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Protein

Adenylate cyclase type 2

Gene

Adcy2

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 in response to G-protein signaling (PubMed:22906005, PubMed:24363043, PubMed:10427002, PubMed:1719547, PubMed:7761832, PubMed:21596131, PubMed:11087399, PubMed:15591060, PubMed:19243146, PubMed:16766715). Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production (PubMed:24363043). Functions in signaling cascades downstream of the muscarinic acetylcholine receptors (PubMed:22906005).10 Publications

Catalytic activityi

ATP = 3',5'-cyclic AMP + diphosphate.10 Publications

Cofactori

Mg2+6 Publications, Mn2+3 PublicationsNote: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).1 Publication1 Publication

Enzyme regulationi

Activated by forskolin (PubMed:1719547, PubMed:22906005, PubMed:24363043). Is not activated by calmodulin (PubMed:1719547). Inhibited by calcium ions, already at micromolar concentration. Activated by the G protein alpha subunit GNAS (PubMed:1719547, PubMed:7761832, PubMed:21596131). Activated by the G protein beta and gamma subunit complex (PubMed:7761832, PubMed:21596131, PubMed:22906005). Phosphorylation by RAF1 results in its activation (By similarity). Phosphorylation by PKC activates the enzyme (PubMed:22906005).By similarity5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi294Magnesium 1; catalyticPROSITE-ProRule annotationCurated1
Metal bindingi294Magnesium 2; catalyticPROSITE-ProRule annotationCurated1 Publication1
Metal bindingi295Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotationCurated1 Publication1
Metal bindingi338Magnesium 1; catalyticPROSITE-ProRule annotationCurated1
Metal bindingi338Magnesium 2; catalyticPROSITE-ProRule annotationCurated1 Publication1
Binding sitei382ATPBy similarity1
Binding sitei938ATP5 Publications1
Binding sitei1065ATP5 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi294 – 299ATPBy similarity6
Nucleotide bindingi336 – 338ATPBy similarity3
Nucleotide bindingi1018 – 1020ATP5 Publications3
Nucleotide bindingi1025 – 1029ATPCombined sources1 Publication5

GO - Molecular functioni

  • adenylate cyclase activity Source: UniProtKB
  • adenylate cyclase binding Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • G-protein beta/gamma-subunit complex binding Source: RGD
  • magnesium ion binding Source: UniProtKB
  • manganese ion binding Source: UniProtKB
  • protein heterodimerization activity Source: BHF-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
  • adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: BHF-UCL
  • cAMP biosynthetic process Source: UniProtKB
  • cAMP-mediated signaling Source: UniProtKB
  • cellular response to forskolin Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

cAMP biosynthesis

Keywords - Ligandi

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

Enzyme and pathway databases

BRENDAi4.6.1.1. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 2 (EC:4.6.1.17 Publications)
Alternative name(s):
ATP pyrophosphate-lyase 2
Adenylate cyclase type II
Adenylyl cyclase 2
Short name:
AC21 Publication
Gene namesi
Name:Adcy2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi619965. Adcy2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 44CytoplasmicSequence analysisAdd BLAST44
Transmembranei45 – 65HelicalSequence analysisAdd BLAST21
Transmembranei75 – 95HelicalSequence analysisAdd BLAST21
Transmembranei107 – 127HelicalSequence analysisAdd BLAST21
Transmembranei132 – 152HelicalSequence analysisAdd BLAST21
Transmembranei157 – 177HelicalSequence analysisAdd BLAST21
Transmembranei186 – 206HelicalSequence analysisAdd BLAST21
Topological domaini207 – 600CytoplasmicSequence analysisAdd BLAST394
Transmembranei601 – 621HelicalSequence analysisAdd BLAST21
Transmembranei626 – 646HelicalSequence analysisAdd BLAST21
Transmembranei679 – 699HelicalSequence analysisAdd BLAST21
Transmembranei734 – 754HelicalSequence analysisAdd BLAST21
Transmembranei763 – 783HelicalSequence analysisAdd BLAST21
Transmembranei800 – 820HelicalSequence analysisAdd BLAST21
Topological domaini821 – 1090CytoplasmicSequence analysisCuratedAdd BLAST270

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • dendrite Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • intracellular Source: BHF-UCL
  • membrane Source: UniProtKB
  • membrane raft Source: BHF-UCL
  • plasma membrane Source: BHF-UCL
  • protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi490S → A: Reduces activation by PKC. Abolishes activation by PKC; when associated with A-543. 1 Publication1
Mutagenesisi490S → D: Increases basal level of enzyme activity. Abolishes activation by PKC; when associated with D-543. 1 Publication1
Mutagenesisi543S → A: Reduces activation by PKC. Abolishes activation by PKC; when associated with A-490. 1 Publication1
Mutagenesisi543S → D: Increases basal level of enzyme activity. Abolishes activation by PKC; when associated with D-490. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2958.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001956861 – 1090Adenylate cyclase type 2Add BLAST1090

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei490Phosphoserine; by PKC1 Publication1
Modified residuei543Phosphoserine; by PKC1 Publication1
Glycosylationi712N-linked (GlcNAc...)Sequence analysis1
Glycosylationi717N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Phosphorylated by RAF1 (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP26769.
PRIDEiP26769.

PTM databases

iPTMnetiP26769.
PhosphoSitePlusiP26769.

Expressioni

Tissue specificityi

Expressed in brain, olfactory epithelium and lung.1 Publication

Gene expression databases

BgeeiENSRNOG00000032150.

Interactioni

Subunit structurei

Interacts with RAF1 (By similarity). Interacts with GNAS (PubMed:9417641, PubMed:10427002, PubMed:11087399, PubMed:15591060, PubMed:16766715, PubMed:19243146). Interacts with the G protein beta and gamma subunit complex (PubMed:21596131).By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PDE4DQ08499-23EBI-1027877,EBI-8095525From a different organism.

GO - Molecular functioni

  • adenylate cyclase binding Source: BHF-UCL
  • G-protein beta/gamma-subunit complex binding Source: RGD
  • protein heterodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi249536. 1 interactor.
DIPiDIP-164N.
IntActiP26769. 7 interactors.
MINTiMINT-8041796.
STRINGi10116.ENSRNOP00000038994.

Chemistry databases

BindingDBiP26769.

Structurei

Secondary structure

11090
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi879 – 891Combined sources13
Helixi895 – 898Combined sources4
Turni903 – 908Combined sources6
Helixi909 – 923Combined sources15
Helixi924 – 927Combined sources4
Helixi929 – 931Combined sources3
Beta strandi934 – 940Combined sources7
Beta strandi943 – 948Combined sources6
Helixi967 – 987Combined sources21
Turni988 – 991Combined sources4
Beta strandi997 – 1010Combined sources14
Beta strandi1012 – 1014Combined sources3
Beta strandi1016 – 1021Combined sources6
Helixi1022 – 1032Combined sources11
Beta strandi1039 – 1041Combined sources3
Helixi1043 – 1052Combined sources10
Beta strandi1056 – 1064Combined sources9
Turni1065 – 1067Combined sources3
Beta strandi1068 – 1075Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AB8X-ray2.20A/B871-1090[»]
1AZSX-ray2.30B870-1081[»]
1CJKX-ray3.00B870-1081[»]
1CJTX-ray2.80B870-1081[»]
1CJUX-ray2.80B870-1081[»]
1CJVX-ray3.00B870-1081[»]
1CS4X-ray2.50B870-1081[»]
1CULX-ray2.40B874-1081[»]
1TL7X-ray2.80B870-1081[»]
1U0HX-ray2.90B870-1081[»]
2GVDX-ray2.90B870-1081[»]
2GVZX-ray3.27B870-1081[»]
3C14X-ray2.68B870-1081[»]
3C15X-ray2.78B870-1081[»]
3C16X-ray2.87B870-1081[»]
3G82X-ray3.11B870-1081[»]
3MAAX-ray3.00B870-1081[»]
ProteinModelPortaliP26769.
SMRiP26769.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26769.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni904 – 921Interaction with GNAS1 PublicationAdd BLAST18
Regioni989 – 992Interaction with GNAS1 Publication4

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.6 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.
InParanoidiP26769.
KOiK08042.
PhylomeDBiP26769.

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.

P26769-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRRRRYLRDR AEAAAAAAAG GGEGLQRSRD WLYESYYCMS QQHPLIVFLL
60 70 80 90 100
LIVMGACLAL LAVFFALGLE VEDHVAFLIT VPTALAIFFA IFILVCIESV
110 120 130 140 150
FKKLLRVFSL VIWICLVAMG YLFMCFGGTV SAWDQVSFFL FIIFVVYTML
160 170 180 190 200
PFNMRDAIIA SILTSSSHTI VLSVYLSATP GAKEHLFWQI LANVIIFICG
210 220 230 240 250
NLAGAYHKHL MELALQQTYR DTCNCIKSRI KLEFEKRQQE RLLLSLLPAH
260 270 280 290 300
IAMEMKAEII QRLQGPKAGQ MENTNNFHNL YVKRHTNVSI LYADIVGFTR
310 320 330 340 350
LASDCSPGEL VHMLNELFGK FDQIAKENEC MRIKILGDCY YCVSGLPISL
360 370 380 390 400
PNHAKNCVKM GLDMCEAIKK VRDATGVDIN MRVGVHSGNV LCGVIGLQKW
410 420 430 440 450
QYDVWSHDVT LANHMEAGGV PGRVHISSVT LEHLNGAYKV EEGDGEIRDP
460 470 480 490 500
YLKQHLVKTY FVINPKGERR SPQHLFRPRH TLDGAKMRAS VRMTRYLESW
510 520 530 540 550
GAAKPFAHLH HRDSMTTENG KISTTDVPMG QHNFQNRTLR TKSQKKRFEE
560 570 580 590 600
ELNERMIQAI DGINAQKQWL KSEDIQRISL LFYNKNIEKE YRATALPAFK
610 620 630 640 650
YYVTCACLIF LCIFIVQILV LPKTSILGFS FGAAFLSLIF ILFVCFAGQL
660 670 680 690 700
LQCSKKASTS LMWLLKSSGI IANRPWPRIS LTIVTTAIIL TMAVFNMFFL
710 720 730 740 750
SNSEETTLPT ANTSNANVSV PDNQASILHA RNLFFLPYFI YSCILGLISC
760 770 780 790 800
SVFLRVNYEL KMLIMMVALV GYNTILLHTH AHVLDAYSQV LFQRPGIWKD
810 820 830 840 850
LKTMGSVSLS IFFITLLVLG RQSEYYCRLD FLWKNKFKKE REEIETMENL
860 870 880 890 900
NRVLLENVLP AHVAEHFLAR SLKNEELYHQ SYDCVCVMFA SIPDFKEFYT
910 920 930 940 950
ESDVNKEGLE CLRLLNEIIA DFDDLLSKPK FSGVEKIKTI GSTYMAATGL
960 970 980 990 1000
SAIPSQEHAQ EPERQYMHIG TMVEFAYALV GKLDAINKHS FNDFKLRVGI
1010 1020 1030 1040 1050
NHGPVIAGVI GAQKPQYDIW GNTVNVASRM DSTGVLDKIQ VTEETSLILQ
1060 1070 1080 1090
TLGYTCTCRG IINVKGKGDL KTYFVNTEMS RSLSQSNLAS
Length:1,090
Mass (Da):123,316
Last modified:August 1, 1992 - v1
Checksum:i935CE44DF73199B3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M80550 mRNA. Translation: AAA40682.1.
PIRiA41541.
RefSeqiNP_112269.1. NM_031007.1.
UniGeneiRn.10731.

Genome annotation databases

GeneIDi81636.
KEGGirno:81636.
UCSCiRGD:619965. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M80550 mRNA. Translation: AAA40682.1.
PIRiA41541.
RefSeqiNP_112269.1. NM_031007.1.
UniGeneiRn.10731.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AB8X-ray2.20A/B871-1090[»]
1AZSX-ray2.30B870-1081[»]
1CJKX-ray3.00B870-1081[»]
1CJTX-ray2.80B870-1081[»]
1CJUX-ray2.80B870-1081[»]
1CJVX-ray3.00B870-1081[»]
1CS4X-ray2.50B870-1081[»]
1CULX-ray2.40B874-1081[»]
1TL7X-ray2.80B870-1081[»]
1U0HX-ray2.90B870-1081[»]
2GVDX-ray2.90B870-1081[»]
2GVZX-ray3.27B870-1081[»]
3C14X-ray2.68B870-1081[»]
3C15X-ray2.78B870-1081[»]
3C16X-ray2.87B870-1081[»]
3G82X-ray3.11B870-1081[»]
3MAAX-ray3.00B870-1081[»]
ProteinModelPortaliP26769.
SMRiP26769.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249536. 1 interactor.
DIPiDIP-164N.
IntActiP26769. 7 interactors.
MINTiMINT-8041796.
STRINGi10116.ENSRNOP00000038994.

Chemistry databases

BindingDBiP26769.
ChEMBLiCHEMBL2958.

PTM databases

iPTMnetiP26769.
PhosphoSitePlusiP26769.

Proteomic databases

PaxDbiP26769.
PRIDEiP26769.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi81636.
KEGGirno:81636.
UCSCiRGD:619965. rat.

Organism-specific databases

CTDi108.
RGDi619965. Adcy2.

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiP26769.
KOiK08042.
PhylomeDBiP26769.

Enzyme and pathway databases

BRENDAi4.6.1.1. 5301.

Miscellaneous databases

EvolutionaryTraceiP26769.
PROiP26769.

Gene expression databases

BgeeiENSRNOG00000032150.

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 nameiADCY2_RAT
AccessioniPrimary (citable) accession number: P26769
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: November 2, 2016
This is version 148 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

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.