UniProt functional annotation for P30803



	UniProt functional annotation for P30803

UniProt code: P30803.

Organism: Canis lupus familiaris (Dog) (Canis familiaris).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.

Function: [Isoform 1]: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:1618857, PubMed:8428899, PubMed:10427002, PubMed:11087399, PubMed:15591060, PubMed:16766715, PubMed:19243146). Mediates signaling downstream of ADRB1. Regulates the increase of free cytosolic Ca(2+) in response to increased blood glucose levels and contributes to the regulation of Ca(2+)-dependent insulin secretion (By similarity). {ECO:0000250|UniProtKB:O95622, ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:15591060, ECO:0000269|PubMed:1618857, ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:19243146, ECO:0000269|PubMed:8428899}.

Function: [Isoform 2]: Lacks catalytic activity by itself, but can associate with isoform 1 to form active adenylyl cyclase. {ECO:0000269|PubMed:8428899}.

Catalytic activity: Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1; Evidence={ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:15591060, ECO:0000269|PubMed:1618857, ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:19243146, ECO:0000269|PubMed:8428899};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:19243146}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:16766715}; Note=Binds 2 magnesium ions per subunit (PubMed:16766715, PubMed:19243146). Is also active with manganese (in vitro) (PubMed:11087399, PubMed:16766715). {ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:16766715, ECO:0000305|PubMed:19243146};

Activity regulation: Activated by forskolin (PubMed:1618857, PubMed:8428899). Activated by GNAS. Activity is further increased by interaction with the G-protein beta and gamma subunit complex formed by GNB1 and GNG2 (By similarity). Is not activated by calmodulin. Inhibited by adenosine and ATP analogs. Inhibited by calcium ions, already at micromolar concentrations (PubMed:1618857). Phosphorylation by RAF1 results in its activation (By similarity). {ECO:0000250|UniProtKB:O95622, ECO:0000269|PubMed:1618857, ECO:0000269|PubMed:8428899}.

Subunit: Interacts with GNAS (PubMed:9417641, PubMed:10427002, PubMed:11087399, PubMed:15591060, PubMed:16766715, PubMed:19243146). Interacts with GNB1 and GNG2 (By similarity). Part of a complex containing AKAP5, ADCY6, PDE4C and PKD2 (By similarity). Interacts with RAF1 (By similarity). {ECO:0000250|UniProtKB:O95622, ECO:0000250|UniProtKB:P84309, ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:15591060, ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:19243146, ECO:0000269|PubMed:9417641}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:1618857, ECO:0000269|PubMed:8428899}; Multi-pass membrane protein {ECO:0000305}. Cell projection, cilium {ECO:0000250|UniProtKB:P84309}.

Tissue specificity: Isoform 1 is detected in heart, and at lower levels in brain (PubMed:1618857). Isoform 2 is detected in heart (PubMed:8428899). {ECO:0000269|PubMed:1618857, ECO:0000269|PubMed:8428899}.

Domain: The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate- binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain. {ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:15591060, ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:19243146}.

Similarity: Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. {ECO:0000255|PROSITE-ProRule:PRU00099}.

Annotations taken from UniProtKB at the EBI.


Organism:		Canis lupus familiaris (Dog) (Canis familiaris).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.



Function:		[Isoform 1]: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:1618857, PubMed:8428899, PubMed:10427002, PubMed:11087399, PubMed:15591060, PubMed:16766715, PubMed:19243146). Mediates signaling downstream of ADRB1. Regulates the increase of free cytosolic Ca(2+) in response to increased blood glucose levels and contributes to the regulation of Ca(2+)-dependent insulin secretion (By similarity). {ECO:0000250\|UniProtKB:O95622, ECO:0000269\|PubMed:10427002, ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:15591060, ECO:0000269\|PubMed:1618857, ECO:0000269\|PubMed:16766715, ECO:0000269\|PubMed:19243146, ECO:0000269\|PubMed:8428899}.



Function:		[Isoform 2]: Lacks catalytic activity by itself, but can associate with isoform 1 to form active adenylyl cyclase. {ECO:0000269\|PubMed:8428899}.


Catalytic activity:		Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1; Evidence={ECO:0000269\|PubMed:10427002, ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:15591060, ECO:0000269\|PubMed:1618857, ECO:0000269\|PubMed:16766715, ECO:0000269\|PubMed:19243146, ECO:0000269\|PubMed:8428899};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:16766715, ECO:0000269\|PubMed:19243146}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:16766715}; Note=Binds 2 magnesium ions per subunit (PubMed:16766715, PubMed:19243146). Is also active with manganese (in vitro) (PubMed:11087399, PubMed:16766715). {ECO:0000269\|PubMed:10427002, ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:16766715, ECO:0000305\|PubMed:19243146};
Activity regulation:		Activated by forskolin (PubMed:1618857, PubMed:8428899). Activated by GNAS. Activity is further increased by interaction with the G-protein beta and gamma subunit complex formed by GNB1 and GNG2 (By similarity). Is not activated by calmodulin. Inhibited by adenosine and ATP analogs. Inhibited by calcium ions, already at micromolar concentrations (PubMed:1618857). Phosphorylation by RAF1 results in its activation (By similarity). {ECO:0000250\|UniProtKB:O95622, ECO:0000269\|PubMed:1618857, ECO:0000269\|PubMed:8428899}.
Subunit:		Interacts with GNAS (PubMed:9417641, PubMed:10427002, PubMed:11087399, PubMed:15591060, PubMed:16766715, PubMed:19243146). Interacts with GNB1 and GNG2 (By similarity). Part of a complex containing AKAP5, ADCY6, PDE4C and PKD2 (By similarity). Interacts with RAF1 (By similarity). {ECO:0000250\|UniProtKB:O95622, ECO:0000250\|UniProtKB:P84309, ECO:0000269\|PubMed:10427002, ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:15591060, ECO:0000269\|PubMed:16766715, ECO:0000269\|PubMed:19243146, ECO:0000269\|PubMed:9417641}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:1618857, ECO:0000269\|PubMed:8428899}; Multi-pass membrane protein {ECO:0000305}. Cell projection, cilium {ECO:0000250\|UniProtKB:P84309}.
Tissue specificity:		Isoform 1 is detected in heart, and at lower levels in brain (PubMed:1618857). Isoform 2 is detected in heart (PubMed:8428899). {ECO:0000269\|PubMed:1618857, ECO:0000269\|PubMed:8428899}.
Domain:		The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate- binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain. {ECO:0000269\|PubMed:10427002, ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:15591060, ECO:0000269\|PubMed:16766715, ECO:0000269\|PubMed:19243146}.
Similarity:		Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. {ECO:0000255\|PROSITE-ProRule:PRU00099}.