Overview
| Uniprot ID | Q9NX46 |
|---|
| Protein Name | ADP-ribosylhydrolase ARH3 |
|---|
| Gene Name | ADPRS |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 131 |
FKKLLNPKCRDVFEP |
Function
ADP-ribosylhydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine and threonine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose (PubMed:21498885, PubMed:29907568, PubMed:30045870, PubMed:30401461, PubMed:30830864, PubMed:33186521, PubMed:33769608, PubMed:33894202, PubMed:34019811, PubMed:34321462, PubMed:34479984, PubMed:34625544). Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response (PubMed:28650317, PubMed:29234005, PubMed:30045870, PubMed:33186521, PubMed:34019811, PubMed:34625544). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802, PubMed:33186521, PubMed:34625544). Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (PubMed:16278211, PubMed:33769608). Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (PubMed:16278211). Also hydrolyzes free poly(ADP-ribose) in mitochondria (PubMed:22433848). Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (PubMed:17075046, PubMed:21498885). Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers (PubMed:21498885)
Protein Sequence
10
MAAAAMAAAA
20
GGGAGAARSL
30
SRFRGCLAGA
40
LLGDCVGSFY
50
EAHDTVDLTS
60
VLRHVQSLEP
70
DPGTPGSERT
80
EALYYTDDTA
90
MARALVQSLL
100
AKEAFDEVDM
110
AHRFAQEYKK
120
DPDRGYGAGV
130
VTVFKKLLNP
140
KCRDVFEPAR
150
AQFNGKGSYG
160
NGGAMRVAGI
170
SLAYSSVQDV
180
QKFARLSAQL
190
THASSLGYNG
200
AILQALAVHL
210
ALQGESSSEH
220
FLKQLLGHME
230
DLEGDAQSVL
240
DARELGMEER
250
PYSSRLKKIG
260
ELLDQASVTR
270
EEVVSELGNG
280
IAAFESVPTA
290
IYCFLRCMEP
300
DPEIPSAFNS
310
LQRTLIYSIS
320
LGGDTDTIAT
330
MAGAIAGAYY
340
GMDQVPESWQ
350
QSCEGYEETD
360
ILAQSLHRVF
QKS
Gene Ontology
| Classification |
GO ID |
Description |
| Biological Process |
GO:0006287 |
base-excision repair, gap-filling |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005759 |
mitochondrial matrix |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0090734 |
site of DNA damage |
| Molecular Function |
GO:0140292 |
ADP-ribosylserine hydrolase activity |
| Molecular Function |
GO:0004553 |
hydrolase activity, hydrolyzing O-glycosyl compounds |
| Molecular Function |
GO:0000287 |
magnesium ion binding |
| Molecular Function |
GO:0061463 |
O-acetyl-ADP-ribose deacetylase activity |
| Molecular Function |
GO:0004649 |
poly(ADP-ribose) glycohydrolase activity |
| Biological Process |
GO:0071451 |
cellular response to superoxide |
| Biological Process |
GO:0006281 |
DNA repair |
| Biological Process |
GO:0060546 |
negative regulation of necroptotic process |
| Biological Process |
GO:0140290 |
peptidyl-serine ADP-deribosylation |
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.