PDE5A

Protein identityUniProt · HPA

UniProt accession

O76074

Gene

PDE5A

Ensembl

ENSG00000138735

Chromosome

4

Canonical length

875 aa

Protein class

Enzymes, FDA approved drug targets, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Basal body,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

875 residues, UniProt reviewed canonical sequence.

>O76074|PDE5A
     1  MERAGPSFGQ QRQQQQPQQQ KQQQRDQDSV EAWLDDHWDF TFSYFVRKAT REMVNAWFAE
    61  RVHTIPVCKE GIRGHTESCS CPLQQSPRAD NSAPGTPTRK ISASEFDRPL RPIVVKDSEG
   121  TVSFLSDSEK KEQMPLTPPR FDHDEGDQCS RLLELVKDIS SHLDVTALCH KIFLHIHGLI
   181  SADRYSLFLV CEDSSNDKFL ISRLFDVAEG STLEEVSNNC IRLEWNKGIV GHVAALGEPL
   241  NIKDAYEDPR FNAEVDQITG YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE
   301  KDFAAYLAFC GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS
   361  FMQVQKCTIF IVDEDCSDSF SSVFHMECEE LEKSSDTLTR EHDANKINYM YAQYVKNTME
   421  PLNIPDVSKD KRFPWTTENT GNVNQQCIRS LLCTPIKNGK KNKVIGVCQL VNKMEENTGK
   481  VKPFNRNDEQ FLEAFVIFCG LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETREL
   541  QSLAAAVVPS AQTLKITDFS FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL
   601  SVKKNYRKNV AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LEILALLIAA LSHDLDHRGV
   661  NNSYIQRSEH PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK TTLKIIKQAI
   721  LATDLALYIK RRGEFFELIR KNQFNLEDPH QKELFLAMLM TACDLSAITK PWPIQQRIAE
   781  LVATEFFDQG DRERKELNIE PTDLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCF
   841  PLLDGCRKNR QKWQALAEQQ EKMLINGESG QAKRN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDE5A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

56 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.51

gnomAD pLI

0

gnomAD missense Z

2.1

DepMap mean gene effect

0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cGMP catabolic process
• negative regulation of cAMP/PKA signal transduction
• signal transduction

Molecular functions

• 3',5'-cyclic-AMP phosphodiesterase activity
• 3',5'-cyclic-GMP phosphodiesterase activity
• 3',5'-cyclic-nucleotide phosphodiesterase activity
• cGMP binding
• metal ion binding

Cellular components

• cytosol

Protein domainsUniProt · Pfam · InterPro

• 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain
• GAF domain
• HD/PDEase domain
• 3'5'-cyclic nucleotide phosphodiesterase
• 3'5'-cyclic nucleotide phosphodiesterase, conserved site
• GAF-like domain superfamily
• 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily
• 3'5'-cyclic nucleotide phosphodiesterase
• GAF domain

KeywordsUniProt

• Allosteric enzyme
• cGMP
• cGMP-binding
• Hydrolase
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Repeat
• Zinc

InteractionsUniProt · HPA

Protein binding partners of PDE5A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AIPL1