ADP-ribosylhydrolase ARH3 (ADP-ribose glycohydrolase ARH3) (ADP-ribosylhydrolase 3) (O-acetyl-ADP-ribose deacetylase ARH3) (EC 3.5.1.-) (Poly(ADP-ribose) glycohydrolase ARH3) (EC 3.2.1.143) ([Protein ADP-ribosylarginine] hydrolase-like protein 2) ([Protein ADP-ribosylserine] hydrolase) (EC 3.2.2.-)
1_MAAAA 6_ MAAAA 11_ GGGAG 16_ AARSL 21_ SRFRG 26_ CLAGA 31_ LLGDC 36_ VGSFY 41_ EAHDT 46_ VDLTS 51_ VLRHV 56_ QSLEP 61_ DPGTP 66_ GSERT 71_ EALYY 76_ TDDTA 81_ MARAL 86_ VQSLL 91_ AKEAF 96_ DEVDM 101_ AHRFA 106_ QEYKK 111_ DPDRG 116_ YGAGV 121_ VTVFK 126_ KLLNP 131_ KCRDV 136_ FEPAR 141_ AQFNG 146_ KGSYG 151_ NGGAM 156_ RVAGI 161_ SLAYS 166_ SVQDV 171_ QKFAR 176_ LSAQL 181_ THASS 186_ LGYNG 191_ AILQA 196_ LAVHL 201_ ALQGE 206_ SSSEH 211_ FLKQL 216_ LGHME 221_ DLEGD 226_ AQSVL 231_ DAREL 236_ GMEER 241_ PYSSR 246_ LKKIG 251_ ELLDQ 256_ ASVTR 261_ EEVVS 266_ ELGNG 271_ IAAFE 276_ SVPTA 281_ IYCFL 286_ RCMEP 291_ DPEIP 296_ SAFNS 301_ LQRTL 306_ IYSIS 311_ LGGDT 316_ DTIAT 321_ MAGAI 326_ AGAYY 331_ GMDQV 336_ PESWQ 341_ QSCEG 346_ YEETD 351_ ILAQS 356_LHRVF
1: 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:21498885, PubMed:29907568, PubMed:30045870, PubMed:30401461, PubMed:30830864, PubMed:33186521, PubMed:33769608, PubMed:33894202, PubMed:34019811, PubMed:34321462, PubMed:34479984, PubMed:34625544). 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:28650317, PubMed:29234005, PubMed:30045870, PubMed:33186521, PubMed:34019811, PubMed:34625544). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802, PubMed:33186521, PubMed:34625544). Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (PubMed:16278211, PubMed:33769608). 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:16278211). Also hydrolyzes free poly(ADP-ribose) in mitochondria (PubMed:22433848). Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (PubMed:17075046, PubMed:21498885). 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 (PubMed:21498885)