NUD18_HUMAN
ID NUD18_HUMAN Reviewed; 323 AA.
AC Q6ZVK8; Q8IZ75; Q9H687;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 3.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=8-oxo-dGDP phosphatase NUDT18;
DE EC=3.6.1.58;
DE AltName: Full=2-hydroxy-dADP phosphatase;
DE AltName: Full=7,8-dihydro-8-oxoguanine phosphatase;
DE AltName: Full=MutT homolog 3;
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 18;
DE Short=Nudix motif 18;
GN Name=NUDT18; Synonyms=MTH3;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cerebellum;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [4]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND FUNCTION.
RX PubMed=22556419; DOI=10.1074/jbc.m112.363010;
RA Takagi Y., Setoyama D., Ito R., Kamiya H., Yamagata Y., Sekiguchi M.;
RT "Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and
RT deoxyguanosine diphosphates: comparison with MTH1 and MTH2.";
RL J. Biol. Chem. 287:21541-21549(2012).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 26-179.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the nudix domain of human nudt18.";
RL Submitted (MAR-2009) to the PDB data bank.
CC -!- FUNCTION: Mediates the hydrolysis of oxidized nucleoside diphosphate
CC derivatives. Hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing
CC deoxyribo- and ribonucleoside diphosphates to the monophosphates.
CC Hydrolyzes 8-oxo-dGDP and 8-oxo-GDP with the same efficiencies.
CC Hydrolyzes also 8-OH-dADP and 2-OH-dADP. Exhibited no or minimal
CC hydrolysis activity against 8-oxo-dGTP, 8-oxo-GTP, dGTP, GTP, dGDP and
CC GDP. Probably removes oxidized guanine nucleotides from both the DNA
CC and RNA precursor pools. {ECO:0000269|PubMed:22556419}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-oxo-dGDP + H2O = 8-oxo-dGMP + H(+) + phosphate;
CC Xref=Rhea:RHEA:32063, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:63224, ChEBI:CHEBI:63715; EC=3.6.1.58;
CC Evidence={ECO:0000269|PubMed:22556419};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250, ECO:0000269|PubMed:22556419};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250, ECO:0000269|PubMed:22556419};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.7 uM for 8-Oxo-dGDP {ECO:0000269|PubMed:22556419};
CC KM=11.7 uM for 8-Oxo-GDP {ECO:0000269|PubMed:22556419};
CC Vmax=212 pmol/min/ug enzyme toward 8-Oxo-dGDP (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:22556419};
CC Vmax=246 pmol/min/ug enzyme toward 8-Oxo-GDP (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:22556419};
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:22556419};
CC -!- INTERACTION:
CC Q6ZVK8; Q96GX9: APIP; NbExp=4; IntAct=EBI-740486, EBI-359248;
CC Q6ZVK8; P49366: DHPS; NbExp=3; IntAct=EBI-740486, EBI-741925;
CC Q6ZVK8; P33316: DUT; NbExp=3; IntAct=EBI-740486, EBI-353224;
CC Q6ZVK8; Q96CN4: EVI5L; NbExp=3; IntAct=EBI-740486, EBI-749523;
CC Q6ZVK8; Q9BPX1: HSD17B14; NbExp=3; IntAct=EBI-740486, EBI-742664;
CC Q6ZVK8; P49902: NT5C2; NbExp=3; IntAct=EBI-740486, EBI-742084;
CC Q6ZVK8; P22234: PAICS; NbExp=3; IntAct=EBI-740486, EBI-712261;
CC Q6ZVK8; Q8TBN0: RAB3IL1; NbExp=3; IntAct=EBI-740486, EBI-743796;
CC Q6ZVK8; Q9UI14: RABAC1; NbExp=3; IntAct=EBI-740486, EBI-712367;
CC Q6ZVK8; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-740486, EBI-750109;
CC Q6ZVK8; P03410: tax; Xeno; NbExp=4; IntAct=EBI-740486, EBI-9676218;
CC Q6ZVK8; P14079: tax; Xeno; NbExp=5; IntAct=EBI-740486, EBI-9675698;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6ZVK8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZVK8-2; Sequence=VSP_032276, VSP_032277;
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC85853.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK026147; BAB15376.1; -; mRNA.
DR EMBL; AK124446; BAC85853.1; ALT_INIT; mRNA.
DR EMBL; BC016902; AAH16902.1; -; mRNA.
DR CCDS; CCDS75706.1; -. [Q6ZVK8-1]
DR RefSeq; NP_079091.3; NM_024815.3. [Q6ZVK8-1]
DR PDB; 3GG6; X-ray; 2.10 A; A=26-179.
DR PDB; 4HVY; X-ray; 1.46 A; A=26-179.
DR PDBsum; 3GG6; -.
DR PDBsum; 4HVY; -.
DR AlphaFoldDB; Q6ZVK8; -.
DR SMR; Q6ZVK8; -.
DR BioGRID; 122961; 52.
DR IntAct; Q6ZVK8; 43.
DR MINT; Q6ZVK8; -.
DR STRING; 9606.ENSP00000480722; -.
DR iPTMnet; Q6ZVK8; -.
DR PhosphoSitePlus; Q6ZVK8; -.
DR BioMuta; NUDT18; -.
DR DMDM; 460018323; -.
DR EPD; Q6ZVK8; -.
DR jPOST; Q6ZVK8; -.
DR MassIVE; Q6ZVK8; -.
DR MaxQB; Q6ZVK8; -.
DR PaxDb; Q6ZVK8; -.
DR PeptideAtlas; Q6ZVK8; -.
DR PRIDE; Q6ZVK8; -.
DR ProteomicsDB; 68421; -. [Q6ZVK8-1]
DR ProteomicsDB; 68422; -. [Q6ZVK8-2]
DR Antibodypedia; 74437; 182 antibodies from 21 providers.
DR DNASU; 79873; -.
DR Ensembl; ENST00000611621.2; ENSP00000480722.1; ENSG00000275074.2. [Q6ZVK8-1]
DR GeneID; 79873; -.
DR KEGG; hsa:79873; -.
DR MANE-Select; ENST00000611621.2; ENSP00000480722.1; NM_024815.4; NP_079091.3.
DR UCSC; uc033beu.2; human. [Q6ZVK8-1]
DR CTD; 79873; -.
DR DisGeNET; 79873; -.
DR GeneCards; NUDT18; -.
DR HGNC; HGNC:26194; NUDT18.
DR HPA; ENSG00000275074; Low tissue specificity.
DR MIM; 615791; gene.
DR neXtProt; NX_Q6ZVK8; -.
DR OpenTargets; ENSG00000275074; -.
DR PharmGKB; PA142671238; -.
DR VEuPathDB; HostDB:ENSG00000275074; -.
DR eggNOG; KOG0648; Eukaryota.
DR GeneTree; ENSGT00390000002931; -.
DR HOGENOM; CLU_061042_2_0_1; -.
DR InParanoid; Q6ZVK8; -.
DR OMA; DHADGIC; -.
DR OrthoDB; 421639at2759; -.
DR PhylomeDB; Q6ZVK8; -.
DR TreeFam; TF106355; -.
DR BioCyc; MetaCyc:ENSG00000173566-MON; -.
DR PathwayCommons; Q6ZVK8; -.
DR Reactome; R-HSA-2393930; Phosphate bond hydrolysis by NUDT proteins. [Q6ZVK8-1]
DR SABIO-RK; Q6ZVK8; -.
DR SignaLink; Q6ZVK8; -.
DR BioGRID-ORCS; 79873; 12 hits in 287 CRISPR screens.
DR EvolutionaryTrace; Q6ZVK8; -.
DR GenomeRNAi; 79873; -.
DR Pharos; Q6ZVK8; Tbio.
DR PRO; PR:Q6ZVK8; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q6ZVK8; protein.
DR Bgee; ENSG00000275074; Expressed in body of pancreas and 117 other tissues.
DR ExpressionAtlas; Q6ZVK8; baseline and differential.
DR Genevisible; Q6ZVK8; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0044717; F:8-hydroxy-dADP phosphatase activity; IDA:UniProtKB.
DR GO; GO:0044715; F:8-oxo-dGDP phosphatase activity; IDA:UniProtKB.
DR GO; GO:0044716; F:8-oxo-GDP phosphatase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0046057; P:dADP catabolic process; IDA:UniProtKB.
DR GO; GO:0046067; P:dGDP catabolic process; IDA:UniProtKB.
DR GO; GO:0046712; P:GDP catabolic process; IDA:UniProtKB.
DR GO; GO:0055086; P:nucleobase-containing small molecule metabolic process; TAS:Reactome.
DR CDD; cd04671; Nudix_Hydrolase_13; 1.
DR InterPro; IPR020476; Nudix_hydrolase.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR020084; NUDIX_hydrolase_CS.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR InterPro; IPR042970; NUDT18_NUDIX.
DR Pfam; PF00293; NUDIX; 1.
DR PRINTS; PR00502; NUDIXFAMILY.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
DR PROSITE; PS00893; NUDIX_BOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Hydrolase; Magnesium; Manganese;
KW Metal-binding; Nucleotide metabolism; Reference proteome.
FT CHAIN 1..323
FT /note="8-oxo-dGDP phosphatase NUDT18"
FT /id="PRO_0000324567"
FT DOMAIN 37..167
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT MOTIF 76..97
FT /note="Nudix box"
FT BINDING 91
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 95
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_032276"
FT VAR_SEQ 101..125
FT /note="EPETLLSVEERGPSWVRFVFLARPT -> MSVDSARAALLSTQTLPAPSPTS
FT PP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_032277"
FT CONFLICT 177
FT /note="L -> P (in Ref. 1; BAB15376)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="M -> V (in Ref. 1; BAB15376/BAC85853)"
FT /evidence="ECO:0000305"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:4HVY"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:4HVY"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:4HVY"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:4HVY"
FT HELIX 84..96
FT /evidence="ECO:0007829|PDB:4HVY"
FT STRAND 98..112
FT /evidence="ECO:0007829|PDB:4HVY"
FT STRAND 115..127
FT /evidence="ECO:0007829|PDB:4HVY"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:4HVY"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:3GG6"
FT STRAND 140..146
FT /evidence="ECO:0007829|PDB:4HVY"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:4HVY"
FT HELIX 158..172
FT /evidence="ECO:0007829|PDB:4HVY"
SQ SEQUENCE 323 AA; 35501 MW; 8162BA4BDEC4374D CRC64;
MASEGLAGAL ASVLAGQGSS VHSCDSAPAG EPPAPVRLRK NVCYVVLAVF LSEQDEVLLI
QEAKRECRGS WYLPAGRMEP GETIVEALQR EVKEEAGLHC EPETLLSVEE RGPSWVRFVF
LARPTGGILK TSKEADAESL QAAWYPRTSL PTPLRAHDIL HLVELAAQYR QQARHPLILP
QELPCDLVCQ RLVATFTSAQ TVWVLVGTVG MPHLPVTACG LDPMEQRGGM KMAVLRLLQE
CLTLHHLVVE IKGLLGLQHL GRDHSDGICL NVLVTVAFRS PGIQDEPPKV RGENFSWWKV
MEEDLQSQLL QRLQGSSVVP VNR
