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Protein

Adenylate cyclase type 1

Gene

ADCY1

Organism
Homo sapiens (Human)
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. Mediates responses to increased cellular Ca2+/calmodulin levels (By similarity). May be involved in regulatory processes in the central nervous system. May play a role in memory and learning. Plays a role in the regulation of the circadian rhythm of daytime contrast sensitivity probably by modulating the rhythmic synthesis of cyclic AMP in the retina (By similarity).By similarity

Catalytic activityi

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

Cofactori

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

Enzyme regulationi

Activated by calcium/calmodulin. Activated by forskolin. Activated by the G protein alpha subunit GNAS. Inhibited by the G protein beta and gamma subunit complex. Inhibited by the ATP analogs adenosine, 2'-deoxyadenosine and 2'-deoxy-3'-AMP.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi308Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi308Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi309Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi352Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi352Magnesium 2; catalyticPROSITE-ProRule annotation1
Binding sitei396ATPBy similarity1
Binding sitei920ATPBy similarity1
Binding sitei1044ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi308 – 313ATPBy similarity6
Nucleotide bindingi350 – 352ATPBy similarity3
Nucleotide bindingi997 – 999ATPBy similarity3
Nucleotide bindingi1004 – 1008ATPBy similarity5

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Biological rhythms, cAMP biosynthesis

Keywords - Ligandi

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

Enzyme and pathway databases

BioCyciZFISH:HS09128-MONOMER.
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-442720. CREB phosphorylation through the activation of Adenylate Cyclase.
R-HSA-5610787. Hedgehog 'off' state.
SIGNORiQ08828.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 1 (EC:4.6.1.1By similarity)
Alternative name(s):
ATP pyrophosphate-lyase 1
Adenylate cyclase type I
Adenylyl cyclase 1
Ca(2+)/calmodulin-activated adenylyl cyclase
Gene namesi
Name:ADCY1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:232. ADCY1.

Subcellular locationi

  • Membrane By similarity; Multi-pass membrane protein By similarity
  • Cell membrane 1 Publication; Multi-pass membrane protein Curated
  • Cytoplasm By similarity
  • Membrane raft By similarity

  • Note: Expressed in the cytoplasm of supporting cells and hair cells of the cochlea vestibule, as well as to the cochlear hair cell nuclei and stereocilia.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 63CytoplasmicSequence analysisAdd BLAST63
Transmembranei64 – 84HelicalSequence analysisAdd BLAST21
Transmembranei88 – 108HelicalSequence analysisAdd BLAST21
Transmembranei125 – 145HelicalSequence analysisAdd BLAST21
Transmembranei158 – 178HelicalSequence analysisAdd BLAST21
Transmembranei183 – 203HelicalSequence analysisAdd BLAST21
Transmembranei214 – 234HelicalSequence analysisAdd BLAST21
Topological domaini235 – 610CytoplasmicSequence analysisAdd BLAST376
Transmembranei611 – 631HelicalSequence analysisAdd BLAST21
Transmembranei635 – 655HelicalSequence analysisAdd BLAST21
Transmembranei674 – 694HelicalSequence analysisAdd BLAST21
Transmembranei725 – 745HelicalSequence analysisAdd BLAST21
Transmembranei753 – 773HelicalSequence analysisAdd BLAST21
Transmembranei775 – 794HelicalSequence analysisAdd BLAST20
Topological domaini795 – 1119CytoplasmicSequence analysisAdd BLAST325

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • membrane raft Source: UniProtKB-SubCell
  • nucleus Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal recessive, 44 (DFNB44)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic deafness characterized by prelingual profound hearing loss affecting all frequencies.
See also OMIM:610154

Keywords - Diseasei

Deafness, Non-syndromic deafness

Organism-specific databases

DisGeNETi107.
MalaCardsiADCY1.
MIMi610154. phenotype.
OpenTargetsiENSG00000164742.
Orphaneti90636. Autosomal recessive non-syndromic sensorineural deafness type DFNB.
PharmGKBiPA24560.

Chemistry databases

ChEMBLiCHEMBL2899.
DrugBankiDB00131. Adenosine monophosphate.
DB00171. Adenosine triphosphate.

Polymorphism and mutation databases

BioMutaiADCY1.
DMDMi62512172.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001956821 – 1119Adenylate cyclase type 1Add BLAST1119

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei551PhosphoserineBy similarity1
Glycosylationi704N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ08828.
PeptideAtlasiQ08828.
PRIDEiQ08828.

PTM databases

iPTMnetiQ08828.
PhosphoSitePlusiQ08828.

Expressioni

Tissue specificityi

Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level) (PubMed:11549699). Brain, retina and adrenal medulla.2 Publications

Gene expression databases

BgeeiENSG00000164742.
CleanExiHS_ADCY1.
ExpressionAtlasiQ08828. baseline and differential.
GenevisibleiQ08828. HS.

Organism-specific databases

HPAiCAB018364.
HPA068274.

Interactioni

Subunit structurei

Interacts with CALM.By similarity

Protein-protein interaction databases

STRINGi9606.ENSP00000297323.

Chemistry databases

BindingDBiQ08828.

Structurei

3D structure databases

ProteinModelPortaliQ08828.
SMRiQ08828.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni493 – 520Interaction with calmodulinBy similarityAdd BLAST28
Regioni1024 – 1047Interaction with calmodulinBy similarityAdd BLAST24

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
Contains 2 guanylate cyclase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000119042.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiQ08828.
KOiK08041.
OMAiCLPWAWS.
OrthoDBiEOG091G05JR.
PhylomeDBiQ08828.
TreeFamiTF313845.

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.

Q08828-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGAPRGGGG GGGGAGEPGG AERAAGTSRR RGLRACDEEF ACPELEALFR
60 70 80 90 100
GYTLRLEQAA TLKALAVLSL LAGALALAEL LGAPGPAPGL AKGSHPVHCV
110 120 130 140 150
LFLALLVVTN VRSLQVPQLQ QVGQLALLFS LTFALLCCPF ALGGPARGSA
160 170 180 190 200
GAAGGPATAE QGVWQLLLVT FVSYALLPVR SLLAIGFGLV VAASHLLVTA
210 220 230 240 250
TLVPAKRPRL WRTLGANALL FVGVNMYGVF VRILTERSQR KAFLQARSCI
260 270 280 290 300
EDRLRLEDEN EKQERLLMSL LPRNVAMEMK EDFLKPPERI FHKIYIQRHD
310 320 330 340 350
NVSILFADIV GFTGLASQCT AQELVKLLNE LFGKFDELAT ENHCRRIKIL
360 370 380 390 400
GDCYYCVSGL TQPKTDHAHC CVEMGLDMID TITSVAEATE VDLNMRVGLH
410 420 430 440 450
TGRVLCGVLG LRKWQYDVWS NDVTLANVME AAGLPGKVHI TKTTLACLNG
460 470 480 490 500
DYEVEPGYGH ERNSFLKTHN IETFFIVPSH RRKIFPGLIL SDIKPAKRMK
510 520 530 540 550
FKTVCYLLVQ LMHCRKMFKA EIPFSNVMTC EDDDKRRALR TASEKLRNRS
560 570 580 590 600
SFSTNVVYTT PGTRVNRYIS RLLEARQTEL EMADLNFFTL KYKHVEREQK
610 620 630 640 650
YHQLQDEYFT SAVVLTLILA ALFGLVYLLI FPQSVVVLLL LVFCICFLVA
660 670 680 690 700
CVLYLHITRV QCFPGCLTIQ IRTVLCIFIV VLIYSVAQGC VVGCLPWAWS
710 720 730 740 750
SKPNSSLVVL SSGGQRTALP TLPCESTHHA LLCCLVGTLP LAIFFRVSSL
760 770 780 790 800
PKMILLSGLT TSYILVLELS GYTRTGGGAV SGRSYEPIVA ILLFSCALAL
810 820 830 840 850
HARQVDIRLR LDYLWAAQAE EEREDMEKVK LDNRRILFNL LPAHVAQHFL
860 870 880 890 900
MSNPRNMDLY YQSYSQVGVM FASIPNFNDF YIELDGNNMG VECLRLLNEI
910 920 930 940 950
IADFDELMEK DFYKDIEKIK TIGSTYMAAV GLAPTSGTKA KKSISSHLST
960 970 980 990 1000
LADFAIEMFD VLDEINYQSY NDFVLRVGIN VGPVVAGVIG ARRPQYDIWG
1010 1020 1030 1040 1050
NTVNVASRMD STGVQGRIQV TEEVHRLLRR CPYHFVCRGK VSVKGKGEML
1060 1070 1080 1090 1100
TYFLEGRTDG NGSQIRSLGL DRKMCPFGRA GLQGRRPPVC PMPGVSVRAG
1110
LPPHSPGQYL PSAAAGKEA
Length:1,119
Mass (Da):123,440
Last modified:April 12, 2005 - v2
Checksum:iE8DDC8FCB58743D7
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029186456P → L.Corresponds to variant rs12721473dbSNPEnsembl.1
Natural variantiVAR_029187940A → T.Corresponds to variant rs45444695dbSNPEnsembl.1
Natural variantiVAR_048246984V → M.Corresponds to variant rs2293106dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC069008 Genomic DNA. Translation: AAS07467.1.
AC091439 Genomic DNA. No translation available.
CH236960 Genomic DNA. Translation: EAL23741.1.
L05500 mRNA. Translation: AAA02907.1.
CCDSiCCDS34631.1.
PIRiA47007.
RefSeqiNP_066939.1. NM_021116.2.
UniGeneiHs.192215.

Genome annotation databases

EnsembliENST00000297323; ENSP00000297323; ENSG00000164742.
GeneIDi107.
KEGGihsa:107.
UCSCiuc003tne.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC069008 Genomic DNA. Translation: AAS07467.1.
AC091439 Genomic DNA. No translation available.
CH236960 Genomic DNA. Translation: EAL23741.1.
L05500 mRNA. Translation: AAA02907.1.
CCDSiCCDS34631.1.
PIRiA47007.
RefSeqiNP_066939.1. NM_021116.2.
UniGeneiHs.192215.

3D structure databases

ProteinModelPortaliQ08828.
SMRiQ08828.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000297323.

Chemistry databases

BindingDBiQ08828.
ChEMBLiCHEMBL2899.
DrugBankiDB00131. Adenosine monophosphate.
DB00171. Adenosine triphosphate.

PTM databases

iPTMnetiQ08828.
PhosphoSitePlusiQ08828.

Polymorphism and mutation databases

BioMutaiADCY1.
DMDMi62512172.

Proteomic databases

PaxDbiQ08828.
PeptideAtlasiQ08828.
PRIDEiQ08828.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000297323; ENSP00000297323; ENSG00000164742.
GeneIDi107.
KEGGihsa:107.
UCSCiuc003tne.5. human.

Organism-specific databases

CTDi107.
DisGeNETi107.
GeneCardsiADCY1.
H-InvDBHIX0033533.
HGNCiHGNC:232. ADCY1.
HPAiCAB018364.
HPA068274.
MalaCardsiADCY1.
MIMi103072. gene.
610154. phenotype.
neXtProtiNX_Q08828.
OpenTargetsiENSG00000164742.
Orphaneti90636. Autosomal recessive non-syndromic sensorineural deafness type DFNB.
PharmGKBiPA24560.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000119042.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiQ08828.
KOiK08041.
OMAiCLPWAWS.
OrthoDBiEOG091G05JR.
PhylomeDBiQ08828.
TreeFamiTF313845.

Enzyme and pathway databases

BioCyciZFISH:HS09128-MONOMER.
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-442720. CREB phosphorylation through the activation of Adenylate Cyclase.
R-HSA-5610787. Hedgehog 'off' state.
SIGNORiQ08828.

Miscellaneous databases

ChiTaRSiADCY1. human.
GeneWikiiADCY1.
GenomeRNAii107.
PROiQ08828.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164742.
CleanExiHS_ADCY1.
ExpressionAtlasiQ08828. baseline and differential.
GenevisibleiQ08828. HS.

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...

Entry informationi

Entry nameiADCY1_HUMAN
AccessioniPrimary (citable) accession number: Q08828
Secondary accession number(s): A4D2L8, Q75MI1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: April 12, 2005
Last modified: November 2, 2016
This is version 157 of the entry and version 2 of the sequence. [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. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  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. 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.