UniProt functional annotation for P36639



	UniProt functional annotation for P36639

UniProt code: P36639.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Antimutagenic (PubMed:8226881, PubMed:7713500, PubMed:10608900). Plays a redundant role in sanitizing oxidized nucleotide pools, such as 8-oxo-dGTP pools (PubMed:28679043). Acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress (PubMed:12857738, PubMed:24695224, PubMed:24695225). Hydrolyzes 8-oxo-dGTP, 8-oxo-dATP and 2-OH-dATP, thus preventing misincorporation of oxidized purine nucleoside triphosphates into DNA and subsequently preventing A:T to C:G and G:C to T:A transversions (PubMed:8226881, PubMed:10373420, PubMed:10608900, PubMed:11756418, PubMed:12857738, PubMed:16607562, PubMed:24695224, PubMed:24695225, PubMed:26999531, PubMed:28035004). Able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8- oxo-GTP and 8-oxo-ATP (PubMed:10373420, PubMed:11139615). Does not play a role in U8 snoRNA decapping activity. Binds U8 snoRNA (By similarity). {ECO:0000250|UniProtKB:P53368, ECO:0000269|PubMed:10373420, ECO:0000269|PubMed:10608900, ECO:0000269|PubMed:11139615, ECO:0000269|PubMed:11756418, ECO:0000269|PubMed:12857738, ECO:0000269|PubMed:16607562, ECO:0000269|PubMed:22556419, ECO:0000269|PubMed:24695224, ECO:0000269|PubMed:24695225, ECO:0000269|PubMed:26999531, ECO:0000269|PubMed:28035004, ECO:0000269|PubMed:28679043, ECO:0000269|PubMed:7713500, ECO:0000269|PubMed:8226881}.

Catalytic activity: Reaction=8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate + H(+); Xref=Rhea:RHEA:31575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:63224, ChEBI:CHEBI:77896; EC=3.6.1.55; Evidence={ECO:0000269|PubMed:10373420, ECO:0000269|PubMed:10608900, ECO:0000269|PubMed:11139615, ECO:0000269|PubMed:11756418, ECO:0000269|PubMed:12857738, ECO:0000269|PubMed:16607562, ECO:0000269|PubMed:21787772, ECO:0000269|PubMed:22556419, ECO:0000269|PubMed:24695224, ECO:0000269|PubMed:24695225, ECO:0000269|PubMed:26999531, ECO:0000269|PubMed:28035004, ECO:0000269|PubMed:7782328, ECO:0000269|PubMed:8226881};

Catalytic activity: Reaction=2-hydroxy-dATP + H2O = 2-hydroxy-dAMP + diphosphate + H(+); Xref=Rhea:RHEA:31583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:63212, ChEBI:CHEBI:77897; EC=3.6.1.56; Evidence={ECO:0000269|PubMed:10373420, ECO:0000269|PubMed:11139615, ECO:0000269|PubMed:11756418, ECO:0000269|PubMed:12857738, ECO:0000269|PubMed:16607562, ECO:0000269|PubMed:24695224, ECO:0000269|PubMed:24695225, ECO:0000269|PubMed:26999531, ECO:0000269|PubMed:28035004};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305|PubMed:15133035}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000305|PubMed:15133035};

Activity regulation: 2-hydroxy-dATPase activity is inhibited by 2-OH- dADP, 8-OH-dGDP and 8-OH-dGTP. 8-OH-dGTPase activity is inhibited by 8- OH-dGDP, 2-OH-dADP and 2-OH-dATP. {ECO:0000269|PubMed:10373420}.

Biophysicochemical properties: Kinetic parameters: KM=8.3 uM for 2-hydroxy-dATP (at 30 degrees Celsius and pH 8.0) {ECO:0000269|PubMed:11139615}; KM=5.7 uM for 2-hydroxy-dATP (at 30 degrees Celsius and pH 7.2) {ECO:0000269|PubMed:11139615}; KM=4.3 uM for 2-hydroxy-rATP (at 30 degrees Celsius and pH 8.0) {ECO:0000269|PubMed:11139615}; KM=13.9 uM for 8-hydroxy-dATP (at 30 degrees Celsius and pH 8.0) {ECO:0000269|PubMed:11139615}; KM=51.0 uM for 8-hydroxy-rATP (at 30 degrees Celsius and pH 8.0) {ECO:0000269|PubMed:11139615}; KM=15.2 uM for 8-hydroxy-dGTP (at 30 degrees Celsius and pH 8.0) {ECO:0000269|PubMed:11139615}; KM=12.8 uM for 8-hydroxy-dGTP (at 30 degrees Celsius and pH 7.2) {ECO:0000269|PubMed:11139615}; KM=13.2 uM for 8-hydroxy-dGTP (at 22 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:21787772}; KM=55.0 uM for 8-hydroxy-rGTP (at 30 degrees Celsius and pH 8.0) {ECO:0000269|PubMed:11139615}; KM=258 uM for dGTP (at 30 degrees Celsius and pH 8.0) {ECO:0000269|PubMed:11139615}; Note=The kinetic constants are determined for the recombinant enzyme expressed in E.coli. 2-hydroxy-rATP shows the best catalytic efficiency.; pH dependence: Optimum pH is 7.8-8.2 with 8-hydroxy-dGTP as substrate, and 8.0-8.5 with 2-hydroxy-dATP as substrate. {ECO:0000269|PubMed:10373420, ECO:0000269|PubMed:11139615, ECO:0000269|PubMed:21787772};

Subunit: Monomer. {ECO:0000269|PubMed:15133035, ECO:0000269|PubMed:21787772}.

Subcellular location: [Isoform p18]: Cytoplasm, cytosol {ECO:0000269|PubMed:12857738, ECO:0000269|PubMed:16607562, ECO:0000269|PubMed:7782328}. Mitochondrion matrix {ECO:0000269|PubMed:7782328, ECO:0000305|PubMed:12857738, ECO:0000305|PubMed:16607562}. Nucleus {ECO:0000269|PubMed:12857738, ECO:0000269|PubMed:7782328}. Note=Mostly present in cytosol (PubMed:7782328). A minor proportion is mitochondrial (PubMed:7782328). A very small amount of the protein is associated with nuclei (PubMed:7782328). Variant Met-124 has decreased efficiency in translocation to mitochondria (PubMed:16607562). {ECO:0000269|PubMed:16607562, ECO:0000269|PubMed:7782328}.

Subcellular location: [Isoform p26]: Mitochondrion matrix {ECO:0000269|PubMed:16607562}.

Tissue specificity: Widely expressed with highest expression in thymus, testis, embryo and proliferating blood lymphocytes. {ECO:0000269|PubMed:9211940}.

Developmental stage: In peripheral blood lymphocytes, expressed at much higher levels in proliferating cells than in resting cells. {ECO:0000269|PubMed:9211940}.

Ptm: 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%. {ECO:0000269|PubMed:10536140}.

Miscellaneous: [Isoform p26]: 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.

Similarity: Belongs to the Nudix hydrolase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Antimutagenic (PubMed:8226881, PubMed:7713500, PubMed:10608900). Plays a redundant role in sanitizing oxidized nucleotide pools, such as 8-oxo-dGTP pools (PubMed:28679043). Acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress (PubMed:12857738, PubMed:24695224, PubMed:24695225). Hydrolyzes 8-oxo-dGTP, 8-oxo-dATP and 2-OH-dATP, thus preventing misincorporation of oxidized purine nucleoside triphosphates into DNA and subsequently preventing A:T to C:G and G:C to T:A transversions (PubMed:8226881, PubMed:10373420, PubMed:10608900, PubMed:11756418, PubMed:12857738, PubMed:16607562, PubMed:24695224, PubMed:24695225, PubMed:26999531, PubMed:28035004). Able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8- oxo-GTP and 8-oxo-ATP (PubMed:10373420, PubMed:11139615). Does not play a role in U8 snoRNA decapping activity. Binds U8 snoRNA (By similarity). {ECO:0000250\|UniProtKB:P53368, ECO:0000269\|PubMed:10373420, ECO:0000269\|PubMed:10608900, ECO:0000269\|PubMed:11139615, ECO:0000269\|PubMed:11756418, ECO:0000269\|PubMed:12857738, ECO:0000269\|PubMed:16607562, ECO:0000269\|PubMed:22556419, ECO:0000269\|PubMed:24695224, ECO:0000269\|PubMed:24695225, ECO:0000269\|PubMed:26999531, ECO:0000269\|PubMed:28035004, ECO:0000269\|PubMed:28679043, ECO:0000269\|PubMed:7713500, ECO:0000269\|PubMed:8226881}.


Catalytic activity:		Reaction=8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate + H(+); Xref=Rhea:RHEA:31575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:63224, ChEBI:CHEBI:77896; EC=3.6.1.55; Evidence={ECO:0000269\|PubMed:10373420, ECO:0000269\|PubMed:10608900, ECO:0000269\|PubMed:11139615, ECO:0000269\|PubMed:11756418, ECO:0000269\|PubMed:12857738, ECO:0000269\|PubMed:16607562, ECO:0000269\|PubMed:21787772, ECO:0000269\|PubMed:22556419, ECO:0000269\|PubMed:24695224, ECO:0000269\|PubMed:24695225, ECO:0000269\|PubMed:26999531, ECO:0000269\|PubMed:28035004, ECO:0000269\|PubMed:7782328, ECO:0000269\|PubMed:8226881};
Catalytic activity:		Reaction=2-hydroxy-dATP + H2O = 2-hydroxy-dAMP + diphosphate + H(+); Xref=Rhea:RHEA:31583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:63212, ChEBI:CHEBI:77897; EC=3.6.1.56; Evidence={ECO:0000269\|PubMed:10373420, ECO:0000269\|PubMed:11139615, ECO:0000269\|PubMed:11756418, ECO:0000269\|PubMed:12857738, ECO:0000269\|PubMed:16607562, ECO:0000269\|PubMed:24695224, ECO:0000269\|PubMed:24695225, ECO:0000269\|PubMed:26999531, ECO:0000269\|PubMed:28035004};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305\|PubMed:15133035}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000305\|PubMed:15133035};
Activity regulation:		2-hydroxy-dATPase activity is inhibited by 2-OH- dADP, 8-OH-dGDP and 8-OH-dGTP. 8-OH-dGTPase activity is inhibited by 8- OH-dGDP, 2-OH-dADP and 2-OH-dATP. {ECO:0000269\|PubMed:10373420}.
Biophysicochemical properties:		Kinetic parameters: KM=8.3 uM for 2-hydroxy-dATP (at 30 degrees Celsius and pH 8.0) {ECO:0000269\|PubMed:11139615}; KM=5.7 uM for 2-hydroxy-dATP (at 30 degrees Celsius and pH 7.2) {ECO:0000269\|PubMed:11139615}; KM=4.3 uM for 2-hydroxy-rATP (at 30 degrees Celsius and pH 8.0) {ECO:0000269\|PubMed:11139615}; KM=13.9 uM for 8-hydroxy-dATP (at 30 degrees Celsius and pH 8.0) {ECO:0000269\|PubMed:11139615}; KM=51.0 uM for 8-hydroxy-rATP (at 30 degrees Celsius and pH 8.0) {ECO:0000269\|PubMed:11139615}; KM=15.2 uM for 8-hydroxy-dGTP (at 30 degrees Celsius and pH 8.0) {ECO:0000269\|PubMed:11139615}; KM=12.8 uM for 8-hydroxy-dGTP (at 30 degrees Celsius and pH 7.2) {ECO:0000269\|PubMed:11139615}; KM=13.2 uM for 8-hydroxy-dGTP (at 22 degrees Celsius and pH 7.5) {ECO:0000269\|PubMed:21787772}; KM=55.0 uM for 8-hydroxy-rGTP (at 30 degrees Celsius and pH 8.0) {ECO:0000269\|PubMed:11139615}; KM=258 uM for dGTP (at 30 degrees Celsius and pH 8.0) {ECO:0000269\|PubMed:11139615}; Note=The kinetic constants are determined for the recombinant enzyme expressed in E.coli. 2-hydroxy-rATP shows the best catalytic efficiency.; pH dependence: Optimum pH is 7.8-8.2 with 8-hydroxy-dGTP as substrate, and 8.0-8.5 with 2-hydroxy-dATP as substrate. {ECO:0000269\|PubMed:10373420, ECO:0000269\|PubMed:11139615, ECO:0000269\|PubMed:21787772};
Subunit:		Monomer. {ECO:0000269\|PubMed:15133035, ECO:0000269\|PubMed:21787772}.
Subcellular location:		[Isoform p18]: Cytoplasm, cytosol {ECO:0000269\|PubMed:12857738, ECO:0000269\|PubMed:16607562, ECO:0000269\|PubMed:7782328}. Mitochondrion matrix {ECO:0000269\|PubMed:7782328, ECO:0000305\|PubMed:12857738, ECO:0000305\|PubMed:16607562}. Nucleus {ECO:0000269\|PubMed:12857738, ECO:0000269\|PubMed:7782328}. Note=Mostly present in cytosol (PubMed:7782328). A minor proportion is mitochondrial (PubMed:7782328). A very small amount of the protein is associated with nuclei (PubMed:7782328). Variant Met-124 has decreased efficiency in translocation to mitochondria (PubMed:16607562). {ECO:0000269\|PubMed:16607562, ECO:0000269\|PubMed:7782328}.
Subcellular location:		[Isoform p26]: Mitochondrion matrix {ECO:0000269\|PubMed:16607562}.
Tissue specificity:		Widely expressed with highest expression in thymus, testis, embryo and proliferating blood lymphocytes. {ECO:0000269\|PubMed:9211940}.
Developmental stage:		In peripheral blood lymphocytes, expressed at much higher levels in proliferating cells than in resting cells. {ECO:0000269\|PubMed:9211940}.
Ptm:		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%. {ECO:0000269\|PubMed:10536140}.
Miscellaneous:		[Isoform p26]: 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.
Similarity:		Belongs to the Nudix hydrolase family. {ECO:0000305}.