ADPRS_CHICK
ID ADPRS_CHICK Reviewed; 367 AA.
AC Q5ZI51;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 87.
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=RCJMB04_30e5 {ECO:0000303|PubMed:15642098};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CB; TISSUE=Bursa of Fabricius;
RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6;
RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P.,
RA Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P.,
RA Hayashizaki Y., Buerstedde J.-M.;
RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene
RT function analysis.";
RL Genome Biol. 6:R6.1-R6.9(2005).
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-41) blocks substrate entrance to Mg(2+) in the unliganded
CC closed state. In presence of substrate, Glu-41 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; AJ720933; CAG32592.1; -; mRNA.
DR RefSeq; NP_001006312.1; NM_001006312.1.
DR AlphaFoldDB; Q5ZI51; -.
DR SMR; Q5ZI51; -.
DR STRING; 9031.ENSGALP00000003617; -.
DR PaxDb; Q5ZI51; -.
DR GeneID; 419626; -.
DR KEGG; gga:419626; -.
DR CTD; 419626; -.
DR VEuPathDB; HostDB:geneid_419626; -.
DR eggNOG; ENOG502QUER; Eukaryota.
DR InParanoid; Q5ZI51; -.
DR OrthoDB; 988788at2759; -.
DR PhylomeDB; Q5ZI51; -.
DR PRO; PR:Q5ZI51; -.
DR Proteomes; UP000000539; 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..367
FT /note="ADP-ribosylhydrolase ARH3"
FT /id="PRO_0000277615"
FT BINDING 41
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 79
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 80
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 80
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 81
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 149..155
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 185
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 238
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 274
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 317
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT BINDING 320
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT SITE 41
FT /note="Glutamate flap"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
SQ SEQUENCE 367 AA; 39909 MW; 605113FC6622FF89 CRC64;
MAAAGAGSGR AAVSRSRPPP ARFRGCLAGA LLGDCLGAVF EGRSVVKLPD LLSFLRGLEP
PGGEGEPAGS ARRETLSYTD DTAMSRCVVQ SLLAKREFDE VDMAKRFAEE YKKEPNRGYG
MAVVNVFKKL LSPQCSDVFE PARAQFNGKG SYGNGGAMRV AGIPLTYSDV QDVKKFAKLS
AELTHANSLG YNGAILQALA VHLALQGEVS RETFLEQLIS HMEDIEADDK SLTDARALGF
EDLPFSRRLK KIKEFLELSS VPKEDVLFEL GNGIAALRSV PTAIYSFLRC MEADPDIPEH
YNNLQRTIIY CISLGGDTNT IATMAGAIAG AYYGEEQVPP SWEQSCEAFQ ETQKMANSLH
ELYCQQL
