UniProtKB - Q03343 (ADCY6_RAT)
Protein
Adenylate cyclase type 6
Gene
Adcy6
Organism
Rattus norvegicus (Rat)
Status
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
- EC:4.6.1.15 Publications
Cofactori
Mg2+1 Publication, Mn2+2 PublicationsNote: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).By similarity
Activity 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 382 | Magnesium 1; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 382 | Magnesium 2; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 383 | Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 426 | Magnesium 1; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 426 | Magnesium 2; catalyticPROSITE-ProRule annotation | 1 | |
Binding sitei | 470 | ATPBy similarity | 1 | |
Binding sitei | 1029 | ATPBy similarity | 1 | |
Binding sitei | 1150 | ATPBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 382 – 387 | ATPBy similarity | 6 | |
Nucleotide bindingi | 424 – 426 | ATPBy similarity | 3 | |
Nucleotide bindingi | 1103 – 1105 | ATPBy similarity | 3 | |
Nucleotide bindingi | 1110 – 1114 | ATPBy similarity | 5 |
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
- protein kinase C binding Source: RGD
- scaffold protein binding Source: RGD
- signaling receptor binding Source: RGD
- SNARE binding Source: ParkinsonsUK-UCL
GO - Biological processi
- adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: UniProtKB
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway Source: GO_Central
- cAMP biosynthetic process Source: RGD
- cellular response to catecholamine stimulus Source: RGD
- cellular response to forskolin Source: UniProtKB
- cellular response to prostaglandin E stimulus Source: RGD
- cellular response to vasopressin Source: UniProtKB
- circadian rhythm Source: RGD
- dopamine receptor signaling pathway Source: RGD
- maintenance of protein location in plasma membrane Source: ParkinsonsUK-UCL
- negative regulation of neuron projection development Source: ParkinsonsUK-UCL
- negative regulation of urine volume Source: UniProtKB
- regulation of blood vessel diameter Source: RGD
- renal water homeostasis Source: UniProtKB
Keywordsi
Molecular function | Lyase |
Biological process | cAMP biosynthesis |
Ligand | ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-RNO-170660, Adenylate cyclase activating pathway R-RNO-170670, Adenylate cyclase inhibitory pathway R-RNO-400042, Adrenaline,noradrenaline inhibits insulin secretion R-RNO-418597, G alpha (z) signalling events R-RNO-5610787, Hedgehog 'off' state |
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 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 2035, Adcy6 |
Subcellular locationi
Plasma membrane
- Cell membrane 3 Publications; Multi-pass membrane protein Curated
Other locations
- cilium By similarity
- stereocilium By similarity
Endosome
- endosome Source: RGD
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
- intrinsic component of plasma membrane Source: UniProtKB
- microvillus membrane Source: RGD
- plasma membrane Source: ParkinsonsUK-UCL
Other locations
- cilium Source: UniProtKB-SubCell
- membrane Source: BHF-UCL
- membrane raft Source: RGD
- stereocilium Source: UniProtKB-SubCell
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 149 | CytoplasmicSequence analysisAdd BLAST | 149 | |
Transmembranei | 150 – 166 | HelicalSequence analysisAdd BLAST | 17 | |
Transmembranei | 179 – 195 | HelicalSequence analysisAdd BLAST | 17 | |
Transmembranei | 212 – 228 | HelicalSequence analysisAdd BLAST | 17 | |
Transmembranei | 237 – 253 | HelicalSequence analysisAdd BLAST | 17 | |
Transmembranei | 257 – 273 | HelicalSequence analysisAdd BLAST | 17 | |
Transmembranei | 287 – 303 | HelicalSequence analysisAdd BLAST | 17 | |
Topological domaini | 304 – 671 | CytoplasmicSequence analysisAdd BLAST | 368 | |
Transmembranei | 672 – 689 | HelicalSequence analysisAdd BLAST | 18 | |
Transmembranei | 700 – 716 | HelicalSequence analysisAdd BLAST | 17 | |
Transmembranei | 741 – 757 | HelicalSequence analysisAdd BLAST | 17 | |
Topological domaini | 758 – 817 | ExtracellularSequence analysisAdd BLAST | 60 | |
Transmembranei | 818 – 834 | HelicalSequence analysisAdd BLAST | 17 | |
Transmembranei | 837 – 853 | HelicalSequence analysisAdd BLAST | 17 | |
Transmembranei | 895 – 911 | HelicalSequence analysisAdd BLAST | 17 | |
Topological domaini | 912 – 1166 | CytoplasmicSequence analysisAdd BLAST | 255 |
Keywords - Cellular componenti
Cell membrane, Cell projection, Cilium, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 311 | S → A: No effect on phosphorylation by PKC. 1 Publication | 1 | |
Mutagenesisi | 554 | S → A: Reduces phosphorylation by PKC and PKC-mediated inhibition. 1 Publication | 1 | |
Mutagenesisi | 660 | S → A: Abolishes phosphorylation by PKA and PKA-mediated down-regulation of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 660 | S → A: Reduces phosphorylation by PKC and PKC-mediated inhibition. 1 Publication | 1 | |
Mutagenesisi | 917 | T → A: Reduces phosphorylation by PKC, abolishes PKC-mediated inhibition. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL2095179 |
DrugCentrali | Q03343 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000195701 | 1 – 1166 | Adenylate cyclase type 6Add BLAST | 1166 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 53 | PhosphoserineCombined sources | 1 | |
Modified residuei | 554 | Phosphoserine; by PKC; in vitro1 Publication | 1 | |
Modified residuei | 574 | PhosphoserineCombined sources | 1 | |
Modified residuei | 660 | Phosphoserine; by PKA; in vitro1 Publication | 1 | |
Modified residuei | 660 | Phosphoserine; by PKC; in vitro1 Publication | 1 | |
Glycosylationi | 791 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 876 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 917 | Phosphothreonine; by PKC; in vitro1 Publication | 1 |
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, PhosphoproteinProteomic databases
PaxDbi | Q03343 |
PRIDEi | Q03343 |
PTM databases
GlyGeni | Q03343, 2 sites |
iPTMneti | Q03343 |
PhosphoSitePlusi | Q03343 |
SwissPalmi | Q03343 |
Expressioni
Tissue specificityi
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 PublicationGO - Molecular functioni
- protein kinase binding Source: BHF-UCL
- protein kinase C binding Source: RGD
- scaffold protein binding Source: RGD
- signaling receptor binding Source: RGD
- SNARE binding Source: ParkinsonsUK-UCL
Protein-protein interaction databases
IntActi | Q03343, 2 interactors |
STRINGi | 10116.ENSRNOP00000016624 |
Chemistry databases
BindingDBi | Q03343 |
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
Keywords - Domaini
Repeat, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3619, Eukaryota |
InParanoidi | Q03343 |
PhylomeDBi | Q03343 |
Family and domain databases
Gene3Di | 3.30.70.1230, 2 hits |
InterProi | View protein in InterPro IPR001054, A/G_cyclase IPR018297, A/G_cyclase_CS IPR032628, AC_N IPR030672, Adcy IPR009398, Adcy_conserved_dom IPR029787, Nucleotide_cyclase |
Pfami | View protein in Pfam PF16214, AC_N, 1 hit PF06327, DUF1053, 1 hit PF00211, Guanylate_cyc, 2 hits |
PIRSFi | PIRSF039050, Ade_cyc, 1 hit |
SMARTi | View protein in SMART SM00044, CYCc, 2 hits |
SUPFAMi | SSF55073, SSF55073, 2 hits |
PROSITEi | View protein in PROSITE PS00452, GUANYLATE_CYCLASE_1, 2 hits PS50125, GUANYLATE_CYCLASE_2, 2 hits |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
Q03343-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0G2K429 | A0A0G2K429_RAT | Adenylate cyclase type 6 | Adcy6 rCG_50695 | 1,180 | Annotation score: | ||
F1LSD1 | F1LSD1_RAT | Adenylate cyclase type 6 | Adcy6 rCG_50695 | 1,166 | Annotation score: |
Sequence cautioni
The sequence AAA40678 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 80 | K → E in AAA40678 (PubMed:1409703).Curated | 1 | |
Sequence conflicti | 130 | R → P in AAA40678 (PubMed:1409703).Curated | 1 | |
Sequence conflicti | 538 | G → A in AAA40678 (PubMed:1409703).Curated | 1 | |
Sequence conflicti | 790 | I → L in AAA40678 (PubMed:1409703).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L01115 mRNA Translation: AAA40676.1 M96160 mRNA Translation: AAA40678.1 Different initiation. |
PIRi | A47202 |
RefSeqi | NP_036953.4, NM_012821.4 |
Genome annotation databases
GeneIDi | 25289 |
KEGGi | rno:25289 |
UCSCi | RGD:2035, rat |
Similar proteinsi
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. |
PIRi | A47202 |
RefSeqi | NP_036953.4, NM_012821.4 |
3D structure databases
SMRi | Q03343 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | Q03343, 2 interactors |
STRINGi | 10116.ENSRNOP00000016624 |
Chemistry databases
BindingDBi | Q03343 |
ChEMBLi | CHEMBL2095179 |
DrugCentrali | Q03343 |
PTM databases
GlyGeni | Q03343, 2 sites |
iPTMneti | Q03343 |
PhosphoSitePlusi | Q03343 |
SwissPalmi | Q03343 |
Proteomic databases
PaxDbi | Q03343 |
PRIDEi | Q03343 |
Genome annotation databases
GeneIDi | 25289 |
KEGGi | rno:25289 |
UCSCi | RGD:2035, rat |
Organism-specific databases
CTDi | 112 |
RGDi | 2035, Adcy6 |
Phylogenomic databases
eggNOGi | KOG3619, Eukaryota |
InParanoidi | Q03343 |
PhylomeDBi | Q03343 |
Enzyme and pathway databases
Reactomei | R-RNO-170660, Adenylate cyclase activating pathway R-RNO-170670, Adenylate cyclase inhibitory pathway R-RNO-400042, Adrenaline,noradrenaline inhibits insulin secretion R-RNO-418597, G alpha (z) signalling events R-RNO-5610787, Hedgehog 'off' state |
Miscellaneous databases
PROi | PR:Q03343 |
Family and domain databases
Gene3Di | 3.30.70.1230, 2 hits |
InterProi | View protein in InterPro IPR001054, A/G_cyclase IPR018297, A/G_cyclase_CS IPR032628, AC_N IPR030672, Adcy IPR009398, Adcy_conserved_dom IPR029787, Nucleotide_cyclase |
Pfami | View protein in Pfam PF16214, AC_N, 1 hit PF06327, DUF1053, 1 hit PF00211, Guanylate_cyc, 2 hits |
PIRSFi | PIRSF039050, Ade_cyc, 1 hit |
SMARTi | View protein in SMART SM00044, CYCc, 2 hits |
SUPFAMi | SSF55073, SSF55073, 2 hits |
PROSITEi | View protein in PROSITE PS00452, GUANYLATE_CYCLASE_1, 2 hits PS50125, GUANYLATE_CYCLASE_2, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ADCY6_RAT | |
Accessioni | Q03343Primary (citable) accession number: Q03343 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1993 |
Last sequence update: | October 1, 1993 | |
Last modified: | December 2, 2020 | |
This is version 169 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families