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Protein

Adenylate cyclase type 3

Gene

Adcy3

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:2255909, PubMed:1633161, PubMed:24363043). Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis (PubMed:2255909). Required for the perception of odorants. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet (By similarity).By similarity3 Publications

Catalytic activityi

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

Cofactori

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

Enzyme regulationi

Activated by forskolin (PubMed:2255909, PubMed:1633161, PubMed:24363043). After forskolin treatment, activity is further increased by calcium/calmodulin (PubMed:1633161). In the absence of forskolin, calcium/calmodulin has little effect on enzyme activity (PubMed:1633161).3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi324 – 3241Magnesium 1; catalyticPROSITE-ProRule annotation
Metal bindingi324 – 3241Magnesium 2; catalyticPROSITE-ProRule annotation
Metal bindingi325 – 3251Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation
Metal bindingi368 – 3681Magnesium 1; catalyticPROSITE-ProRule annotation
Metal bindingi368 – 3681Magnesium 2; catalyticPROSITE-ProRule annotation
Binding sitei412 – 4121ATPBy similarity
Binding sitei975 – 9751ATPBy similarity
Binding sitei1109 – 11091ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi324 – 3296ATPBy similarity
Nucleotide bindingi366 – 3683ATPBy similarity
Nucleotide bindingi1062 – 10643ATPBy similarity
Nucleotide bindingi1069 – 10735ATPBy similarity

GO - Molecular functioni

  • adenylate cyclase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • calcium- and calmodulin-responsive adenylate cyclase activity Source: RGD
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • acrosome reaction Source: UniProtKB
  • 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: UniProtKB
  • cAMP-mediated signaling Source: GO_Central
  • cellular response to forskolin Source: UniProtKB
  • female meiotic division Source: RGD
  • intracellular signal transduction Source: RGD
  • olfactory learning Source: UniProtKB
  • sensory perception of smell Source: RGD
  • single fertilization Source: UniProtKB
  • sperm motility Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

cAMP biosynthesis, Olfaction, Sensory transduction

Keywords - Ligandi

ATP-binding, Calmodulin-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 3 (EC:4.6.1.13 Publications)
Alternative name(s):
ATP pyrophosphate-lyase 3
Adenylate cyclase type III1 Publication
Short name:
AC-III
Adenylate cyclase, olfactive type
Adenylyl cyclase 3
Short name:
AC3
Gene namesi
Name:Adcy3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi71009. Adcy3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 7979CytoplasmicSequence analysisAdd
BLAST
Transmembranei80 – 10021HelicalSequence analysisAdd
BLAST
Transmembranei105 – 12521HelicalSequence analysisAdd
BLAST
Transmembranei139 – 15921HelicalSequence analysisAdd
BLAST
Transmembranei173 – 19321HelicalSequence analysisAdd
BLAST
Transmembranei226 – 24621HelicalSequence analysisAdd
BLAST
Transmembranei381 – 40121HelicalSequence analysisAdd
BLAST
Topological domaini402 – 630229CytoplasmicSequence analysisAdd
BLAST
Transmembranei631 – 65121HelicalSequence analysisAdd
BLAST
Transmembranei662 – 68221HelicalSequence analysisAdd
BLAST
Transmembranei706 – 72621HelicalSequence analysisAdd
BLAST
Transmembranei755 – 77521HelicalSequence analysisAdd
BLAST
Transmembranei777 – 79721HelicalSequence analysisAdd
BLAST
Transmembranei833 – 85321HelicalSequence analysisAdd
BLAST
Topological domaini854 – 1144291CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cilium Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • membrane Source: RGD
  • membrane raft Source: RGD
  • nucleus Source: RGD
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi465 – 4651K → R: Abolishes sumoylation. Abolishes location at cilia in the olfactory epithelium. 1 Publication

Chemistry

ChEMBLiCHEMBL2095179.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11441144Adenylate cyclase type 3PRO_0000195689Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki465 – 465Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO3)1 Publication
Modified residuei523 – 5231PhosphoserineBy similarity
Modified residuei578 – 5781PhosphoserineBy similarity
Glycosylationi734 – 7341N-linked (GlcNAc...)Sequence analysis
Modified residuei1076 – 10761Phosphoserine; by CaMK2By similarity

Post-translational modificationi

N-glycosylated.1 Publication
Sumoylated. Sumoylation is required for targeting ot olfactory cilia.1 Publication
Rapidly phosphorylated after stimulation by odorants or forskolin. Phosphorylation by CaMK2 at Ser-1076 down-regulates enzyme activity.By similarity

Keywords - PTMi

Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP21932.
PRIDEiP21932.

PTM databases

PhosphoSiteiP21932.

Expressioni

Tissue specificityi

Detected on cilia on the olfactory epithelium (at protein level) (PubMed:2255909, PubMed:25908845). Detected on cilia on the olfactory epithelium.1 Publication

Interactioni

Protein-protein interaction databases

BioGridi249093. 1 interaction.
STRINGi10116.ENSRNOP00000005389.

Chemistry

BindingDBiP21932.

Structurei

3D structure databases

ProteinModelPortaliP21932.
SMRiP21932. Positions 307-493, 914-1101.
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 modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules.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.
InParanoidiP21932.
KOiK08043.
PhylomeDBiP21932.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR032628. AC_N.
IPR030672. Adcy.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF16214. AC_N. 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.

P21932-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTEDQGFSDP EYSAEYSAEY SVSLPSDPDR GVGRTHEISV RNSGSCLCLP
60 70 80 90 100
RFMRLTFVPE SLENLYQTYF KRQRHETLLV LVVFAALFDC YVVVMCAVVF
110 120 130 140 150
SSDKLAPLMV AGVGLVLDII LFVLCKKGLL PDRVSRKVVP YLLWLLITAQ
160 170 180 190 200
IFSYLGLNFS RAHAASDTVG WQAFFVFSFF ITLPLSLSPI VIISVVSCVV
210 220 230 240 250
HTLVLGVTVA QQQQDELEGM QLLREILANV FLYLCAIIVG IMSYYMADRK
260 270 280 290 300
HRKAFLEARQ SLEVKMNLEE QSQQQENLML SILPKHVADE MLKDMKKDES
310 320 330 340 350
QKDQQQFNTM YMYRHENVSI LFADIVGFTQ LSSACSAQEL VKLLNELFAR
360 370 380 390 400
FDKLAAKYHQ LRIKILGDCY YCICGLPDYR EDHAVCSILM GLAMVEAISY
410 420 430 440 450
VREKTKTGVD MRVGVHTGTV LGGVLGQKRW QYDVWSTDVT VANKMEAGGI
460 470 480 490 500
PGRVHISQST MDCLKGEFDV EPGDGGSRCD YLDEKGIETY LIIASKPEVK
510 520 530 540 550
KTAQNGLNGS ALPNGAPASK PSSPALIETK EPNGSAHASG STSEEAEEQE
560 570 580 590 600
AQADNPSFPN PRRRLRLQDL ADRVVDASED EHELNQLLNE ALLERESAQV
610 620 630 640 650
VKKRNTFLLT MRFMDPEMET RYSVEKEKQS GAAFSCSCVV LFCTAMVEIL
660 670 680 690 700
IDPWLMTNYV TFVVGEVLLL ILTICSMAAI FPRAFPKKLV AFSSWIDRTR
710 720 730 740 750
WARNTWAMLA IFILVMANVV DMLSCLQYYM GPYNVTTGIE LDGGCMENPK
760 770 780 790 800
YYNYVAVLSL IATIMLVQVS HMVKLTLMLL VTGAVTAINL YAWCPVFDEY
810 820 830 840 850
DHKRFQEKDS PMVALEKMQV LSTPGLNGTD SRLPLVPSKY SMTVMMFVMM
860 870 880 890 900
LSFYYFSRHV EKLARTLFLW KIEVHDQKER VYEMRRWNEA LVTNMLPEHV
910 920 930 940 950
ARHFLGSKKR DEELYSQSYD EIGVMFASLP NFADFYTEES INNGGIECLR
960 970 980 990 1000
FLNEIISDFD SLLDNPKFRV ITKIKTIGST YMAASGVTPD VNTNGFTSSS
1010 1020 1030 1040 1050
KEEKSDKERW QHLADLADFA LAMKDTLTNI NNQSFNNFML RIGMNKGGVL
1060 1070 1080 1090 1100
AGVIGARKPH YDIWGNTVNV ASRMESTGVM GNIQVVEETQ VILREYGFRF
1110 1120 1130 1140
VRRGPIFVKG KGELLTFFLK GRDRPAAFPN GSSVTLPHQV VDNP
Length:1,144
Mass (Da):128,936
Last modified:May 1, 1991 - v1
Checksum:i21098D028DDBAB55
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55075 mRNA. Translation: AAA40677.1.
PIRiA39833.
RefSeqiNP_570135.2. NM_130779.2.
UniGeneiRn.87800.

Genome annotation databases

GeneIDi64508.
KEGGirno:64508.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55075 mRNA. Translation: AAA40677.1.
PIRiA39833.
RefSeqiNP_570135.2. NM_130779.2.
UniGeneiRn.87800.

3D structure databases

ProteinModelPortaliP21932.
SMRiP21932. Positions 307-493, 914-1101.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249093. 1 interaction.
STRINGi10116.ENSRNOP00000005389.

Chemistry

BindingDBiP21932.
ChEMBLiCHEMBL2095179.

PTM databases

PhosphoSiteiP21932.

Proteomic databases

PaxDbiP21932.
PRIDEiP21932.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi64508.
KEGGirno:64508.

Organism-specific databases

CTDi109.
RGDi71009. Adcy3.

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiP21932.
KOiK08043.
PhylomeDBiP21932.

Enzyme and pathway databases

BRENDAi4.6.1.1. 5301.

Miscellaneous databases

PROiP21932.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR032628. AC_N.
IPR030672. Adcy.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF16214. AC_N. 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. "Identification of a specialized adenylyl cyclase that may mediate odorant detection."
    Bakalyar H.A., Reed R.R.
    Science 250:1403-1406(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    Tissue: Olfactory epithelium.
  2. "Stimulation of the type III olfactory adenylyl cyclase by calcium and calmodulin."
    Choi E.J., Xia Z., Storm D.R.
    Biochemistry 31:6492-6498(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION.
  3. "Inactivation of the mouse adenylyl cyclase 3 gene disrupts male fertility and spermatozoon function."
    Livera G., Xie F., Garcia M.A., Jaiswal B., Chen J., Law E., Storm D.R., Conti M.
    Mol. Endocrinol. 19:1277-1290(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  4. "Non-raft adenylyl cyclase 2 defines a cAMP signaling compartment that selectively regulates IL-6 expression in airway smooth muscle cells: differential regulation of gene expression by AC isoforms."
    Bogard A.S., Birg A.V., Ostrom R.S.
    Naunyn Schmiedebergs Arch. Pharmacol. 387:329-339(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION, ENZYME REGULATION.
  5. "SUMOylation regulates ciliary localization of olfactory signaling proteins."
    McIntyre J.C., Joiner A.M., Zhang L., Iniguez-Lluhi J., Martens J.R.
    J. Cell Sci. 128:1934-1945(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION, MUTAGENESIS OF LYS-465, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiADCY3_RAT
AccessioniPrimary (citable) accession number: P21932
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: July 6, 2016
This is version 133 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.