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ADCY6 adenylate cyclase 6 [ Homo sapiens (human) ]

Gene ID: 112, updated on 11-Apr-2024

Summary

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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
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Genomic context

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See ADCY6 in Genome Data Viewer
Location:
12q13.12
Exon count:
26
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (48766194..48789974, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (48728221..48752002, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (49159977..49182872, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene KAT8 regulatory NSL complex subunit 2 Neighboring gene small nucleolar RNA, H/ACA box 2B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6285 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4409 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4410 Neighboring gene MPRA-validated peak1722 silencer Neighboring gene MPRA-validated peak1723 silencer Neighboring gene cyclin T1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6286 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:49110605-49111605 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:49117404-49118078 Neighboring gene sperm microtubule inner protein 11 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6288 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:49161309-49161888 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:49161889-49162469 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:49176393-49177210 Neighboring gene microRNA 4701 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:49181275-49181819 Neighboring gene Sharpr-MPRA regulatory region 15276 Neighboring gene ADCY6 divergent transcript Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:49194958-49195556 Neighboring gene chromosome 20 open reading frame 27 pseudogene Neighboring gene uncharacterized LOC101927241 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:49208339-49208840 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:49208841-49209340 Neighboring gene calcium voltage-gated channel auxiliary subunit beta 3

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: 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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Related articles in PubMed

  1. Gene expression and DNA methylation analyses suggest that immune process-related ADCY6 is a prognostic factor of luminal-like breast cancer. Li W, et al. J Cell Biochem, 2020 Jul. PMID 31886586
  2. Expanding the clinical and molecular spectrum of lethal congenital contracture syndrome 8 associated with biallelic variants of ADCY6. Agolini E, et al. Clin Genet, 2020 Apr. PMID 31846058
  3. Association of adenylyl cyclase 6 rs3730070 polymorphism and hemolytic level in patients with sickle cell anemia. Cita KC, et al. Blood Cells Mol Dis, 2016 May. PMID 27067484
  4. Increased blood pressure and hyperdynamic cardiovascular responses in carriers of a common hyperfunctional variant of adenylyl cyclase 6. Hodges GJ, et al. J Pharmacol Exp Ther, 2010 Nov. PMID 20732959
  5. Real-time monitoring of cAMP levels in living endothelial cells: thrombin transiently inhibits adenylyl cyclase 6. Werthmann RC, et al. J Physiol, 2009 Aug 15. PMID 19546162, Free PMC Article

See all (73) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  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.
  7. 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.
  8. 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.
  9. 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.
  10. 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
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EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

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

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA0422, DKFZp779F075

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-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 dopamine receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
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
NP_001377760.1
NP_001399748.1
NP_001399749.1
NP_001399750.1
NP_001399751.1
NP_056085.1
XP_006719273.1
XP_016874232.1
XP_047284129.1
XP_054226875.1
XP_054226876.1
XP_054226877.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

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

  1. NG_042166.1 RefSeqGene

    Range
    5008..27903
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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)

  2. 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)

  3. NM_001412819.1 → NP_001399748.1  adenylate cyclase type 6 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC117498
    UniProtKB/Swiss-Prot
    O43306, Q9NR75, Q9UDB0

  4. NM_001412820.1 → NP_001399749.1  adenylate cyclase type 6 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC117498
    UniProtKB/Swiss-Prot
    O43306, Q9NR75, Q9UDB0

  5. NM_001412821.1 → NP_001399750.1  adenylate cyclase type 6 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC117498
    UniProtKB/Swiss-Prot
    O43306, Q9NR75, Q9UDB0

  6. NM_001412822.1 → NP_001399751.1  adenylate cyclase type 6 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC117498
    UniProtKB/Swiss-Prot
    O43306, Q9NR75, Q9UDB0

  7. 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

  1. NR_182049.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC117498

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    48766194..48789974 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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)

  2. XM_047428173.1 → XP_047284129.1  adenylate cyclase type 6 isoform X1

    UniProtKB/Swiss-Prot
    O43306, Q9NR75, Q9UDB0

  3. 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

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    48728221..48752002 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    UniProtKB/Swiss-Prot
    O43306, Q9NR75, Q9UDB0

  2. XM_054370901.1 → XP_054226876.1  adenylate cyclase type 6 isoform X1

    UniProtKB/Swiss-Prot
    O43306, Q9NR75, Q9UDB0

  3. XM_054370902.1 → XP_054226877.1  adenylate cyclase type 6 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. 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.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O43306.2 GenPept UniProtKB/Swiss-Prot:O43306

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