P36639 (8ODP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
7,8-dihydro-8-oxoguanine triphosphatase
EC=3.6.1.-

Alternative name(s):
8-oxo-dGTPase
Nucleoside diphosphate-linked moiety X motif 1
Short name=Nudix motif 1

Gene names

Name:	NUDT1
Synonyms:	MTH1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	197 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Antimutagenic. Responsible for preventing misincorporation of 8-oxo-dGTP into DNA thus preventing A:T to C:G transversions. Ref.10
Catalytic activity	8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate. Ref.10
Cofactor	Binds 1 magnesium ion per subunit Probable. Ref.11
Subunit structure	Monomer. Ref.11
Tissue specificity	Widely expressed with highest expression in thymus, testis, embryo and proliferating blood lymphocytes. Ref.3
Developmental stage	In peripheral blood lymphocytes, expressed at much higher levels in proliferating cells than in resting cells. Ref.3
Post-translational modification	The N-terminus is blocked.
Polymorphism	A polymorphism between Met-1 and Met-19 removes a stop codon before the initiation codon for isoform p22 and gives rise to the production of isoform p26. The allele frequency of isoform p26 is about 20%.
Sequence similarities	Belongs to the Nudix hydrolase family. Contains 1 nudix hydrolase domain.

Ontologies

Keywords
Coding sequence diversity	Alternative initiation Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	DNA protection Inferred from direct assay Ref.10. Source: UniProtKB DNA repair Inferred from electronic annotation. Source: InterPro response to oxidative stress Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: HPA
Molecular function	8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity Inferred from direct assay Ref.10. Source: UniProtKB GTPase activity Traceable author statement. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative initiation. [Align] [Select]

Isoform p26 (identifier: P36639-1)

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.

Note: Derived from a B-type mRNA with a polymorphic alteration (GU-->GC) at the beginning of exon 2c that converts an in-frame UGA to CGA yielding another in-frame AUG further upstream.

Isoform p22 (identifier: P36639-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: Missing.

Isoform p21 (identifier: P36639-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: Missing.

Isoform p18 (identifier: P36639-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-41: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 197

197

7,8-dihydro-8-oxoguanine triphosphatase

PRO_0000019944

Regions

Domain

44 – 173

130

Nudix hydrolase

Region

76 – 79

4

Substrate binding Probable

Motif

78 – 99

22

Nudix box

Sites

Metal binding

78

1

Magnesium; via carbonyl oxygen By similarity

Metal binding

93

1

Magnesium By similarity

Metal binding

96

1

Magnesium By similarity

Metal binding

97

1

Magnesium By similarity

Natural variations

Alternative sequence

1 – 41

41

Missing in isoform p18.

VSP_018814

Alternative sequence

1 – 26

26

Missing in isoform p21.

VSP_018813

Alternative sequence

1 – 18

18

Missing in isoform p22.

VSP_018812

Natural variant

124

1

V → M. Ref.3 Ref.9
Corresponds to variant rs4866 [ dbSNP | Ensembl ].

VAR_013757

Experimental info

Mutagenesis

77

1

G → R: Reduces activity by 97%. Ref.10

Mutagenesis

78

1

G → F: Loss of activity. Ref.10

Mutagenesis

80

1

V → E: Loss of activity. Ref.10

Mutagenesis

81

1

Q → P: Reduces activity by 97%. Ref.10

Mutagenesis

83

1

G → I: Reduces activity by 60%. Ref.10

Mutagenesis

86

1

I → K: Loss of activity. Ref.10

Mutagenesis

88

1

D → P: Loss of activity. Ref.10

Mutagenesis

89

1

G → M: Loss of activity. Ref.10

Mutagenesis

90

1

A → P: Loss of activity. Ref.10

Mutagenesis

94

1

L → P: Loss of activity. Ref.10

Mutagenesis

95

1

Q → P: Loss of activity. Ref.10

Mutagenesis

96

1

E → G: Loss of activity. Ref.10

Mutagenesis

97

1

E → Y: Loss of activity. Ref.10

Mutagenesis

98

1

S → R: Loss of activity. Ref.10

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

197

Helix Strand Turn

Details...

Beta strand

46 – 51

6

Beta strand

56 – 70

15

Helix

86 – 98

13

Beta strand

107 – 115

9

Beta strand

121 – 127

7

Beta strand

140 – 148

9

Turn

155 – 157

3

Helix

161 – 170

10

Beta strand

173 – 184

12

Beta strand

186 – 194

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform p26 [UniParc]. Last modified July 28, 2009. Version 3. Checksum: 82AFF5E1CE287957	FASTA	197	22,520
	10 20 30 40 50 60 MYWSNQITRR LGERVQGFMS GISPQQMGEP EGSWSGKNPG TMGASRLYTL VLVLQPQRVL 70 80 90 100 110 120 LGMKKRGFGA GRWNGFGGKV QEGETIEDGA RRELQEESGL TVDALHKVGQ IVFEFVGEPE 130 140 150 160 170 180 LMDVHVFCTD SIQGTPVESD EMRPCWFQLD QIPFKDMWPD DSYWFPLLLQ KKKFHGYFKF 190 QGQDTILDYT LREVDTV
	Isoform p22 [UniParc]. Checksum: 7C9F192384F66C61	FASTA	179	20,296
	10 20 30 40 50 60 MSGISPQQMG EPEGSWSGKN PGTMGASRLY TLVLVLQPQR VLLGMKKRGF GAGRWNGFGG 70 80 90 100 110 120 KVQEGETIED GARRELQEES GLTVDALHKV GQIVFEFVGE PELMDVHVFC TDSIQGTPVE 130 140 150 160 170 SDEMRPCWFQ LDQIPFKDMW PDDSYWFPLL LQKKKFHGYF KFQGQDTILD YTLREVDTV
	Isoform p21 [UniParc]. Checksum: 06DE501D75A8B3D6	FASTA	171	19,467
	10 20 30 40 50 60 MGEPEGSWSG KNPGTMGASR LYTLVLVLQP QRVLLGMKKR GFGAGRWNGF GGKVQEGETI 70 80 90 100 110 120 EDGARRELQE ESGLTVDALH KVGQIVFEFV GEPELMDVHV FCTDSIQGTP VESDEMRPCW 130 140 150 160 170 FQLDQIPFKD MWPDDSYWFP LLLQKKKFHG YFKFQGQDTI LDYTLREVDT V
	Isoform p18 [UniParc]. Checksum: B9FB669FF0ACFF5F	FASTA	156	17,952
	10 20 30 40 50 60 MGASRLYTLV LVLQPQRVLL GMKKRGFGAG RWNGFGGKVQ EGETIEDGAR RELQEESGLT 70 80 90 100 110 120 VDALHKVGQI VFEFVGEPEL MDVHVFCTDS IQGTPVESDE MRPCWFQLDQ IPFKDMWPDD 130 140 150 SYWFPLLLQK KKFHGYFKFQ GQDTILDYTL REVDTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis." Sakumi K., Furuichi M., Tsuzuki T., Kakuma T., Kawabata S., Maki H., Sekiguchi M. J. Biol. Chem. 268:23524-23530(1993) [PubMed: 8226881] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P18), PARTIAL PROTEIN SEQUENCE.
[2]	"Genomic structure and chromosome location of the human mutT homologue gene MTH1 encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion." Furuichi M., Yoshida M.C., Oda H., Tajiri T., Nakabeppu Y., Tsuzuki T., Sekiguchi M. Genomics 24:485-490(1994) [PubMed: 7713500] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Regulation of expression of the human MTH1 gene encoding 8-oxo-dGTPase. Alternative splicing of transcription products." Oda H., Nakabeppu Y., Furuichi M., Sekiguchi M. J. Biol. Chem. 272:17843-17850(1997) [PubMed: 9211940] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P18), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, VARIANT MET-124.
[4]	"Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism." Oda H., Taketomi A., Maruyama R., Itoh R., Nishioka K., Yakushiji H., Suzuki T., Sekiguchi M., Nakabeppu Y. Nucleic Acids Res. 27:4335-4343(1999) [PubMed: 10536140] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE INITIATION.
[5]	NIEHS SNPs program Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS P18 AND P22), VARIANT MET-124. Tissue: Bone, Lymph and Muscle.
[10]	"Functional significance of the conserved residues for the 23-residue module among MTH1 and MutT family proteins." Fujii Y., Shimokawa H., Sekiguchi M., Nakabeppu Y. J. Biol. Chem. 274:38251-38259(1999) [PubMed: 10608900] [Abstract] Cited for: MUTAGENESIS OF GLY-77; GLY-78; VAL-80; GLN-81; GLY-83; ILE-86; ASP-88; GLY-89; ALA-90; LEU-94; GLN-95; GLU-96; GLU-97 AND SER-98, FUNCTION, CATALYTIC ACTIVITY.
[11]	"Structure of human MTH1, a Nudix family hydrolase that selectively degrades oxidized purine nucleoside triphosphates." Mishima M., Sakai Y., Itoh N., Kamiya H., Furuichi M., Takahashi M., Yamagata Y., Iwai S., Nakabeppu Y., Shirakawa M. J. Biol. Chem. 279:33806-33815(2004) [PubMed: 15133035] [Abstract] Cited for: STRUCTURE BY NMR OF 42-197, SUBUNIT, COFACTOR, SUBSTRATE BINDING SITE.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D16581 mRNA. Translation: BAA04013.1.
D38594 Genomic DNA. Translation: BAA07601.1.
AB025233 mRNA. Translation: BAA83791.1.
AB025234 mRNA. Translation: BAA83792.1.
AB025235 mRNA. Translation: BAA83793.1.
AB025236 mRNA. Translation: BAA83794.1.
AB025237 mRNA. Translation: BAA83795.1.
AB025238 mRNA. Translation: BAA83796.1.
AB025239 mRNA. Translation: BAA83797.1.
AB025240 mRNA. Translation: BAA83798.1.
AB025241 mRNA. Translation: BAA83799.1.
AB025242 mRNA. Translation: BAA83800.1.
DQ230907 Genomic DNA. Translation: ABB02181.1.
AC004971 Genomic DNA. No translation available.
CH236953 Genomic DNA. Translation: EAL23948.1.
CH471144 Genomic DNA. Translation: EAW87227.1.
BC014618 mRNA. Translation: AAH14618.1.
BC040144 mRNA. Translation: AAH40144.2.
BC065367 mRNA. Translation: AAH65367.1.

IPI

IPI00004392.
IPI00396056.
IPI00759462.
IPI00759578.

RefSeq

NP_002443.3. NM_002452.3.
NP_945186.1. NM_198948.1.
NP_945187.1. NM_198949.1.
NP_945188.1. NM_198950.1.
NP_945190.1. NM_198952.1.
NP_945191.1. NM_198953.1.
NP_945192.1. NM_198954.1.

UniGene

Hs.534331.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IRY	NMR	-	A	42-197	[»]
3Q93	X-ray	1.80	A/B	42-197	[»]
3ZR0	X-ray	1.80	A/B	42-197	[»]
3ZR1	X-ray	1.90	A/B	42-197	[»]

ProteinModelPortal

P36639.

SMR

P36639. Positions 44-197.

ModBase

Search...

Protein-protein interaction databases

IntAct

P36639. 4 interactions.

STRING

P36639.

Polymorphism databases

DMDM

254763430.

Proteomic databases

PRIDE

P36639.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000343985; ENSP00000339503; ENSG00000106268.
ENST00000397048; ENSP00000380241; ENSG00000106268.
ENST00000397049; ENSP00000380242; ENSG00000106268.

GeneID

4521.

KEGG

hsa:4521.

Organism-specific databases

CTD

4521.

GeneCards

GC07P002248.

HGNC

HGNC:8048. NUDT1.

HPA

HPA012636.

MIM

600312. gene.

neXtProt

NX_P36639.

PharmGKB

PA31830.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG322338.

HOVERGEN

HBG000032.

InParanoid

P36639.

OMA

QWFQLDQ.

Gene expression databases

ArrayExpress

P36639.

Bgee

P36639.

CleanEx

HS_NUDT1.

Genevestigator

P36639.

GermOnline

ENSG00000106268. Homo sapiens.

Family and domain databases

InterPro

IPR020476. Nudix_hydrolase.
IPR020084. NUDIX_hydrolase_CS.
IPR000086. NUDIX_hydrolase_dom.
IPR015797. NUDIX_hydrolase_dom-like.
IPR003563. OxG-triPHTase.
[Graphical view]

Gene3D

G3DSA:3.90.79.10. NUDIX_hydrolase. 1 hit.

KO

K03574.

Pfam

PF00293. NUDIX. 1 hit.
[Graphical view]

PRINTS

PR01403. 8OXTPHPHTASE.
PR00502. NUDIXFAMILY.

SUPFAM

SSF55811. NUDIX_hydrolase. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

NextBio

17452.

SOURCE

Search...

Entry information

Entry name

8ODP_HUMAN

Accession

Primary (citable) accession number: P36639
Secondary accession number(s): A4D205 , Q6P0Y6, Q8IV95, Q9UBM0, Q9UBM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	July 28, 2009
Last modified:	January 25, 2012
This is version 111 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.