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Protein

Adenylate cyclase type 3

Gene

ADCY3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis. 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

Catalytic activityi

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

Cofactori

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

Activity regulationi

Activated by forskolin. After forskolin treatment, activity is further increased by calcium/calmodulin. In the absence of forskolin, calcium/calmodulin has little effect on enzyme activity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi324Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi324Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi325Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi368Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi368Magnesium 2; catalyticPROSITE-ProRule annotation1
Binding sitei412ATPBy similarity1
Binding sitei975ATPBy similarity1
Binding sitei1109ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi324 – 329ATPBy similarity6
Nucleotide bindingi366 – 368ATPBy similarity3
Nucleotide bindingi1062 – 1064ATPBy similarity3
Nucleotide bindingi1069 – 1073ATPBy similarity5

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Lyase
Biological processcAMP biosynthesis, Olfaction, Sensory transduction
LigandATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-163359 Glucagon signaling in metabolic regulation
R-HSA-163615 PKA activation
R-HSA-164378 PKA activation in glucagon signalling
R-HSA-170660 Adenylate cyclase activating pathway
R-HSA-170670 Adenylate cyclase inhibitory pathway
R-HSA-418555 G alpha (s) signalling events
R-HSA-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
R-HSA-432040 Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-442720 CREB phosphorylation through the activation of Adenylate Cyclase
R-HSA-5610787 Hedgehog 'off' state
SIGNORiO60266

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 3 (EC:4.6.1.1)
Alternative name(s):
ATP pyrophosphate-lyase 3
Adenylate cyclase type III
Short name:
AC-III
Adenylate cyclase, olfactive type
Adenylyl cyclase 3Curated
Short name:
AC31 Publication
Gene namesi
Name:ADCY3
Synonyms:KIAA0511
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000138031.14
HGNCiHGNC:234 ADCY3
MIMi600291 gene
neXtProtiNX_O60266

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 – 79CytoplasmicSequence analysisAdd BLAST79
Transmembranei80 – 100HelicalSequence analysisAdd BLAST21
Transmembranei105 – 125HelicalSequence analysisAdd BLAST21
Transmembranei139 – 159HelicalSequence analysisAdd BLAST21
Transmembranei173 – 193HelicalSequence analysisAdd BLAST21
Transmembranei226 – 246HelicalSequence analysisAdd BLAST21
Transmembranei381 – 401HelicalSequence analysisAdd BLAST21
Topological domaini402 – 632CytoplasmicSequence analysisAdd BLAST231
Transmembranei633 – 653HelicalSequence analysisAdd BLAST21
Transmembranei664 – 684HelicalSequence analysisAdd BLAST21
Transmembranei708 – 728HelicalSequence analysisAdd BLAST21
Transmembranei754 – 774HelicalSequence analysisAdd BLAST21
Transmembranei775 – 795HelicalSequence analysisAdd BLAST21
Transmembranei833 – 853HelicalSequence analysisAdd BLAST21
Topological domaini854 – 1144CytoplasmicSequence analysisAdd BLAST291

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Obesity (OBESITY)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.
See also OMIM:601665
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0807921118Missing in OBESITY; risk factor. 1 PublicationCorresponds to variant dbSNP:rs750852737Ensembl.1

Keywords - Diseasei

Obesity

Organism-specific databases

DisGeNETi109
MalaCardsiADCY3
MIMi601665 phenotype
617885 phenotype
OpenTargetsiENSG00000138031
PharmGKBiPA164741137

Chemistry databases

ChEMBLiCHEMBL2097167

Polymorphism and mutation databases

BioMutaiADCY3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001956871 – 1144Adenylate cyclase type 3Add BLAST1144

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki465Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO3)By similarity
Modified residuei525PhosphoserineCombined sources1
Modified residuei580PhosphoserineBy similarity1
Glycosylationi736N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1076Phosphoserine; by CaMK2By similarity1

Post-translational modificationi

Sumoylated. Sumoylation is required for targeting ot olfactory cilia.By similarity
N-glycosylated.By similarity
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

EPDiO60266
MaxQBiO60266
PaxDbiO60266
PeptideAtlasiO60266
PRIDEiO60266
ProteomicsDBi49298

PTM databases

iPTMnetiO60266
PhosphoSitePlusiO60266

Expressioni

Tissue specificityi

Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level) (PubMed:11549699). Expressed in brain, heart, kidney, liver, lung, pancreas islets, placenta, and skeletal muscle (PubMed:9920776). Detected in testis (PubMed:15705663).3 Publications

Gene expression databases

BgeeiENSG00000138031 Expressed in 224 organ(s), highest expression level in tibial nerve
CleanExiHS_ADCY3
ExpressionAtlasiO60266 baseline and differential
GenevisibleiO60266 HS

Organism-specific databases

HPAiCAB010223

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106623, 17 interactors
IntActiO60266, 2 interactors
MINTiO60266
STRINGi9606.ENSP00000260600

Structurei

3D structure databases

ProteinModelPortaliO60266
SMRiO60266
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

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3619 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00760000119042
HOGENOMiHOG000006941
HOVERGENiHBG050458
InParanoidiO60266
KOiK08043
PhylomeDBiO60266
TreeFamiTF313845

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
IPR029787 Nucleotide_cyclase
PfamiView protein in Pfam
PF16214 AC_N, 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

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O60266-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MPRNQGFSEP EYSAEYSAEY SVSLPSDPDR GVGRTHEISV RNSGSCLCLP
60 70 80 90 100
RFMRLTFVPE SLENLYQTYF KRQRHETLLV LVVFAALFDC YVVVMCAVVF
110 120 130 140 150
SSDKLASLAV AGIGLVLDII LFVLCKKGLL PDRVTRRVLP YVLWLLITAQ
160 170 180 190 200
IFSYLGLNFA RAHAASDTVG WQVFFVFSFF ITLPLSLSPI VIISVVSCVV
210 220 230 240 250
HTLVLGVTVA QQQQEELKGM QLLREILANV FLYLCAIAVG 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 YLEEKGIETY LIIASKPEVK
510 520 530 540 550
KTATQNGLNG SALPNGAPAS SKSSSPALIE TKEPNGSAHS SGSTSEKPEE
560 570 580 590 600
QDAQADNPSF PNPRRRLRLQ DLADRVVDAS EDEHELNQLL NEALLERESA
610 620 630 640 650
QVVKKRNTFL LSMRFMDPEM ETRYSVEKEK QSGAAFSCSC VVLLCTALVE
660 670 680 690 700
ILIDPWLMTN YVTFMVGEIL LLILTICSLA AIFPRAFPKK LVAFSTWIDR
710 720 730 740 750
TRWARNTWAM LAIFILVMAN VVDMLSCLQY YTGPSNATAG METEGSCLEN
760 770 780 790 800
PKYYNYVAVL SLIATIMLVQ VSHMVKLTLM LLVAGAVATI NLYAWRPVFD
810 820 830 840 850
EYDHKRFREH DLPMVALEQM QGFNPGLNGT DRLPLVPSKY SMTVMVFLMM
860 870 880 890 900
LSFYYFSRHV EKLARTLFLW KIEVHDQKER VYEMRRWNEA LVTNMLPEHV
910 920 930 940 950
ARHFLGSKKR DEELYSQTYD EIGVMFASLP NFADFYTEES INNGGIECLR
960 970 980 990 1000
FLNEIISDFD SLLDNPKFRV ITKIKTIGST YMAASGVTPD VNTNGFASSN
1010 1020 1030 1040 1050
KEDKSERERW QHLADLADFA LAMKDTLTNI NNQSFNNFML RIGMNKGGVL
1060 1070 1080 1090 1100
AGVIGARKPH YDIWGNTVNV ASRMESTGVM GNIQVVEETQ VILREYGFRF
1110 1120 1130 1140
VRRGPIFVKG KGELLTFFLK GRDKLATFPN GPSVTLPHQV VDNS
Length:1,144
Mass (Da):128,960
Last modified:November 28, 2006 - v3
Checksum:iB75D39DD0A8ACA12
GO
Isoform 2 (identifier: O60266-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-389: Missing.
     452-452: G → GGSKIEERLYSCVVAPTLRLRWE
     725-770: Missing.

Note: No experimental confirmation available.
Show »
Length:731
Mass (Da):82,289
Checksum:i960E91B8B64A5C8F
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MSC1A0A0A0MSC1_HUMAN
Adenylate cyclase
ADCY3
1,145Annotation score:
C9JLX3C9JLX3_HUMAN
Adenylate cyclase type 3
ADCY3
482Annotation score:
U3KQ91U3KQ91_HUMAN
Adenylate cyclase type 3
ADCY3
791Annotation score:
H7C1A6H7C1A6_HUMAN
Adenylate cyclase type 3
ADCY3
298Annotation score:
C9JYB5C9JYB5_HUMAN
Adenylate cyclase type 3
ADCY3
154Annotation score:
U3KQR1U3KQR1_HUMAN
Adenylate cyclase type 3
ADCY3
49Annotation score:
H7C1S5H7C1S5_HUMAN
Adenylate cyclase type 3
ADCY3
198Annotation score:
C9J969C9J969_HUMAN
Adenylate cyclase type 3
ADCY3
112Annotation score:

Polymorphismi

Genetic variations at the ADCY3 locus define the body mass index quantitative trait locus 19 (BMIQ19) [MIMi:617885]. Variance in body mass index is a susceptibility factor for obesity.2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08079164N → I1 PublicationCorresponds to variant dbSNP:rs541941351Ensembl.1
Natural variantiVAR_048248107S → P1 PublicationCorresponds to variant dbSNP:rs11676272Ensembl.1
Natural variantiVAR_0807921118Missing in OBESITY; risk factor. 1 PublicationCorresponds to variant dbSNP:rs750852737Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0558131 – 389Missing in isoform 2. 1 PublicationAdd BLAST389
Alternative sequenceiVSP_055814452G → GGSKIEERLYSCVVAPTLRL RWE in isoform 2. 1 Publication1
Alternative sequenceiVSP_055815725 – 770Missing in isoform 2. 1 PublicationAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF033861 mRNA Translation: AAD13403.1
AK095173 mRNA Translation: BAG52998.1
AC012073 Genomic DNA Translation: AAY14787.1
BC126235 mRNA Translation: AAI26236.1
AB011083 mRNA Translation: BAA25437.1
CCDSiCCDS1715.1 [O60266-1]
RefSeqiNP_001307542.1, NM_001320613.1
NP_004027.2, NM_004036.4 [O60266-1]
UniGeneiHs.467898
Hs.611397

Genome annotation databases

EnsembliENST00000260600; ENSP00000260600; ENSG00000138031 [O60266-1]
GeneIDi109
KEGGihsa:109
UCSCiuc002rfs.5 human [O60266-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF033861 mRNA Translation: AAD13403.1
AK095173 mRNA Translation: BAG52998.1
AC012073 Genomic DNA Translation: AAY14787.1
BC126235 mRNA Translation: AAI26236.1
AB011083 mRNA Translation: BAA25437.1
CCDSiCCDS1715.1 [O60266-1]
RefSeqiNP_001307542.1, NM_001320613.1
NP_004027.2, NM_004036.4 [O60266-1]
UniGeneiHs.467898
Hs.611397

3D structure databases

ProteinModelPortaliO60266
SMRiO60266
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106623, 17 interactors
IntActiO60266, 2 interactors
MINTiO60266
STRINGi9606.ENSP00000260600

Chemistry databases

ChEMBLiCHEMBL2097167

PTM databases

iPTMnetiO60266
PhosphoSitePlusiO60266

Polymorphism and mutation databases

BioMutaiADCY3

Proteomic databases

EPDiO60266
MaxQBiO60266
PaxDbiO60266
PeptideAtlasiO60266
PRIDEiO60266
ProteomicsDBi49298

Protocols and materials databases

DNASUi109
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000260600; ENSP00000260600; ENSG00000138031 [O60266-1]
GeneIDi109
KEGGihsa:109
UCSCiuc002rfs.5 human [O60266-1]

Organism-specific databases

CTDi109
DisGeNETi109
EuPathDBiHostDB:ENSG00000138031.14
GeneCardsiADCY3
H-InvDBiHIX0001880
HIX0030389
HIX0161886
HGNCiHGNC:234 ADCY3
HPAiCAB010223
MalaCardsiADCY3
MIMi600291 gene
601665 phenotype
617885 phenotype
neXtProtiNX_O60266
OpenTargetsiENSG00000138031
PharmGKBiPA164741137
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3619 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00760000119042
HOGENOMiHOG000006941
HOVERGENiHBG050458
InParanoidiO60266
KOiK08043
PhylomeDBiO60266
TreeFamiTF313845

Enzyme and pathway databases

ReactomeiR-HSA-163359 Glucagon signaling in metabolic regulation
R-HSA-163615 PKA activation
R-HSA-164378 PKA activation in glucagon signalling
R-HSA-170660 Adenylate cyclase activating pathway
R-HSA-170670 Adenylate cyclase inhibitory pathway
R-HSA-418555 G alpha (s) signalling events
R-HSA-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
R-HSA-432040 Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-442720 CREB phosphorylation through the activation of Adenylate Cyclase
R-HSA-5610787 Hedgehog 'off' state
SIGNORiO60266

Miscellaneous databases

GeneWikiiADCY3
GenomeRNAii109
PROiPR:O60266
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138031 Expressed in 224 organ(s), highest expression level in tibial nerve
CleanExiHS_ADCY3
ExpressionAtlasiO60266 baseline and differential
GenevisibleiO60266 HS

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
IPR029787 Nucleotide_cyclase
PfamiView protein in Pfam
PF16214 AC_N, 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 nameiADCY3_HUMAN
AccessioniPrimary (citable) accession number: O60266
Secondary accession number(s): B3KT86, Q53T54, Q9UDB1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 28, 2006
Last modified: November 7, 2018
This is version 184 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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