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    ADCY6 adenylate cyclase 6 [ Homo sapiens (human) ]

    Gene ID: 112, updated on 3-Nov-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
    mouse all
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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_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_000012.12Genomic 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 adipose secreted signaling protein 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 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?
    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
    		Compare labs

    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-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
    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_2024_08

    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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