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    PDE5A phosphodiesterase 5A [ Homo sapiens (human) ]

    Gene ID: 8654, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PDE5Aprovided by HGNC
    Official Full Name
    phosphodiesterase 5Aprovided by HGNC
    Primary source
    HGNC:HGNC:8784
    See related
    Ensembl:ENSG00000138735 MIM:603310; AllianceGenome:HGNC:8784
    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
    CN5A; PDE5; CGB-PDE
    Summary
    This gene encodes a cGMP-binding, cGMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family. This phosphodiesterase specifically hydrolyzes cGMP to 5'-GMP. It is involved in the regulation of intracellular concentrations of cyclic nucleotides and is important for smooth muscle relaxation in the cardiovascular system. Alternative splicing of this gene results in three transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in prostate (RPKM 31.5), esophagus (RPKM 20.9) and 20 other tissues See more
    Orthologs
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    Genomic context

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    See PDE5A in Genome Data Viewer
    Location:
    4q26
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (119494403..119628804, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (122799522..122933950, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (120415558..120549959, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 1217, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21856 Neighboring gene septin 7 pseudogene 14 Neighboring gene general transcription factor IIi pseudogene 12 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15655 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:120453269-120453878 Neighboring gene MPRA-validated peak5097 silencer Neighboring gene small nucleolar RNA SNORA11 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15656 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21857 Neighboring gene uncharacterized LOC107986192 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15657 Neighboring gene uncharacterized LOC105377397 Neighboring gene uncharacterized LOC124900920

    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. Identification and regulation of human PDE5A gene promoter. Lin CS, et al. Biochem Biophys Res Commun, 2001 Jan 26. PMID 11162575
    2. Identification of cytosolic phosphodiesterases in the erythrocyte: a possible role for PDE5. Adderley SP, et al. Med Sci Monit, 2011 May. PMID 21525805, Free PMC Article
    3. Crystal structure of the GAF-B domain from human phosphodiesterase 5. Russwurm M, et al. Proteins, 2011 May. PMID 21425347
    4. Distinct allostery induced in the cyclic GMP-binding, cyclic GMP-specific phosphodiesterase (PDE5) by cyclic GMP, sildenafil, and metal ions. Biswas KH, et al. J Biol Chem, 2011 Mar 11. PMID 21193396, Free PMC Article
    5. Retraction: Expression of phosphodiesterase type 5A in human spermatozoa and influence of its inhibition on motility and functional sperm parameters. Foresta C, et al. J Endocrinol Invest, 2010 Jul 1. PMID 20595799

    See all (108) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CircPDE5A-encoded novel regulator of the PI3K/AKT pathway inhibits esophageal squamous cell carcinoma progression by promoting USP14-mediated de-ubiquitination of PIK3IP1.
      Title: CircPDE5A-encoded novel regulator of the PI3K/AKT pathway inhibits esophageal squamous cell carcinoma progression by promoting USP14-mediated de-ubiquitination of PIK3IP1.
    2. LncRNA ARAP1-AS1 targets miR-516b-5p/PDE5A axis to facilitate the progression of thyroid cancer.
      Title: LncRNA ARAP1-AS1 targets miR-516b-5p/PDE5A axis to facilitate the progression of thyroid cancer.
    3. Cellular Redox Metabolism Is Modulated by the Distinct Localization of Cyclic Nucleotide Phosphodiesterase 5A Isoforms.
      Title: Cellular Redox Metabolism Is Modulated by the Distinct Localization of Cyclic Nucleotide Phosphodiesterase 5A Isoforms.
    4. Identification of a Functional PDE5A Variant at the Chromosome 4q27 Coronary Artery Disease Locus in an Extended Myocardial Infarction Family.
      Title: Identification of a Functional PDE5A Variant at the Chromosome 4q27 Coronary Artery Disease Locus in an Extended Myocardial Infarction Family.
    5. Influencing Factors for Erectile Dysfunction of Young Adults with No Response to PDE5i.
      Title: Influencing Factors for Erectile Dysfunction of Young Adults with No Response to PDE5i.
    6. Changes in the expression and function of the PDE5 pathway in the obstructed urinary bladder.
      Title: Changes in the expression and function of the PDE5 pathway in the obstructed urinary bladder.
    7. Over-expression of PDE5 in Oral Squamous Cell Carcinoma - Effect of Sildenafil Citrate.
      Title: Over-expression of PDE5 in Oral Squamous Cell Carcinoma - Effect of Sildenafil Citrate.
    8. Muscle Damage in Systemic Sclerosis and CXCL10: The Potential Therapeutic Role of PDE5 Inhibition.
      Title: Muscle Damage in Systemic Sclerosis and CXCL10: The Potential Therapeutic Role of PDE5 Inhibition.
    9. Discovery of Novel Agents on Spindle Assembly Checkpoint to Sensitize Vinorelbine-Induced Mitotic Cell Death Against Human Non-Small Cell Lung Cancers.
      Title: Discovery of Novel Agents on Spindle Assembly Checkpoint to Sensitize Vinorelbine-Induced Mitotic Cell Death Against Human Non-Small Cell Lung Cancers.
    10. Regulation of PDE5 expression in normal prostate, benign prostatic hyperplasia, and adenocarcinoma.
      Title: Regulation of PDE5 expression in normal prostate, benign prostatic hyperplasia, and adenocarcinoma.
    Submit: New GeneRIF Correction See all GeneRIFs (69)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3',5'-cyclic-AMP phosphodiesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 3',5'-cyclic-GMP phosphodiesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 3',5'-cyclic-GMP phosphodiesterase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables 3',5'-cyclic-nucleotide phosphodiesterase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables cGMP binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cAMP-mediated signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cGMP catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of cardiac muscle contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in oocyte development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of cardiac muscle hypertrophy IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of oocyte development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of nitric oxide mediated signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in relaxation of cardiac muscle IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    cGMP-specific 3',5'-cyclic phosphodiesterase
    Names
    cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase
    cGMP-specific phosphodiesterase PDE5A2
    cGMP-specific phosphodiesterase type 5A
    phosphodiesterase 5A, cGMP-specific
    phosphodiesterase isozyme 5
    NP_001074.2
    NP_236914.2
    NP_246273.2
    XP_016864280.1
    XP_054207125.1

    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.

    mRNA and Protein(s)

    1. NM_001083.4 → NP_001074.2  cGMP-specific 3',5'-cyclic phosphodiesterase isoform 1

      See identical proteins and their annotated locations for NP_001074.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1, also known as PDE5A1).
      Source sequence(s)
      AC093752, AF043731, AY264918, BM978332
      Consensus CDS
      CCDS3713.1
      UniProtKB/Swiss-Prot
      A0AV69, A8K2C4, O75026, O75887, O76074, Q86UI0, Q86V66, Q9Y6Z6
      UniProtKB/TrEMBL
      I6NLS4
      Related
      ENSP00000347046.3, ENST00000354960.8
      Conserved Domains (2) summary
      smart00065
      Location:164 → 321
      GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
      pfam00233
      Location:612 → 847
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    2. NM_033430.3 → NP_236914.2  cGMP-specific 3',5'-cyclic phosphodiesterase isoform 2

      See identical proteins and their annotated locations for NP_236914.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and 5' coding region, and uses an alternate start codon, compared to variant 1. The encoded isoform (2, also known as PDE5A2) has a distinct and shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AC080089, AC093752, AF043732, AY264918, BM978332
      Consensus CDS
      CCDS34055.1
      UniProtKB/TrEMBL
      I6NLS4
      Related
      ENSP00000264805.5, ENST00000264805.9
      Conserved Domains (2) summary
      smart00065
      Location:122 → 279
      GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
      pfam00233
      Location:570 → 805
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    3. NM_033437.4 → NP_246273.2  cGMP-specific 3',5'-cyclic phosphodiesterase isoform 3

      See identical proteins and their annotated locations for NP_246273.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream start codon, compared to variant 1. The encoded isoform (3, also known as PDE5A3) is shorter at the N-terminus, compared to isoform 1. There are no publicly available full-length transcripts supporting this variant; it is represented based on full-length cloning by RT-PCR in PMID:10679255.
      Source sequence(s)
      AC093752, AF155194, BC126233, BM978332, CD511199
      UniProtKB/TrEMBL
      G5E9C5, I6NLS4
      Related
      ENSP00000377957.1, ENST00000394439.5
      Conserved Domains (2) summary
      smart00065
      Location:112 → 269
      GAF; Domain present in phytochromes and cGMP-specific phosphodiesterases
      pfam00233
      Location:560 → 795
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    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_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      119494403..119628804 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017008791.3 → XP_016864280.1  cGMP-specific 3',5'-cyclic phosphodiesterase isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      122799522..122933950 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054351150.1 → XP_054207125.1  cGMP-specific 3',5'-cyclic phosphodiesterase isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O76074.2 GenPept UniProtKB/Swiss-Prot:O76074

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