UniProt functional annotation for O00408

UniProt code: O00408.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Plays an important role in growth and invasion of malignant melanoma cells (e.g. pseudomyxoma peritonei (PMP) cell line) (PubMed:24705027). {ECO:0000269|PubMed:24705027}.
 
Function: [Isoform PDE2A2]: Regulates mitochondrial cAMP levels and respiration (By similarity). Involved in the regulation of mitochondria morphology/dynamics and apoptotic cell death via local modulation of cAMP/PKA signaling in the mitochondrion, including the monitoring of local cAMP levels at the outer mitochondrial membrane and of PKA- dependent phosphorylation of DNM1L (PubMed:28463107). {ECO:0000250|UniProtKB:Q922S4, ECO:0000269|PubMed:28463107}.
 
Catalytic activity: Reaction=a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'- phosphate + H(+); Xref=Rhea:RHEA:14653, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57867, ChEBI:CHEBI:58464; EC=3.1.4.17;
Cofactor: Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Evidence={ECO:0000250}; Note=Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. {ECO:0000250};
Subunit: Homodimer. {ECO:0000269|PubMed:15938621, ECO:0000269|PubMed:19828435, ECO:0000269|PubMed:23899287}.
Subcellular location: [Isoform PDE2A3]: Cell membrane {ECO:0000269|PubMed:19632989, ECO:0000269|PubMed:28463107}; Lipid- anchor {ECO:0000269|PubMed:19632989}.
Subcellular location: [Isoform PDE2A2]: Mitochondrion matrix {ECO:0000250|UniProtKB:Q922S4}. Mitochondrion inner membrane {ECO:0000269|PubMed:28463107}. Mitochondrion outer membrane {ECO:0000269|PubMed:28463107}.
Subcellular location: [Isoform PDE2A1]: Cytoplasm {ECO:0000269|PubMed:19632989, ECO:0000269|PubMed:28463107}.
Subcellular location: [Isoform 5]: Mitochondrion {ECO:0000305}.
Tissue specificity: Expressed in brain and to a lesser extent in heart, placenta, lung, skeletal muscle, kidney and pancreas.
Domain: GAF 1 functions as a dimerization domain, whereas GAF 2 binds cGMP, which causes activation of the catalytic activity of the enzyme. {ECO:0000250|UniProtKB:Q922S4}.
Miscellaneous: cGMP binds at an allosteric activator site. {ECO:0000250}.
Miscellaneous: [Isoform PDE2A1]: Soluble form. {ECO:0000305}.
Miscellaneous: [Isoform PDE2A2]: Contains a transit peptide at positions 1-17. {ECO:0000305}.
Similarity: Belongs to the cyclic nucleotide phosphodiesterase family. PDE2 subfamily. {ECO:0000305}.
Sequence caution: Sequence=AAS75515.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.