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Protein

Adenylate cyclase type 5

Gene

ADCY5

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 Ca2+ in response to increased blood glucose levels and contributes to the regulation of Ca2+-dependent insulin secretion (By similarity).By similarity7 Publications
Isoform 2: Lacks catalytic activity by itself, but can associate with isoform 1 to form active adenylyl cyclase.1 Publication

Catalytic activityi

ATP = 3',5'-cyclic AMP + diphosphate.7 Publications

Cofactori

Mg2+3 Publications, Mn2+2 PublicationsNote: Binds 2 magnesium ions per subunit (PubMed:16766715, PubMed:19243146). Is also active with manganese (in vitro) (PubMed:11087399, PubMed:16766715).1 Publication3 Publications

Enzyme regulationi

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).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi477Magnesium 1; catalyticCombined sources1 Publication1
Metal bindingi477Magnesium 2; catalytic1 Publication1
Metal bindingi478Magnesium 2; via carbonyl oxygen; catalytic1 Publication1
Metal bindingi521Magnesium 1; catalyticCombined sources1 Publication1
Metal bindingi521Magnesium 2; catalytic1 Publication1
Binding sitei565ATP4 Publications1
Binding sitei1127ATPBy similarity1
Binding sitei1248ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi477 – 482ATP4 Publications6
Nucleotide bindingi519 – 521ATP4 Publications3
Nucleotide bindingi1201 – 1203ATPBy similarity3
Nucleotide bindingi1208 – 1212ATPBy similarity5

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

cAMP biosynthesis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-CFA-418555. G alpha (s) signalling events.
R-CFA-418594. G alpha (i) signalling events.
R-CFA-418597. G alpha (z) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 5 (EC:4.6.1.17 Publications)
Alternative name(s):
ATP pyrophosphate-lyase 5
Adenylate cyclase type V
Adenylyl cyclase 5
Ca(2+)-inhibitable adenylyl cyclase
Gene namesi
Name:ADCY5
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

Subcellular locationi

  • Cell membrane 2 Publications; Multi-pass membrane protein Curated
  • Cell projectioncilium By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 244CytoplasmicSequence analysisAdd BLAST244
Transmembranei245 – 265HelicalSequence analysisAdd BLAST21
Transmembranei271 – 291HelicalSequence analysisAdd BLAST21
Transmembranei302 – 322HelicalSequence analysisAdd BLAST21
Transmembranei328 – 348HelicalSequence analysisAdd BLAST21
Transmembranei352 – 372HelicalSequence analysisAdd BLAST21
Transmembranei377 – 397HelicalSequence analysisAdd BLAST21
Topological domaini398 – 765CytoplasmicSequence analysisCuratedAdd BLAST368
Transmembranei766 – 786HelicalSequence analysisAdd BLAST21
Transmembranei792 – 812HelicalSequence analysisAdd BLAST21
Transmembranei839 – 859HelicalSequence analysisAdd BLAST21
Transmembranei908 – 928HelicalSequence analysisAdd BLAST21
Transmembranei930 – 950HelicalSequence analysisAdd BLAST21
Transmembranei988 – 1008HelicalSequence analysisAdd BLAST21
Topological domaini1009 – 1265CytoplasmicSequence analysisCuratedAdd BLAST257

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi477D → A or N: Almost abolishes enzyme activity. Abolishes enzyme activity; when associated with A-521 or N-521. 1 Publication1
Mutagenesisi521D → A or N: Almost abolishes enzyme activity. Abolishes enzyme activity; when associated with A-396 or N-396. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001956931 – 1265Adenylate cyclase type 5Add BLAST1265

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei16Omega-N-methylarginineBy similarity1
Modified residuei113PhosphoserineBy similarity1
Modified residuei168PhosphoserineBy similarity1
Modified residuei669PhosphoserineBy similarity1
Modified residuei757PhosphoserineBy similarity1
Glycosylationi873N-linked (GlcNAc...)Sequence analysis1
Glycosylationi890N-linked (GlcNAc...)Sequence analysis1
Glycosylationi976N-linked (GlcNAc...)Sequence analysis1
Modified residuei1015PhosphothreonineBy similarity1

Keywords - PTMi

Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

PaxDbiP30803.

Expressioni

Tissue specificityi

Isoform 1 is detected in heart, and at lower levels in brain (PubMed:1618857). Isoform 2 is detected in heart (PubMed:8428899).2 Publications

Interactioni

Subunit structurei

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).By similarity6 Publications

Protein-protein interaction databases

DIPiDIP-179N.
IntActiP30803. 1 interactor.
STRINGi9615.ENSCAFP00000017783.

Structurei

Secondary structure

11265
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi464 – 479Combined sources16
Helixi481 – 487Combined sources7
Helixi490 – 511Combined sources22
Beta strandi514 – 519Combined sources6
Beta strandi522 – 527Combined sources6
Helixi536 – 558Combined sources23
Beta strandi563 – 577Combined sources15
Beta strandi579 – 582Combined sources4
Beta strandi586 – 589Combined sources4
Helixi590 – 600Combined sources11
Beta strandi603 – 605Combined sources3
Beta strandi606 – 609Combined sources4
Turni612 – 619Combined sources8
Beta strandi623 – 625Combined sources3
Helixi628 – 630Combined sources3
Helixi633 – 637Combined sources5
Beta strandi643 – 645Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AZSX-ray2.30A442-656[»]
1CJKX-ray3.00A445-661[»]
1CJTX-ray2.80A445-661[»]
1CJUX-ray2.80A445-661[»]
1CJVX-ray3.00A445-661[»]
1CS4X-ray2.50A442-661[»]
1CULX-ray2.40A445-661[»]
1TL7X-ray2.80A445-661[»]
1U0HX-ray2.90A442-661[»]
2GVDX-ray2.90A444-661[»]
2GVZX-ray3.27A444-661[»]
3C14X-ray2.68A444-661[»]
3C15X-ray2.78A444-661[»]
3C16X-ray2.87A444-661[»]
3G82X-ray3.11A444-661[»]
3MAAX-ray3.00A444-661[»]
ProteinModelPortaliP30803.
SMRiP30803.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30803.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini472 – 599Guanylate cyclase 1PROSITE-ProRule annotationAdd BLAST128
Domaini1075 – 1214Guanylate cyclase 2PROSITE-ProRule annotationAdd BLAST140

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.5 Publications

Sequence similaritiesi

Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation
Contains 2 guanylate cyclase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiP30803.
KOiK08045.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR032628. AC_N.
IPR030672. Adcy.
IPR009398. Adcy_conserved_dom.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF16214. AC_N. 1 hit.
PF06327. DUF1053. 1 hit.
PF00211. Guanylate_cyc. 2 hits.
[Graphical view]
PIRSFiPIRSF039050. Ade_cyc. 1 hit.
SMARTiSM00044. CYCc. 2 hits.
[Graphical view]
SUPFAMiSSF55073. SSF55073. 2 hits.
PROSITEiPS00452. GUANYLATE_CYCLASE_1. 2 hits.
PS50125. GUANYLATE_CYCLASE_2. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P30803-1) [UniParc]FASTAAdd to basket
Also known as: V

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
MSGPRSASPP GCAATRGGPE HRAAWGEAEA RANGHPHAAG GATRGCSKKP
60 70 80 90 100
GGAVTPQLQQ QQQQQQHEQQ HEQQQHEQQQ HVQQQQRLAK RWRGDDDPPL
110 120 130 140 150
GGDDPLAGGF GFSFRSRSAW QERGGDDCGR GSRRRRRGAA GGGSSRAPPA
160 170 180 190 200
GGGGGPAAAG GAEVRPRSVE LGLDERRGRG RAEPEPEAEA GAPGGDRGAR
210 220 230 240 250
DGDGPAGPGA CCRALLQIFR SKKFPSDKLE RLYQRYFFRL NQSSLTMLMA
260 270 280 290 300
VLVLVCLVML AFHAARPPLR LPHLAVLAAA VGVILVMAVL CNRAAFHQDH
310 320 330 340 350
MGLACYALIA VVLAVQVVGL LLPQPRSASE GIWWTVFFIY TIYTLLPVRM
360 370 380 390 400
RAAVLSGVLL SALHLAIALR ANAQDRFLLK QLVSNVLIFS CTNIVGVCTH
410 420 430 440 450
YPAEVSQRQA FQETRECIQA RLHSQRENQQ QERLLLSVLP RHVAMEMKAD
460 470 480 490 500
INAKQEDMMF HKIYIQKHDN VSILFADIEG FTSLASQCTA QELVMTLNEL
510 520 530 540 550
FARFDKLAAE NHCLRIKILG DCYYCVSGLP EARADHAHCC VEMGMDMIEA
560 570 580 590 600
ISLVREVTGV NVNMRVGIHS GRVHCGVLGL RKWQFDVWSN DVTLANHMEA
610 620 630 640 650
GGKAGRIHIT KATLSYLNGD YEVEPGCGGE RNAYLKEHSI ETFLILRCTQ
660 670 680 690 700
KRKEEKAMIA KMNRQRTNSI GHNPPHWGAE RPFYNHLGGN QVSKEMKRMG
710 720 730 740 750
FEDPKDKNAQ ESANPEDEVD EFLGRAIDAR SIDRLRSEHV RKFLLTFREP
760 770 780 790 800
DLEKKYSKQV DDRFGAYVAC ASLVFLFICF VQITIVPHSV FMLSFYLTCF
810 820 830 840 850
LLLTLVVFVS VIYSCVKLFP GPLQSLSRKI VRSKTNSTLV GVFTITLVFL
860 870 880 890 900
SAFVNMFMCN SEDLLGCLAD EHNISTSRVN ACHVAASAAN LSLGDEQGFC
910 920 930 940 950
GTPWPSCNFP EYFTYSVLLS LLACSVFLQI SCIGKLVLML AIELIYVLVV
960 970 980 990 1000
EVPRVTLFDN ADLLVTANAI DFNNNNGTSQ CPEHATKVAL KVVTPIIISV
1010 1020 1030 1040 1050
FVLALYLHAQ QVESTARLDF LWKLQATEEK EEMEELQAYN RRLLHNILPK
1060 1070 1080 1090 1100
DVAAHFLARE RRNDELYYQS CECVAVMFAS IANFSEFYVE LEANNEGVEC
1110 1120 1130 1140 1150
LRVLNEIIAD FDEIISEDRF RQLEKIKTIG STYMAASGLN DSTYDKVGKT
1160 1170 1180 1190 1200
HIKALADFAM KLMDQMKYIN EHSFNNFQMK IGLNIGPVVA GVIGARKPQY
1210 1220 1230 1240 1250
DIWGNTVNVA SRMDSTGVPD RIQVTTDMYQ VLAANTYQLE CRGVVKVKGK
1260
GEMMTYFLNG GPPLS
Length:1,265
Mass (Da):140,319
Last modified:May 30, 2000 - v2
Checksum:i414322F64153DFB4
GO
Isoform 2 (identifier: P30803-2) [UniParc]FASTAAdd to basket
Also known as: V-alpha

The sequence of this isoform differs from the canonical sequence as follows:
     653-677: KEEKAMIAKMNRQRTNSIGHNPPHW → VRRGGGGPRPGGADSPGWWGASAGP
     678-1265: Missing.

Show »
Length:677
Mass (Da):73,690
Checksum:iAAB94BCFEBE08CC0
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000242653 – 677KEEKA…NPPHW → VRRGGGGPRPGGADSPGWWG ASAGP in isoform 2. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_000243678 – 1265Missing in isoform 2. 1 PublicationAdd BLAST588

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M88649 mRNA. Translation: AAC32726.1.
M97886 mRNA. Translation: AAA30827.1. Sequence problems.
PIRiA42904.
A45195.
RefSeqiNP_001161932.1. NM_001168460.1. [P30803-1]
UniGeneiCfa.1267.

Genome annotation databases

GeneIDi403859.
KEGGicfa:403859.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M88649 mRNA. Translation: AAC32726.1.
M97886 mRNA. Translation: AAA30827.1. Sequence problems.
PIRiA42904.
A45195.
RefSeqiNP_001161932.1. NM_001168460.1. [P30803-1]
UniGeneiCfa.1267.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AZSX-ray2.30A442-656[»]
1CJKX-ray3.00A445-661[»]
1CJTX-ray2.80A445-661[»]
1CJUX-ray2.80A445-661[»]
1CJVX-ray3.00A445-661[»]
1CS4X-ray2.50A442-661[»]
1CULX-ray2.40A445-661[»]
1TL7X-ray2.80A445-661[»]
1U0HX-ray2.90A442-661[»]
2GVDX-ray2.90A444-661[»]
2GVZX-ray3.27A444-661[»]
3C14X-ray2.68A444-661[»]
3C15X-ray2.78A444-661[»]
3C16X-ray2.87A444-661[»]
3G82X-ray3.11A444-661[»]
3MAAX-ray3.00A444-661[»]
ProteinModelPortaliP30803.
SMRiP30803.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-179N.
IntActiP30803. 1 interactor.
STRINGi9615.ENSCAFP00000017783.

Proteomic databases

PaxDbiP30803.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi403859.
KEGGicfa:403859.

Organism-specific databases

CTDi111.

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiP30803.
KOiK08045.

Enzyme and pathway databases

ReactomeiR-CFA-418555. G alpha (s) signalling events.
R-CFA-418594. G alpha (i) signalling events.
R-CFA-418597. G alpha (z) signalling events.

Miscellaneous databases

EvolutionaryTraceiP30803.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR032628. AC_N.
IPR030672. Adcy.
IPR009398. Adcy_conserved_dom.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF16214. AC_N. 1 hit.
PF06327. DUF1053. 1 hit.
PF00211. Guanylate_cyc. 2 hits.
[Graphical view]
PIRSFiPIRSF039050. Ade_cyc. 1 hit.
SMARTiSM00044. CYCc. 2 hits.
[Graphical view]
SUPFAMiSSF55073. SSF55073. 2 hits.
PROSITEiPS00452. GUANYLATE_CYCLASE_1. 2 hits.
PS50125. GUANYLATE_CYCLASE_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiADCY5_CANLF
AccessioniPrimary (citable) accession number: P30803
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: May 30, 2000
Last modified: November 30, 2016
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.