ADPRS
entrez
54936
canonical
uniprot
Q9NX46
canonical
ensembl
ENSG00000116863
resolver
ensp
ENSP00000362273
resolver
enst
ENST00000373178
resolver
genesymbol
ADPRHL2
resolver
genesymbol
ADPRS
resolver
genesymbol_syn
ADPRHL2
resolver
genesymbol_syn
ARH3
resolver
hgnc
HGNC:21304
resolver
uniprot
B7ZAN4
resolver
uniprot
Q53G94
resolver
uniprot
Q6IAB8
resolver
uniprot
Q9BY47
resolver
uniprot_entry
ADPRS_HUMAN
resolver
uniprot_entry
B7ZAN4_HUMAN
resolver
uniprot_sec
Q53G94
resolver
uniprot_sec
Q6IAB8
resolver
uniprot_sec
Q9BY47
resolver
activity_regulation
ACTIVITY REGULATION: The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage (PubMed:29907568, PubMed:34321462). The glutamate flap (Glu-41) blocks substrate entrance to Mg(2+) in the unliganded closed state (PubMed:29907568, PubMed:30045870, PubMed:34321462). In presence of substrate, Glu-41 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose (PubMed:29907568, PubMed:30045870, PubMed:34321462). {ECO:0000269|PubMed:29907568, ECO:0000269|PubMed:30045870, ECO:0000269|PubMed:34321462}.
uniprot
proteins
amino_acid_sequence
MAAAAMAAAAGGGAGAARSLSRFRGCLAGALLGDCVGSFYEAHDTVDLTSVLRHVQSLEPDPGTPGSERTEALYYTDDTAMARALVQSLLAKEAFDEVDMAHRFAQEYKKDPDRGYGAGVVTVFKKLLNPKCRDVFEPARAQFNGKGSYGNGGAMRVAGISLAYSSVQDVQKFARLSAQLTHASSLGYNGAILQALAVHLALQGESSSEHFLKQLLGHMEDLEGDAQSVLDARELGMEERPYSSRLKKIGELLDQASVTREEVVSELGNGIAAFESVPTAIYCFLRCMEPDPEIPSAFNSLQRTLIYSISLGGDTDTIATMAGAIAGAYYGMDQVPESWQQSCEGYEETDILAQSLHRVFQKS
uniprot
proteins
disease_involvement
DISEASE: Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (CONDSIAS) [MIM:618170]: An autosomal recessive neurodegenerative disorder characterized by pediatric onset of progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. {ECO:0000269|PubMed:30100084, ECO:0000269|PubMed:30401461, ECO:0000269|PubMed:30830864, ECO:0000269|PubMed:34019811, ECO:0000269|PubMed:34479984}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.2.1.143
uniprot
proteins
ec_number
3.2.2.-
uniprot
proteins
ec_number
3.5.1.-
uniprot
proteins
function
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). {ECO:0000269|PubMed:16278211, ECO:0000269|PubMed:17075046, ECO:0000269|PubMed:21498885, ECO:0000269|PubMed:22433848, ECO:0000269|PubMed:28650317, ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:29480802, ECO:0000269|PubMed:29907568, ECO:0000269|PubMed:30045870, ECO:0000269|PubMed:30401461, ECO:0000269|PubMed:30830864, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33769608, ECO:0000269|PubMed:33894202, ECO:0000269|PubMed:34019811, ECO:0000269|PubMed:34321462, ECO:0000269|PubMed:34479984, ECO:0000269|PubMed:34625544}.
uniprot
proteins
mass_dalton
38947
uniprot
proteins
mutagenesis
MUTAGEN 34; /note="D->G: Reduces hydrolase activity."; /evidence="ECO:0000269|PubMed:34321462"; MUTAGEN 41; /note="E->A,Q: Significant loss of activity. Does not affect recruitment to DNA lesion regions following DNA damage. Strongly reduced ability to hydrolyze proteins ADP-ribosylated on serine."; /evidence="ECO:0000269|PubMed:17015823, ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:30045870, ECO:0000269|PubMed:34321462"; MUTAGEN 76; /note="T->R: Abolishes hydrolase activity."; /evidence="ECO:0000269|PubMed:34321462"; MUTAGEN 77..78; /note="DD->AA: Retains ability to bind proteins ADP-ribosylated on serine but is unable to hydrolyze them."; /evidence="ECO:0000269|PubMed:29234005"; MUTAGEN 77..78; /note="DD->NN: Complete loss of activity."; /evidence="ECO:0000269|PubMed:16278211, ECO:0000269|PubMed:17075046, ECO:0000269|PubMed:28650317"; MUTAGEN 77; /note="D->N,A: Complete loss of activity. Abolishes Mg(2+) binding. Retains ability to bind ADP-ribose. Does not affect recruitment to DNA lesion regions following DNA damage. Strongly reduced ability to hydrolyze proteins ADP-ribosylated on serine."; /evidence="ECO:0000269|PubMed:17015823, ECO:0000269|PubMed:28650317, ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:30045870, ECO:0000269|PubMed:31599159, ECO:0000269|PubMed:33769608, ECO:0000269|PubMed:33894202, ECO:0000269|PubMed:34019811, ECO:0000269|PubMed:34321462, ECO:0000269|PubMed:34479984"; MUTAGEN 78; /note="D->A: Abolishes hydrolase activity."; /evidence="ECO:0000269|PubMed:33894202"; MUTAGEN 78; /note="D->N: Complete loss of activity."; /evidence="ECO:0000269|PubMed:28650317, ECO:0000269|PubMed:31599159, ECO:0000269|PubMed:33769608, ECO:0000269|PubMed:34019811, ECO:0000269|PubMed:34321462, ECO:0000269|PubMed:34479984"; MUTAGEN 115; /note="G->D: Abolished ability to bind and hydrolyze proteins ADP-ribosylated on serine. No effect on hydrolase activity."; /evidence="ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:34321462"; MUTAGEN 143; /note="F->L: Abolishes hydrolase activity."; /evidence="ECO:0000269|PubMed:34321462"; MUTAGEN 148; /note="S->A: Complete loss of activity. Abolished recruitment to DNA lesion regions following DNA damage. Abolished ability to hydrolyze proteins ADP-ribosylated on serine."; /evidence="ECO:0000269|PubMed:17015823, ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:30045870, ECO:0000269|PubMed:34321462"; MUTAGEN 149; /note="Y->A: Significant loss of activity. Abolished recruitment to DNA lesion regions following DNA damage. Abolished ability to hydrolyze proteins ADP-ribosylated on serine."; /evidence="ECO:0000269|PubMed:17015823, ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:30045870"; MUTAGEN 149; /note="Y->L: No effect on hydrolase activity."; /evidence="ECO:0000269|PubMed:34321462"; MUTAGEN 150; /note="G->E: Reduces hydrolase activity."; /evidence="ECO:0000269|PubMed:34321462"; MUTAGEN 151; /note="N->A: Partial loss of activity."; /evidence="ECO:0000269|PubMed:17015823"; MUTAGEN 182; /note="H->Q,A: Complete loss of activity. Abolished recruitment to DNA lesion regions following DNA damage. Abolished ability to hydrolyze proteins ADP-ribosylated on serine."; /evidence="ECO:0000269|PubMed:17015823, ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:30045870"; MUTAGEN 185; /note="S->P: No effect on hydrolase activity."; /evidence="ECO:0000269|PubMed:34321462"; MUTAGEN 186; /note="L->V: No effect on hydrolase activity."; /evidence="ECO:0000269|PubMed:34321462"; MUTAGEN 238..239; /note="EE->QQ: Slight reduction in activity toward poly(ADP-ribose). Does not affect ability to degrade O-acetyl-ADP-D-ribose."; /evidence="ECO:0000269|PubMed:16278211, ECO:0000269|PubMed:17075046"; MUTAGEN 261..262; /note="EE->QQ: Slight reduction in activity toward poly(ADP-ribose). Does not affect ability to degrade O-acetyl-ADP-D-ribose."; /evidence="ECO:0000269|PubMed:16278211, ECO:0000269|PubMed:17075046"; MUTAGEN 269; /note="N->A: No effect on hydrolase activity."; /evidence="ECO:0000269|PubMed:34321462"; MUTAGEN 270; /note="G->C: No effect on hydrolase activity."; /evidence="ECO:0000269|PubMed:34321462"; MUTAGEN 271; /note="I->A: No effect on hydrolase activity."; /evidence="ECO:0000269|PubMed:34321462"; MUTAGEN 314; /note="D->A,E: Complete loss of activity. Abolishes Mg(2+) and ADP-ribose binding. Does not affect recruitment to DNA lesion regions following DNA damage. Retains ability to bind proteins ADP-ribosylated on serine but is unable to hydrolyze them."; /evidence="ECO:0000269|PubMed:17015823, ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:29907568, ECO:0000269|PubMed:30045870, ECO:0000269|PubMed:33894202"; MUTAGEN 314; /note="D->N: Significant loss of activity."; /evidence="ECO:0000269|PubMed:17015823"; MUTAGEN 316; /note="D->A: Abolishes hydrolase activity."; /evidence="ECO:0000269|PubMed:33894202"; MUTAGEN 317; /note="T->A: Complete loss of activity. Does not affect recruitment to DNA lesion regions following DNA damage. Retains ability to bind proteins ADP-ribosylated on serine but is unable to hydrolyze them."; /evidence="ECO:0000269|PubMed:17015823, ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:30045870"; MUTAGEN 317; /note="T->S: Partial loss of activity."; /evidence="ECO:0000269|PubMed:17015823
uniprot
proteins
protein_family
ADP-ribosylglycohydrolase family
uniprot
proteins
pubmed
12070318
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16278211
uniprot
proteins
pubmed
16511307
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17015823
uniprot
proteins
pubmed
17075046
uniprot
proteins
pubmed
17327674
uniprot
proteins
pubmed
17991898
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21498885
uniprot
proteins
pubmed
21892188
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22433848
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
28650317
uniprot
proteins
pubmed
29234005
uniprot
proteins
pubmed
29480802
uniprot
proteins
pubmed
29907568
uniprot
proteins
pubmed
30045870
uniprot
proteins
pubmed
30100084
uniprot
proteins
pubmed
30401461
uniprot
proteins
pubmed
30830864
uniprot
proteins
pubmed
31599159
uniprot
proteins
pubmed
33186521
uniprot
proteins
pubmed
33769608
uniprot
proteins
pubmed
33894202
uniprot
proteins
pubmed
34019811
uniprot
proteins
pubmed
34321462
uniprot
proteins
pubmed
34479984
uniprot
proteins
pubmed
34625544
uniprot
proteins
pubmed
37268618
uniprot
proteins
sequence_length
363
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17991898, ECO:0000269|PubMed:34479984}. Cytoplasm {ECO:0000269|PubMed:16278211, ECO:0000269|PubMed:34479984}. Chromosome {ECO:0000269|PubMed:30045870}. Mitochondrion matrix {ECO:0000269|PubMed:17991898, ECO:0000269|PubMed:34479984, ECO:0000305|PubMed:22433848}. Note=Recruited to DNA lesion regions following DNA damage; ADP-D-ribose-recognition is required for recruitment to DNA damage sites. {ECO:0000269|PubMed:30045870}.
uniprot
proteins