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ADCY4 adenylate cyclase 4 [ Homo sapiens (human) ]

Gene ID: 196883, updated on 11-Apr-2024

Summary

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Official Symbol
ADCY4provided by HGNC
Official Full Name
adenylate cyclase 4provided by HGNC
Primary source
HGNC:HGNC:235
See related
Ensembl:ENSG00000129467 MIM:600292; AllianceGenome:HGNC:235
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
AC4
Summary
This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). Mouse studies show that adenylate cyclase 4, along with adenylate cyclases 2 and 3, is expressed in olfactory cilia, suggesting that several different adenylate cyclases may couple to olfactory receptors and that there may be multiple receptor-mediated mechanisms for the generation of cAMP signals. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]
Expression
Broad expression in placenta (RPKM 14.4), fat (RPKM 11.6) and 23 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
14q12
Exon count:
26
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (24318359..24335071, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (18516694..18533416, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (24787565..24804277, complement)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene NOP9 nucleolar protein Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5635 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5636 Neighboring gene cell death inducing DFFA like effector b Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:24785286-24785786 Neighboring gene leukotriene B4 receptor 2 Neighboring gene leukotriene B4 receptor Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:24790818-24791777 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5637 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5638 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5639 Neighboring gene Sharpr-MPRA regulatory region 10023 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8214 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8215 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8216 Neighboring gene receptor interacting serine/threonine kinase 3 Neighboring gene uncharacterized LOC124903413

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. Epigenetic identification of ADCY4 as a biomarker for breast cancer: an integrated analysis of adenylate cyclases. Fan Y, et al. Epigenomics, 2019 Nov. PMID 31584294
  2. Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice. Wong ST, et al. Neuron, 2000 Sep. PMID 11055432
  3. Human bronchial smooth muscle cells express adenylyl cyclase isoforms 2, 4, and 6 in distinct membrane microdomains. Bogard AS, et al. J Pharmacol Exp Ther, 2011 Apr. PMID 21228062, Free PMC Article
  4. Mammalian adenylyl cyclase family members are randomly located on different chromosomes. Gaudin C, et al. Hum Genet, 1994 Nov. PMID 7959689
  5. Mapping of adenylyl cyclase genes type I, II, III, IV, V, and VI in mouse. Edelhoff S, et al. Mamm Genome, 1995 Feb. PMID 7766992

See all (26) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. ADCY4 may be used as an epigenetic biomarker for breast cancer, as well as a possible target for therapy.
    Title: Epigenetic identification of ADCY4 as a biomarker for breast cancer: an integrated analysis of adenylate cyclases.
  2. AC4 and AC2, both isoforms stimulated by Gbetagamma, are expressed in bronchial nonlipid raft membrane fractions where they colocalize with and couple to prostanoid EP2 receptors.
    Title: Human bronchial smooth muscle cells express adenylyl cyclase isoforms 2, 4, and 6 in distinct membrane microdomains.
  3. This paper reports the presence of adenylyl cyclases 2, 3, and 4 in mouse olfactory cilia.
    Title: Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice.
  4. The HIV-1 regulatory protein Tat was shown to inhibit the activity of adenylyl cyclase in rat microglial cells.
    Title: Human immunodeficiency virus type 1 Tat protein decreases cyclic AMP synthesis in rat microglia cultures.
Submit: New GeneRIF Correction

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

EBI GWAS Catalog

Description
Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment.
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

Potential readthrough

Included gene: RIPK3

Homology

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 ISS
Inferred from Sequence or Structural Similarity
more info
  
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 
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-inhibiting G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in adenylate cyclase-modulating G protein-coupled receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cAMP biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cAMP biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in intracellular signal transduction IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in dendrite 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 TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
adenylate cyclase type 4
Names
ATP pyrophosphate-lyase 4
adenylate cyclase type IV
adenylyl cyclase 4
NP_001185497.1
NP_001185521.1
NP_640340.2

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.

mRNA and Protein(s)

  1. NM_001198568.2 → NP_001185497.1  adenylate cyclase type 4

    See identical proteins and their annotated locations for NP_001185497.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.
    Source sequence(s)
    AK122714, AL096870, BC117473
    Consensus CDS
    CCDS9627.1
    UniProtKB/Swiss-Prot
    B3KV74, D3DS75, Q17R40, Q6ZTM6, Q8NFM4, Q96ML7
    UniProtKB/TrEMBL
    Q86TZ7
    Related
    ENSP00000393177.2, ENST00000418030.7
    Conserved Domains (4) summary
    smart00044
    Location:219 → 422
    CYCc; Adenylyl- / guanylyl cyclase, catalytic domain
    pfam00211
    Location:864 → 1063
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam06327
    Location:479 → 583
    DUF1053; Domain of Unknown Function (DUF1053)
    pfam16214
    Location:115 → 246
    AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region

  2. NM_001198592.2 → NP_001185521.1  adenylate cyclase type 4

    See identical proteins and their annotated locations for NP_001185521.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2 and 3 encode the same protein.
    Source sequence(s)
    AK122714, BX248285
    Consensus CDS
    CCDS9627.1
    UniProtKB/Swiss-Prot
    B3KV74, D3DS75, Q17R40, Q6ZTM6, Q8NFM4, Q96ML7
    UniProtKB/TrEMBL
    Q86TZ7
    Related
    ENSP00000452250.2, ENST00000554068.6
    Conserved Domains (4) summary
    smart00044
    Location:219 → 422
    CYCc; Adenylyl- / guanylyl cyclase, catalytic domain
    pfam00211
    Location:864 → 1063
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam06327
    Location:479 → 583
    DUF1053; Domain of Unknown Function (DUF1053)
    pfam16214
    Location:115 → 246
    AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region

  3. NM_139247.4 → NP_640340.2  adenylate cyclase type 4

    See identical proteins and their annotated locations for NP_640340.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.
    Source sequence(s)
    AK122714
    Consensus CDS
    CCDS9627.1
    UniProtKB/Swiss-Prot
    B3KV74, D3DS75, Q17R40, Q6ZTM6, Q8NFM4, Q96ML7
    UniProtKB/TrEMBL
    Q86TZ7
    Related
    ENSP00000312126.4, ENST00000310677.8
    Conserved Domains (4) summary
    smart00044
    Location:219 → 422
    CYCc; Adenylyl- / guanylyl cyclase, catalytic domain
    pfam00211
    Location:864 → 1063
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam06327
    Location:479 → 583
    DUF1053; Domain of Unknown Function (DUF1053)
    pfam16214
    Location:115 → 246
    AC_N; Adenylyl cyclase N-terminal extracellular and transmembrane region

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_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    24318359..24335071 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_018654722.1 Reference GRCh38.p14 PATCHES

    Range
    619337..636049 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    18516694..18533416 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8NFM4.1 GenPept UniProtKB/Swiss-Prot:Q8NFM4

Gene LinkOut

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