P84309 · ADCY5_MOUSE
- ProteinAdenylate cyclase type 5
- GeneAdcy5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1262 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates signaling downstream of ADRB1. Regulates the increase of free cytosolic Ca2+ in response to increased blood glucose levels and contributes to the regulation of Ca2+-dependent insulin secretion.
Catalytic activity
- ATP = 3',5'-cyclic AMP + diphosphate
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Note: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).
Activity regulation
Activated by G(s) G alpha protein GNAS (By similarity).
Inhibited by G(i) G alpha protein GNAI1 (By similarity).
Activity is further increased by interaction with the G-protein beta and gamma subunit complex formed by GNB1 and GNG2 (By similarity).
Activated by forskolin (By similarity).
Is not activated by calmodulin. Inhibited by adenosine and ATP analogs (By similarity).
Inhibited by calcium ions, already at micromolar concentrations (By similarity).
Phosphorylation by RAF1 results in its activation (By similarity).
Inhibited by G(i) G alpha protein GNAI1 (By similarity).
Activity is further increased by interaction with the G-protein beta and gamma subunit complex formed by GNB1 and GNG2 (By similarity).
Activated by forskolin (By similarity).
Is not activated by calmodulin. Inhibited by adenosine and ATP analogs (By similarity).
Inhibited by calcium ions, already at micromolar concentrations (By similarity).
Phosphorylation by RAF1 results in its activation (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 475 | Mg2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 475 | Mg2+ 2 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 475-480 | ATP (UniProtKB | ChEBI) | ||||
Sequence: DIEGFT | ||||||
Binding site | 476 | Mg2+ 2 (UniProtKB | ChEBI); catalytic | ||||
Sequence: I | ||||||
Binding site | 517-519 | ATP (UniProtKB | ChEBI) | ||||
Sequence: LGD | ||||||
Binding site | 519 | Mg2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 519 | Mg2+ 2 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 563 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1124 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 1198-1200 | ATP (UniProtKB | ChEBI) | ||||
Sequence: DIW | ||||||
Binding site | 1205-1209 | ATP (UniProtKB | ChEBI) | ||||
Sequence: NVASR | ||||||
Binding site | 1245 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAdenylate cyclase type 5
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP84309
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-196 | Cytoplasmic | ||||
Sequence: MSGSKSVSPPGYAAQTAASPAPRGGPEHRAAWGEADSRANGYPHAPGGSTRGSTKRSGGAVTPQQQQRLASRWRGGDDDEDPPLSGDDPLAGGFGFSFRSKSAWQERGGDDGGRGSRRQRRGAAGGGSTRAPPAGGSGSSAAAAAAAGGTEVRPRSVELGLEERRGKGRAAEELEPGTGIVEDGDGSEDGGSSVAS | ||||||
Transmembrane | 197-217 | Helical | ||||
Sequence: GSGTGAVLSLGACCLALLQIF | ||||||
Transmembrane | 243-263 | Helical | ||||
Sequence: LTMLMAVLVLVCLVMLAFHAA | ||||||
Transmembrane | 269-289 | Helical | ||||
Sequence: IAYLAVLAAAVGVILIMAVLC | ||||||
Transmembrane | 300-320 | Helical | ||||
Sequence: GLACYALIAVVLAVQVVGLLL | ||||||
Transmembrane | 326-346 | Helical | ||||
Sequence: ASEGIWWTVFFIYTIYTLLPV | ||||||
Transmembrane | 375-395 | Helical | ||||
Sequence: FLLKQLVSNVLIFSCTNIVGV | ||||||
Topological domain | 396-763 | Cytoplasmic | ||||
Sequence: CTHYPAEVSQRQAFQETRECIQARLHSQRENQQQERLLLSVLPRHVAMEMKADINAKQEDMMFHKIYIQKHDNVSILFADIEGFTSLASQCTAQELVMTLNELFARFDKLAAENHCLRIKILGDCYYCVSGLPEARADHAHCCVEMGMDMIEAISLVREVTGVNVNMRVGIHSGRVHCGVLGLRKWQFDVWSNDVTLANHMEAGGKAGRIHITKATLNYLNGDYEVEPGCGGDRNAYLKEHSIETFLILSCTQKRKEEKAMIAKMNRQRTNSIGHNPPHWGAERPFYNHLGGNQVSKEMKRMGFEDPKDKNAQESANPEDEVDEFLGRAIDARSIDRLRSEHVRKFLLTFREPDLEKKYSKQVDDRFG | ||||||
Transmembrane | 764-784 | Helical | ||||
Sequence: AYVACASLVFLFICFVQITIV | ||||||
Transmembrane | 790-810 | Helical | ||||
Sequence: MLSFYLSCFLLLALVVFVSVI | ||||||
Transmembrane | 837-857 | Helical | ||||
Sequence: LVGVFTITLVFLSAFVNMFMC | ||||||
Topological domain | 858-910 | Extracellular | ||||
Sequence: NSKNLVGCLAEEHNITVNQVNACHVMESAFNYSLGDEQGFCGSPQPNCNFPEY | ||||||
Transmembrane | 911-931 | Helical | ||||
Sequence: FTYSVLLSLLACSVFLQISCI | ||||||
Transmembrane | 936-956 | Helical | ||||
Sequence: LMLAIEFIYVLIVEVPGVTLF | ||||||
Transmembrane | 985-1005 | Helical | ||||
Sequence: VALKVVTPIIISVFVLALYLH | ||||||
Topological domain | 1006-1262 | Cytoplasmic | ||||
Sequence: AQQVESTARLDFLWKLQATEEKEEMEELQAYNRRLLHNILPKDVAAHFLARERRNDELYYQSCECVAVMFASIANFSEFYVELEANNEGVECLRLLNEIIADFDEIISEDRFRQLEKIKTIGSTYMAASGLNDSTYDKAGKTHIKAIADFAMKLMDQMKYINEHSFNNFQMKIGLNIGPVVAGVIGARKPQYDIWGNTVNVASRMDSTGVPDRIQVTTDMYQVLAANTYQLECRGVVKVKGKGEMMTYFLNGGPPLS |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000195695 | 1-1262 | Adenylate cyclase type 5 | |||
Sequence: MSGSKSVSPPGYAAQTAASPAPRGGPEHRAAWGEADSRANGYPHAPGGSTRGSTKRSGGAVTPQQQQRLASRWRGGDDDEDPPLSGDDPLAGGFGFSFRSKSAWQERGGDDGGRGSRRQRRGAAGGGSTRAPPAGGSGSSAAAAAAAGGTEVRPRSVELGLEERRGKGRAAEELEPGTGIVEDGDGSEDGGSSVASGSGTGAVLSLGACCLALLQIFRSKKFPSDKLERLYQRYFFRLNQSSLTMLMAVLVLVCLVMLAFHAARPPLQIAYLAVLAAAVGVILIMAVLCNRAAFHQDHMGLACYALIAVVLAVQVVGLLLPQPRSASEGIWWTVFFIYTIYTLLPVRMRAAVLSGVLLSALHLAISLHTNSQDQFLLKQLVSNVLIFSCTNIVGVCTHYPAEVSQRQAFQETRECIQARLHSQRENQQQERLLLSVLPRHVAMEMKADINAKQEDMMFHKIYIQKHDNVSILFADIEGFTSLASQCTAQELVMTLNELFARFDKLAAENHCLRIKILGDCYYCVSGLPEARADHAHCCVEMGMDMIEAISLVREVTGVNVNMRVGIHSGRVHCGVLGLRKWQFDVWSNDVTLANHMEAGGKAGRIHITKATLNYLNGDYEVEPGCGGDRNAYLKEHSIETFLILSCTQKRKEEKAMIAKMNRQRTNSIGHNPPHWGAERPFYNHLGGNQVSKEMKRMGFEDPKDKNAQESANPEDEVDEFLGRAIDARSIDRLRSEHVRKFLLTFREPDLEKKYSKQVDDRFGAYVACASLVFLFICFVQITIVPHSLFMLSFYLSCFLLLALVVFVSVIYACVKLFPTPLQTLSRKIVRSKKNSTLVGVFTITLVFLSAFVNMFMCNSKNLVGCLAEEHNITVNQVNACHVMESAFNYSLGDEQGFCGSPQPNCNFPEYFTYSVLLSLLACSVFLQISCIGKLVLMLAIEFIYVLIVEVPGVTLFDNADLLVTANAIDFSNNGTSQCPEHATKVALKVVTPIIISVFVLALYLHAQQVESTARLDFLWKLQATEEKEEMEELQAYNRRLLHNILPKDVAAHFLARERRNDELYYQSCECVAVMFASIANFSEFYVELEANNEGVECLRLLNEIIADFDEIISEDRFRQLEKIKTIGSTYMAASGLNDSTYDKAGKTHIKAIADFAMKLMDQMKYINEHSFNNFQMKIGLNIGPVVAGVIGARKPQYDIWGNTVNVASRMDSTGVPDRIQVTTDMYQVLAANTYQLECRGVVKVKGKGEMMTYFLNGGPPLS | ||||||
Modified residue | 23 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 97 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 156 | Phosphoserine | ||||
Sequence: S | ||||||
Glycosylation | 239 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 667 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 755 | Phosphoserine | ||||
Sequence: S | ||||||
Glycosylation | 834 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 871 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 888 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 973 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 1012 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Phosphorylated by RAF1.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-194 | Disordered | ||||
Sequence: MSGSKSVSPPGYAAQTAASPAPRGGPEHRAAWGEADSRANGYPHAPGGSTRGSTKRSGGAVTPQQQQRLASRWRGGDDDEDPPLSGDDPLAGGFGFSFRSKSAWQERGGDDGGRGSRRQRRGAAGGGSTRAPPAGGSGSSAAAAAAAGGTEVRPRSVELGLEERRGKGRAAEELEPGTGIVEDGDGSEDGGSSV | ||||||
Compositional bias | 50-71 | Polar residues | ||||
Sequence: TRGSTKRSGGAVTPQQQQRLAS | ||||||
Compositional bias | 104-118 | Basic and acidic residues | ||||
Sequence: WQERGGDDGGRGSRR | ||||||
Compositional bias | 156-172 | Basic and acidic residues | ||||
Sequence: SVELGLEERRGKGRAAE | ||||||
Domain | 470-597 | Guanylate cyclase 1 | ||||
Sequence: SILFADIEGFTSLASQCTAQELVMTLNELFARFDKLAAENHCLRIKILGDCYYCVSGLPEARADHAHCCVEMGMDMIEAISLVREVTGVNVNMRVGIHSGRVHCGVLGLRKWQFDVWSNDVTLANHME | ||||||
Coiled coil | 1019-1045 | |||||
Sequence: WKLQATEEKEEMEELQAYNRRLLHNIL | ||||||
Domain | 1072-1211 | Guanylate cyclase 2 | ||||
Sequence: AVMFASIANFSEFYVELEANNEGVECLRLLNEIIADFDEIISEDRFRQLEKIKTIGSTYMAASGLNDSTYDKAGKTHIKAIADFAMKLMDQMKYINEHSFNNFQMKIGLNIGPVVAGVIGARKPQYDIWGNTVNVASRMD |
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.
Sequence similarities
Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P84309-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length1,262
- Mass (Da)139,122
- Last updated2007-01-09 v2
- Checksum342966E7CA67E28D
P84309-2
- Name2
- Differences from canonical
- 1259-1262: PPLS → LGHDGVVGKLKAGLGVSMELKGLLFHCGEVTPPHNVWGTGTGRRVACAILSPHLHAQRQCPVRETGLLTREARGHQARSSGSEQKKIFIK
Features
Showing features for sequence conflict, compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 25 | in Ref. 2; AAH90846 | ||||
Sequence: G → S | ||||||
Compositional bias | 50-71 | Polar residues | ||||
Sequence: TRGSTKRSGGAVTPQQQQRLAS | ||||||
Compositional bias | 104-118 | Basic and acidic residues | ||||
Sequence: WQERGGDDGGRGSRR | ||||||
Compositional bias | 156-172 | Basic and acidic residues | ||||
Sequence: SVELGLEERRGKGRAAE | ||||||
Sequence conflict | 686 | in Ref. 1; BAE28048 | ||||
Sequence: G → D | ||||||
Sequence conflict | 924 | in Ref. 2; AAH90846 | ||||
Sequence: V → M | ||||||
Alternative sequence | VSP_022224 | 1259-1262 | in isoform 2 | |||
Sequence: PPLS → LGHDGVVGKLKAGLGVSMELKGLLFHCGEVTPPHNVWGTGTGRRVACAILSPHLHAQRQCPVRETGLLTREARGHQARSSGSEQKKIFIK |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK147649 EMBL· GenBank· DDBJ | BAE28048.1 EMBL· GenBank· DDBJ | mRNA | ||
AK160942 EMBL· GenBank· DDBJ | BAE36104.1 EMBL· GenBank· DDBJ | mRNA | ||
BC035550 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
BC090846 EMBL· GenBank· DDBJ | AAH90846.1 EMBL· GenBank· DDBJ | mRNA |