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    ADCY4 adenylate cyclase 4 [ Homo sapiens (human) ]

    Gene ID: 196883, updated on 28-Oct-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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    See ADCY4 in Genome Data Viewer
    Location:
    14q12
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (24318359..24335071, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (18516694..18533416, complement)
    RS_2024_09 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 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. Mammalian adenylyl cyclase family members are randomly located on different chromosomes. Gaudin C, et al. Hum Genet, 1994 Nov. PMID 7959689
    4. 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
    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 (27) 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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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