Overview
| Uniprot ID | Q9NR19 |
| Protein Name | Acetyl-coenzyme A synthetase, cytoplasmic |
| Gene Name | ACSS2 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 271 |
TSQSPPIKRSCPDVQ |
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)
Protein Sequence
10
MGLPEERVRS
20
GSGSRGQEEA
30
GAGGRARSWS
40
PPPEVSRSAH
50
VPSLQRYREL
60
HRRSVEEPRE
70
FWGDIAKEFY
80
WKTPCPGPFL
90
RYNFDVTKGK
100
IFIEWMKGAT
110
TNICYNVLDR
120
NVHEKKLGDK
130
VAFYWEGNEP
140
GETTQITYHQ
150
LLVQVCQFSN
160
VLRKQGIQKG
170
DRVAIYMPMI
180
PELVVAMLAC
190
ARIGALHSIV
200
FAGFSSESLC
210
ERILDSSCSL
220
LITTDAFYRG
230
EKLVNLKELA
240
DEALQKCQEK
250
GFPVRCCIVV
260
KHLGRAELGM
270
GDSTSQSPPI
280
KRSCPDVQIS
290
WNQGIDLWWH
300
ELMQEAGDEC
310
EPEWCDAEDP
320
LFILYTSGST
330
GKPKGVVHTV
340
GGYMLYVATT
350
FKYVFDFHAE
360
DVFWCTADIG
370
WITGHSYVTY
380
GPLANGATSV
390
LFEGIPTYPD
400
VNRLWSIVDK
410
YKVTKFYTAP
420
TAIRLLMKFG
430
DEPVTKHSRA
440
SLQVLGTVGE
450
PINPEAWLWY
460
HRVVGAQRCP
470
IVDTFWQTET
480
GGHMLTPLPG
490
ATPMKPGSAT
500
FPFFGVAPAI
510
LNESGEELEG
520
EAEGYLVFKQ
530
PWPGIMRTVY
540
GNHERFETTY
550
FKKFPGYYVT
560
GDGCQRDQDG
570
YYWITGRIDD
580
MLNVSGHLLS
590
TAEVESALVE
600
HEAVAEAAVV
610
GHPHPVKGEC
620
LYCFVTLCDG
630
HTFSPKLTEE
640
LKKQIREKIG
650
PIATPDYIQN
660
APGLPKTRSG
670
KIMRRVLRKI
680
AQNDHDLGDM
690
STVADPSVIS
700
HLFSHRCLTI
Q
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005759 |
mitochondrial matrix |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0003987 |
acetate-CoA ligase activity |
| Molecular Function |
GO:0016208 |
AMP binding |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0003682 |
chromatin binding |
| Molecular Function |
GO:0050218 |
propionate-CoA ligase activity |
| Molecular Function |
GO:0003713 |
transcription coactivator activity |
| Biological Process |
GO:0019413 |
acetate biosynthetic process |
| Biological Process |
GO:0006085 |
acetyl-CoA biosynthetic process |
| Biological Process |
GO:0019427 |
acetyl-CoA biosynthetic process from acetate |
| Biological Process |
GO:0006351 |
DNA-templated transcription |
| Biological Process |
GO:0006068 |
ethanol catabolic process |
| Biological Process |
GO:0008610 |
lipid biosynthetic process |
| Biological Process |
GO:0007616 |
long-term memory |
| Biological Process |
GO:0019542 |
propionate biosynthetic process |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.