UniProt functional annotation for P33316



	UniProt functional annotation for P33316

UniProt code: P33316.

Organism: Homo sapiens (Human).

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

Function: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA. {ECO:0000269|PubMed:17880943, ECO:0000269|PubMed:8631816, ECO:0000269|PubMed:8805593}.

Catalytic activity: Reaction=dUTP + H2O = diphosphate + dUMP + H(+); Xref=Rhea:RHEA:10248, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:61555, ChEBI:CHEBI:246422; EC=3.6.1.23; Evidence={ECO:0000269|PubMed:17880943, ECO:0000269|PubMed:8631816, ECO:0000269|PubMed:8805593};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:8805593};

Activity regulation: Phosphorylation is necessary for activity.

Biophysicochemical properties: Kinetic parameters: KM=2.5 uM for dUTP {ECO:0000269|PubMed:8631816}; Note=kM is identical for both isoform 2 and isoform 3. {ECO:0000269|PubMed:8631816};

Pathway: Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP (dUTP route): step 2/2. {ECO:0000269|PubMed:8631816, ECO:0000269|PubMed:8805593}.

Subunit: Homotrimer. {ECO:0000269|PubMed:17880943, ECO:0000269|PubMed:8805593}.

Subcellular location: [Isoform 2]: Nucleus {ECO:0000269|PubMed:8631816, ECO:0000269|PubMed:9070952}.

Subcellular location: [Isoform 3]: Mitochondrion {ECO:0000269|PubMed:8631816, ECO:0000269|PubMed:9070952}.

Tissue specificity: Found in a variety of tissues. Isoform 3 expression is constitutive, while isoform 2 expression correlates with the onset of DNA replication (at protein level). Isoform 2 degradation coincides with the cessation of nuclear DNA replication (at protein level). {ECO:0000269|PubMed:9228092}.

Ptm: Nuclear isoform 2 is phosphorylated in vivo on Ser-11, a reaction that can be catalyzed in vitro by CDC2. Phosphorylation in mature T- cells occurs in a cell cycle-dependent manner. Isoform 3 is not phosphorylated. {ECO:0000269|PubMed:8389461}.

Miscellaneous: Each trimer binds three substrate molecules. The ligands are bound between subunits, and for each substrate molecule, residues from adjacent subunits contribute to the binding interactions.

Miscellaneous: [Isoform 2]: Major isoform. {ECO:0000305}.

Similarity: Belongs to the dUTPase family. {ECO:0000305}.

Sequence caution: Sequence=AAB71393.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB93866.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB94642.1; Type=Frameshift; Evidence={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:		This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA. {ECO:0000269\|PubMed:17880943, ECO:0000269\|PubMed:8631816, ECO:0000269\|PubMed:8805593}.


Catalytic activity:		Reaction=dUTP + H2O = diphosphate + dUMP + H(+); Xref=Rhea:RHEA:10248, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:61555, ChEBI:CHEBI:246422; EC=3.6.1.23; Evidence={ECO:0000269\|PubMed:17880943, ECO:0000269\|PubMed:8631816, ECO:0000269\|PubMed:8805593};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:8805593};
Activity regulation:		Phosphorylation is necessary for activity.
Biophysicochemical properties:		Kinetic parameters: KM=2.5 uM for dUTP {ECO:0000269\|PubMed:8631816}; Note=kM is identical for both isoform 2 and isoform 3. {ECO:0000269\|PubMed:8631816};
Pathway:		Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP (dUTP route): step 2/2. {ECO:0000269\|PubMed:8631816, ECO:0000269\|PubMed:8805593}.
Subunit:		Homotrimer. {ECO:0000269\|PubMed:17880943, ECO:0000269\|PubMed:8805593}.
Subcellular location:		[Isoform 2]: Nucleus {ECO:0000269\|PubMed:8631816, ECO:0000269\|PubMed:9070952}.
Subcellular location:		[Isoform 3]: Mitochondrion {ECO:0000269\|PubMed:8631816, ECO:0000269\|PubMed:9070952}.
Tissue specificity:		Found in a variety of tissues. Isoform 3 expression is constitutive, while isoform 2 expression correlates with the onset of DNA replication (at protein level). Isoform 2 degradation coincides with the cessation of nuclear DNA replication (at protein level). {ECO:0000269\|PubMed:9228092}.
Ptm:		Nuclear isoform 2 is phosphorylated in vivo on Ser-11, a reaction that can be catalyzed in vitro by CDC2. Phosphorylation in mature T- cells occurs in a cell cycle-dependent manner. Isoform 3 is not phosphorylated. {ECO:0000269\|PubMed:8389461}.
Miscellaneous:		Each trimer binds three substrate molecules. The ligands are bound between subunits, and for each substrate molecule, residues from adjacent subunits contribute to the binding interactions.
Miscellaneous:		[Isoform 2]: Major isoform. {ECO:0000305}.
Similarity:		Belongs to the dUTPase family. {ECO:0000305}.
Sequence caution:		Sequence=AAB71393.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB93866.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAB94642.1; Type=Frameshift; Evidence={ECO:0000305};