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Protein

Adenylate cyclase type 6

Gene

Adcy6

Organism
Rattus norvegicus (Rat)
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:1409703, PubMed:15385642, PubMed:17110384, PubMed:21606183). Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells (PubMed:21606183). 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 (PubMed:21606183). 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 similarity4 Publications

Catalytic activityi

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

Cofactori

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

Enzyme regulationi

Activated by forskolin (PubMed:9391159). Inhibited by calcium ions, already at micromolar concentrations (By similarity). Inhibited by adenosine, AMP and their analogs (By similarity). Activated by GNAS (PubMed:9391159, PubMed:17110384). Is further activated by the complex formed by GNB1 and GNG2 (PubMed:17110384). Phosphorylation by RAF1 results in its activation (PubMed:15385642).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi382Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi382Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi383Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi426Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi426Magnesium 2; catalyticPROSITE-ProRule annotation1
Binding sitei470ATPBy similarity1
Binding sitei1029ATPBy similarity1
Binding sitei1150ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi382 – 387ATPBy similarity6
Nucleotide bindingi424 – 426ATPBy similarity3
Nucleotide bindingi1103 – 1105ATPBy similarity3
Nucleotide bindingi1110 – 1114ATPBy similarity5

GO - Molecular functioni

  • adenylate cyclase activity Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • calcium- and calmodulin-responsive adenylate cyclase activity Source: RGD
  • metal ion binding Source: UniProtKB-KW
  • protein kinase binding Source: BHF-UCL
  • receptor binding Source: RGD
  • SNARE binding Source: ParkinsonsUK-UCL

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:4.6.1.15 Publications)
Alternative name(s):
ATP pyrophosphate-lyase 6
Adenylate cyclase type VI
Short name:
ACVI
Adenylyl cyclase 6
Short name:
AC61 Publication
Ca(2+)-inhibitable adenylyl cyclase
Gene namesi
Name:Adcy6
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2035. Adcy6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 149CytoplasmicSequence analysisAdd BLAST149
Transmembranei150 – 166HelicalSequence analysisAdd BLAST17
Transmembranei179 – 195HelicalSequence analysisAdd BLAST17
Transmembranei212 – 228HelicalSequence analysisAdd BLAST17
Transmembranei237 – 253HelicalSequence analysisAdd BLAST17
Transmembranei257 – 273HelicalSequence analysisAdd BLAST17
Transmembranei287 – 303HelicalSequence analysisAdd BLAST17
Topological domaini304 – 671CytoplasmicSequence analysisAdd BLAST368
Transmembranei672 – 689HelicalSequence analysisAdd BLAST18
Transmembranei700 – 716HelicalSequence analysisAdd BLAST17
Transmembranei741 – 757HelicalSequence analysisAdd BLAST17
Topological domaini758 – 817ExtracellularSequence analysisAdd BLAST60
Transmembranei818 – 834HelicalSequence analysisAdd BLAST17
Transmembranei837 – 853HelicalSequence analysisAdd BLAST17
Transmembranei895 – 911HelicalSequence analysisAdd BLAST17
Topological domaini912 – 1166CytoplasmicSequence analysisAdd BLAST255

GO - Cellular componenti

  • cilium Source: UniProtKB-SubCell
  • endosome Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • intrinsic component of plasma membrane Source: UniProtKB
  • membrane Source: BHF-UCL
  • membrane raft Source: RGD
  • microvillus membrane Source: RGD
  • plasma membrane Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi311S → A: No effect on phosphorylation by PKC. 1 Publication1
Mutagenesisi554S → A: Reduces phosphorylation by PKC and PKC-mediated inhibition. 1 Publication1
Mutagenesisi660S → A: Abolishes phosphorylation by PKA and PKA-mediated down-regulation of enzyme activity. 1 Publication1
Mutagenesisi660S → A: Reduces phosphorylation by PKC and PKC-mediated inhibition. 1 Publication1
Mutagenesisi917T → A: Reduces phosphorylation by PKC, abolishes PKC-mediated inhibition. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2095179.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001957011 – 1166Adenylate cyclase type 6Add BLAST1166

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei53PhosphoserineCombined sources1
Modified residuei85PhosphoserineBy similarity1
Modified residuei554Phosphoserine; by PKC; in vitro1 Publication1
Modified residuei574PhosphoserineCombined sources1
Modified residuei660Phosphoserine; by PKA; in vitro1 Publication1
Modified residuei660Phosphoserine; by PKC; in vitro1 Publication1
Glycosylationi791N-linked (GlcNAc...)Sequence analysis1
Glycosylationi876N-linked (GlcNAc...)Sequence analysis1
Modified residuei917Phosphothreonine; by PKC; in vitro1 Publication1

Post-translational modificationi

Phosphorylation by RAF1 increases enzyme activity (PubMed:15385642). Phosphorylation by PKA on Ser-660 inhibits the GNAS-mediated increase in catalytic activity (PubMed:9391159). Phosphorylation by PKC on Ser-554, Ser-660 and Thr-917 inhibits catalytic activity (PubMed:11877398).3 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ03343.
PRIDEiQ03343.

PTM databases

iPTMnetiQ03343.
PhosphoSitePlusiQ03343.
SwissPalmiQ03343.

Expressioni

Tissue specificityi

Detected in brain and kidney (PubMed:1409703). Detected in vascular smooth muscle cells (PubMed:21606183).2 Publications

Interactioni

Subunit structurei

Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (By similarity). Interacts with RAF1 (PubMed:15385642). Interacts (via cytoplasmic N-terminus) with GNAS, GNB1 and GNG2 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • protein kinase binding Source: BHF-UCL
  • receptor binding Source: RGD
  • SNARE binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

IntActiQ03343. 2 interactors.
STRINGi10116.ENSRNOP00000016624.

Structurei

3D structure databases

ProteinModelPortaliQ03343.
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.
InParanoidiQ03343.
KOiK08046.
PhylomeDBiQ03343.

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.

Q03343-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSWFSGLLVP KVDERKTAWG ERNGQKRPRQ ATRARGFCAP RYMSCLKNVE
60 70 80 90 100
PPSPTPAART RCPWQDEAFI RRAGPGRGVK LGLRSVALGF DDTEVTTPMG
110 120 130 140 150
TAEVAPDTSP RSGPSCWHRL AQVFQSKQFR SAKLERLYQR YFFQMNQSSL
160 170 180 190 200
TLLMAVLVLL MAVLLTFHAA PALPQPAYVA LLTCASVLFV VLMVVCNRHS
210 220 230 240 250
FRQDSMWVVS YVVLGILAAV QVGGALAANP RSPSAGLWCP VFFVYITYTL
260 270 280 290 300
LPIRMRAAVL SGLGLSTLHL ILAWHLNNGD PFLWKQLGAN VVLFLCTNAI
310 320 330 340 350
GVCTHYPAEV SQRQAFQETR GYIQARLHLQ HENRQQERLL 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
NHMEAGGRAG RIHITRATLQ YLNGDYEVEP GRGGERNGYL KEQCIETFLI
560 570 580 590 600
LGASQKRKEE KAMLVKLQRT RANSMEGLMP RWVPDRAFSR TKDSKAFRQM
610 620 630 640 650
GIDDSSKENR GAQDALNPED EVDEFLGRAI DARSIDQLRK DHVRRFLLTF
660 670 680 690 700
QREDLEKKYS RKVDPRFGAY VACALLVFCF ICFIQFLVFP HSALILGIYA
710 720 730 740 750
GIFLLLLVTV LICAVCSCGS FFPNALQRLS RSIVRSRVHS TAVGVFSVLL
760 770 780 790 800
VFISAIANMF TCSHTPLRTC AARMLNLTPS DVTACHLRQI NYSLGLEAPL
810 820 830 840 850
CEGTAPTCSF PEYFVGSVLL SLLASSVFLH ISSIGKLVMT FVLGFIYLLL
860 870 880 890 900
LLLGPPATIF DNYDLLLSVH GLASSNETFD GLDCPAVGRV ALKYMTPVIL
910 920 930 940 950
LVFALALYLH AQQVESTARL DFLWKLQATG EKEEMEELQA YNRRLLHNIL
960 970 980 990 1000
PKDVAAHFLA RERRNDELYY QSCECVAVMF ASIANFSEFY VELEANNEGV
1010 1020 1030 1040 1050
ECLRLLNEII ADFDEIISEE RFRQLEKIKT IGSTYMAASG LNASTYDQVG
1060 1070 1080 1090 1100
RSHITALADY AMRLMEQMKH INEHSFNNFQ MKIGLNMGPV VAGVIGARKP
1110 1120 1130 1140 1150
QYDIWGNTVN VSSRMDSTGV PDRIQVTTDL YQVLAAKGYQ LECRGVVKVK
1160
GKGEMTTYFL NGGPSS
Length:1,166
Mass (Da):130,506
Last modified:October 1, 1993 - v1
Checksum:i5042C650546E4E79
GO

Sequence cautioni

The sequence AAA40678 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti80K → E in AAA40678 (PubMed:1409703).Curated1
Sequence conflicti130R → P in AAA40678 (PubMed:1409703).Curated1
Sequence conflicti538G → A in AAA40678 (PubMed:1409703).Curated1
Sequence conflicti790I → L in AAA40678 (PubMed:1409703).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L01115 mRNA. Translation: AAA40676.1.
M96160 mRNA. Translation: AAA40678.1. Different initiation.
PIRiA47202.
RefSeqiNP_036953.4. NM_012821.4.
UniGeneiRn.3313.

Genome annotation databases

GeneIDi25289.
KEGGirno:25289.
UCSCiRGD:2035. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L01115 mRNA. Translation: AAA40676.1.
M96160 mRNA. Translation: AAA40678.1. Different initiation.
PIRiA47202.
RefSeqiNP_036953.4. NM_012821.4.
UniGeneiRn.3313.

3D structure databases

ProteinModelPortaliQ03343.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ03343. 2 interactors.
STRINGi10116.ENSRNOP00000016624.

Chemistry databases

ChEMBLiCHEMBL2095179.

PTM databases

iPTMnetiQ03343.
PhosphoSitePlusiQ03343.
SwissPalmiQ03343.

Proteomic databases

PaxDbiQ03343.
PRIDEiQ03343.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25289.
KEGGirno:25289.
UCSCiRGD:2035. rat.

Organism-specific databases

CTDi112.
RGDi2035. Adcy6.

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiQ03343.
KOiK08046.
PhylomeDBiQ03343.

Miscellaneous databases

PROiQ03343.

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 nameiADCY6_RAT
AccessioniPrimary (citable) accession number: Q03343
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: November 2, 2016
This is version 144 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.