ADPRH_HUMAN
ID ADPRH_HUMAN Reviewed; 357 AA.
AC P54922; B2R8H1; D3DN83;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=ADP-ribosylhydrolase ARH1 {ECO:0000305};
DE EC=3.2.2.19 {ECO:0000269|PubMed:30472116};
DE AltName: Full=ADP-ribose-L-arginine cleaving enzyme;
DE AltName: Full=[Protein ADP-ribosylarginine] hydrolase;
DE Short=ADP-ribosylarginine hydrolase;
DE Short=hARH1 {ECO:0000303|PubMed:30472116};
GN Name=ADPRH; Synonyms=ARH1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8349667; DOI=10.1016/s0021-9258(17)46780-9;
RA Takada T., Iida K., Moss J.;
RT "Cloning and site-directed mutagenesis of human ADP-ribosylarginine
RT hydrolase.";
RL J. Biol. Chem. 268:17837-17843(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-55 AND ASP-56.
RX PubMed=31599159; DOI=10.1021/acschembio.9b00429;
RA Stevens L.A., Kato J., Kasamatsu A., Oda H., Lee D.Y., Moss J.;
RT "The ARH and Macrodomain Families of alpha-ADP-ribose-acceptor Hydrolases
RT Catalyze alpha-NAD+ Hydrolysis.";
RL ACS Chem. Biol. 14:2576-2584(2019).
RN [6] {ECO:0007744|PDB:3HFW}
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) IN COMPLEX WITH ADP AND MAGNESIUM,
RP AND SUBUNIT.
RX PubMed=19407395; DOI=10.1107/s1744309109014067;
RA Kernstock S., Koch-Nolte F., Mueller-Dieckmann J., Weiss M.S.,
RA Mueller-Dieckmann C.;
RT "Cloning, expression, purification and crystallization as well as X-ray
RT fluorescence and preliminary X-ray diffraction analyses of human ADP-
RT ribosylhydrolase 1.";
RL Acta Crystallogr. F 65:529-532(2009).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.23 ANGSTROMS) IN COMPLEX WITH MAGNESIUM AND
RP ADP-RIBOSE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF
RP SER-54; ASP-55; ASP-56; ASP-302 AND SER-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).
CC -!- FUNCTION: Specifically acts as an arginine mono-ADP-ribosylhydrolase by
CC mediating the removal of mono-ADP-ribose attached to arginine residues
CC on proteins. {ECO:0000269|PubMed:30472116, ECO:0000269|PubMed:8349667}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(omega)-(ADP-D-ribosyl)-L-arginyl-[protein] = ADP-D-
CC ribose + L-arginyl-[protein]; Xref=Rhea:RHEA:14885, Rhea:RHEA-
CC COMP:10532, Rhea:RHEA-COMP:15087, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:29965, ChEBI:CHEBI:57967, ChEBI:CHEBI:142554;
CC EC=3.2.2.19; Evidence={ECO:0000269|PubMed:30472116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14886;
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:0000269|PubMed:31599159};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:30472116};
CC Note=Binds 2 magnesium ions per subunit. {ECO:0000269|PubMed:30472116};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:19407395}.
CC -!- INTERACTION:
CC P54922; Q96BD6: SPSB1; NbExp=3; IntAct=EBI-6657604, EBI-2659201;
CC P54922; Q12800: TFCP2; NbExp=3; IntAct=EBI-6657604, EBI-717422;
CC -!- SIMILARITY: Belongs to the ADP-ribosylglycohydrolase family.
CC {ECO:0000305}.
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DR EMBL; L13291; AAA35555.1; -; mRNA.
DR EMBL; AK313369; BAG36168.1; -; mRNA.
DR EMBL; CH471052; EAW79562.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79563.1; -; Genomic_DNA.
DR EMBL; BC063883; AAH63883.1; -; mRNA.
DR EMBL; BC074769; AAH74769.1; -; mRNA.
DR CCDS; CCDS2990.1; -.
DR PIR; B47411; B47411.
DR RefSeq; NP_001116.1; NM_001125.3.
DR RefSeq; NP_001278878.1; NM_001291949.1.
DR RefSeq; NP_001278879.1; NM_001291950.1.
DR RefSeq; XP_011510740.1; XM_011512438.2.
DR PDB; 3HFW; X-ray; 1.92 A; A=1-357.
DR PDB; 6G28; X-ray; 1.23 A; A=1-357.
DR PDB; 6G2A; X-ray; 1.80 A; A=1-357.
DR PDB; 6IUX; X-ray; 1.20 A; A=2-357.
DR PDBsum; 3HFW; -.
DR PDBsum; 6G28; -.
DR PDBsum; 6G2A; -.
DR PDBsum; 6IUX; -.
DR AlphaFoldDB; P54922; -.
DR SMR; P54922; -.
DR BioGRID; 106651; 11.
DR IntAct; P54922; 9.
DR MINT; P54922; -.
DR STRING; 9606.ENSP00000420200; -.
DR iPTMnet; P54922; -.
DR PhosphoSitePlus; P54922; -.
DR BioMuta; ADPRH; -.
DR DMDM; 1703392; -.
DR OGP; P54922; -.
DR EPD; P54922; -.
DR jPOST; P54922; -.
DR MassIVE; P54922; -.
DR MaxQB; P54922; -.
DR PaxDb; P54922; -.
DR PeptideAtlas; P54922; -.
DR PRIDE; P54922; -.
DR ProteomicsDB; 56748; -.
DR Antibodypedia; 32747; 134 antibodies from 22 providers.
DR DNASU; 141; -.
DR Ensembl; ENST00000357003.8; ENSP00000349496.3; ENSG00000144843.12.
DR Ensembl; ENST00000465513.1; ENSP00000417430.1; ENSG00000144843.12.
DR Ensembl; ENST00000478399.5; ENSP00000420200.1; ENSG00000144843.12.
DR Ensembl; ENST00000478927.5; ENSP00000417528.1; ENSG00000144843.12.
DR GeneID; 141; -.
DR KEGG; hsa:141; -.
DR MANE-Select; ENST00000357003.8; ENSP00000349496.3; NM_001125.4; NP_001116.1.
DR UCSC; uc003ecs.3; human.
DR CTD; 141; -.
DR DisGeNET; 141; -.
DR GeneCards; ADPRH; -.
DR HGNC; HGNC:269; ADPRH.
DR HPA; ENSG00000144843; Low tissue specificity.
DR MIM; 603081; gene.
DR neXtProt; NX_P54922; -.
DR OpenTargets; ENSG00000144843; -.
DR PharmGKB; PA24590; -.
DR VEuPathDB; HostDB:ENSG00000144843; -.
DR eggNOG; ENOG502QPMI; Eukaryota.
DR GeneTree; ENSGT00530000063627; -.
DR HOGENOM; CLU_047061_0_0_1; -.
DR InParanoid; P54922; -.
DR OMA; ACWWGAM; -.
DR OrthoDB; 1112828at2759; -.
DR PhylomeDB; P54922; -.
DR TreeFam; TF329417; -.
DR BRENDA; 3.2.2.19; 2681.
DR PathwayCommons; P54922; -.
DR SignaLink; P54922; -.
DR BioGRID-ORCS; 141; 10 hits in 1067 CRISPR screens.
DR EvolutionaryTrace; P54922; -.
DR GenomeRNAi; 141; -.
DR Pharos; P54922; Tbio.
DR PRO; PR:P54922; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P54922; protein.
DR Bgee; ENSG00000144843; Expressed in monocyte and 132 other tissues.
DR ExpressionAtlas; P54922; baseline and differential.
DR Genevisible; P54922; HS.
DR GO; GO:0005776; C:autophagosome; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0055037; C:recycling endosome; IBA:GO_Central.
DR GO; GO:0003875; F:ADP-ribosylarginine hydrolase activity; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030955; F:potassium ion binding; IDA:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0051725; P:protein de-ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0036211; P:protein modification process; IMP:UniProtKB.
DR GO; GO:2000785; P:regulation of autophagosome assembly; IBA:GO_Central.
DR Gene3D; 1.10.4080.10; -; 1.
DR InterPro; IPR012108; ADP-ribosylarg_hydro.
DR InterPro; IPR005502; Ribosyl_crysJ1.
DR InterPro; IPR036705; Ribosyl_crysJ1_sf.
DR Pfam; PF03747; ADP_ribosyl_GH; 1.
DR PIRSF; PIRSF016939; ADP_ribslarg_hdr; 1.
DR SUPFAM; SSF101478; SSF101478; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Magnesium; Metal-binding; Reference proteome.
FT CHAIN 1..357
FT /note="ADP-ribosylhydrolase ARH1"
FT /id="PRO_0000157283"
FT BINDING 54
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19407395,
FT ECO:0000269|PubMed:30472116, ECO:0007744|PDB:3HFW"
FT BINDING 55
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19407395,
FT ECO:0000269|PubMed:30472116, ECO:0007744|PDB:3HFW"
FT BINDING 56
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19407395,
FT ECO:0000269|PubMed:30472116, ECO:0007744|PDB:3HFW"
FT BINDING 85
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:19407395,
FT ECO:0007744|PDB:3HFW"
FT BINDING 101..103
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:19407395,
FT ECO:0007744|PDB:3HFW"
FT BINDING 124
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000305|PubMed:19407395, ECO:0007744|PDB:3HFW"
FT BINDING 130
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000305|PubMed:19407395, ECO:0007744|PDB:3HFW"
FT BINDING 163..165
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000305|PubMed:19407395, ECO:0007744|PDB:3HFW"
FT BINDING 263..265
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000305|PubMed:19407395, ECO:0007744|PDB:3HFW"
FT BINDING 269..270
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000305|PubMed:19407395, ECO:0007744|PDB:3HFW"
FT BINDING 302
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30472116"
FT BINDING 304
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19407395,
FT ECO:0000269|PubMed:30472116, ECO:0007744|PDB:3HFW"
FT BINDING 304
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30472116"
FT BINDING 305
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30472116"
FT MUTAGEN 54
FT /note="S->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:30472116"
FT MUTAGEN 55
FT /note="D->N: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000269|PubMed:31599159"
FT MUTAGEN 56
FT /note="D->N: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:30472116,
FT ECO:0000269|PubMed:31599159"
FT MUTAGEN 302
FT /note="D->N: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:30472116"
FT MUTAGEN 305
FT /note="S->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:30472116"
FT HELIX 2..19
FT /evidence="ECO:0007829|PDB:6IUX"
FT TURN 20..26
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 30..39
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 55..70
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 76..90
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 101..109
FT /evidence="ECO:0007829|PDB:6IUX"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:6IUX"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 136..141
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 148..160
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 166..183
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 191..209
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 213..218
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 221..234
FT /evidence="ECO:0007829|PDB:6IUX"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:6G28"
FT HELIX 251..261
FT /evidence="ECO:0007829|PDB:6IUX"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 273..285
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 289..296
FT /evidence="ECO:0007829|PDB:6IUX"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 303..318
FT /evidence="ECO:0007829|PDB:6IUX"
FT TURN 319..322
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:6IUX"
FT TURN 328..330
FT /evidence="ECO:0007829|PDB:6IUX"
FT HELIX 334..348
FT /evidence="ECO:0007829|PDB:6IUX"
SQ SEQUENCE 357 AA; 39507 MW; 4E23B12FAE84F12B CRC64;
MEKYVAAMVL SAAGDALGYY NGKWEFLQDG EKIHRQLAQL GGLDALDVGR WRVSDDTVMH
LATAEALVEA GKAPKLTQLY YLLAKHYQDC MEDMDGRAPG GASVHNAMQL KPGKPNGWRI
PFNSHEGGCG AAMRAMCIGL RFPHHSQLDT LIQVSIESGR MTHHHPTGYL GALASALFTA
YAVNSRPPLQ WGKGLMELLP EAKKYIVQSG YFVEENLQHW SYFQTKWENY LKLRGILDGE
SAPTFPESFG VKERDQFYTS LSYSGWGGSS GHDAPMIAYD AVLAAGDSWK ELAHRAFFHG
GDSDSTAAIA GCWWGVMYGF KGVSPSNYEK LEYRNRLEET ARALYSLGSK EDTVISL
