Q6ZVK8 (NUD18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
8-oxo-dGDP phosphatase NUDT18
EC=3.6.1.58

Alternative name(s):
2-hydroxy-dADP phosphatase
7,8-dihydro-8-oxoguanine phosphatase
MutT homolog 3
Nucleoside diphosphate-linked moiety X motif 18
Short name=Nudix motif 18

Gene names

Name:	NUDT18
Synonyms:	MTH3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	323 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates the hydrolyzis of oxidized nucleoside diphosphate derivatives. Hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing deoxyribo- and ribonucleoside diphosphates to the monophosphates. Hydrolyzes 8-oxo-dGDP and 8-oxo-GDP with the same efficiencies. Hydrolyzes also 8-OH-dADP and 2-OH-dADP. Exhibited no or minimal hydrolyzis activity against 8-oxo-dGTP, 8-oxo-GTP, dGTP, GTP, dGDP and GDP. Probably removes oxidized guanine nucleotides from both the DNA and RNA precursor pools. Ref.4
Catalytic activity	8-oxo-dGDP + H2O = 8-oxo-dGMP + phosphate. Ref.4
Cofactor	Manganese By similarity. Magnesium. Ref.4
Sequence similarities	Belongs to the Nudix hydrolase family. Contains 1 nudix hydrolase domain.
Biophysicochemical properties	Kinetic parameters: KM=10.7 µM for 8-Oxo-dGDP Ref.4 KM=11.7 µM for 8-Oxo-GDP Vmax=212 pmol/min/µg enzyme toward 8-Oxo-dGDP (at 30 degrees Celsius) Vmax=246 pmol/min/µg enzyme toward 8-Oxo-GDP (at 30 degrees Celsius) pH dependence: Optimum pH is 8.5.
Sequence caution	The sequence BAC85853.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Nucleotide metabolism
Coding sequence diversity	Alternative splicing
Ligand	Magnesium Manganese Metal-binding
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	GDP catabolic process Inferred from direct assay Ref.4. Source: UniProtKB dADP catabolic process Inferred from direct assay Ref.4. Source: UniProtKB dGDP catabolic process Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	8-hydroxy-dADP phosphatase activity Inferred from direct assay Ref.4. Source: UniProtKB 8-oxo-GDP phosphatase activity Inferred from direct assay Ref.4. Source: UniProtKB 8-oxo-dGDP phosphatase activity Inferred from direct assay Ref.4. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APIP	Q96GX9	3	EBI-740486,EBI-359248
DHPS	P49366	3	EBI-740486,EBI-741925
DUT	P33316	3	EBI-740486,EBI-353224
EVI5L	Q96CN4	3	EBI-740486,EBI-749523
HSD17B14	Q9BPX1	3	EBI-740486,EBI-742664
NT5C2	P49902	3	EBI-740486,EBI-742084
PAICS	P22234	3	EBI-740486,EBI-712261
RAB3IL1	Q8TBN0	3	EBI-740486,EBI-743796
RABAC1	Q9UI14	3	EBI-740486,EBI-712367

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6ZVK8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q6ZVK8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.
     101-125: EPETLLSVEERGPSWVRFVFLARPT → MSVDSARAALLSTQTLPAPSPTSPP

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 323

323

8-oxo-dGDP phosphatase NUDT18

PRO_0000324567

Regions

Domain

37 – 167

131

Nudix hydrolase

Motif

76 – 97

22

Nudix box

Sites

Metal binding

91

1

Magnesium or manganese By similarity

Metal binding

95

1

Magnesium or manganese By similarity

Natural variations

Alternative sequence

1 – 100

100

Missing in isoform 2.

VSP_032276

Alternative sequence

101 – 125

25

EPETL…LARPT → MSVDSARAALLSTQTLPAPS PTSPP in isoform 2.

VSP_032277

Experimental info

Sequence conflict

177

1

L → P in BAB15376. Ref.1

Sequence conflict

224

1

M → V in BAB15376. Ref.1

Sequence conflict

224

1

M → V in BAC85853. Ref.1

Secondary structure

1

.

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.

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323

Helix Strand Turn

Details...

Beta strand

43 – 49

7

Beta strand

55 – 61

7

Beta strand

74 – 77

4

Helix

84 – 96

13

Beta strand

98 – 112

15

Beta strand

115 – 127

13

Helix

132 – 134

3

Beta strand

136 – 138

3

Beta strand

140 – 146

7

Beta strand

152 – 155

4

Helix

159 – 174

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 6, 2013. Version 3. Checksum: 8162BA4BDEC4374D	FASTA	323	35,501
	10 20 30 40 50 60 MASEGLAGAL ASVLAGQGSS VHSCDSAPAG EPPAPVRLRK NVCYVVLAVF LSEQDEVLLI 70 80 90 100 110 120 QEAKRECRGS WYLPAGRMEP GETIVEALQR EVKEEAGLHC EPETLLSVEE RGPSWVRFVF 130 140 150 160 170 180 LARPTGGILK TSKEADAESL QAAWYPRTSL PTPLRAHDIL HLVELAAQYR QQARHPLILP 190 200 210 220 230 240 QELPCDLVCQ RLVATFTSAQ TVWVLVGTVG MPHLPVTACG LDPMEQRGGM KMAVLRLLQE 250 260 270 280 290 300 CLTLHHLVVE IKGLLGLQHL GRDHSDGICL NVLVTVAFRS PGIQDEPPKV RGENFSWWKV 310 320 MEEDLQSQLL QRLQGSSVVP VNR
	Isoform 2 [UniParc]. Checksum: ED9DD93D505E8709	FASTA	223	24,463
	10 20 30 40 50 60 MSVDSARAAL LSTQTLPAPS PTSPPGGILK TSKEADAESL QAAWYPRTSL PTPLRAHDIL 70 80 90 100 110 120 HLVELAAQYR QQARHPLILP QELPCDLVCQ RLVATFTSAQ TVWVLVGTVG MPHLPVTACG 130 140 150 160 170 180 LDPMEQRGGM KMAVLRLLQE CLTLHHLVVE IKGLLGLQHL GRDHSDGICL NVLVTVAFRS 190 200 210 220 PGIQDEPPKV RGENFSWWKV MEEDLQSQLL QRLQGSSVVP VNR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Cerebellum.
[2]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[4]	"Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates: comparison with MTH1 and MTH2." Takagi Y., Setoyama D., Ito R., Kamiya H., Yamagata Y., Sekiguchi M. J. Biol. Chem. 287:21541-21549(2012) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, FUNCTION.
[5]	"Crystal structure of the nudix domain of human nudt18." Structural genomics consortium (SGC) Submitted (MAR-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 26-179.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK026147 mRNA. Translation: BAB15376.1.
AK124446 mRNA. Translation: BAC85853.1. Different initiation.
BC016902 mRNA. Translation: AAH16902.1.

IPI

IPI00217911.
IPI00396292.

RefSeq

NP_079091.3. NM_024815.3.

UniGene

Hs.527101.
Hs.740821.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GG6	X-ray	2.10	A	26-179	[»]

ProteinModelPortal

Q6ZVK8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q6ZVK8. 32 interactions.

MINT

MINT-1436358.

STRING

9606.ENSP00000307852.

PTM databases

PhosphoSite

Q6ZVK8.

Polymorphism databases

DMDM

172046172.

Proteomic databases

PaxDb

Q6ZVK8.

PRIDE

Q6ZVK8.

Protocols and materials databases

DNASU

79873.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000309188; ENSP00000307852; ENSG00000173566.

GeneID

79873.

KEGG

hsa:79873.

UCSC

uc003xaq.1. human.

Organism-specific databases

CTD

79873.

GeneCards

GC08M022021.

HGNC

HGNC:26194. NUDT18.

HPA

HPA028581.

neXtProt

NX_Q6ZVK8.

PharmGKB

PA142671238.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1051.

HOGENOM

HOG000035136.

HOVERGEN

HBG108203.

InParanoid

Q6ZVK8.

OrthoDB

EOG4KKZ2Z.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q6ZVK8.

Bgee

Q6ZVK8.

CleanEx

HS_NUDT18.

Genevestigator

Q6ZVK8.

Family and domain databases

Gene3D

3.90.79.10. 1 hit.

InterPro

IPR020476. Nudix_hydrolase.
IPR020084. NUDIX_hydrolase_CS.
IPR000086. NUDIX_hydrolase_dom.
IPR015797. NUDIX_hydrolase_dom-like.
[Graphical view]

Pfam

PF00293. NUDIX. 1 hit.
[Graphical view]

PRINTS

PR00502. NUDIXFAMILY.

SUPFAM

SSF55811. NUDIX_hydrolase. 1 hit.

PROSITE

PS51462. NUDIX. 1 hit.
PS00893. NUDIX_BOX. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q6ZVK8.

GenomeRNAi

79873.

NextBio

69645.

Entry information

Entry name

NUD18_HUMAN

Accession

Primary (citable) accession number: Q6ZVK8
Secondary accession number(s): Q8IZ75, Q9H687

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	March 6, 2013
Last modified:	May 1, 2013
This is version 76 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.