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Protein

Adenylate cyclase type 2

Gene

Adcy2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

Activity 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

GO - Biological processi

Keywordsi

Molecular functionLyase
Biological processcAMP biosynthesis
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi619965 Adcy2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence analysis1
Glycosylationi717N-linked (GlcNAc...) asparagineSequence 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

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi249536, 1 interactor
DIPiDIP-164N
IntActiP26769, 8 interactors
MINTiP26769
STRINGi10116.ENSRNOP00000038994

Chemistry databases

BindingDBiP26769

Structurei

Secondary structure

11090
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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
InterProiView protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR032628 AC_N
IPR030672 Adcy
IPR009398 Adcy_conserved_dom
IPR029787 Nucleotide_cyclase
PfamiView protein in Pfam
PF16214 AC_N, 1 hit
PF06327 DUF1053, 1 hit
PF00211 Guanylate_cyc, 2 hits
PIRSFiPIRSF039050 Ade_cyc, 1 hit
SMARTiView protein in SMART
SM00044 CYCc, 2 hits
SUPFAMiSSF55073 SSF55073, 2 hits
PROSITEiView protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 2 hits
PS50125 GUANYLATE_CYCLASE_2, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F1LV12F1LV12_RAT
Adenylate cyclase type 2
Adcy2
852Annotation score:

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

Similar proteinsi

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, 8 interactors
MINTiP26769
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
PROiPR:P26769

Family and domain databases

Gene3Di3.30.70.1230, 2 hits
InterProiView protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR032628 AC_N
IPR030672 Adcy
IPR009398 Adcy_conserved_dom
IPR029787 Nucleotide_cyclase
PfamiView protein in Pfam
PF16214 AC_N, 1 hit
PF06327 DUF1053, 1 hit
PF00211 Guanylate_cyc, 2 hits
PIRSFiPIRSF039050 Ade_cyc, 1 hit
SMARTiView protein in SMART
SM00044 CYCc, 2 hits
SUPFAMiSSF55073 SSF55073, 2 hits
PROSITEiView protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 2 hits
PS50125 GUANYLATE_CYCLASE_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiADCY2_RAT
AccessioniPrimary (citable) accession number: P26769
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: November 7, 2018
This is version 160 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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