ADPRS_DANRE
ID ADPRS_DANRE Reviewed; 370 AA.
AC Q66HT8; A7MCF6;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 106.
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=zgc:92867 {ECO:0000303|Ref.1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Ovary;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (SEP-2004) 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-35) blocks substrate entrance to Mg(2+) in the unliganded
CC closed state. In presence of substrate, Glu-35 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH81683.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305};
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DR EMBL; BC081683; AAH81683.1; ALT_SEQ; mRNA.
DR EMBL; BC152161; AAI52162.1; -; mRNA.
DR RefSeq; NP_001004565.2; NM_001004565.2.
DR AlphaFoldDB; Q66HT8; -.
DR SMR; Q66HT8; -.
DR STRING; 7955.ENSDARP00000027022; -.
DR PaxDb; Q66HT8; -.
DR Ensembl; ENSDART00000011706; ENSDARP00000027022; ENSDARG00000019338.
DR Ensembl; ENSDART00000181081; ENSDARP00000157106; ENSDARG00000110712.
DR GeneID; 796446; -.
DR KEGG; dre:796446; -.
DR CTD; 54936; -.
DR ZFIN; ZDB-GENE-040912-85; adprs.
DR eggNOG; ENOG502QUER; Eukaryota.
DR GeneTree; ENSGT00390000015369; -.
DR HOGENOM; CLU_024566_6_0_1; -.
DR InParanoid; Q66HT8; -.
DR OMA; IPPSWEQ; -.
DR OrthoDB; 988788at2759; -.
DR PhylomeDB; Q66HT8; -.
DR TreeFam; TF324754; -.
DR Reactome; R-DRE-110362; POLB-Dependent Long Patch Base Excision Repair.
DR PRO; PR:Q66HT8; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 17.
DR Bgee; ENSDARG00000019338; Expressed in testis and 23 other tissues.
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..370
FT /note="ADP-ribosylhydrolase ARH3"
FT /id="PRO_0000277616"
FT BINDING 35
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 66
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 66
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 67
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 135..141
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 171
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 225
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 261
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 304
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 306
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 306
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 307
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT SITE 35
FT /note="Glutamate flap"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT CONFLICT 345
FT /note="R -> H (in Ref. 1; AAI52162)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 370 AA; 40103 MW; FC07F4F67AB7B784 CRC64;
MSAAARVVAP VMMLSRFRGA LVGSVLGDCI GGEFEGAVDV PLDRVLQHLS ALEDDTRGDG
ILQYSDDTAM MRCVADSLLT RMTFDERDMA QRFAKEYSHS PGRGYGSGVV QVLRKLASPH
LKDVFQPAQA QFGGRGSFGN GGAMRAVPFA LAFRSRADVR KYSRFGAMLT HSCSLGYNGA
ALQALAVHLS LQGALALPKD FIDKLISEME ELEKDETAKH DAKALNLSEF PYCSRLHRVK
ELMDKTSVSI EEVISELGNG IAALQSVPTA IFCVLYCLEP QDGLPERFGG LERTIAYSLA
LGGDTDTIAC MAGAIAGAHY GIDSIPLSWQ VSCEGVDEAD DLARRLYDLY CLPQHNEDRG
NNQPHTTNTD
