UniProt functional annotation for P26769



	UniProt functional annotation for P26769

UniProt code: P26769.

Organism: Rattus norvegicus (Rat).

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

Function: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:22906005, PubMed:24363043, PubMed:10427002, PubMed:1719547, PubMed:7761832, PubMed:21596131, PubMed:11087399, PubMed:15591060, PubMed:19243146, PubMed:16766715). Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production (PubMed:24363043). Functions in signaling cascades downstream of the muscarinic acetylcholine receptors (PubMed:22906005). {ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:15591060, ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:1719547, ECO:0000269|PubMed:19243146, ECO:0000269|PubMed:21596131, ECO:0000269|PubMed:22906005, ECO:0000269|PubMed:24363043, ECO:0000269|PubMed:7761832}.

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:16766715, ECO:0000269|PubMed:1719547, ECO:0000269|PubMed:19243146, ECO:0000269|PubMed:21596131, ECO:0000269|PubMed:22906005, ECO:0000269|PubMed:24363043, ECO:0000269|PubMed:7761832};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:1719547, ECO:0000269|PubMed:19243146, ECO:0000269|PubMed:7761832}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:16766715}; Note=Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro). {ECO:0000269|PubMed:16766715, ECO:0000305|PubMed:10427002};

Activity regulation: Activated by forskolin (PubMed:1719547, PubMed:22906005, PubMed:24363043). Is not activated by calmodulin (PubMed:1719547). Inhibited by calcium ions, already at micromolar concentration. Activated by the G protein alpha subunit GNAS (PubMed:1719547, PubMed:7761832, PubMed:21596131). Activated by the G protein beta and gamma subunit complex (PubMed:7761832, PubMed:21596131, PubMed:22906005). Phosphorylation by RAF1 results in its activation (By similarity). Phosphorylation by PKC activates the enzyme (PubMed:22906005). {ECO:0000250|UniProtKB:Q08462, ECO:0000269|PubMed:1719547, ECO:0000269|PubMed:21596131, ECO:0000269|PubMed:22906005, ECO:0000269|PubMed:24363043, ECO:0000269|PubMed:7761832}.

Subunit: Interacts with RAF1 (By similarity). Interacts with GNAS (PubMed:9417641, PubMed:10427002, PubMed:11087399, PubMed:15591060, PubMed:16766715, PubMed:19243146). Interacts with the G protein beta and gamma subunit complex (PubMed:21596131). {ECO:0000250|UniProtKB:Q08462, ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:15591060, ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:19243146, ECO:0000269|PubMed:21596131, ECO:0000269|PubMed:9417641}.

Subcellular location: Membrane {ECO:0000269|PubMed:1719547, ECO:0000269|PubMed:22906005}; Multi-pass membrane protein {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:1719547, ECO:0000269|PubMed:7761832}; Multi-pass membrane protein {ECO:0000305}. Cytoplasm {ECO:0000250|UniProtKB:Q08462}.

Tissue specificity: Expressed in brain, olfactory epithelium and lung. {ECO:0000269|PubMed:1719547}.

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, ECO:0000269|PubMed:9417641}.

Ptm: Phosphorylated by RAF1 (By similarity). {ECO:0000250|UniProtKB:Q08462}.

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

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:22906005, PubMed:24363043, PubMed:10427002, PubMed:1719547, PubMed:7761832, PubMed:21596131, PubMed:11087399, PubMed:15591060, PubMed:19243146, PubMed:16766715). Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production (PubMed:24363043). Functions in signaling cascades downstream of the muscarinic acetylcholine receptors (PubMed:22906005). {ECO:0000269\|PubMed:10427002, ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:15591060, ECO:0000269\|PubMed:16766715, ECO:0000269\|PubMed:1719547, ECO:0000269\|PubMed:19243146, ECO:0000269\|PubMed:21596131, ECO:0000269\|PubMed:22906005, ECO:0000269\|PubMed:24363043, ECO:0000269\|PubMed:7761832}.


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:16766715, ECO:0000269\|PubMed:1719547, ECO:0000269\|PubMed:19243146, ECO:0000269\|PubMed:21596131, ECO:0000269\|PubMed:22906005, ECO:0000269\|PubMed:24363043, ECO:0000269\|PubMed:7761832};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:10427002, ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:16766715, ECO:0000269\|PubMed:1719547, ECO:0000269\|PubMed:19243146, ECO:0000269\|PubMed:7761832}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269\|PubMed:10427002, ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:16766715}; Note=Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro). {ECO:0000269\|PubMed:16766715, ECO:0000305\|PubMed:10427002};
Activity regulation:		Activated by forskolin (PubMed:1719547, PubMed:22906005, PubMed:24363043). Is not activated by calmodulin (PubMed:1719547). Inhibited by calcium ions, already at micromolar concentration. Activated by the G protein alpha subunit GNAS (PubMed:1719547, PubMed:7761832, PubMed:21596131). Activated by the G protein beta and gamma subunit complex (PubMed:7761832, PubMed:21596131, PubMed:22906005). Phosphorylation by RAF1 results in its activation (By similarity). Phosphorylation by PKC activates the enzyme (PubMed:22906005). {ECO:0000250\|UniProtKB:Q08462, ECO:0000269\|PubMed:1719547, ECO:0000269\|PubMed:21596131, ECO:0000269\|PubMed:22906005, ECO:0000269\|PubMed:24363043, ECO:0000269\|PubMed:7761832}.
Subunit:		Interacts with RAF1 (By similarity). Interacts with GNAS (PubMed:9417641, PubMed:10427002, PubMed:11087399, PubMed:15591060, PubMed:16766715, PubMed:19243146). Interacts with the G protein beta and gamma subunit complex (PubMed:21596131). {ECO:0000250\|UniProtKB:Q08462, ECO:0000269\|PubMed:10427002, ECO:0000269\|PubMed:11087399, ECO:0000269\|PubMed:15591060, ECO:0000269\|PubMed:16766715, ECO:0000269\|PubMed:19243146, ECO:0000269\|PubMed:21596131, ECO:0000269\|PubMed:9417641}.
Subcellular location:		Membrane {ECO:0000269\|PubMed:1719547, ECO:0000269\|PubMed:22906005}; Multi-pass membrane protein {ECO:0000305}. Cell membrane {ECO:0000269\|PubMed:1719547, ECO:0000269\|PubMed:7761832}; Multi-pass membrane protein {ECO:0000305}. Cytoplasm {ECO:0000250\|UniProtKB:Q08462}.
Tissue specificity:		Expressed in brain, olfactory epithelium and lung. {ECO:0000269\|PubMed:1719547}.
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, ECO:0000269\|PubMed:9417641}.
Ptm:		Phosphorylated by RAF1 (By similarity). {ECO:0000250\|UniProtKB:Q08462}.
Similarity:		Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. {ECO:0000255\|PROSITE-ProRule:PRU00099}.