ADPRS_LATCH
ID ADPRS_LATCH Reviewed; 356 AA.
AC H3BCW1;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2012, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=ADP-ribosylhydrolase ARH3 {ECO:0000305};
DE AltName: Full=ADP-ribose glycohydrolase ARH3 {ECO:0000305};
DE Short=LchARH3 {ECO:0000303|PubMed:30472116};
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:0000269|PubMed:30472116};
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:0000312|Ensembl:ENSLACP00000019732},
GN arh3 {ECO:0000303|PubMed:30472116};
OS Latimeria chalumnae (Coelacanth).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Coelacanthiformes; Coelacanthidae; Latimeria.
OX NCBI_TaxID=7897;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=9215903; DOI=10.1093/genetics/146.3.995;
RA Zardoya R., Meyer A.;
RT "The complete DNA sequence of the mitochondrial genome of a 'living
RT fossil,' the coelacanth (Latimeria chalumnae).";
RL Genetics 146:995-1010(1997).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 10-356 IN COMPLEX WITH MAGNESIUM
RP AND ADP-RIBOSE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF GLU-33; ASP-63; ASP-64; ASP-303 AND ASP-305.
RX PubMed=30472116; DOI=10.1016/j.chembiol.2018.11.001;
RA Rack J.G.M., Ariza A., Drown B.S., Henfrey C., Bartlett E., Shirai T.,
RA Hergenrother P.J., Ahel I.;
RT "(ADP-ribosyl)hydrolases: Structural Basis for Differential Substrate
RT Recognition and Inhibition.";
RL Cell Chem. Biol. 0:0-0(2018).
RN [3] {ECO:0007744|PDB:7AQM}
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 10-356 IN COMPLEX WITH
RP METHYL-ADP-RIBOSE.
RX PubMed=34321462; DOI=10.1038/s41467-021-24723-3;
RA Rack J.G.M., Liu Q., Zorzini V., Voorneveld J., Ariza A.,
RA Honarmand Ebrahimi K., Reber J.M., Krassnig S.C., Ahel D.,
RA van der Marel G.A., Mangerich A., McCullagh J.S.O., Filippov D.V., Ahel I.;
RT "Mechanistic insights into the three steps of poly(ADP-ribosylation)
RT reversal.";
RL Nat. Commun. 12:4581-4581(2021).
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 (PubMed:30472116). Specifically acts as a serine
CC mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose
CC attached to serine residues on proteins, thereby playing a key role in
CC DNA damage response (PubMed:30472116). Serine ADP-ribosylation of
CC proteins constitutes the primary form of ADP-ribosylation of proteins
CC in response to DNA damage (By similarity). Does not hydrolyze ADP-
CC ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (By
CC similarity). Also able to degrade protein free poly(ADP-ribose), which
CC is synthesized in response to DNA damage: free poly(ADP-ribose) acts as
CC a potent cell death signal and its degradation by ADPRHL2 protects
CC cells from poly(ADP-ribose)-dependent cell death, a process named
CC parthanatos (PubMed:30472116). Also hydrolyzes free poly(ADP-ribose) in
CC mitochondria (By similarity). Specifically digests O-acetyl-ADP-D-
CC ribose, a product of deacetylation reactions catalyzed by sirtuins (By
CC similarity). Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer,
CC rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose
CC isomers (By similarity). {ECO:0000250|UniProtKB:Q9NX46,
CC ECO:0000269|PubMed:30472116}.
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:0000269|PubMed:30472116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52217;
CC Evidence={ECO:0000269|PubMed:30472116};
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:0000269|PubMed:30472116};
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:0000269|PubMed:30472116};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000305|PubMed:30472116};
CC Note=Binds 2 magnesium ions per subunit. {ECO:0000269|PubMed:30472116};
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 (By similarity).
CC The glutamate flap (Glu-33) blocks substrate entrance to Mg(2+) in the
CC unliganded closed state (By similarity). In presence of substrate, Glu-
CC 33 is ejected from the active site: this closed-to-open transition
CC significantly widens the substrate-binding channel and precisely
CC positions the scissile 1''-O-linkage for cleavage while securing
CC tightly 2'- and 3'-hydroxyls of ADP-ribose (By similarity). Activity is
CC inhibited by calcium (PubMed:30472116). {ECO:0000250|UniProtKB:Q9NX46,
CC ECO:0000269|PubMed:30472116}.
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; AFYH01014263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AFYH01014264; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_005988572.1; XM_005988510.2.
DR PDB; 6G1P; X-ray; 1.55 A; A/B=10-356.
DR PDB; 6G1Q; X-ray; 2.10 A; A/B=10-356.
DR PDB; 6HGZ; X-ray; 1.86 A; A/B=10-356.
DR PDB; 6HH3; X-ray; 1.82 A; A/B=10-356.
DR PDB; 6HH4; X-ray; 1.66 A; A/B=10-356.
DR PDB; 6HH5; X-ray; 1.95 A; A/B=10-356.
DR PDB; 6HOZ; X-ray; 1.77 A; A/B=10-356.
DR PDB; 7AQM; X-ray; 2.50 A; A/B=10-356.
DR PDBsum; 6G1P; -.
DR PDBsum; 6G1Q; -.
DR PDBsum; 6HGZ; -.
DR PDBsum; 6HH3; -.
DR PDBsum; 6HH4; -.
DR PDBsum; 6HH5; -.
DR PDBsum; 6HOZ; -.
DR PDBsum; 7AQM; -.
DR AlphaFoldDB; H3BCW1; -.
DR SMR; H3BCW1; -.
DR STRING; 7897.ENSLACP00000019731; -.
DR Ensembl; ENSLACT00000019870; ENSLACP00000019732; ENSLACG00000017349.
DR GeneID; 102353686; -.
DR KEGG; lcm:102353686; -.
DR CTD; 54936; -.
DR GeneTree; ENSGT00390000015369; -.
DR HOGENOM; CLU_024566_6_0_1; -.
DR OrthoDB; 988788at2759; -.
DR Proteomes; UP000008672; Unassembled WGS sequence.
DR Bgee; ENSLACG00000017349; Expressed in chordate pharynx and 6 other tissues.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004649; F:poly(ADP-ribose) glycohydrolase activity; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0060546; P:negative regulation of necroptotic process; ISS:UniProtKB.
DR GO; GO:0140290; P:peptidyl-serine ADP-deribosylation; IDA: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 1: Evidence at protein level;
KW 3D-structure; Chromosome; Cytoplasm; DNA damage; DNA repair; Hydrolase;
KW Magnesium; Metal-binding; Mitochondrion; Nucleus; Reference proteome.
FT CHAIN 1..356
FT /note="ADP-ribosylhydrolase ARH3"
FT /id="PRO_5003580722"
FT BINDING 26
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:34321462,
FT ECO:0007744|PDB:7AQM"
FT BINDING 33
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000269|PubMed:34321462, ECO:0007744|PDB:7AQM"
FT BINDING 62
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30472116"
FT BINDING 63
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000269|PubMed:34321462, ECO:0007744|PDB:7AQM"
FT BINDING 63
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30472116"
FT BINDING 64
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000269|PubMed:34321462, ECO:0007744|PDB:7AQM"
FT BINDING 132..138
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30472116"
FT BINDING 168
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30472116"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30472116"
FT BINDING 303
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000269|PubMed:34321462, ECO:0007744|PDB:7AQM"
FT BINDING 305
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000269|PubMed:34321462, ECO:0007744|PDB:7AQM"
FT BINDING 305
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000269|PubMed:34321462, ECO:0007744|PDB:7AQM"
FT BINDING 306
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30472116"
FT SITE 33
FT /note="Glutamate flap"
FT /evidence="ECO:0000250|UniProtKB:Q9NX46"
FT MUTAGEN 33
FT /note="E->Q: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:30472116"
FT MUTAGEN 63
FT /note="D->N: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:30472116"
FT MUTAGEN 64
FT /note="D->N: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:30472116"
FT MUTAGEN 303
FT /note="D->N: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:30472116"
FT MUTAGEN 305
FT /note="D->N: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:30472116"
FT HELIX 12..29
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 40..52
FT /evidence="ECO:0007829|PDB:6G1P"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 63..77
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 83..96
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 106..114
FT /evidence="ECO:0007829|PDB:6G1P"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:6HH4"
FT HELIX 123..131
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 138..141
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 144..149
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 153..165
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 171..187
FT /evidence="ECO:0007829|PDB:6G1P"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:6HH5"
FT HELIX 194..209
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 230..243
FT /evidence="ECO:0007829|PDB:6G1P"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 249..255
FT /evidence="ECO:0007829|PDB:6G1P"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 266..275
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 289..299
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 304..319
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 326..329
FT /evidence="ECO:0007829|PDB:6G1P"
FT HELIX 335..352
FT /evidence="ECO:0007829|PDB:6G1P"
SQ SEQUENCE 356 AA; 38819 MW; 72731420F3F2CB80 CRC64;
MSAVGRLAAV SLAQVRGALC GALLGDCMGA EFEGSDAVEL PDVLEFVRLL EKEKKAGTLF
YTDDTAMTRA VIQSLIAKPD FDEVDMAKRF AEEYKKEPTR GYGAGVVQVF KKLLSPKYSD
VFQPAREQFD GKGSYGNGGA MRVASIALAY PNIQDVIKFA RRSAQLTHAS PLGYNGAILQ
ALAVHFALQG ELKRDTFLEQ LIGEMERIEG GEMSASDAGE HDRPNEVKLP FCSRLKKIKE
FLASSNVPKA DIVDELGHGI AALESVPTAI YSFLHCMESD PDIPDLYNNL QRTIIYSISL
GGDTDTIATM AGAIAGAYYG MDQVTPSWKR SCEAIVETEE SAVKLYELYC KQLKTP
