ADCY1

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

Activity 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 key	Position(s)	DescriptionActions	Length
Metal bindingⁱ	308	Magnesium 1; catalyticPROSITE-ProRule annotation	1
Metal bindingⁱ	308	Magnesium 2; catalyticPROSITE-ProRule annotation	1
Metal bindingⁱ	309	Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation	1
Metal bindingⁱ	352	Magnesium 1; catalyticPROSITE-ProRule annotation	1
Metal bindingⁱ	352	Magnesium 2; catalyticPROSITE-ProRule annotation	1
Binding siteⁱ	396	ATPBy similarity	1
Binding siteⁱ	920	ATPBy similarity	1
Binding siteⁱ	1044	ATPBy similarity	1

Regions

Feature key	Position(s)	DescriptionActions	Length
Nucleotide bindingⁱ	308 – 313	ATPBy similarity	6
Nucleotide bindingⁱ	350 – 352	ATPBy similarity	3
Nucleotide bindingⁱ	997 – 999	ATPBy similarity	3
Nucleotide bindingⁱ	1004 – 1008	ATPBy similarity	5

GO - Molecular functionⁱ

adenylate cyclase activity Source: Reactome
ATP binding Source: UniProtKB-KW
calcium- and calmodulin-responsive adenylate cyclase activity Source: UniProtKB
calmodulin binding Source: UniProtKB-KW
guanylate cyclase activity Source: GO_Central
metal ion binding Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: UniProtKB
adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: Reactome
axonogenesis Source: Ensembl
brain development Source: Ensembl
cAMP biosynthetic process Source: UniProtKB
cAMP-mediated signaling Source: UniProtKB
cellular response to calcium ion Source: UniProtKB
cellular response to forskolin Source: UniProtKB
cellular response to glucagon stimulus Source: Reactome
cGMP biosynthetic process Source: GO_Central
circadian rhythm Source: Ensembl
G-protein coupled receptor signaling pathway Source: Reactome
long-term memory Source: Ensembl
regulation of circadian rhythm Source: UniProtKB
renal water homeostasis Source: Reactome
response to lithium ion Source: Ensembl
signal transduction Source: GO_Central

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Calmodulin-binding, Lyase
Biological process	Biological rhythms, cAMP biosynthesis
Ligand	ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	4.6.1.1 2681
Reactomeⁱ	R-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
SIGNORⁱ	Q08828

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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 7

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000164742.14
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:232 ADCY1
MIMⁱ	103072 gene
neXtProtⁱ	NX_Q08828

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	1 – 63	CytoplasmicSequence analysisAdd BLAST	63
Transmembraneⁱ	64 – 84	HelicalSequence analysisAdd BLAST	21
Transmembraneⁱ	88 – 108	HelicalSequence analysisAdd BLAST	21
Transmembraneⁱ	125 – 145	HelicalSequence analysisAdd BLAST	21
Transmembraneⁱ	158 – 178	HelicalSequence analysisAdd BLAST	21
Transmembraneⁱ	183 – 203	HelicalSequence analysisAdd BLAST	21
Transmembraneⁱ	214 – 234	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	235 – 610	CytoplasmicSequence analysisAdd BLAST	376
Transmembraneⁱ	611 – 631	HelicalSequence analysisAdd BLAST	21
Transmembraneⁱ	635 – 655	HelicalSequence analysisAdd BLAST	21
Transmembraneⁱ	674 – 694	HelicalSequence analysisAdd BLAST	21
Transmembraneⁱ	725 – 745	HelicalSequence analysisAdd BLAST	21
Transmembraneⁱ	753 – 773	HelicalSequence analysisAdd BLAST	21
Transmembraneⁱ	775 – 794	HelicalSequence analysisAdd BLAST	20
Topological domainⁱ	795 – 1119	CytoplasmicSequence analysisAdd BLAST	325

Keywords - Cellular componentⁱ

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Keywords - Diseaseⁱ

Deafness, Non-syndromic deafness

Organism-specific databases

DisGeNET More...DisGeNETⁱ	107
MalaCards human disease database More...MalaCardsⁱ	ADCY1
MIMⁱ	610154 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000164742
Orphanetⁱ	90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
PharmGKBⁱ	PA24560

Chemistry databases

ChEMBLⁱ	CHEMBL2899
Drug and drug target database More...DrugBankⁱ	DB00131 Adenosine monophosphate DB00171 Adenosine triphosphate

Polymorphism and mutation databases

BioMutaⁱ	ADCY1
DMDMⁱ	62512172

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000195682	1 – 1119	Adenylate cyclase type 1Add BLAST		1119

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	551	PhosphoserineBy similarity		1
Glycosylationⁱ	704	N-linked (GlcNAc...) asparagineSequence analysis		1

Post-translational modificationⁱ

N-glycosylated.By similarity

Keywords - PTMⁱ

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbⁱ	Q08828
PeptideAtlas More...PeptideAtlasⁱ	Q08828
PRIDEⁱ	Q08828
ProteomicsDBⁱ	58648

PTM databases

iPTMnetⁱ	Q08828
PhosphoSitePlusⁱ	Q08828

Expressionⁱ

Tissue specificityⁱ

Gene expression databases

Bgeeⁱ	ENSG00000164742 Expressed in 177 organ(s), highest expression level in neocortex
CleanExⁱ	HS_ADCY1
ExpressionAtlasⁱ	Q08828 baseline and differential
Genevisibleⁱ	Q08828 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB018364 HPA068274

HPAⁱ

CAB018364
HPA068274

Interactionⁱ

Subunit structureⁱ

Interacts with CALM.By similarity

GO - Molecular functionⁱ

calmodulin binding Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	106621, 2 interactors
STRINGⁱ	9606.ENSP00000297323

Chemistry databases

BindingDBⁱ	Q08828

BindingDBⁱ

Q08828

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q08828
SMRⁱ	Q08828
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	493 – 520	Interaction with calmodulinBy similarityAdd BLAST		28
Regionⁱ	1024 – 1047	Interaction with calmodulinBy similarityAdd BLAST		24

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

eggNOGⁱ	KOG3619 Eukaryota COG2114 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000119042
HOGENOMⁱ	HOG000006941
HOVERGENⁱ	HBG050458
InParanoidⁱ	Q08828
KEGG Orthology (KO) More...KOⁱ	K08041
OMAⁱ	WAWSSKP
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G05JR
PhylomeDBⁱ	Q08828
TreeFamⁱ	TF313845

Family and domain databases

Gene3Dⁱ	3.30.70.1230, 2 hits
InterProⁱ	View protein in InterPro IPR001054 A/G_cyclase IPR018297 A/G_cyclase_CS IPR032628 AC_N IPR030672 Adcy IPR029787 Nucleotide_cyclase
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF16214 AC_N, 1 hit PF00211 Guanylate_cyc, 2 hits
PIRSFⁱ	PIRSF039050 Ade_cyc, 1 hit
SMARTⁱ	View protein in SMART SM00044 CYCc, 2 hits
SUPFAMⁱ	SSF55073 SSF55073, 2 hits
PROSITEⁱ	View 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.ⁱShow all

Q08828-1 [UniParc]FASTA Add 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

Computationally mapped potential isoform sequencesⁱ

There is 1 potential isoform mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation
	C9J1J0	C9J1J0_HUMAN		Adenylate cyclase 1 (Brain), isofor... Adenylate cyclase 1 (Brain), isoform CRA_e (Adenylate cyclase type 1)	ADCY1 hCG_19245	338	Annotation score:

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_029186	456	P → L. Corresponds to variant dbSNP:rs12721473Ensembl.	1
Natural variantⁱVAR_029187	940	A → T. Corresponds to variant dbSNP:rs45444695Ensembl.	1
Natural variantⁱVAR_048246	984	V → M. Corresponds to variant dbSNP:rs2293106Ensembl.	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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS34631.1
PIRⁱ	A47007
NCBI Reference Sequences More...RefSeqⁱ	NP_066939.1, NM_021116.2
UniGeneⁱ	Hs.192215

Genome annotation databases

Ensemblⁱ	ENST00000297323; ENSP00000297323; ENSG00000164742
GeneIDⁱ	107
KEGGⁱ	hsa:107
UCSC genome browser More...UCSCⁱ	uc003tne.5 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q08828	Adenylate cyclase		PANPA		1069	UniRef100_Q08828
Adenylate cyclase		GORGO		1058
Brain adenylate cyclase 1 (Fragment)		synthetic construct		413
Adenylate cyclase 1 (Brain), isoform CRA_b		HUMAN		894
Brain adenylate cyclase 1 (Fragment)		synthetic construct		312
+1

Protein	Similar proteins		Species	Score	Length	Source
Q08828	Adenylate cyclase type 1		MOUSE		1118	UniRef90_O88444
Adenylate cyclase		PANPA		1069
Adenylate cyclase		GORGO		1058
Brain adenylate cyclase 1 (Fragment)		synthetic construct		413
Adenylate cyclase 1 (Brain), isoform CRA_b		HUMAN		894
+43

Protein	Similar proteins		Species	Score	Length	Source
Q08828	Adenylate cyclase type 1		MOUSE		1118	UniRef50_O88444
Adenylate cyclase		PAPAN		1119
Adenylate cyclase		PANTR		1119
Adenylate cyclase		Cebus capucinus imitator		1119
Adenylate cyclase		AOTNA		1119
+92

Entry informationⁱ

Entry nameⁱ	ADCY1_HUMAN
Accessionⁱ	Q08828Primary (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:	September 12, 2018
	This is version 169 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q08828 (ADCY1_HUMAN)

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Adenylate cyclase type 1

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Plasma membrane

Other locations

Cytosol

Extracellular region or secreted

Nucleus

Plasma Membrane

Other locations

Topology

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Keywords - Diseasei

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Computationally mapped potential isoform sequencesi

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Computationally mapped potential isoform sequencesⁱ

Keywords - Coding sequence diversityⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ