Tchem ADCY6 Adenylate cyclase type 6

Protein Summary

Description

Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors (PubMed:17916776, PubMed:17110384). Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells (PubMed:17916776). Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption. Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion. Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (By similarity). Signaling mediates cAMP-dependent activation of protein kinase PKA. This promotes increased phosphorylation of various proteins, including AKT. Plays a role in regulating cardiac sarcoplasmic reticulum Ca(2+) uptake and storage, and is required for normal heart ventricular contractibility. May contribute to normal heart function (By similarity). Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol (PubMed:17916776). Contributes to bone cell responses to mechanical stimuli (By similarity). This gene encodes a member of the adenylyl cyclase family of proteins, which are required for the synthesis of cyclic AMP. All members of this family have an intracellular N-terminus, a tandem repeat of six transmembrane domains separated by a cytoplasmic loop, and a C-terminal cytoplasmic domain. The two cytoplasmic regions bind ATP and form the catalytic core of the protein. Adenylyl cyclases are important effectors of transmembrane signaling pathways and are regulated by the activity of G protein coupled receptor signaling. This protein belongs to a small subclass of adenylyl cyclase proteins that are functionally related and are inhibited by protein kinase A, calcium ions and nitric oxide. A mutation in this gene is associated with arthrogryposis multiplex congenita. [provided by RefSeq, May 2015]

Uniprot Accession IDs

• O43306
• Q9NR75
• Q9UDB0

Gene Name

• ADCY6

Ensembl ID

• ENST00000307885
• ENSP00000311405
• ENSG00000174233
• ENST00000357869
• ENSP00000350536
• ENST00000550422
• ENSP00000446730

Symbol

• KIAA0422
• AC6
• LCCS8

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.99
molecular function	0.95
disease perturbation	0.79
pathway	0.75
small molecule perturbation	0.73

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 196.88   (req: < 5)

Gene RIFs: 22   (req: <= 3)

Antibodies: 162   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 196.88   (req: >= 5)

Gene RIFs: 22   (req: > 3)

Antibodies: 162   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 19

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (1)

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1 – 1 of 1

NKY80

ADCY6Tchem Enzyme

-log(-) : 5.15

Protein-Protein Interactions (483)

Explore Interacting Targets

1 – 10 of 483

• See Interactions on String-DB

LGALS8

Tchem

Novelty:  0.00623836

p_int:  0.999994706

p_ni:  0.000005294

Data Source:  BioPlex

NEUROG3

Tbio

Family:  TF

Novelty:  0.00341077

p_int:  0.998263373

p_ni:  0.001736627

Data Source:  BioPlex

B4GAT1

Tbio

Family:  Enzyme

Novelty:  0.14959923

p_int:  0.99816879

p_ni:  0.00183121

Data Source:  BioPlex

YIPF3

Tbio

Novelty:  0.12021667

p_int:  0.996853287

p_ni:  0.003146701

p_wrong:  1.2e-8

Data Source:  BioPlex

ANKMY2

Tdark

Novelty:  0.50777631

p_int:  0.996465395

p_ni:  0.003534427

p_wrong:  1.78e-7

Score:  0.242

Data Source:  BioPlex,STRINGDB

IPPK

Tbio

Family:  Enzyme

Novelty:  0.02169701

p_int:  0.991189407

p_ni:  0.008810585

p_wrong:  7e-9

Data Source:  BioPlex

SYNE4

Tbio

Novelty:  0.0739848

p_int:  0.989123375

p_ni:  0.010875609

p_wrong:  0.000001016

Data Source:  BioPlex

ZNRF4

Tbio

Novelty:  0.16505328

p_int:  0.987830143

p_ni:  0.012169636

p_wrong:  2.21e-7

Data Source:  BioPlex

LGALS3

Tchem

Novelty:  0.00032754

p_int:  0.981675538

p_ni:  0.01832413

p_wrong:  3.32e-7

Data Source:  BioPlex

NKAIN1

Tdark

Family:  Enzyme

Novelty:  0.52190272

p_int:  0.96807185

p_ni:  0.031924958

p_wrong:  0.000003191

Data Source:  BioPlex

Nearest Tclin Targets (33)

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Upstream (19)

Downstream (14)

1 – 5 of 19

CALM3

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  19

1: Inflammatory mediator regulation of TRP channels

2: Aldosterone synthesis and secretion

3: Oxytocin signaling pathway

4: Gastric acid secretion

more:  15 more common pathways

CALM1

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  19

1: Inflammatory mediator regulation of TRP channels

2: Aldosterone synthesis and secretion

3: Oxytocin signaling pathway

4: Gastric acid secretion

more:  15 more common pathways

PRKCD

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  5

1: Inflammatory mediator regulation of TRP channels

2: Chemokine signaling pathway

3: GnRH signaling pathway

4: Estrogen signaling pathway

5: Vascular smooth muscle contraction

CALM2

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  19

1: Inflammatory mediator regulation of TRP channels

2: Aldosterone synthesis and secretion

3: Oxytocin signaling pathway

4: Gastric acid secretion

more:  15 more common pathways

PDE4A

Tclin

Family:  Enzyme

KEGG Distance:  1

Common Pathways:  5

1: Parathyroid hormone synthesis, secretion and action

2: cAMP signaling pathway

3: Metabolic pathways

4: Purine metabolism

5: Morphine addiction

Pathways (111)

Reactome (36)

KEGG (50)

PathwayCommons (17)

WikiPathways (8)

Activation of GABAB receptors (R-HSA-991365)

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5

1 – 5 of 36

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of GABAB receptors	39 targets	R-HSA-991365
Reactome	Adenylate cyclase activating pathway	10 targets	R-HSA-170660
Reactome	Adenylate cyclase inhibitory pathway	14 targets	R-HSA-170670
Reactome	Adrenaline,noradrenaline inhibits insulin secretion	28 targets	R-HSA-400042
Reactome	Aquaporin-mediated transport	55 targets	R-HSA-445717

Name	Explore in Pharos	Explore in Source
Activation of GABAB receptors	39 targets	R-HSA-991365
Adenylate cyclase activating pathway	10 targets	R-HSA-170660
Adenylate cyclase inhibitory pathway	14 targets	R-HSA-170670
Adrenaline,noradrenaline inhibits insulin secretion	28 targets	R-HSA-400042
Aquaporin-mediated transport	55 targets	R-HSA-445717

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (24)

Functions (5)

Components (5)

Processes (14)

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10

1 – 5 of 5

GO Term	Evidence	Assigned by
adenylate cyclase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein kinase C binding	Inferred from Direct Assay (IDA)	UniProtKB
protein kinase binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (5)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
bone density	EFO_0003923	1	1	2		49.5
leukocyte count	EFO_0004308	1	1	1		46.5
calcium measurement	EFO_0004838	1	1	1		40.7
testosterone measurement	EFO_0004908	1	1	1		28.1
self reported educational attainment	EFO_0004784	1	1	1		4.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 5

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
bone density	EFO_0003923	2		49.5
leukocyte count	EFO_0004308	1		46.5
calcium measurement	EFO_0004838	1		40.7
testosterone measurement	EFO_0004908	1		28.1
self reported educational attainment	EFO_0004784	1		4.5

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UniProt Keyword Find Similar Targets

No Header	No Header
Alternative splicing
ATP-binding
cAMP biosynthesis
Cell membrane
Cell projection
Cilium
Complete proteome
Disease mutation
Glycoprotein
Lyase

GWAS Trait Find Similar Targets

No Header	No Header
bone density
calcium measurement
leukocyte count
self reported educational attainment
testosterone measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
homeostasis/metabolism phenotype
muscle phenotype
renal/urinary system phenotype

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	adenylate cyclase 6	VGNC:12756	451866
Macaque	adenylate cyclase 6		707978
Mouse	adenylate cyclase 6	MGI:87917	11512
Rat	adenylate cyclase 6	RGD:2035	25289
Dog	adenylate cyclase 6	VGNC:37623	477625

Species	Name	OMA	EggNOG	Inparanoid
Chimp	adenylate cyclase 6
Macaque	adenylate cyclase 6
Mouse	adenylate cyclase 6
Rat	adenylate cyclase 6
Dog	adenylate cyclase 6

Publication Statistics

PubMed Score 196.88

PubMed score by year

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PubTator Score 52.59

PubTator score by year

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Related Publications

Text Mined References (50)

GeneRif Annotations (22)

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PMID	Year	Title