UniProt functional annotation for Q9Y233



	UniProt functional annotation for Q9Y233

UniProt code: Q9Y233.

Organism: Homo sapiens (Human).

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

Function: Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition. {ECO:0000250|UniProtKB:Q8CA95, ECO:0000269|PubMed:17389385}.

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; Evidence={ECO:0000269|PubMed:17389385};

Catalytic activity: Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165, ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:17389385};

Catalytic activity: Reaction=3',5'-cyclic GMP + H2O = GMP + H(+); Xref=Rhea:RHEA:16957, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57746, ChEBI:CHEBI:58115; Evidence={ECO:0000269|PubMed:17389385};

Cofactor: Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Evidence={ECO:0000269|PubMed:17389385}; 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:0000269|PubMed:17389385};

Activity regulation: Inhibited by dipyridamole and moderately by IBMX. cGMP acts as an allosteric activator. {ECO:0000269|PubMed:16330539}.

Biophysicochemical properties: Kinetic parameters: KM=56 nM for cAMP {ECO:0000269|PubMed:17389385}; KM=4.4 uM for cGMP {ECO:0000269|PubMed:17389385}; Vmax=507 nmol/min/mg enzyme for cAMP {ECO:0000269|PubMed:17389385}; Vmax=1860 nmol/min/mg enzyme for cGMP {ECO:0000269|PubMed:17389385};

Pathway: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.

Pathway: Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1.

Subunit: Homodimer. {ECO:0000269|PubMed:18477562}.

Subcellular location: Cytoplasm. Note=Located mostly to soluble cellular fractions.

Tissue specificity: Abundant in the putamen and caudate nucleus regions of brain and testis, moderately expressed in the thyroid gland, pituitary gland, thalamus and cerebellum. {ECO:0000269|PubMed:10373451, ECO:0000269|PubMed:27058447}.

Domain: The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity.

Domain: Composed of a C-terminal catalytic domain containing two divalent metal sites and an N-terminal regulatory domain which contains one cyclic nucleotide-binding region.

Ptm: [Isoform PDE10A2]: Phosphorylated on Thr-16. {ECO:0000269|PubMed:10441464}.

Disease: Dyskinesia, limb and orofacial, infantile-onset (IOLOD) [MIM:616921]: An autosomal recessive, early-onset hyperkinetic movement disorder characterized by axial hypotonia, dyskinesia of the limbs and trunk, orofacial dyskinesia, drooling, and dysarthria. The severity of the hyperkinesis is variable. {ECO:0000269|PubMed:27058446}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Striatal degeneration, autosomal dominant 2 (ADSD2) [MIM:616922]: An autosomal dominant disorder characterized by striatal degeneration and dysfunction of basal ganglia, resulting in hyperkinesis. {ECO:0000269|PubMed:27058447}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the cyclic nucleotide phosphodiesterase family. {ECO:0000305}.

Sequence caution: Sequence=AAD32596.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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:		Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition. {ECO:0000250\|UniProtKB:Q8CA95, ECO:0000269\|PubMed:17389385}.


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; Evidence={ECO:0000269\|PubMed:17389385};
Catalytic activity:		Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165, ChEBI:CHEBI:456215; Evidence={ECO:0000269\|PubMed:17389385};
Catalytic activity:		Reaction=3',5'-cyclic GMP + H2O = GMP + H(+); Xref=Rhea:RHEA:16957, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57746, ChEBI:CHEBI:58115; Evidence={ECO:0000269\|PubMed:17389385};
Cofactor:		Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Evidence={ECO:0000269\|PubMed:17389385}; 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:0000269\|PubMed:17389385};
Activity regulation:		Inhibited by dipyridamole and moderately by IBMX. cGMP acts as an allosteric activator. {ECO:0000269\|PubMed:16330539}.
Biophysicochemical properties:		Kinetic parameters: KM=56 nM for cAMP {ECO:0000269\|PubMed:17389385}; KM=4.4 uM for cGMP {ECO:0000269\|PubMed:17389385}; Vmax=507 nmol/min/mg enzyme for cAMP {ECO:0000269\|PubMed:17389385}; Vmax=1860 nmol/min/mg enzyme for cGMP {ECO:0000269\|PubMed:17389385};
Pathway:		Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.
Pathway:		Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1.
Subunit:		Homodimer. {ECO:0000269\|PubMed:18477562}.
Subcellular location:		Cytoplasm. Note=Located mostly to soluble cellular fractions.
Tissue specificity:		Abundant in the putamen and caudate nucleus regions of brain and testis, moderately expressed in the thyroid gland, pituitary gland, thalamus and cerebellum. {ECO:0000269\|PubMed:10373451, ECO:0000269\|PubMed:27058447}.
Domain:		The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity.
Domain:		Composed of a C-terminal catalytic domain containing two divalent metal sites and an N-terminal regulatory domain which contains one cyclic nucleotide-binding region.
Ptm:		[Isoform PDE10A2]: Phosphorylated on Thr-16. {ECO:0000269\|PubMed:10441464}.
Disease:		Dyskinesia, limb and orofacial, infantile-onset (IOLOD) [MIM:616921]: An autosomal recessive, early-onset hyperkinetic movement disorder characterized by axial hypotonia, dyskinesia of the limbs and trunk, orofacial dyskinesia, drooling, and dysarthria. The severity of the hyperkinesis is variable. {ECO:0000269\|PubMed:27058446}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Striatal degeneration, autosomal dominant 2 (ADSD2) [MIM:616922]: An autosomal dominant disorder characterized by striatal degeneration and dysfunction of basal ganglia, resulting in hyperkinesis. {ECO:0000269\|PubMed:27058447}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the cyclic nucleotide phosphodiesterase family. {ECO:0000305}.
Sequence caution:		Sequence=AAD32596.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};