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Protein

Adenylate cyclase type 2

Gene

ADCY2

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 (PubMed:15385642). Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production. Functions in signaling cascades downstream of the muscarinic acetylcholine receptors (By similarity).By similarity1 Publication

Catalytic activityi

ATP = 3',5'-cyclic AMP + diphosphate.1 Publication

Cofactori

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

Activity regulationi

Activated by forskolin (PubMed:15385642). Is not activated by calmodulin. Inhibited by calcium ions, already at micromolar concentration. Activated by the G protein alpha subunit GNAS. Activated by the G protein beta and gamma subunit complex (By similarity). Phosphorylation by RAF1 results in its activation (PubMed:15385642). Phosphorylation by PKC activates the enzyme (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi295Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi295Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi296Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi339Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi339Magnesium 2; catalyticPROSITE-ProRule annotation1
Binding sitei383ATPBy similarity1
Binding sitei939ATPBy similarity1
Binding sitei1066ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi295 – 300ATPBy similarity6
Nucleotide bindingi337 – 339ATPBy similarity3
Nucleotide bindingi1019 – 1021ATPBy similarity3
Nucleotide bindingi1026 – 1030ATPBy similarity5

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 2681
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-5610787 Hedgehog 'off' state
SIGNORiQ08462

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 2 (EC:4.6.1.11 Publication)
Alternative name(s):
ATP pyrophosphate-lyase 2
Adenylate cyclase type II
Adenylyl cyclase 2
Gene namesi
Name:ADCY2
Synonyms:KIAA1060
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000078295.15
HGNCiHGNC:233 ADCY2
MIMi103071 gene
neXtProtiNX_Q08462

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 – 45CytoplasmicSequence analysisAdd BLAST45
Transmembranei46 – 66HelicalSequence analysisAdd BLAST21
Transmembranei76 – 96HelicalSequence analysisAdd BLAST21
Transmembranei108 – 128HelicalSequence analysisAdd BLAST21
Transmembranei133 – 153HelicalSequence analysisAdd BLAST21
Transmembranei159 – 179HelicalSequence analysisAdd BLAST21
Transmembranei187 – 207HelicalSequence analysisAdd BLAST21
Topological domaini208 – 601CytoplasmicSequence analysisAdd BLAST394
Transmembranei602 – 622HelicalSequence analysisAdd BLAST21
Transmembranei628 – 652HelicalSequence analysisAdd BLAST25
Transmembranei680 – 701HelicalSequence analysisAdd BLAST22
Transmembranei734 – 755HelicalSequence analysisAdd BLAST22
Transmembranei763 – 780HelicalSequence analysisAdd BLAST18
Transmembranei801 – 821HelicalSequence analysisAdd BLAST21
Topological domaini822 – 1091CytoplasmicSequence analysisAdd BLAST270

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi108
OpenTargetsiENSG00000078295
PharmGKBiPA24561

Chemistry databases

ChEMBLiCHEMBL3760
DrugBankiDB02587 Colforsin

Polymorphism and mutation databases

BioMutaiADCY2
DMDMi118572617

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001956841 – 1091Adenylate cyclase type 2Add BLAST1091

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei491Phosphoserine; by PKCBy similarity1
Modified residuei544Phosphoserine; by PKCBy similarity1
Glycosylationi713N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi716N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Phosphorylated by RAF1.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ08462
MaxQBiQ08462
PaxDbiQ08462
PeptideAtlasiQ08462
PRIDEiQ08462
ProteomicsDBi58613

PTM databases

iPTMnetiQ08462
PhosphoSitePlusiQ08462

Expressioni

Tissue specificityi

Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level) (PubMed:11549699). Expressed in brain, especially in caudate nucleus, cerebellum and hippocampus.2 Publications

Gene expression databases

BgeeiENSG00000078295 Expressed in 198 organ(s), highest expression level in Brodmann (1909) area 9
CleanExiHS_ADCY2
ExpressionAtlasiQ08462 baseline and differential
GenevisibleiQ08462 HS

Organism-specific databases

HPAiCAB031482
HPA038015
HPA038483

Interactioni

Subunit structurei

Interacts with RAF1 (PubMed:15385642). Interacts with GNAS. Interacts with the G protein beta and gamma subunit complex (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106622, 10 interactors
CORUMiQ08462
DIPiDIP-422N
IntActiQ08462, 1 interactor
STRINGi9606.ENSP00000342952

Structurei

3D structure databases

ProteinModelPortaliQ08462
SMRiQ08462
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni905 – 922Interaction with GNASBy similarityAdd BLAST18
Regioni990 – 993Interaction with GNASBy similarity4

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 helix

Phylogenomic databases

eggNOGiKOG3619 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00760000119042
HOGENOMiHOG000006941
HOVERGENiHBG050458
InParanoidiQ08462
KOiK08042
OMAiLTMAVFN
OrthoDBiEOG091G05JR
PhylomeDBiQ08462
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
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

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 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q08462-1) [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
MWQEAMRRRR YLRDRSEEAA GGGDGLPRSR DWLYESYYCM SQQHPLIVFL
60 70 80 90 100
LLIVMGSCLA LLAVFFALGL EVEDHVAFLI TVPTALAIFF AIFILVCIES
110 120 130 140 150
VFKKLLRLFS LVIWICLVAM GYLFMCFGGT VSPWDQVSFF LFIIFVVYTM
160 170 180 190 200
LPFNMRDAII ASVLTSSSHT IVLSVCLSAT PGGKEHLVWQ ILANVIIFIC
210 220 230 240 250
GNLAGAYHKH LMELALQQTY QDTCNCIKSR IKLEFEKRQQ ERLLLSLLPA
260 270 280 290 300
HIAMEMKAEI IQRLQGPKAG QMENTNNFHN LYVKRHTNVS ILYADIVGFT
310 320 330 340 350
RLASDCSPGE LVHMLNELFG KFDQIAKENE CMRIKILGDC YYCVSGLPIS
360 370 380 390 400
LPNHAKNCVK MGLDMCEAIK KVRDATGVDI NMRVGVHSGN VLCGVIGLQK
410 420 430 440 450
WQYDVWSHDV TLANHMEAGG VPGRVHISSV TLEHLNGAYK VEEGDGDIRD
460 470 480 490 500
PYLKQHLVKT YFVINPKGER RSPQHLFRPR HTLDGAKMRA SVRMTRYLES
510 520 530 540 550
WGAAKPFAHL HHRDSMTTEN GKISTTDVPM GQHNFQNRTL RTKSQKKRFE
560 570 580 590 600
EELNERMIQA IDGINAQKQW LKSEDIQRIS LLFYNKVLEK EYRATALPAF
610 620 630 640 650
KYYVTCACLI FFCIFIVQIL VLPKTSVLGI SFGAAFLLLA FILFVCFAGQ
660 670 680 690 700
LLQCSKKASP LLMWLLKSSG IIANRPWPRI SLTIITTAII LMMAVFNMFF
710 720 730 740 750
LSDSEETIPP TANTTNTSFS ASNNQVAILR AQNLFFLPYF IYSCILGLIS
760 770 780 790 800
CSVFLRVNYE LKMLIMMVAL VGYNTILLHT HAHVLGDYSQ VLFERPGIWK
810 820 830 840 850
DLKTMGSVSL SIFFITLLVL GRQNEYYCRL DFLWKNKFKK EREEIETMEN
860 870 880 890 900
LNRVLLENVL PAHVAEHFLA RSLKNEELYH QSYDCVCVMF ASIPDFKEFY
910 920 930 940 950
TESDVNKEGL ECLRLLNEII ADFDDLLSKP KFSGVEKIKT IGSTYMAATG
960 970 980 990 1000
LSAVPSQEHS QEPERQYMHI GTMVEFAFAL VGKLDAINKH SFNDFKLRVG
1010 1020 1030 1040 1050
INHGPVIAGV IGAQKPQYDI WGNTVNVASR MDSTGVLDKI QVTEETSLVL
1060 1070 1080 1090
QTLGYTCTCR GIINVKGKGD LKTYFVNTEM SRSLSQSNVA S
Length:1,091
Mass (Da):123,603
Last modified:November 28, 2006 - v5
Checksum:i41FD8BC607C075D1
GO
Isoform 2 (identifier: Q08462-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: MWQEAMRRRR...LLLIVMGSCL → MDLRWARDLH...KRWRIQREES
     60-239: Missing.

Note: No experimental confirmation available.
Show »
Length:911
Mass (Da):103,158
Checksum:i658C0FA201D0E85E
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6REB8D6REB8_HUMAN
Adenylate cyclase type 2
ADCY2
100Annotation score:
H0YA58H0YA58_HUMAN
Adenylate cyclase type 2
ADCY2
76Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti188 – 207VWQIL…LAGAY → GLADPGQCDHFHLWEPGXTN in AAP97285 (Ref. 1) CuratedAdd BLAST20
Sequence conflicti675R → Q in CAA52282 (PubMed:1427768).Curated1
Sequence conflicti675R → Q in AAA64923 (PubMed:1427768).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029012147V → L1 PublicationCorresponds to variant dbSNP:rs13166360Ensembl.1
Natural variantiVAR_048247163V → I. Corresponds to variant dbSNP:rs34043481Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0558111 – 59MWQEA…MGSCL → MDLRWARDLHLREASRSVAF TTLRLGAVTTGLLTFREPGD KEKSGKGLGKRWRIQREES in isoform 2. 1 PublicationAdd BLAST59
Alternative sequenceiVSP_05581260 – 239Missing in isoform 2. 1 PublicationAdd BLAST180

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF410885 mRNA Translation: AAP97285.1
AK294555 mRNA Translation: BAH11807.1
AC010346 Genomic DNA No translation available.
AC010437 Genomic DNA No translation available.
AC024577 Genomic DNA No translation available.
AC093305 Genomic DNA No translation available.
AC113366 Genomic DNA No translation available.
BC111743 mRNA Translation: AAI11744.1
AB028983 mRNA Translation: BAA83012.1
X74210 mRNA Translation: CAA52282.1
L21993 mRNA Translation: AAA64923.1
CCDSiCCDS3872.2 [Q08462-1]
PIRiI37136
RefSeqiNP_065433.2, NM_020546.2 [Q08462-1]
UniGeneiHs.481545

Genome annotation databases

EnsembliENST00000338316; ENSP00000342952; ENSG00000078295 [Q08462-1]
GeneIDi108
KEGGihsa:108
UCSCiuc003jdz.2 human [Q08462-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF410885 mRNA Translation: AAP97285.1
AK294555 mRNA Translation: BAH11807.1
AC010346 Genomic DNA No translation available.
AC010437 Genomic DNA No translation available.
AC024577 Genomic DNA No translation available.
AC093305 Genomic DNA No translation available.
AC113366 Genomic DNA No translation available.
BC111743 mRNA Translation: AAI11744.1
AB028983 mRNA Translation: BAA83012.1
X74210 mRNA Translation: CAA52282.1
L21993 mRNA Translation: AAA64923.1
CCDSiCCDS3872.2 [Q08462-1]
PIRiI37136
RefSeqiNP_065433.2, NM_020546.2 [Q08462-1]
UniGeneiHs.481545

3D structure databases

ProteinModelPortaliQ08462
SMRiQ08462
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106622, 10 interactors
CORUMiQ08462
DIPiDIP-422N
IntActiQ08462, 1 interactor
STRINGi9606.ENSP00000342952

Chemistry databases

ChEMBLiCHEMBL3760
DrugBankiDB02587 Colforsin

PTM databases

iPTMnetiQ08462
PhosphoSitePlusiQ08462

Polymorphism and mutation databases

BioMutaiADCY2
DMDMi118572617

Proteomic databases

EPDiQ08462
MaxQBiQ08462
PaxDbiQ08462
PeptideAtlasiQ08462
PRIDEiQ08462
ProteomicsDBi58613

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338316; ENSP00000342952; ENSG00000078295 [Q08462-1]
GeneIDi108
KEGGihsa:108
UCSCiuc003jdz.2 human [Q08462-1]

Organism-specific databases

CTDi108
DisGeNETi108
EuPathDBiHostDB:ENSG00000078295.15
GeneCardsiADCY2
HGNCiHGNC:233 ADCY2
HPAiCAB031482
HPA038015
HPA038483
MIMi103071 gene
neXtProtiNX_Q08462
OpenTargetsiENSG00000078295
PharmGKBiPA24561
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3619 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00760000119042
HOGENOMiHOG000006941
HOVERGENiHBG050458
InParanoidiQ08462
KOiK08042
OMAiLTMAVFN
OrthoDBiEOG091G05JR
PhylomeDBiQ08462
TreeFamiTF313845

Enzyme and pathway databases

BRENDAi4.6.1.1 2681
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-5610787 Hedgehog 'off' state
SIGNORiQ08462

Miscellaneous databases

ChiTaRSiADCY2 human
GeneWikiiADCY2
GenomeRNAii108
PROiPR:Q08462
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000078295 Expressed in 198 organ(s), highest expression level in Brodmann (1909) area 9
CleanExiHS_ADCY2
ExpressionAtlasiQ08462 baseline and differential
GenevisibleiQ08462 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
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_HUMAN
AccessioniPrimary (citable) accession number: Q08462
Secondary accession number(s): B7Z2C1
, Q2NKL8, Q9UDB2, Q9UPU2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: November 28, 2006
Last modified: November 7, 2018
This is version 173 of the entry and version 5 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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