UniProt functional annotation for P03958



	UniProt functional annotation for P03958

UniProt code: P03958.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Catalyzes the hydrolytic deamination of adenosine and 2- deoxyadenosine (PubMed:9272950). Plays an important role in purine metabolism and in adenosine homeostasis (PubMed:9272950, PubMed:10720488). Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events (PubMed:11435465). Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte- epithelial cell adhesion (By similarity). Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion (By similarity). Enhances CD4+ T-cell differentiation and proliferation (By similarity). Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change (By similarity). Stimulates plasminogen activation (By similarity). Plays a role in male fertility (By similarity). Plays a protective role in early postimplantation embryonic development (PubMed:9272950). {ECO:0000250|UniProtKB:P00813, ECO:0000250|UniProtKB:P56658, ECO:0000269|PubMed:10720488, ECO:0000269|PubMed:11435465, ECO:0000269|PubMed:9272950}.

Catalytic activity: Reaction=adenosine + H(+) + H2O = inosine + NH4(+); Xref=Rhea:RHEA:24408, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16335, ChEBI:CHEBI:17596, ChEBI:CHEBI:28938; EC=3.5.4.4; Evidence={ECO:0000269|PubMed:8634299, ECO:0000269|PubMed:8672487, ECO:0000269|PubMed:8942668, ECO:0000269|PubMed:9272950, ECO:0000269|PubMed:9622483};

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:1925539, ECO:0000269|PubMed:8634299, ECO:0000269|PubMed:9622483}; Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:1925539, ECO:0000269|PubMed:8634299, ECO:0000269|PubMed:9622483};

Biophysicochemical properties: Kinetic parameters: KM=20 uM for adenosine {ECO:0000269|PubMed:8634299, ECO:0000269|PubMed:8672487}; pH dependence: Optimum pH is 6-8.5. {ECO:0000269|PubMed:8634299, ECO:0000269|PubMed:8672487};

Subunit: Interacts with DPP4 (via extracellular domain). Interacts with PLG (via Kringle 4 domain); the interaction stimulates PLG activation when in complex with DPP4. {ECO:0000250|UniProtKB:P00813}.

Subcellular location: Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Extracellular side {ECO:0000250}. Cell junction {ECO:0000250|UniProtKB:P00813}. Cytoplasmic vesicle lumen {ECO:0000269|PubMed:8783262}. Cytoplasm {ECO:0000250}. Lysosome {ECO:0000250|UniProtKB:P00813}. Note=Colocalized with DPP4 at the cell surface. {ECO:0000250|UniProtKB:P00813}.

Tissue specificity: Detected in brain neurons in the median emninence (at protein level) (PubMed:8783262). Expressed in secondary deciduum (at protein level) (PubMed:9272950). Found in all tissues, occurs in large amounts in T-lymphocytes and, at the time of weaning, in gastrointestinal tissues. {ECO:0000269|PubMed:8783262, ECO:0000269|PubMed:9272950}.

Developmental stage: Expressed in trophoblast at 7.5 dpc and 9.5 dpc. {ECO:0000269|PubMed:9272950}.

Disruption phenotype: Lethal at perinatal stages. Fetuses are viable up to 18 dpc, but after this survival decreases rapidly. Fewer that 10% of mutant pups are born live, and these die within hours after birth. Mutant fetuses display much higher than normal levels of adenosine and dATP, respiratory distress, hepatocellular degeneration and necrosis. Prenatal lethality can be avoided using an ADA expression vector with a trophoblast-specific promoter. Mutant mice die after about three weeks due to immunodeficiency, disturbances in purine metabolism and severe lung inflammation. {ECO:0000269|PubMed:10899903, ECO:0000269|PubMed:7670465, ECO:0000269|PubMed:7731963}.

Similarity: Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Catalyzes the hydrolytic deamination of adenosine and 2- deoxyadenosine (PubMed:9272950). Plays an important role in purine metabolism and in adenosine homeostasis (PubMed:9272950, PubMed:10720488). Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events (PubMed:11435465). Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte- epithelial cell adhesion (By similarity). Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion (By similarity). Enhances CD4+ T-cell differentiation and proliferation (By similarity). Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change (By similarity). Stimulates plasminogen activation (By similarity). Plays a role in male fertility (By similarity). Plays a protective role in early postimplantation embryonic development (PubMed:9272950). {ECO:0000250\|UniProtKB:P00813, ECO:0000250\|UniProtKB:P56658, ECO:0000269\|PubMed:10720488, ECO:0000269\|PubMed:11435465, ECO:0000269\|PubMed:9272950}.


Catalytic activity:		Reaction=adenosine + H(+) + H2O = inosine + NH4(+); Xref=Rhea:RHEA:24408, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16335, ChEBI:CHEBI:17596, ChEBI:CHEBI:28938; EC=3.5.4.4; Evidence={ECO:0000269\|PubMed:8634299, ECO:0000269\|PubMed:8672487, ECO:0000269\|PubMed:8942668, ECO:0000269\|PubMed:9272950, ECO:0000269\|PubMed:9622483};
Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269\|PubMed:1925539, ECO:0000269\|PubMed:8634299, ECO:0000269\|PubMed:9622483}; Note=Binds 1 zinc ion per subunit. {ECO:0000269\|PubMed:1925539, ECO:0000269\|PubMed:8634299, ECO:0000269\|PubMed:9622483};
Biophysicochemical properties:		Kinetic parameters: KM=20 uM for adenosine {ECO:0000269\|PubMed:8634299, ECO:0000269\|PubMed:8672487}; pH dependence: Optimum pH is 6-8.5. {ECO:0000269\|PubMed:8634299, ECO:0000269\|PubMed:8672487};
Subunit:		Interacts with DPP4 (via extracellular domain). Interacts with PLG (via Kringle 4 domain); the interaction stimulates PLG activation when in complex with DPP4. {ECO:0000250\|UniProtKB:P00813}.
Subcellular location:		Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Extracellular side {ECO:0000250}. Cell junction {ECO:0000250\|UniProtKB:P00813}. Cytoplasmic vesicle lumen {ECO:0000269\|PubMed:8783262}. Cytoplasm {ECO:0000250}. Lysosome {ECO:0000250\|UniProtKB:P00813}. Note=Colocalized with DPP4 at the cell surface. {ECO:0000250\|UniProtKB:P00813}.
Tissue specificity:		Detected in brain neurons in the median emninence (at protein level) (PubMed:8783262). Expressed in secondary deciduum (at protein level) (PubMed:9272950). Found in all tissues, occurs in large amounts in T-lymphocytes and, at the time of weaning, in gastrointestinal tissues. {ECO:0000269\|PubMed:8783262, ECO:0000269\|PubMed:9272950}.
Developmental stage:		Expressed in trophoblast at 7.5 dpc and 9.5 dpc. {ECO:0000269\|PubMed:9272950}.
Disruption phenotype:		Lethal at perinatal stages. Fetuses are viable up to 18 dpc, but after this survival decreases rapidly. Fewer that 10% of mutant pups are born live, and these die within hours after birth. Mutant fetuses display much higher than normal levels of adenosine and dATP, respiratory distress, hepatocellular degeneration and necrosis. Prenatal lethality can be avoided using an ADA expression vector with a trophoblast-specific promoter. Mutant mice die after about three weeks due to immunodeficiency, disturbances in purine metabolism and severe lung inflammation. {ECO:0000269\|PubMed:10899903, ECO:0000269\|PubMed:7670465, ECO:0000269\|PubMed:7731963}.
Similarity:		Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. {ECO:0000305}.