H3BCW1 · ADPRS_LATCH

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).

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

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).

Features

Showing features for binding site, site.

TypeIDPosition(s)Description
Binding site26Mg2+ 1 (UniProtKB | ChEBI)
Binding site33Mg2+ 2 (UniProtKB | ChEBI)
Site33Glutamate flap
Binding site62Mg2+ 1 (UniProtKB | ChEBI)
Binding site63Mg2+ 1 (UniProtKB | ChEBI)
Binding site63substrate
Binding site64Mg2+ 1 (UniProtKB | ChEBI)
Binding site132-138substrate
Binding site168substrate
Binding site260substrate
Binding site303Mg2+ 2 (UniProtKB | ChEBI)
Binding site305Mg2+ 1 (UniProtKB | ChEBI)
Binding site305Mg2+ 2 (UniProtKB | ChEBI)
Binding site306Mg2+ 2 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentchromosome
Cellular Componentmitochondrial matrix
Cellular Componentnucleus
Molecular Functionmagnesium ion binding
Molecular Functionpoly(ADP-ribose) glycohydrolase activity
Biological ProcessDNA repair
Biological Processnegative regulation of necroptotic process
Biological Processpeptidyl-serine ADP-deribosylation

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    ADP-ribosylhydrolase ARH3
  • Alternative names
    • ADP-ribose glycohydrolase ARH3
      (LchARH3
      )
    • ADP-ribosylhydrolase 3
    • O-acetyl-ADP-ribose deacetylase ARH3
      (EC:3.5.1.-
      ) . EC:3.5.1.- (UniProtKB | ENZYME | Rhea)
    • Poly(ADP-ribose) glycohydrolase ARH3
      (EC:3.2.1.143
      ) . EC:3.2.1.143 (UniProtKB | ENZYME | Rhea)
    • [Protein ADP-ribosylarginine] hydrolase-like protein 2
    • [Protein ADP-ribosylserine] hydrolase (EC:3.2.2.-) . EC:3.2.2.- (UniProtKB | ENZYME | Rhea)

Gene names

    • Name
      adprs
    • Synonyms
      adprhl2, arh3

Organism names

Accessions

  • Primary accession
    H3BCW1

Proteomes

Subcellular Location

Nucleus
Cytoplasm
Chromosome
Mitochondrion matrix
Note: Recruited to DNA lesion regions following DNA damage; ADP-D-ribose-recognition is required for recruitment to DNA damage sites.

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis33Complete loss of activity.
Mutagenesis63Complete loss of activity.
Mutagenesis64Complete loss of activity.
Mutagenesis303Complete loss of activity.
Mutagenesis305Complete loss of activity.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_50035807221-356ADP-ribosylhydrolase ARH3

Expression

Gene expression databases

Interaction

Subunit

Monomer.

Protein-protein interaction databases

Family & Domains

Sequence similarities

Belongs to the ADP-ribosylglycohydrolase family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    356
  • Mass (Da)
    38,819
  • Last updated
    2012-04-18 v1
  • Checksum
    72731420F3F2CB80
MSAVGRLAAVSLAQVRGALCGALLGDCMGAEFEGSDAVELPDVLEFVRLLEKEKKAGTLFYTDDTAMTRAVIQSLIAKPDFDEVDMAKRFAEEYKKEPTRGYGAGVVQVFKKLLSPKYSDVFQPAREQFDGKGSYGNGGAMRVASIALAYPNIQDVIKFARRSAQLTHASPLGYNGAILQALAVHFALQGELKRDTFLEQLIGEMERIEGGEMSASDAGEHDRPNEVKLPFCSRLKKIKEFLASSNVPKADIVDELGHGIAALESVPTAIYSFLHCMESDPDIPDLYNNLQRTIIYSISLGGDTDTIATMAGAIAGAYYGMDQVTPSWKRSCEAIVETEESAVKLYELYCKQLKTP

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
H3BCW0H3BCW0_LATCHADPRS370

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AFYH01014263
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AFYH01014264
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.

Genome annotation databases

Similar Proteins

Disclaimer

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