ACSS2
entrez
55902
canonical
uniprot
Q9NR19
canonical
ensembl
ENSG00000131069
resolver
ensp
ENSP00000253382
resolver
ensp
ENSP00000353804
resolver
ensp
ENSP00000541427
resolver
ensp
ENSP00000541429
resolver
genesymbol
ACSS2
resolver
genesymbol_syn
ACAS2
resolver
hgnc
HGNC:15814
resolver
uniprot
A6NE90
resolver
uniprot
A6NLR6
resolver
uniprot
Q4G0E8
resolver
uniprot
Q5QPH2
resolver
uniprot
Q5QPH3
resolver
uniprot
Q6DKJ3
resolver
uniprot
Q8N238
resolver
uniprot
Q96EL0
resolver
uniprot
Q96FY7
resolver
uniprot
Q9NQP7
resolver
uniprot
Q9UJ15
resolver
uniprot_entry
ACSA_HUMAN
resolver
uniprot_entry
Q4G0E8_HUMAN
resolver
uniprot_entry
Q6DKJ3_HUMAN
resolver
uniprot_entry
Q96FY7_HUMAN
resolver
uniprot_sec
A6NE90
resolver
uniprot_sec
A6NLR6
resolver
uniprot_sec
Q5QPH2
resolver
uniprot_sec
Q5QPH3
resolver
uniprot_sec
Q8N238
resolver
uniprot_sec
Q96EL0
resolver
uniprot_sec
Q9NQP7
resolver
uniprot_sec
Q9UJ15
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by acetylation at Lys-661 and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3. {ECO:0000250|UniProtKB:Q9QXG4}.
uniprot
proteins
amino_acid_sequence
MGLPEERVRSGSGSRGQEEAGAGGRARSWSPPPEVSRSAHVPSLQRYRELHRRSVEEPREFWGDIAKEFYWKTPCPGPFLRYNFDVTKGKIFIEWMKGATTNICYNVLDRNVHEKKLGDKVAFYWEGNEPGETTQITYHQLLVQVCQFSNVLRKQGIQKGDRVAIYMPMIPELVVAMLACARIGALHSIVFAGFSSESLCERILDSSCSLLITTDAFYRGEKLVNLKELADEALQKCQEKGFPVRCCIVVKHLGRAELGMGDSTSQSPPIKRSCPDVQISWNQGIDLWWHELMQEAGDECEPEWCDAEDPLFILYTSGSTGKPKGVVHTVGGYMLYVATTFKYVFDFHAEDVFWCTADIGWITGHSYVTYGPLANGATSVLFEGIPTYPDVNRLWSIVDKYKVTKFYTAPTAIRLLMKFGDEPVTKHSRASLQVLGTVGEPINPEAWLWYHRVVGAQRCPIVDTFWQTETGGHMLTPLPGATPMKPGSATFPFFGVAPAILNESGEELEGEAEGYLVFKQPWPGIMRTVYGNHERFETTYFKKFPGYYVTGDGCQRDQDGYYWITGRIDDMLNVSGHLLSTAEVESALVEHEAVAEAAVVGHPHPVKGECLYCFVTLCDGHTFSPKLTEELKKQIREKIGPIATPDYIQNAPGLPKTRSGKIMRRVLRKIAQNDHDLGDMSTVADPSVISHLFSHRCLTIQ
uniprot
proteins
ec_number
6.2.1.-
uniprot
proteins
ec_number
6.2.1.1
uniprot
proteins
ec_number
6.2.1.17
uniprot
proteins
function
FUNCTION: Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:10843999, PubMed:28003429, PubMed:28552616, PubMed:38369012, PubMed:39561764). Acetate is the preferred substrate (PubMed:10843999, PubMed:28003429, PubMed:38369012, PubMed:39561764). Can also utilize propionate with a much lower affinity (PubMed:38369012). Catalyzes the conversion of lactate into lactoyl-CoA (PubMed:39561764). Does not catalyze the conversion of butyrate or crotonate to their corresponding acyl-CoAs (PubMed:38369012). Nuclear ACSS2 promotes glucose deprivation-induced lysosomal biogenesis and autophagy, tumor cell survival and brain tumorigenesis (PubMed:28552616). Glucose deprivation results in AMPK-mediated phosphorylation of ACSS2 leading to its translocation to the nucleus where it binds to TFEB and locally produces acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes thereby activating their transcription (PubMed:28552616). The regulation of genes associated with autophagy and lysosomal activity through ACSS2 is important for brain tumorigenesis and tumor survival (PubMed:28552616). Acts as a chromatin-bound transcriptional coactivator that up-regulates histone acetylation and expression of neuronal genes (By similarity). Can be recruited to the loci of memory-related neuronal genes to maintain a local acetyl-CoA pool, providing the substrate for histone acetylation and promoting the expression of specific genes, which is essential for maintaining long-term spatial memory (By similarity). {ECO:0000250|UniProtKB:Q9QXG4, ECO:0000269|PubMed:10843999, ECO:0000269|PubMed:28003429, ECO:0000269|PubMed:28552616, ECO:0000269|PubMed:38369012, ECO:0000269|PubMed:39561764}.
uniprot
proteins
mass_dalton
78580
uniprot
proteins
mutagenesis
MUTAGEN 202; /note="R->A: Reduced acetate-binding but no effect on lactate binding."; /evidence="ECO:0000269|PubMed:39561764"; MUTAGEN 315; /note="Y->A: Reduced acetate-binding but no effect on lactate binding."; /evidence="ECO:0000269|PubMed:39561764"; MUTAGEN 358; /note="D->A: Loss of lactate-binding but no effect on acetate-binding."; /evidence="ECO:0000269|PubMed:39561764"; MUTAGEN 363; /note="T->A: Loss of catalytic activity but no effect on its nuclear translocation upon glucose deprivation. Loss of ability to promote gene transcription for lysosomal biogenesis and autophagy."; /evidence="ECO:0000269|PubMed:28552616"; MUTAGEN 363; /note="T->K: Abolishes lactyl-CoA synthetase activity."; /evidence="ECO:0000269|PubMed:39561764"; MUTAGEN 659; /note="S->A: No effect on catalytic activity. Loss of AMPK-mediated phosphorylation, interaction with KPNA1 and nuclear translocation upon glucose deprivation. Loss of ability to promote gene transcription for lysosomal biogenesis and autophagy."; /evidence="ECO:0000269|PubMed:28552616"; MUTAGEN 664..665; /note="RR->AA: No effect on catalytic activity. Loss of interaction with KPNA1 and nuclear translocation upon glucose deprivation. Loss of ability to promote gene transcription for lysosomal biogenesis and autophagy."; /evidence="ECO:0000269|PubMed:28552616
uniprot
proteins
post_translational_modification
PTM: Reversibly acetylated at Lys-661 (By similarity). The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3 (By similarity). {ECO:0000250|UniProtKB:Q9QXG4}.; PTM: Glucose deprivation results in its AMPK-dependent phosphorylation at Ser-659, which leads to exposure of its nuclear localization signal, required for its interaction with KPNA1 and subsequent translocation to the nucleus. {ECO:0000269|PubMed:28552616}.
uniprot
proteins
protein_family
ATP-dependent AMP-binding enzyme family
uniprot
proteins
pubmed
10843999
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
28003429
uniprot
proteins
pubmed
28552616
uniprot
proteins
pubmed
38369012
uniprot
proteins
pubmed
39561764
uniprot
proteins
sequence_length
701
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10843999, ECO:0000269|PubMed:28003429, ECO:0000269|PubMed:28552616}. Cytoplasm {ECO:0000250|UniProtKB:Q9QXG4}. Nucleus {ECO:0000269|PubMed:28552616}. Note=Glucose deprivation results in its AMPK-dependent phosphorylation and subsequent nuclear translocation (PubMed:28552616). Phosphorylation at Ser-659, leads to exposure of its nuclear localization signal which is required for its interaction with KPNA1 and subsequent translocation to the nucleus (PubMed:28552616). Found in the cytoplasm in undifferentiated neurons and upon differentiation, translocates to nucleus (By similarity). {ECO:0000250|UniProtKB:Q9QXG4, ECO:0000269|PubMed:28552616}.
uniprot
proteins