ADCY6 adenylate cyclase 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ADCY6provided by HGNC
Official Full Name: adenylate cyclase 6provided by HGNC
Primary source: HGNC:HGNC:237
See related: Ensembl:ENSG00000174233 MIM:600294; AllianceGenome:HGNC:237
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AC6; LCCS8
Summary: 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]
Expression: Ubiquitous expression in fat (RPKM 25.0), heart (RPKM 17.1) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q13.12

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (48766194..48789974, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (48728221..48752002, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (49159977..49183757, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Gene expression and DNA methylation analyses suggest that immune process-related ADCY6 is a prognostic factor of luminal-like breast cancer.
Title: Gene expression and DNA methylation analyses suggest that immune process-related ADCY6 is a prognostic factor of luminal-like breast cancer.
Expanding the clinical and molecular spectrum of lethal congenital contracture syndrome 8 associated with biallelic variants of ADCY6.
Title: Expanding the clinical and molecular spectrum of lethal congenital contracture syndrome 8 associated with biallelic variants of ADCY6.
Effect of Adenylyl Cyclase Type 6 on Localized Production of cAMP by beta-2 Adrenoceptors in Human Airway Smooth-Muscle Cells
Title: Effect of Adenylyl Cyclase Type 6 on Localized Production of cAMP by β-2 Adrenoceptors in Human Airway Smooth-Muscle Cells.
Data found that direct binding of 4.1G to the N-terminus of AC6 (AC6-N) contributes to the plasma membrane association of AC6-N and the resulting suppression of AC6 cyclase activity.
Title: Activity of Adenylyl Cyclase Type 6 Is Suppressed by Direct Binding of the Cytoskeletal Protein 4.1G.
PDE8 is expressed in lipid rafts of human airway smooth muscle cells(HASM), where it specifically regulates beta2-adrenergic receptor/ AC6 signaling to modulate HASM responsiveness and airway remodeling in asthma.
Title: PDE8 Is Expressed in Human Airway Smooth Muscle and Selectively Regulates cAMP Signaling by β(2)-Adrenergic Receptors and Adenylyl Cyclase 6.
rs3730071G/T and rs77913913G/T of ADCY6 were non-polymorphic with respect to HAPE.
Title: Elevated Vasodilatory Cyclases and Shorter Telomere Length Contribute to High-Altitude Pulmonary Edema.
model suggests Cys1004 in AC6 (subunit C2) and Cys174 in Galphas present at the AC-Galphas interface as the possible residues that might undergo reversible nitrosylation. Docking analysis predicted novel ligands of AC6 that include forskolin-based compounds and its derivatives.
Title: Study of adenylyl cyclase-GαS interactions and identification of novel AC ligands.
Sickle cell anemia patients carrying at least one allele of adcy6 rs3730070-G exhibited lower hemolytic rate than non-carriers in univariate analysis (p=0.006).
Title: Association of adenylyl cyclase 6 rs3730070 polymorphism and hemolytic level in patients with sickle cell anemia.
LRs are essential not only for the proper membrane distribution and maintenance of AC5/6 activity but also for the regulation of D1R- and D5R-mediated AC signaling.
Title: Differential dopamine receptor subtype regulation of adenylyl cyclases in lipid rafts in human embryonic kidney and renal proximal tubule cells.
Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects
Title: Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Lethal congenital contracture syndrome 8 MedGen: C4225385 OMIM: 616287 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	The addition of HIV-1 gp120 with TNF-alpha to human B-cells stimulates cAMP production in a dose-dependent manner	PubMed
Envelope transmembrane glycoprotein gp41	env	Secretion of IL-10 is upregulated by HIV-1 gp41 in monocytes through activation of cAMP/adenylate cyclase and p70 (S6)-kinase; up-regulation of IL-10 is paralleled by an enhanced expression of the chemokine receptor CCR5	PubMed
Nef	nef	HIV-1 induces the upregulation of complement factor C3 in astrocytes and neurons through signaling pathways that involve protein kinase C and adenylate cyclase activation, which is an effect that may contribute to the pathogenesis of AIDS in the brain	PubMed
Tat	tat	HIV-1 Tat inhibits adenylyl cyclase activity in microglia and astrocyte cultures from neonatal rat brain, suggesting that Tat inhibition of cAMP synthesis may contribute to neuronal degeneration and cell death associated with HIV infection	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH78534 (e-PCR)
- UniSTS:50189

PMC156606P4 (e-PCR)
- UniSTS:271411

D10S16 (e-PCR)
- UniSTS:155756

A006M44 (e-PCR)
- UniSTS:8135

ADCY6_211 (e-PCR)
- UniSTS:276975

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables adenylate cyclase activity	IBA Inferred from Biological aspect of Ancestor more info
enables adenylate cyclase activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase C binding	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in adenylate cyclase-activating dopamine receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in blood vessel diameter maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cAMP biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in cAMP biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to catecholamine stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to forskolin	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to prostaglandin E stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to vasopressin	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of urine volume	ISS Inferred from Sequence or Structural Similarity more info
involved_in renal water homeostasis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cilium	IEA Inferred from Electronic Annotation more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in stereocilium	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: adenylate cyclase type 6

Names: ATP pyrophosphate-lyase 6; adenylate cyclase type VI; ca(2+)-inhibitable adenylyl cyclase

NP_001377759.1

EC 4.6.1.1

NP_001377760.1

EC 4.6.1.1

NP_001399748.1

EC 4.6.1.1

NP_001399749.1

EC 4.6.1.1

NP_001399750.1

EC 4.6.1.1

NP_001399751.1

EC 4.6.1.1

NP_056085.1

EC 4.6.1.1

XP_006719273.1

EC 4.6.1.1

XP_016874232.1

EC 4.6.1.1

XP_047284129.1

EC 4.6.1.1

XP_054226875.1

EC 4.6.1.1

XP_054226876.1

EC 4.6.1.1

XP_054226877.1

EC 4.6.1.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_042166.1 RefSeqGene

Range

5008..27903

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001390830.1 → NP_001377759.1 adenylate cyclase type 6 isoform 2

Status: REVIEWED

Source sequence(s)

AC117498

Consensus CDS

CCDS8768.1

Related

ENSP00000446730.1, ENST00000550422.5

Conserved Domains (3) summary

pfam00211
Location:917 → 1111

Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain

pfam16214
Location:16 → 368

AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region

pfam06327
Location:582 → 668

DUF1053; Domain of Unknown Function (DUF1053)
NM_001390831.2 → NP_001377760.1 adenylate cyclase type 6 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (1). Variants 1 and 3-7 all encode the same isoform (1).

Source sequence(s)

AC117498

Consensus CDS

CCDS8767.1

UniProtKB/Swiss-Prot

O43306, Q9NR75, Q9UDB0

Related

ENSP00000311405.4, ENST00000307885.4

Conserved Domains (3) summary

pfam00211
Location:970 → 1164

Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain

pfam16214
Location:16 → 368

AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region

pfam06327
Location:582 → 668

DUF1053; Domain of Unknown Function (DUF1053)
NM_001412819.1 → NP_001399748.1 adenylate cyclase type 6 isoform 1

Status: REVIEWED

Source sequence(s)

AC117498

UniProtKB/Swiss-Prot

O43306, Q9NR75, Q9UDB0
NM_001412820.1 → NP_001399749.1 adenylate cyclase type 6 isoform 1

Status: REVIEWED

Source sequence(s)

AC117498

UniProtKB/Swiss-Prot

O43306, Q9NR75, Q9UDB0
NM_001412821.1 → NP_001399750.1 adenylate cyclase type 6 isoform 1

Status: REVIEWED

Source sequence(s)

AC117498

UniProtKB/Swiss-Prot

O43306, Q9NR75, Q9UDB0
NM_001412822.1 → NP_001399751.1 adenylate cyclase type 6 isoform 1

Status: REVIEWED

Source sequence(s)

AC117498

UniProtKB/Swiss-Prot

O43306, Q9NR75, Q9UDB0
NM_015270.5 → NP_056085.1 adenylate cyclase type 6 isoform 1

See identical proteins and their annotated locations for NP_056085.1

Status: REVIEWED

Source sequence(s)

AC117498, AF250226, BC064923

Consensus CDS

CCDS8767.1

UniProtKB/Swiss-Prot

O43306, Q9NR75, Q9UDB0

Related

ENSP00000350536.4, ENST00000357869.8

Conserved Domains (3) summary

pfam00211
Location:970 → 1164

Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain

pfam16214
Location:16 → 368

AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region

pfam06327
Location:582 → 668

DUF1053; Domain of Unknown Function (DUF1053)

RNA

NR_182049.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC117498

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

48766194..48789974 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006719210.5 → XP_006719273.1 adenylate cyclase type 6 isoform X1

See identical proteins and their annotated locations for XP_006719273.1

UniProtKB/Swiss-Prot

O43306, Q9NR75, Q9UDB0

Conserved Domains (3) summary

pfam00211
Location:970 → 1164

Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain

pfam16214
Location:16 → 368

AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region

pfam06327
Location:582 → 668

DUF1053; Domain of Unknown Function (DUF1053)
XM_047428173.1 → XP_047284129.1 adenylate cyclase type 6 isoform X1

UniProtKB/Swiss-Prot

O43306, Q9NR75, Q9UDB0
XM_017018743.2 → XP_016874232.1 adenylate cyclase type 6 isoform X2

Conserved Domains (4) summary

smart00044
Location:334 → 529

CYCc; Adenylyl- / guanylyl cyclase, catalytic domain

pfam00211
Location:869 → 1063

Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain

pfam06327
Location:582 → 661

DUF1053; Domain of Unknown Function (DUF1053)

pfam16214
Location:16 → 368

AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

48728221..48752002 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054370900.1 → XP_054226875.1 adenylate cyclase type 6 isoform X1

UniProtKB/Swiss-Prot

O43306, Q9NR75, Q9UDB0
XM_054370901.1 → XP_054226876.1 adenylate cyclase type 6 isoform X1

UniProtKB/Swiss-Prot

O43306, Q9NR75, Q9UDB0
XM_054370902.1 → XP_054226877.1 adenylate cyclase type 6 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_020983.2: Suppressed sequence

Description

NM_020983.2: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.