H3BCW1 · ADPRS_LATCH
- ProteinADP-ribosylhydrolase ARH3
- Geneadprs
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids356 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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:30472116).
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:30472116).
Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (By similarity).
Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (By similarity).
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:30472116).
Also hydrolyzes free poly(ADP-ribose) in mitochondria (By similarity).
Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (By similarity).
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 (By similarity).
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:30472116).
Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (By similarity).
Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (By similarity).
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:30472116).
Also hydrolyzes free poly(ADP-ribose) in mitochondria (By similarity).
Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (By similarity).
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 (By similarity).
Catalytic activity
- [(1''->2')-ADP-alpha-D-ribose](n) + H2O = [(1''->2')-ADP-alpha-D-ribose](n-1) + ADP-D-riboseThis reaction proceeds in the forward direction.
[(1''→2')-ADP-α-D-ribose](n) RHEA-COMP:16922 + CHEBI:15377 = [(1''→2')-ADP-α-D-ribose](n−1) RHEA-COMP:16923 + CHEBI:57967 - 1''-O-acetyl-ADP-alpha-D-ribose + H2O = acetate + ADP-D-ribose + H+
- H2O + O-(ADP-D-ribosyl)-L-seryl-[protein] = ADP-D-ribose + L-seryl-[protein]
- alpha-NAD+ + H2O = ADP-D-ribose + H+ + nicotinamide
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Note: Binds 2 magnesium ions per subunit.
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 (By similarity).
The glutamate flap (Glu-33) blocks substrate entrance to Mg2+ in the unliganded closed state (By similarity).
In presence of substrate, Glu-33 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 (By similarity).
Activity is inhibited by calcium (PubMed:30472116).
The glutamate flap (Glu-33) blocks substrate entrance to Mg2+ in the unliganded closed state (By similarity).
In presence of substrate, Glu-33 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 (By similarity).
Activity is inhibited by calcium (PubMed:30472116).
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 26 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 33 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Site | 33 | Glutamate flap | ||||
Sequence: E | ||||||
Binding site | 62 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 63 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 63 | substrate | ||||
Sequence: D | ||||||
Binding site | 64 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 132-138 | substrate | ||||
Sequence: KGSYGNG | ||||||
Binding site | 168 | substrate | ||||
Sequence: H | ||||||
Binding site | 260 | substrate | ||||
Sequence: I | ||||||
Binding site | 303 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 305 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 305 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 306 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: T |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chromosome | |
Cellular Component | mitochondrial matrix | |
Cellular Component | nucleus | |
Molecular Function | magnesium ion binding | |
Molecular Function | poly(ADP-ribose) glycohydrolase activity | |
Biological Process | DNA repair | |
Biological Process | negative regulation of necroptotic process | |
Biological Process | peptidyl-serine ADP-deribosylation |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameADP-ribosylhydrolase ARH3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Coelacanthiformes > Coelacanthidae > Latimeria
Accessions
- Primary accessionH3BCW1
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: Recruited to DNA lesion regions following DNA damage; ADP-D-ribose-recognition is required for recruitment to DNA damage sites.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 33 | Complete loss of activity. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 63 | Complete loss of activity. | ||||
Sequence: D → N | ||||||
Mutagenesis | 64 | Complete loss of activity. | ||||
Sequence: D → N | ||||||
Mutagenesis | 303 | Complete loss of activity. | ||||
Sequence: D → N | ||||||
Mutagenesis | 305 | Complete loss of activity. | ||||
Sequence: D → N |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_5003580722 | 1-356 | ADP-ribosylhydrolase ARH3 | |||
Sequence: MSAVGRLAAVSLAQVRGALCGALLGDCMGAEFEGSDAVELPDVLEFVRLLEKEKKAGTLFYTDDTAMTRAVIQSLIAKPDFDEVDMAKRFAEEYKKEPTRGYGAGVVQVFKKLLSPKYSDVFQPAREQFDGKGSYGNGGAMRVASIALAYPNIQDVIKFARRSAQLTHASPLGYNGAILQALAVHFALQGELKRDTFLEQLIGEMERIEGGEMSASDAGEHDRPNEVKLPFCSRLKKIKEFLASSNVPKADIVDELGHGIAALESVPTAIYSFLHCMESDPDIPDLYNNLQRTIIYSISLGGDTDTIATMAGAIAGAYYGMDQVTPSWKRSCEAIVETEESAVKLYELYCKQLKTP |
Expression
Gene expression databases
Interaction
Structure
Sequence
- Sequence statusComplete
- Length356
- Mass (Da)38,819
- Last updated2012-04-18 v1
- Checksum72731420F3F2CB80
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H3BCW0 | H3BCW0_LATCH | ADPRS | 370 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AFYH01014263 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AFYH01014264 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |