Target Information

Target General Information

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Target ID

T63609 (Former ID: TTDS00500)

Target Name

Adenylate cyclase type 1 (ADCY1)

Synonyms

Ca(2+)/calmodulin-activated adenylyl cyclase; Adenylyl cyclase 1; Adenylate cyclase type I; ATP pyrophosphate-lyase 1

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Gene Name

ADCY1

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Nutritional deficiency [ICD-11: 5B50-5B71]

Function

Mediates responses to increased cellular Ca(2+)/calmodulin levels. 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. Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.

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BioChemical Class

Phosphorus-oxygen lyase

UniProt ID

ADCY1_HUMAN

EC Number

EC 4.6.1.1

Sequence

MAGAPRGGGGGGGGAGEPGGAERAAGTSRRRGLRACDEEFACPELEALFRGYTLRLEQAA
TLKALAVLSLLAGALALAELLGAPGPAPGLAKGSHPVHCVLFLALLVVTNVRSLQVPQLQ
QVGQLALLFSLTFALLCCPFALGGPARGSAGAAGGPATAEQGVWQLLLVTFVSYALLPVR
SLLAIGFGLVVAASHLLVTATLVPAKRPRLWRTLGANALLFVGVNMYGVFVRILTERSQR
KAFLQARSCIEDRLRLEDENEKQERLLMSLLPRNVAMEMKEDFLKPPERIFHKIYIQRHD
NVSILFADIVGFTGLASQCTAQELVKLLNELFGKFDELATENHCRRIKILGDCYYCVSGL
TQPKTDHAHCCVEMGLDMIDTITSVAEATEVDLNMRVGLHTGRVLCGVLGLRKWQYDVWS
NDVTLANVMEAAGLPGKVHITKTTLACLNGDYEVEPGYGHERNSFLKTHNIETFFIVPSH
RRKIFPGLILSDIKPAKRMKFKTVCYLLVQLMHCRKMFKAEIPFSNVMTCEDDDKRRALR
TASEKLRNRSSFSTNVVYTTPGTRVNRYISRLLEARQTELEMADLNFFTLKYKHVEREQK
YHQLQDEYFTSAVVLTLILAALFGLVYLLIFPQSVVVLLLLVFCICFLVACVLYLHITRV
QCFPGCLTIQIRTVLCIFIVVLIYSVAQGCVVGCLPWAWSSKPNSSLVVLSSGGQRTALP
TLPCESTHHALLCCLVGTLPLAIFFRVSSLPKMILLSGLTTSYILVLELSGYTRTGGGAV
SGRSYEPIVAILLFSCALALHARQVDIRLRLDYLWAAQAEEEREDMEKVKLDNRRILFNL
LPAHVAQHFLMSNPRNMDLYYQSYSQVGVMFASIPNFNDFYIELDGNNMGVECLRLLNEI
IADFDELMEKDFYKDIEKIKTIGSTYMAAVGLAPTSGTKAKKSISSHLSTLADFAIEMFD
VLDEINYQSYNDFVLRVGINVGPVVAGVIGARRPQYDIWGNTVNVASRMDSTGVQGRIQV
TEEVHRLLRRCPYHFVCRGKVSVKGKGEMLTYFLEGRTDGNGSQIRSLGLDRKMCPFGRA
GLQGRRPPVCPMPGVSVRAGLPPHSPGQYLPSAAAGKEA

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3D Structure

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AlphaFold

ADReCS ID

BADD_A01671 ; BADD_A04410 ; BADD_A05200

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

Adenosine monophosphate

Drug Info

Approved

Malnutrition

[2], [3]

Mode of Action

[+] 1 Modes of Action

Binder

[+] 1 Binder drugs

Adenosine monophosphate

Drug Info

[1]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Purine metabolism	hsa00230	Affiliated Target
Class: Metabolism => Nucleotide metabolism	Pathway Hierarchy
Rap1 signaling pathway	hsa04015	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Calcium signaling pathway	hsa04020	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
cGMP-PKG signaling pathway	hsa04022	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
cAMP signaling pathway	hsa04024	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Chemokine signaling pathway	hsa04062	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Phospholipase D signaling pathway	hsa04072	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Oocyte meiosis	hsa04114	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
Longevity regulating pathway	hsa04211	Affiliated Target
Class: Organismal Systems => Aging	Pathway Hierarchy
Longevity regulating pathway - multiple species	hsa04213	Affiliated Target
Class: Organismal Systems => Aging	Pathway Hierarchy
Adrenergic signaling in cardiomyocytes	hsa04261	Affiliated Target
Class: Organismal Systems => Circulatory system	Pathway Hierarchy
Vascular smooth muscle contraction	hsa04270	Affiliated Target
Class: Organismal Systems => Circulatory system	Pathway Hierarchy
Apelin signaling pathway	hsa04371	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Gap junction	hsa04540	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Platelet activation	hsa04611	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Circadian entrainment	hsa04713	Affiliated Target
Class: Organismal Systems => Environmental adaptation	Pathway Hierarchy
Thermogenesis	hsa04714	Affiliated Target
Class: Organismal Systems => Environmental adaptation	Pathway Hierarchy
Long-term potentiation	hsa04720	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy
Retrograde endocannabinoid signaling	hsa04723	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy
Glutamatergic synapse	hsa04724	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy
Cholinergic synapse	hsa04725	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy
GABAergic synapse	hsa04727	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy
Inflammatory mediator regulation of TRP channels	hsa04750	Affiliated Target
Class: Organismal Systems => Sensory system	Pathway Hierarchy
Insulin secretion	hsa04911	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
GnRH signaling pathway	hsa04912	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Ovarian steroidogenesis	hsa04913	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Progesterone-mediated oocyte maturation	hsa04914	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Estrogen signaling pathway	hsa04915	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Melanogenesis	hsa04916	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Thyroid hormone synthesis	hsa04918	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Oxytocin signaling pathway	hsa04921	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Regulation of lipolysis in adipocytes	hsa04923	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Aldosterone synthesis and secretion	hsa04925	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Relaxin signaling pathway	hsa04926	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Cortisol synthesis and secretion	hsa04927	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Parathyroid hormone synthesis, secretion and action	hsa04928	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Growth hormone synthesis, secretion and action	hsa04935	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Salivary secretion	hsa04970	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Gastric acid secretion	hsa04971	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Pancreatic secretion	hsa04972	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Bile secretion	hsa04976	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	3	Degree centrality	3.22E-04	Betweenness centrality	4.88E-06
Closeness centrality	1.84E-01	Radiality	1.31E+01	Clustering coefficient	3.33E-01
Neighborhood connectivity	2.00E+01	Topological coefficient	4.28E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Co-Targets

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Co-Targets

Co-Targets Info

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 37 KEGG Pathways	+
1	Purine metabolism
2	Rap1 signaling pathway
3	Calcium signaling pathway
4	cGMP-PKG signaling pathway
5	cAMP signaling pathway
6	Chemokine signaling pathway
7	Oocyte meiosis
8	Adrenergic signaling in cardiomyocytes
9	Vascular smooth muscle contraction
10	Gap junction
11	Platelet activation
12	Circadian entrainment
13	Long-term potentiation
14	Retrograde endocannabinoid signaling
15	Glutamatergic synapse
16	Cholinergic synapse
17	GABAergic synapse
18	Inflammatory mediator regulation of TRP channels
19	Insulin secretion
20	GnRH signaling pathway
21	Ovarian steroidogenesis
22	Progesterone-mediated oocyte maturation
23	Estrogen signaling pathway
24	Melanogenesis
25	Thyroid hormone synthesis
26	Oxytocin signaling pathway
27	Regulation of lipolysis in adipocytes
28	Salivary secretion
29	Gastric acid secretion
30	Pancreatic secretion
31	Bile secretion
32	Morphine addiction
33	Chagas disease (American trypanosomiasis)
34	Amoebiasis
35	HTLV-I infection
36	Pathways in cancer
37	Dilated cardiomyopathy
Panther Pathway	[+] 4 Panther Pathways	+
1	Endothelin signaling pathway
2	Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
3	GABA-B receptor II signaling
4	CCKR signaling map ST
PID Pathway	[+] 3 PID Pathways	+
1	Endothelins
2	LPA receptor mediated events
3	LPA4-mediated signaling events
Reactome	[+] 8 Reactome Pathways	+
1	Glucagon signaling in metabolic regulation
2	PKA activation
3	PKA activation in glucagon signalling
4	G alpha (s) signalling events
5	G alpha (i) signalling events
6	G alpha (z) signalling events
7	Vasopressin regulates renal water homeostasis via Aquaporins
8	Hedgehog 'off' state
WikiPathways	[+] 10 WikiPathways	+
1	Hypothetical Network for Drug Addiction
2	Calcium Regulation in the Cardiac Cell
3	G Protein Signaling Pathways
4	Myometrial Relaxation and Contraction Pathways
5	Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
6	DAG and IP3 signaling
7	Regulation of Water Balance by Renal Aquaporins
8	Opioid Signalling
9	Integration of energy metabolism
10	GPCR downstream signaling

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Ecto- and cytosolic 5'-nucleotidases in normal and AMP deaminase-deficient human skeletal muscle. Biol Chem. 2006 Jan;387(1):53-8.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2455).

REF 3

Emerging drugs for chemotherapy-induced mucositis. Expert Opin Emerg Drugs. 2008 Sep;13(3):511-22.

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