ADPRS_XENTR
ID ADPRS_XENTR Reviewed; 350 AA.
AC Q28FQ6;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=ADP-ribosylhydrolase ARH3 {ECO:0000305};
DE AltName: Full=ADP-ribose glycohydrolase ARH3 {ECO:0000305};
DE AltName: Full=ADP-ribosylhydrolase 3 {ECO:0000250|UniProtKB:Q9NX46};
DE AltName: Full=O-acetyl-ADP-ribose deacetylase ARH3 {ECO:0000305};
DE EC=3.5.1.- {ECO:0000250|UniProtKB:Q9NX46};
DE AltName: Full=Poly(ADP-ribose) glycohydrolase ARH3 {ECO:0000305};
DE EC=3.2.1.143 {ECO:0000250|UniProtKB:Q9NX46};
DE AltName: Full=[Protein ADP-ribosylarginine] hydrolase-like protein 2 {ECO:0000305};
DE AltName: Full=[Protein ADP-ribosylserine] hydrolase;
DE EC=3.2.2.-;
GN Name=adprs;
GN Synonyms=adprhl2 {ECO:0000250|UniProtKB:Q9NX46},
GN arh3 {ECO:0000250|UniProtKB:Q9NX46};
GN ORFNames=TGas084j22.1 {ECO:0000303|Ref.1};
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastrula;
RG Sanger Xenopus tropicalis EST/cDNA project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: ADP-ribosylhydrolase that preferentially hydrolyzes the
CC scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-
CC ribose and acts on different substrates, such as proteins ADP-
CC ribosylated on serine and threonine, free poly(ADP-ribose) and O-
CC acetyl-ADP-D-ribose. Specifically acts as a serine mono-ADP-
CC ribosylhydrolase by mediating the removal of mono-ADP-ribose attached
CC to serine residues on proteins, thereby playing a key role in DNA
CC damage response. Serine ADP-ribosylation of proteins constitutes the
CC primary form of ADP-ribosylation of proteins in response to DNA damage.
CC Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or
CC -asparagine bonds. Also able to degrade protein free poly(ADP-ribose),
CC which is synthesized in response to DNA damage: free poly(ADP-ribose)
CC acts as a potent cell death signal and its degradation by ADPRHL2
CC protects cells from poly(ADP-ribose)-dependent cell death, a process
CC named parthanatos (By similarity). Also hydrolyzes free poly(ADP-
CC ribose) in mitochondria. Specifically digests O-acetyl-ADP-D-ribose, a
CC product of deacetylation reactions catalyzed by sirtuins. Specifically
CC degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-
CC ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers.
CC {ECO:0000250|UniProtKB:Q9NX46}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[(1''->2')-ADP-alpha-D-ribose](n) + H2O = [(1''->2')-ADP-
CC alpha-D-ribose](n-1) + ADP-D-ribose; Xref=Rhea:RHEA:52216, Rhea:RHEA-
CC COMP:16922, Rhea:RHEA-COMP:16923, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57967, ChEBI:CHEBI:142512; EC=3.2.1.143;
CC Evidence={ECO:0000250|UniProtKB:Q9NX46};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1''-O-acetyl-ADP-alpha-D-ribose + H2O = acetate + ADP-D-ribose
CC + H(+); Xref=Rhea:RHEA:58112, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:57967, ChEBI:CHEBI:142511;
CC Evidence={ECO:0000250|UniProtKB:Q9NX46};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-(ADP-D-ribosyl)-L-seryl-[protein] = ADP-D-ribose + L-
CC seryl-[protein]; Xref=Rhea:RHEA:58256, Rhea:RHEA-COMP:9863,
CC Rhea:RHEA-COMP:15091, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999,
CC ChEBI:CHEBI:57967, ChEBI:CHEBI:142556;
CC Evidence={ECO:0000250|UniProtKB:Q9NX46};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alpha-NAD(+) + H2O = ADP-D-ribose + H(+) + nicotinamide;
CC Xref=Rhea:RHEA:68792, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57967, ChEBI:CHEBI:77017;
CC Evidence={ECO:0000250|UniProtKB:Q9NX46};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9NX46};
CC Note=Binds 2 magnesium ions per subunit.
CC {ECO:0000250|UniProtKB:Q9NX46};
CC -!- ACTIVITY REGULATION: The protein undergoes a dramatic conformational
CC switch from closed to open states upon substrate-binding, which enables
CC specific substrate recognition for the 1''-O-linkage. The glutamate
CC flap (Glu-27) blocks substrate entrance to Mg(2+) in the unliganded
CC closed state. In presence of substrate, Glu-27 is ejected from the
CC active site: this closed-to-open transition significantly widens the
CC substrate-binding channel and precisely positions the scissile 1''-O-
CC linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of
CC ADP-ribose. {ECO:0000250|UniProtKB:Q9NX46}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9NX46}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NX46}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9NX46}. Chromosome
CC {ECO:0000250|UniProtKB:Q9NX46}. Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q9NX46}. Note=Recruited to DNA lesion regions
CC following DNA damage; ADP-D-ribose-recognition is required for
CC recruitment to DNA damage sites. {ECO:0000250|UniProtKB:Q9NX46}.
CC -!- SIMILARITY: Belongs to the ADP-ribosylglycohydrolase family.
CC {ECO:0000305}.
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DR EMBL; CR761827; CAJ81573.1; -; mRNA.
DR RefSeq; NP_001016184.1; NM_001016184.2.
DR AlphaFoldDB; Q28FQ6; -.
DR SMR; Q28FQ6; -.
DR STRING; 8364.ENSXETP00000059133; -.
DR PaxDb; Q28FQ6; -.
DR GeneID; 548938; -.
DR KEGG; xtr:548938; -.
DR CTD; 54936; -.
DR Xenbase; XB-GENE-944445; adprs.
DR eggNOG; ENOG502QUER; Eukaryota.
DR InParanoid; Q28FQ6; -.
DR OrthoDB; 988788at2759; -.
DR Reactome; R-XTR-110362; POLB-Dependent Long Patch Base Excision Repair.
DR Proteomes; UP000008143; Chromosome 2.
DR Proteomes; UP000790000; Unplaced.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0090734; C:site of DNA damage; ISS:UniProtKB.
DR GO; GO:0140292; F:ADP-ribosylserine hydrolase activity; ISS:UniProtKB.
DR GO; GO:0004553; F:hydrolase activity, hydrolyzing O-glycosyl compounds; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0061463; F:O-acetyl-ADP-ribose deacetylase activity; ISS:UniProtKB.
DR GO; GO:0004649; F:poly(ADP-ribose) glycohydrolase activity; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR GO; GO:0060546; P:negative regulation of necroptotic process; ISS:UniProtKB.
DR GO; GO:0140290; P:peptidyl-serine ADP-deribosylation; ISS:UniProtKB.
DR Gene3D; 1.10.4080.10; -; 1.
DR InterPro; IPR005502; Ribosyl_crysJ1.
DR InterPro; IPR036705; Ribosyl_crysJ1_sf.
DR Pfam; PF03747; ADP_ribosyl_GH; 1.
DR SUPFAM; SSF101478; SSF101478; 1.
PE 2: Evidence at transcript level;
KW Chromosome; Cytoplasm; DNA damage; DNA repair; Hydrolase; Magnesium;
KW Metal-binding; Mitochondrion; Nucleus; Reference proteome.
FT CHAIN 1..350
FT /note="ADP-ribosylhydrolase ARH3"
FT /id="PRO_0000277617"
FT BINDING 27
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 57
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 58
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 58
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 59
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 127..133
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 163
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 216
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 252
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 295
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 297
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 297
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 298
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT SITE 27
FT /note="Glutamate flap"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
SQ SEQUENCE 350 AA; 39034 MW; 7AACCDD9CDC767F6 CRC64;
MMAAGVSRFR GSLLGALLGD CIGAVFEGHT NVTKEFLFDY MKSLDKGERL KRVLTYTDDT
AMARSIVQSV LENYEFNIED LANRFTTEYN RDPDRGYGMA VVHVFEKLGS GEYKHVFSPA
REQFDGKGSY GNGAAMRVVG ISLAYPRIPD IIEYARTSGM LTHASSLGYN GAILQALAVH
YALQGELAPE TFLDQLLDHM KEVETDKKSR SDALELEMDE FPYCNKLRKI KAFLAREDVT
RKDIVKELGN GIQAFESVPT AIYSFLRCLK PVSELPSELT NLQRTIAFCI LLGGDTDTIA
TMAAAIAGAY HGEEQIPLNW KLSAEGYKDA EDWGEKLHQL YCRRLQSTTS
