Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Adenylate cyclase type 5

Gene

Adcy5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity

Catalytic activityi

ATP = 3',5'-cyclic AMP + diphosphate.By similarity

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).By similarity

Enzyme regulationi

Activated by forskolin. 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 (By similarity). Phosphorylation by RAF1 results in its activation (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi475Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi475Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi476Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi519Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi519Magnesium 2; catalyticPROSITE-ProRule annotation1
Binding sitei563ATPBy similarity1
Binding sitei1124ATPBy similarity1
Binding sitei1245ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi475 – 480ATPBy similarity6
Nucleotide bindingi517 – 519ATPBy similarity3
Nucleotide bindingi1198 – 1200ATPBy similarity3
Nucleotide bindingi1205 – 1209ATPBy similarity5

GO - Molecular functioni

  • adenylate cyclase activity Source: MGI
  • adenylate cyclase binding Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • calcium- and calmodulin-responsive adenylate cyclase activity Source: MGI
  • guanylate cyclase activity Source: GO_Central
  • metal ion binding Source: UniProtKB-KW
  • protein heterodimerization activity Source: BHF-UCL
  • scaffold protein binding Source: MGI

GO - Biological processi

  • adenosine receptor signaling pathway Source: MGI
  • adenylate cyclase-activating dopamine receptor signaling pathway Source: MGI
  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: MGI
  • adenylate cyclase-inhibiting dopamine receptor signaling pathway Source: MGI
  • cAMP biosynthetic process Source: MGI
  • cellular response to forskolin Source: UniProtKB
  • cGMP biosynthetic process Source: GO_Central
  • locomotory behavior Source: MGI
  • neuromuscular process controlling balance Source: MGI
  • positive regulation of cytosolic calcium ion concentration Source: UniProtKB
  • regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB

Keywordsi

Molecular functionLyase
Biological processcAMP biosynthesis
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi4.6.1.1 3474
ReactomeiR-MMU-163359 Glucagon signaling in metabolic regulation
R-MMU-163615 PKA activation
R-MMU-164378 PKA activation in glucagon signalling
R-MMU-170660 Adenylate cyclase activating pathway
R-MMU-170670 Adenylate cyclase inhibitory pathway
R-MMU-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-MMU-400042 Adrenaline,noradrenaline inhibits insulin secretion
R-MMU-418555 G alpha (s) signalling events
R-MMU-418597 G alpha (z) signalling events
R-MMU-432040 Vasopressin regulates renal water homeostasis via Aquaporins
R-MMU-5610787 Hedgehog 'off' state

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 5 (EC:4.6.1.1By similarity)
Alternative name(s):
ATP pyrophosphate-lyase 5
Adenylate cyclase type V
Adenylyl cyclase 5
Gene namesi
Name:Adcy5Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:99673 Adcy5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 196CytoplasmicSequence analysisAdd BLAST196
Transmembranei197 – 217HelicalSequence analysisAdd BLAST21
Transmembranei243 – 263HelicalSequence analysisAdd BLAST21
Transmembranei269 – 289HelicalSequence analysisAdd BLAST21
Transmembranei300 – 320HelicalSequence analysisAdd BLAST21
Transmembranei326 – 346HelicalSequence analysisAdd BLAST21
Transmembranei375 – 395HelicalSequence analysisAdd BLAST21
Topological domaini396 – 763CytoplasmicSequence analysisAdd BLAST368
Transmembranei764 – 784HelicalSequence analysisAdd BLAST21
Transmembranei790 – 810HelicalSequence analysisAdd BLAST21
Transmembranei837 – 857HelicalSequence analysisAdd BLAST21
Topological domaini858 – 910ExtracellularSequence analysisAdd BLAST53
Transmembranei911 – 931HelicalSequence analysisAdd BLAST21
Transmembranei936 – 956HelicalSequence analysisAdd BLAST21
Transmembranei985 – 1005HelicalSequence analysisAdd BLAST21
Topological domaini1006 – 1262CytoplasmicSequence analysisAdd BLAST257

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001956951 – 1262Adenylate cyclase type 5Add BLAST1262

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei23Omega-N-methylarginineCombined sources1
Modified residuei97PhosphoserineCombined sources1
Modified residuei156PhosphoserineCombined sources1
Glycosylationi239N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei667PhosphoserineBy similarity1
Modified residuei755PhosphoserineBy similarity1
Glycosylationi834N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi871N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi888N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi973N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1012PhosphothreonineBy similarity1

Post-translational modificationi

Phosphorylated by RAF1.By similarity

Keywords - PTMi

Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

MaxQBiP84309
PaxDbiP84309
PeptideAtlasiP84309
PRIDEiP84309

PTM databases

iPTMnetiP84309
PhosphoSitePlusiP84309

Expressioni

Gene expression databases

BgeeiENSMUSG00000022840
CleanExiMM_ADCY5
GenevisibleiP84309 MM

Interactioni

Subunit structurei

Interacts with GNAS, GNB1 and GNG2 (By similarity). Part of a complex containing AKAP5, ADCY6, PDE4C and PKD2 (PubMed:21670265). Interacts with RAF1 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • adenylate cyclase binding Source: BHF-UCL
  • protein heterodimerization activity Source: BHF-UCL
  • scaffold protein binding Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000110563

Structurei

3D structure databases

ProteinModelPortaliP84309
SMRiP84309
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini470 – 597Guanylate cyclase 1PROSITE-ProRule annotationAdd BLAST128
Domaini1072 – 1211Guanylate cyclase 2PROSITE-ProRule annotationAdd BLAST140

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1019 – 1045Sequence analysisAdd BLAST27

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi64 – 67Poly-Gln4
Compositional biasi141 – 147Poly-Ala7

Domaini

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.By similarity

Sequence similaritiesi

Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3619 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00760000119042
HOGENOMiHOG000006941
HOVERGENiHBG050458
InParanoidiP84309
KOiK08045
OMAiVRSKMNS
OrthoDBiEOG091G05JR
PhylomeDBiP84309
TreeFamiTF313845

Family and domain databases

Gene3Di3.30.70.1230, 2 hits
InterProiView protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR032628 AC_N
IPR030672 Adcy
IPR009398 Adcy_conserved_dom
IPR029787 Nucleotide_cyclase
PfamiView protein in Pfam
PF16214 AC_N, 1 hit
PF06327 DUF1053, 1 hit
PF00211 Guanylate_cyc, 2 hits
PIRSFiPIRSF039050 Ade_cyc, 1 hit
SMARTiView protein in SMART
SM00044 CYCc, 2 hits
SUPFAMiSSF55073 SSF55073, 2 hits
PROSITEiView protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 2 hits
PS50125 GUANYLATE_CYCLASE_2, 2 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P84309-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSGSKSVSPP GYAAQTAASP APRGGPEHRA AWGEADSRAN GYPHAPGGST
60 70 80 90 100
RGSTKRSGGA VTPQQQQRLA SRWRGGDDDE DPPLSGDDPL AGGFGFSFRS
110 120 130 140 150
KSAWQERGGD DGGRGSRRQR RGAAGGGSTR APPAGGSGSS AAAAAAAGGT
160 170 180 190 200
EVRPRSVELG LEERRGKGRA AEELEPGTGI VEDGDGSEDG GSSVASGSGT
210 220 230 240 250
GAVLSLGACC LALLQIFRSK KFPSDKLERL YQRYFFRLNQ SSLTMLMAVL
260 270 280 290 300
VLVCLVMLAF HAARPPLQIA YLAVLAAAVG VILIMAVLCN RAAFHQDHMG
310 320 330 340 350
LACYALIAVV LAVQVVGLLL PQPRSASEGI WWTVFFIYTI YTLLPVRMRA
360 370 380 390 400
AVLSGVLLSA LHLAISLHTN SQDQFLLKQL VSNVLIFSCT NIVGVCTHYP
410 420 430 440 450
AEVSQRQAFQ ETRECIQARL HSQRENQQQE RLLLSVLPRH VAMEMKADIN
460 470 480 490 500
AKQEDMMFHK IYIQKHDNVS ILFADIEGFT SLASQCTAQE LVMTLNELFA
510 520 530 540 550
RFDKLAAENH CLRIKILGDC YYCVSGLPEA RADHAHCCVE MGMDMIEAIS
560 570 580 590 600
LVREVTGVNV NMRVGIHSGR VHCGVLGLRK WQFDVWSNDV TLANHMEAGG
610 620 630 640 650
KAGRIHITKA TLNYLNGDYE VEPGCGGDRN AYLKEHSIET FLILSCTQKR
660 670 680 690 700
KEEKAMIAKM NRQRTNSIGH NPPHWGAERP FYNHLGGNQV SKEMKRMGFE
710 720 730 740 750
DPKDKNAQES ANPEDEVDEF LGRAIDARSI DRLRSEHVRK FLLTFREPDL
760 770 780 790 800
EKKYSKQVDD RFGAYVACAS LVFLFICFVQ ITIVPHSLFM LSFYLSCFLL
810 820 830 840 850
LALVVFVSVI YACVKLFPTP LQTLSRKIVR SKKNSTLVGV FTITLVFLSA
860 870 880 890 900
FVNMFMCNSK NLVGCLAEEH NITVNQVNAC HVMESAFNYS LGDEQGFCGS
910 920 930 940 950
PQPNCNFPEY FTYSVLLSLL ACSVFLQISC IGKLVLMLAI EFIYVLIVEV
960 970 980 990 1000
PGVTLFDNAD LLVTANAIDF SNNGTSQCPE HATKVALKVV TPIIISVFVL
1010 1020 1030 1040 1050
ALYLHAQQVE STARLDFLWK LQATEEKEEM EELQAYNRRL LHNILPKDVA
1060 1070 1080 1090 1100
AHFLARERRN DELYYQSCEC VAVMFASIAN FSEFYVELEA NNEGVECLRL
1110 1120 1130 1140 1150
LNEIIADFDE IISEDRFRQL EKIKTIGSTY MAASGLNDST YDKAGKTHIK
1160 1170 1180 1190 1200
AIADFAMKLM DQMKYINEHS FNNFQMKIGL NIGPVVAGVI GARKPQYDIW
1210 1220 1230 1240 1250
GNTVNVASRM DSTGVPDRIQ VTTDMYQVLA ANTYQLECRG VVKVKGKGEM
1260
MTYFLNGGPP LS
Length:1,262
Mass (Da):139,122
Last modified:January 9, 2007 - v2
Checksum:i342966E7CA67E28D
GO
Isoform 2 (identifier: P84309-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1259-1262: PPLS → LGHDGVVGKL...GSEQKKIFIK

Note: No experimental confirmation available.
Show »
Length:1,348
Mass (Da):148,383
Checksum:iB4997E3A2BC14305
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25G → S in AAH90846 (PubMed:15489334).Curated1
Sequence conflicti686G → D in BAE28048 (PubMed:16141072).Curated1
Sequence conflicti924V → M in AAH90846 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0222241259 – 1262PPLS → LGHDGVVGKLKAGLGVSMEL KGLLFHCGEVTPPHNVWGTG TGRRVACAILSPHLHAQRQC PVRETGLLTREARGHQARSS GSEQKKIFIK in isoform 2. 1 Publication4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK147649 mRNA Translation: BAE28048.1
AK160942 mRNA Translation: BAE36104.1
BC035550 mRNA No translation available.
BC090846 mRNA Translation: AAH90846.1
CCDSiCCDS37322.1 [P84309-1]
RefSeqiNP_001012783.3, NM_001012765.4 [P84309-1]
UniGeneiMm.41137

Genome annotation databases

EnsembliENSMUST00000114913; ENSMUSP00000110563; ENSMUSG00000022840 [P84309-1]
GeneIDi224129
KEGGimmu:224129
UCSCiuc007zbj.1 mouse [P84309-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiADCY5_MOUSE
AccessioniPrimary (citable) accession number: P84309
Secondary accession number(s): Q3TU67, Q3UH09, Q5BL06
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: January 9, 2007
Last modified: June 20, 2018
This is version 129 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health