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

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: 166.49   (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: 166.49   (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

Active Ligands (1)

Explore Active Ligands

1 – 1 of 1

NKY80

ADCY6Tchem Enzyme

-: 4.80000019

Pathways (111)

Reactome (36)

KEGG (50)

PathwayCommons (17)

WikiPathways (8)

Activation of GABAB receptors (R-HSA-991365)

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Items per page:

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

Gene Ontology Terms (24)

Functions (5)

Components (5)

Processes (14)

Items per page:

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

Protein-Protein Interactions (483)

Explore Interacting Targets

1 – 10 of 483

• See Interactions on String-DB

LGALS8

Tchem

Novelty: 0.00746585

p_int: 0.999994706

p_ni: 0.000005294

Data Source: BioPlex

NEUROG3

Tbio

Family: TF

Novelty: 0.00367513

p_int: 0.998263373

p_ni: 0.001736627

Data Source: BioPlex

B4GAT1

Tbio

Family: Enzyme

Novelty: 0.06386176

p_int: 0.99816879

p_ni: 0.00183121

Data Source: BioPlex

YIPF3

Tbio

Novelty: 0.03141831

p_int: 0.996853287

p_ni: 0.003146701

p_wrong: 1.2e-8

Data Source: BioPlex

ANKMY2

Tdark

Novelty: 1.16129032

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: 0.04063664

p_int: 0.991189407

p_ni: 0.008810585

p_wrong: 7e-9

Data Source: BioPlex

SYNE4

Tdark

Novelty: 0.21538462

p_int: 0.989123375

p_ni: 0.010875609

p_wrong: 0.000001016

Data Source: BioPlex

ZNRF4

Tbio

Novelty: 0.18181818

p_int: 0.987830143

p_ni: 0.012169636

p_wrong: 2.21e-7

Data Source: BioPlex

LGALS3

Tchem

Novelty: 0.00032884

p_int: 0.981675538

p_ni: 0.01832413

p_wrong: 3.32e-7

Data Source: BioPlex

NKAIN1

Tdark

Family: Enzyme

Novelty: 0.60115607

p_int: 0.96807185

p_ni: 0.031924958

p_wrong: 0.000003191

Data Source: BioPlex

Publication Statistics

PubMed Score  166.49

PubMed score by year

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PubTator Score  52.59

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MSWFSGLLVPKVDERKTAWGERNGQKRSRRRGTRAGGFCTPRYMSCLRDAEPPSPTPAGPPRCPWQDDAF

1-70

IRRGGPGKGKELGLRAVALGFEDTEVTTTAGGTAEVAPDAVPRSGRSCWRRLVQVFQSKQFRSAKLERLY

70-140

QRYFFQMNQSSLTLLMAVLVLLTAVLLAFHAAPARPQPAYVALLACAAALFVGLMVVCNRHSFRQDSMWV

140-210

VSYVVLGILAAVQVGGALAADPRSPSAGLWCPVFFVYIAYTLLPIRMRAAVLSGLGLSTLHLILAWQLNR

210-280

GDAFLWKQLGANVLLFLCTNVIGICTHYPAEVSQRQAFQETRGYIQARLHLQHENRQQERLLLSVLPQHV

280-350

AMEMKEDINTKKEDMMFHKIYIQKHDNVSILFADIEGFTSLASQCTAQELVMTLNELFARFDKLAAENHC

350-420

LRIKILGDCYYCVSGLPEARADHAHCCVEMGVDMIEAISLVREVTGVNVNMRVGIHSGRVHCGVLGLRKW

420-490

QFDVWSNDVTLANHMEAGGRAGRIHITRATLQYLNGDYEVEPGRGGERNAYLKEQHIETFLILGASQKRK

490-560

EEKAMLAKLQRTRANSMEGLMPRWVPDRAFSRTKDSKAFRQMGIDDSSKDNRGTQDALNPEDEVDEFLSR

560-630

AIDARSIDQLRKDHVRRFLLTFQREDLEKKYSRKVDPRFGAYVACALLVFCFICFIQLLIFPHSTLMLGI

630-700

YASIFLLLLITVLICAVYSCGSLFPKALQRLSRSIVRSRAHSTAVGIFSVLLVFTSAIANMFTCNHTPIR

700-770

SCAARMLNLTPADITACHLQQLNYSLGLDAPLCEGTMPTCSFPEYFIGNMLLSLLASSVFLHISSIGKLA

770-840

MIFVLGLIYLVLLLLGPPATIFDNYDLLLGVHGLASSNETFDGLDCPAAGRVALKYMTPVILLVFALALY

840-910

LHAQQVESTARLDFLWKLQATGEKEEMEELQAYNRRLLHNILPKDVAAHFLARERRNDELYYQSCECVAV

910-980

MFASIANFSEFYVELEANNEGVECLRLLNEIIADFDEIISEERFRQLEKIKTIGSTYMAASGLNASTYDQ

980-1050

VGRSHITALADYAMRLMEQMKHINEHSFNNFQMKIGLNMGPVVAGVIGARKPQYDIWGNTVNVSSRMDST

1050-1120

GVPDRIQVTTDLYQVLAAKGYQLECRGVVKVKGKGEMTTYFLNGGPSS

1120-1168

MSWFSGLLVPKVDERKTAWGERNGQKRSRRRGTRAGGFCTPRYMSCLRDAEPPSPTPAGPPRCPWQDDAFIRRGGPGKGKELGLRAVALGFEDTEVTTTAGGTAEVAPDAVPRSGRSCWRRLVQVFQSKQFRSAKLERLYQRYFFQMNQSSLTLLMAVLVLLTAVLLAFHAAPARPQPAYVALLACAAALFVGLMVVCNRHSFRQDSMWVVSYVVLGILAAVQVGGALAADPRSPSAGLWCPVFFVYIAYTLLPIRMRAAVLSGLGLSTLHLILAWQLNRGDAFLWKQLGANVLLFLCTNVIGICTHYPAEVSQRQAFQETRGYIQARLHLQHENRQQERLLLSVLPQHVAMEMKEDINTKKEDMMFHKIYIQKHDNVSILFADIEGFTSLASQCTAQELVMTLNELFARFDKLAAENHCLRIKILGDCYYCVSGLPEARADHAHCCVEMGVDMIEAISLVREVTGVNVNMRVGIHSGRVHCGVLGLRKWQFDVWSNDVTLANHMEAGGRAGRIHITRATLQYLNGDYEVEPGRGGERNAYLKEQHIETFLILGASQKRKEEKAMLAKLQRTRANSMEGLMPRWVPDRAFSRTKDSKAFRQMGIDDSSKDNRGTQDALNPEDEVDEFLSRAIDARSIDQLRKDHVRRFLLTFQREDLEKKYSRKVDPRFGAYVACALLVFCFICFIQLLIFPHSTLMLGIYASIFLLLLITVLICAVYSCGSLFPKALQRLSRSIVRSRAHSTAVGIFSVLLVFTSAIANMFTCNHTPIRSCAARMLNLTPADITACHLQQLNYSLGLDAPLCEGTMPTCSFPEYFIGNMLLSLLASSVFLHISSIGKLAMIFVLGLIYLVLLLLGPPATIFDNYDLLLGVHGLASSNETFDGLDCPAAGRVALKYMTPVILLVFALALYLHAQQVESTARLDFLWKLQATGEKEEMEELQAYNRRLLHNILPKDVAAHFLARERRNDELYYQSCECVAVMFASIANFSEFYVELEANNEGVECLRLLNEIIADFDEIISEERFRQLEKIKTIGSTYMAASGLNASTYDQVGRSHITALADYAMRLMEQMKHINEHSFNNFQMKIGLNMGPVVAGVIGARKPQYDIWGNTVNVSSRMDSTGVPDRIQVTTDLYQVLAAKGYQLECRGVVKVKGKGEMTTYFLNGGPSS

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Uniprot Keyword

Alternative splicing
ATP-binding
cAMP biosynthesis
Cell membrane
Cell projection
Cilium
Complete proteome
Disease mutation
Glycoprotein
Lyase