269\|PubMed:22102020, ECO:0000269\|PubMed:9116495}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:9116495}.
Ptm:		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). {ECO:0000250\|UniProtKB:P16638, ECO:0000269\|PubMed:10653665}.
Ptm:		ISGylated. {ECO:0000269\|PubMed:16139798}.
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. {ECO:0000269\|PubMed:23932781}.
Ptm:		Ubiquitinated at Lys-540, Lys-546 and Lys-554 by UBR4, leading to its degradation. Ubiquitination is probably inhibited by acetylation at same site (Probable). {ECO:0000305\|PubMed:23932781}.
Similarity:		In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family. {ECO:0000305}.
Similarity:		In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family. {ECO:0000305}.