Human Gene PDE5A (ENST00000354960.8) from GENCODE V44
  Description: Homo sapiens phosphodiesterase 5A (PDE5A), transcript variant 1, mRNA. (from RefSeq NM_001083)
RefSeq Summary (NM_001083): 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].
Gencode Transcript: ENST00000354960.8
Gencode Gene: ENSG00000138735.16
Transcript (Including UTRs)
   Position: hg38 chr4:119,494,403-119,628,804 Size: 134,402 Total Exon Count: 21 Strand: -
Coding Region
   Position: hg38 chr4:119,498,601-119,628,671 Size: 130,071 Coding Exon Count: 21 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:119,494,403-119,628,804)mRNA (may differ from genome)Protein (875 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PDE5A_HUMAN
DESCRIPTION: RecName: Full=cGMP-specific 3',5'-cyclic phosphodiesterase; EC=3.1.4.35; AltName: Full=cGMP-binding cGMP-specific phosphodiesterase; Short=CGB-PDE;
FUNCTION: Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'- GMP.
CATALYTIC ACTIVITY: Guanosine 3',5'-cyclic phosphate + H(2)O = guanosine 5'-phosphate.
COFACTOR: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
ENZYME REGULATION: Sildenafil (Viagra) is a highly selective and potent inhibitor of PDE5A and is effective in the treatment of penile erectile dysfunction. Also inhibited by zaprinast.
PATHWAY: Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1.
TISSUE SPECIFICITY: Expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung.
DOMAIN: Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain which contains two homologous allosteric cGMP-binding regions, A and B.
PTM: Phosphorylation is regulated by binding of cGMP to the two allosteric sites (By similarity). Phosphorylation by PRKG1 leads to its activation.
SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
SIMILARITY: Contains 2 GAF domains.

-  Primer design for this transcript
 

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: PDE5A
Diseases sorted by gene-association score: priapism (34), nonarteritic anterior ischemic optic neuropathy (29), impotence (23), transient global amnesia (22), sexual disorder (21), prostatitis (19), psychosexual disorder (18), pulmonary hypertension (17), penile disease (12), heart disease (11), vasculogenic impotence (11), peyronie's disease (11), ischemic optic neuropathy (8), optic nerve disease (8), premature ejaculation (6), disease of mental health (6), arteritic anterior ischemic optic neuropathy (6), persistent fetal circulation syndrome (5), functional gastric disease (5), low compliance bladder (5), pure autonomic failure (4), blue color blindness (4), myocardial infarction (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 27.21 RPKM in Artery - Aorta
Total median expression: 288.76 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -51.90133-0.390 Picture PostScript Text
3' UTR -994.704198-0.237 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003018 - GAF
IPR003607 - HD/PDEase_dom
IPR023088 - PDEase
IPR002073 - PDEase_catalytic_dom
IPR023174 - PDEase_CS

Pfam Domains:
PF01590 - GAF domain
PF00233 - 3'5'-cyclic nucleotide phosphodiesterase

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1RKP - X-ray MuPIT 1T9R - X-ray MuPIT 1T9S - X-ray MuPIT 1TBF - X-ray MuPIT 1UDT - X-ray MuPIT 1UDU - X-ray MuPIT 1UHO - X-ray MuPIT 1XOZ - X-ray MuPIT 1XP0 - X-ray MuPIT 2CHM - X-ray MuPIT 2H40 - X-ray MuPIT 2H42 - X-ray MuPIT 2H44 - X-ray MuPIT 2XSS - X-ray MuPIT 3B2R - X-ray MuPIT 3BJC - X-ray MuPIT 3HC8 - X-ray MuPIT 3HDZ - X-ray MuPIT 3JWQ - X-ray MuPIT 3JWR - X-ray 3LFV - X-ray MuPIT 3MF0 - X-ray MuPIT 3SHY - X-ray MuPIT 3SHZ - X-ray MuPIT 3SIE - X-ray MuPIT 3TGE - X-ray MuPIT 3TGG - X-ray MuPIT 3TSE - X-ray 3TSF - X-ray


ModBase Predicted Comparative 3D Structure on O76074
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003824 catalytic activity
GO:0004112 cyclic-nucleotide phosphodiesterase activity
GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
GO:0005515 protein binding
GO:0008081 phosphoric diester hydrolase activity
GO:0016787 hydrolase activity
GO:0030553 cGMP binding
GO:0046872 metal ion binding
GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity

Biological Process:
GO:0007165 signal transduction
GO:0008152 metabolic process
GO:0010613 positive regulation of cardiac muscle hypertrophy
GO:0030823 regulation of cGMP metabolic process
GO:0042130 negative regulation of T cell proliferation
GO:0043406 positive regulation of MAP kinase activity
GO:0046068 cGMP metabolic process
GO:0046069 cGMP catabolic process
GO:0055118 negative regulation of cardiac muscle contraction
GO:0055119 relaxation of cardiac muscle
GO:0060282 positive regulation of oocyte development

Cellular Component:
GO:0005575 cellular_component
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  D89094 - Homo sapiens mRNA for 3',5'-cyclic GMP phosphodiesterase, complete cds.
BC126233 - Homo sapiens phosphodiesterase 5A, cGMP-specific, mRNA (cDNA clone MGC:161511 IMAGE:8991949), complete cds.
AF043731 - Homo sapiens cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase (PDE5A1) mRNA, complete cds.
AJ004865 - Homo sapiens mRNA for cGMP-binding, cGMP-specific phosphodiesterase (HSPDE5A1).
AY264918 - Homo sapiens phosphodiesterase 5A (PDE5A) mRNA, complete cds.
AK290189 - Homo sapiens cDNA FLJ77036 complete cds, highly similar to Homo sapiens cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase (PDE5A1) mRNA.
AB015656 - Homo sapiens mRNA for cGMP-binding cGMP specific phosphodiesterase 5A2, complete cds.
JQ286346 - Homo sapiens phosphodiesterase 5A mRNA, complete cds.
AM392687 - Synthetic construct Homo sapiens clone IMAGE:100002918 for hypothetical protein (PDE5A gene).
AM393432 - Synthetic construct Homo sapiens clone IMAGE:100002919 for hypothetical protein (PDE5A gene).
AM393036 - Synthetic construct Homo sapiens clone IMAGE:100002917 for hypothetical protein (PDE5A gene).
AM393448 - Synthetic construct Homo sapiens clone IMAGE:100002916 for hypothetical protein (PDE5A gene).
AM392735 - Synthetic construct Homo sapiens clone IMAGE:100002678 for hypothetical protein (PDE5A gene).
AM392945 - Synthetic construct Homo sapiens clone IMAGE:100002679 for hypothetical protein (PDE5A gene).
AM393171 - Synthetic construct Homo sapiens clone IMAGE:100002676 for hypothetical protein (PDE5A gene).
AM393311 - Synthetic construct Homo sapiens clone IMAGE:100002674 for hypothetical protein (PDE5A gene).
AM393426 - Synthetic construct Homo sapiens clone IMAGE:100002680 for hypothetical protein (PDE5A gene).
AM393814 - Synthetic construct Homo sapiens clone IMAGE:100002675 for hypothetical protein (PDE5A gene).
AB527373 - Synthetic construct DNA, clone: pF1KE0334, Homo sapiens PDE5A gene for phosphodiesterase 5A, cGMP-specific, without stop codon, in Flexi system.
AM393270 - Synthetic construct Homo sapiens clone IMAGE:100002677 for hypothetical protein (PDE5A gene).
JD021063 - Sequence 2087 from Patent EP1572962.
JD033030 - Sequence 14054 from Patent EP1572962.
JD566526 - Sequence 547550 from Patent EP1572962.
AY266363 - Homo sapiens phosphodiesterase isozyme 5 (PDE5) mRNA, partial cds.
AF043732 - Homo sapiens cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase (PDE5A2) mRNA, partial cds.
AF155193 - Homo sapiens cGMP-specific phosphodiesterase PDE5A2 (PDE5A) mRNA, partial cds.
AF155194 - Homo sapiens cGMP-specific phosphodiesterase PDE5A3 (PDE5A) mRNA, partial cds.
AF155192 - Homo sapiens cGMP-specific phosphodiesterase PDE5A1 (PDE5A) mRNA, partial cds.
JD370392 - Sequence 351416 from Patent EP1572962.
JD496332 - Sequence 477356 from Patent EP1572962.
JD215265 - Sequence 196289 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00230 - Purine metabolism

Reactome (by CSHL, EBI, and GO)

Protein O76074 (Reactome details) participates in the following event(s):

R-HSA-418456 cGMP is degraded by PDEs
R-HSA-418457 cGMP effects
R-HSA-392154 Nitric oxide stimulates guanylate cyclase
R-HSA-418346 Platelet homeostasis
R-HSA-109582 Hemostasis

-  Other Names for This Gene
  Alternate Gene Symbols: A0AV69, A8K2C4, ENST00000354960.1, ENST00000354960.2, ENST00000354960.3, ENST00000354960.4, ENST00000354960.5, ENST00000354960.6, ENST00000354960.7, NM_001083, O75026, O75887, O76074, PDE5, PDE5A_HUMAN, Q86UI0, Q86V66, Q9Y6Z6, uc003idh.1, uc003idh.2, uc003idh.3, uc003idh.4, uc003idh.5
UCSC ID: ENST00000354960.8
RefSeq Accession: NM_001083
Protein: O76074 (aka PDE5A_HUMAN or CN5A_HUMAN)
CCDS: CCDS3713.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.