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 6

Gene

ADCY6

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

Functioni

Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors (PubMed:1528892, PubMed:17110384). Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption. Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion. Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (By similarity). Signaling mediates cAMP-dependent activation of protein kinase PKA (By similarity). This promotes increased phosphorylation of various proteins, including AKT. Plays a role in regulating cardiac sarcoplasmic reticulum Ca2+ uptake and storage, and is required for normal heart ventricular contractibility. May contribute to normal heart function (By similarity). Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol (By similarity). Contributes to bone cell responses to mechanical stimuli (By similarity).By similarity2 Publications

Catalytic activityi

ATP = 3',5'-cyclic AMP + diphosphate.2 Publications

Cofactori

Mg2+By similarity, Mn2+1 PublicationNote: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).By similarity

Enzyme regulationi

Activated by forskolin. Inhibited by calcium ions, already at micromolar concentrations. Inhibited by adenosine, AMP and their analogs (PubMed:1528892). Activated by GNAS (PubMed:17110384). Is further activated by the complex formed by GNB1 and GNG2 (PubMed:17110384). Phosphorylation by RAF1 results in its activation (By similarity).By similarity2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi382 – 3821Magnesium 1; catalyticPROSITE-ProRule annotation
Metal bindingi382 – 3821Magnesium 2; catalyticPROSITE-ProRule annotation
Metal bindingi383 – 3831Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation
Metal bindingi426 – 4261Magnesium 1; catalyticPROSITE-ProRule annotation
Metal bindingi426 – 4261Magnesium 2; catalyticPROSITE-ProRule annotation
Binding sitei470 – 4701ATPBy similarity
Binding sitei1028 – 10281ATPBy similarity
Binding sitei1149 – 11491ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi382 – 3876ATPBy similarity
Nucleotide bindingi424 – 4263ATPBy similarity
Nucleotide bindingi1102 – 11043ATPBy similarity
Nucleotide bindingi1109 – 11135ATPBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

cAMP biosynthesis

Keywords - Ligandi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 6 (EC:4.6.1.12 Publications)
Alternative name(s):
ATP pyrophosphate-lyase 6
Adenylate cyclase type VI
Adenylyl cyclase 6
Ca(2+)-inhibitable adenylyl cyclase
Gene namesi
Name:ADCY6
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 149149CytoplasmicSequence analysisAdd
BLAST
Transmembranei150 – 16617HelicalSequence analysisAdd
BLAST
Transmembranei179 – 19517HelicalSequence analysisAdd
BLAST
Transmembranei212 – 22817HelicalSequence analysisAdd
BLAST
Transmembranei237 – 25317HelicalSequence analysisAdd
BLAST
Transmembranei257 – 27317HelicalSequence analysisAdd
BLAST
Transmembranei287 – 30317HelicalSequence analysisAdd
BLAST
Topological domaini304 – 670367CytoplasmicSequence analysisAdd
BLAST
Transmembranei671 – 68818HelicalSequence analysisAdd
BLAST
Transmembranei699 – 71517HelicalSequence analysisAdd
BLAST
Transmembranei740 – 75617HelicalSequence analysisAdd
BLAST
Topological domaini757 – 81660ExtracellularSequence analysisAdd
BLAST
Transmembranei817 – 83317HelicalSequence analysisAdd
BLAST
Transmembranei836 – 85217HelicalSequence analysisAdd
BLAST
Transmembranei894 – 91017HelicalSequence analysisAdd
BLAST
Topological domaini911 – 1165255CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11651165Adenylate cyclase type 6PRO_0000195698Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei53 – 531PhosphoserineBy similarity
Modified residuei553 – 5531PhosphoserineBy similarity
Modified residuei573 – 5731PhosphoserineBy similarity
Modified residuei659 – 6591PhosphoserineBy similarity
Glycosylationi790 – 7901N-linked (GlcNAc...)Sequence analysis
Glycosylationi875 – 8751N-linked (GlcNAc...)Sequence analysis
Modified residuei916 – 9161PhosphothreonineBy similarity

Post-translational modificationi

Phosphorylation by RAF1 increases enzyme activity. Phosphorylation by PKA on Ser-659 inhibits the GNAS-mediated increase in catalytic activity. Phosphorylation by PKC on Ser-553, Ser-659 and Thr-916 inhibits catalytic activity.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP30804.

Expressioni

Tissue specificityi

Detected in brain and heart.1 Publication

Interactioni

Subunit structurei

Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (By similarity). Interacts with RAF1. Interacts (via cytoplasmic N-terminus) with GNAS, GNB1 and GNG2 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000013079.

Structurei

3D structure databases

ProteinModelPortaliP30804.
SMRiP30804. Positions 362-550, 967-1142.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

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
Contains 2 guanylate cyclase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiP30804.

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]

Sequencei

Sequence statusi: Complete.

P30804-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSWFSGLLVP KVDERKTAWG ERNGQKRPRR GTRTSGFCTP RYMSCLRDAQ
60 70 80 90 100
PPSPTPAAPP RCPWQDEAFI RRGGPGKGTE LGLRAVALGF EDTEAMSAVG
110 120 130 140 150
AAGGGPDVTP GSRRSCWRRL AQVFQSKQFR SAKLERLYQR YFFQMNQSSL
160 170 180 190 200
TLLMAVLVLL TAVLLAFHAA PARPQPAYVA LLACAATLFV ALMVVCNRHS
210 220 230 240 250
FRQDSMWVVS YVVLGILAAV QVGGALAANP RSPSVGLWCP VFFVYITYTL
260 270 280 290 300
LPIRMRAAVF SGLGLSTLHL ILAWQLNRGD AFLWKQLGAN MLLFLCTNVI
310 320 330 340 350
GICTHYPAEV SQRQAFQETR GYIQARLHLP DENRQQERLL LSVLPQHVAM
360 370 380 390 400
EMKEDINTKK EDMMFHKIYI QKHDNVSILF ADIEGFTSLA SQCTAQELVM
410 420 430 440 450
TLNELFARFD KLAAENHCLR IKILGDCYYC VSGLPEARAD HAHCCVEMGV
460 470 480 490 500
DMIEAISLVR EVTGVNVNMR VGIHSGRVHC GVLGLRKWQF DVWSNDVTLA
510 520 530 540 550
NHMEAARAGR IHITRATLQY LNGDYEVEPG RGGERNAYLK EQHIETFLIL
560 570 580 590 600
GASQKRKEEK AMLAKLQRTR ANSMEGLMPR WVPDRAFSRT KDSKAFRQMG
610 620 630 640 650
IDDSSKDNRG AQDALNPEDE VDEFLGRAID ARSIDQLRKD HVRRFLLTFQ
660 670 680 690 700
REDLEKKYSR KVDPRFGAYV ACALLVFCFI CFIQLLVFPH STVMLGIYAS
710 720 730 740 750
IFVLLLITVL TCAVYSCGSL FPKALRRLSR SIVRSRAHST VVGIFSVLLV
760 770 780 790 800
FTSAIANMFT CNHTPIRTCA ARMLNVTPAD ITACHLQQLN YSLGLDAPLC
810 820 830 840 850
EGTAPTCSFP EYFVGNMLLS LLASSVFLHI SSIGKLAMIF VLGLIYLVLL
860 870 880 890 900
LLGPPSTIFD NYDLLLGVHG LASSNDTFDG LDCPAAGRVA LKYMTPVILL
910 920 930 940 950
VFALALYLHA QQVESTARLD FLWKLQATGE KEEMEELQAY NRRLLHNILP
960 970 980 990 1000
KDVAAHFLAR ERRNDELYYQ SCECVAVMFA SIANFSEFYV ELEANNEGVE
1010 1020 1030 1040 1050
CLRLLNEIIA DFDEIISEER FRQLEKIKTI GSTYMAASGL NASTYDQAGR
1060 1070 1080 1090 1100
SHITALADYA MRLMEQMKHI NEHSFNNFQM KIGLNMGPVV AGVIGARKPQ
1110 1120 1130 1140 1150
YDIWGNTVNV SSRMDSTGVP DRIQVTTDLY QVLAAKRYQL ECRGVVKVKG
1160
KGEMTTYFLN GGPPS
Length:1,165
Mass (Da):130,324
Last modified:July 1, 1993 - v1
Checksum:iBA9D2D329120615E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94968 mRNA. No translation available.
PIRiA46180.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94968 mRNA. No translation available.
PIRiA46180.

3D structure databases

ProteinModelPortaliP30804.
SMRiP30804. Positions 362-550, 967-1142.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000013079.

Proteomic databases

PaxDbiP30804.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiP30804.

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...

Publicationsi

  1. "Cloning and characterization of a sixth adenylyl cyclase isoform: types V and VI constitute a subgroup within the mammalian adenylyl cyclase family."
    Katsushika S., Chen L., Kawabe J., Nilakantan R., Halnon N.J., Homcy C.J., Ishikawa Y.
    Proc. Natl. Acad. Sci. U.S.A. 89:8774-8778(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, COFACTOR, ENZYME REGULATION, TISSUE SPECIFICITY.
    Tissue: Heart.
  2. "Conditional stimulation of type V and VI adenylyl cyclases by G protein betagamma subunits."
    Gao X., Sadana R., Dessauer C.W., Patel T.B.
    J. Biol. Chem. 282:294-302(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiADCY6_CANLF
AccessioniPrimary (citable) accession number: P30804
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: December 9, 2015
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.