PDE3A

Protein identityUniProt · HPA

UniProt accession

Q14432

Gene

PDE3A

Ensembl

ENSG00000172572

Chromosome

12

Canonical length

1141 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted membrane proteins

Subcellular location

Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI-PDE) family. cGI-PDE enzymes hydrolyze both cAMP and cGMP, and play critical roles in many cellular processes by regulating the amplitude and duration of intracellular cyclic nucleotide signals. The encoded protein mediates platelet aggregation and also plays important roles in cardiovascular function by regulating vascular smooth muscle contraction and relaxation. Inhibitors of the encoded protein may be effective in treating congestive heart failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

Canonical amino-acid sequenceUniProt

1141 residues, UniProt reviewed canonical sequence.

>Q14432|PDE3A
     1  MAVPGDAARV RDKPVHSGVS QAPTAGRDCH HRADPASPRD SGCRGCWGDL VLQPLRSSRK
    61  LSSALCAGSL SFLLALLVRL VRGEVGCDLE QCKEAAAAEE EEAAPGAEGG VFPGPRGGAP
   121  GGGARLSPWL QPSALLFSLL CAFFWMGLYL LRAGVRLPLA VALLAACCGG EALVQIGLGV
   181  GEDHLLSLPA AGVVLSCLAA ATWLVLRLRL GVLMIALTSA VRTVSLISLE RFKVAWRPYL
   241  AYLAGVLGIL LARYVEQILP QSAEAAPREH LGSQLIAGTK EDIPVFKRRR RSSSVVSAEM
   301  SGCSSKSHRR TSLPCIPREQ LMGHSEWDHK RGPRGSQSSG TSITVDIAVM GEAHGLITDL
   361  LADPSLPPNV CTSLRAVSNL LSTQLTFQAI HKPRVNPVTS LSENYTCSDS EESSEKDKLA
   421  IPKRLRRSLP PGLLRRVSST WTTTTSATGL PTLEPAPVRR DRSTSIKLQE APSSSPDSWN
   481  NPVMMTLTKS RSFTSSYAIS AANHVKAKKQ SRPGALAKIS PLSSPCSSPL QGTPASSLVS
   541  KISAVQFPES ADTTAKQSLG SHRALTYTQS APDLSPQILT PPVICSSCGR PYSQGNPADE
   601  PLERSGVATR TPSRTDDTAQ VTSDYETNNN SDSSDIVQNE DETECLREPL RKASACSTYA
   661  PETMMFLDKP ILAPEPLVMD NLDSIMEQLN TWNFPIFDLV ENIGRKCGRI LSQVSYRLFE
   721  DMGLFEAFKI PIREFMNYFH ALEIGYRDIP YHNRIHATDV LHAVWYLTTQ PIPGLSTVIN
   781  DHGSTSDSDS DSGFTHGHMG YVFSKTYNVT DDKYGCLSGN IPALELMALY VAAAMHDYDH
   841  PGRTNAFLVA TSAPQAVLYN DRSVLENHHA AAAWNLFMSR PEYNFLINLD HVEFKHFRFL
   901  VIEAILATDL KKHFDFVAKF NGKVNDDVGI DWTNENDRLL VCQMCIKLAD INGPAKCKEL
   961  HLQWTDGIVN EFYEQGDEEA SLGLPISPFM DRSAPQLANL QESFISHIVG PLCNSYDSAG
  1021  LMPGKWVEDS DESGDTDDPE EEEEEAPAPN EEETCENNES PKKKTFKRRK IYCQITQHLL
  1081  QNHKMWKKVI EEEQRLAGIE NQSLDQTPQS HSSEQIQAIK EEEEEKGKPR GEEIPTQKPD
  1141  Q

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDE3A 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

6

Mean surface accessibility (rSASA)

0.49

Highest tissue expression

28 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PDE3A.

Disease | AllUniProt

Conditions PDE3A is implicated in, by any mechanism.

• Hypertension and brachydactyly syndrome (HTNB) MIM:112410

Disease | GeneticClinVar

10 pathogenic / likely-pathogenic of 381 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Brachydactyly-arterial hypertension syndrome
• Inborn genetic diseases

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)

0.52

gnomAD pLI

0

gnomAD missense Z

0.59

DepMap mean gene effect

0.15

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic signaling pathway
• cellular response to cGMP
• cellular response to transforming growth factor beta stimulus
• G protein-coupled receptor signaling pathway
• lipid metabolic process
• negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
• negative regulation of apoptotic process
• negative regulation of cAMP/PKA signal transduction
• negative regulation of vascular permeability
• oocyte maturation
• positive regulation of vascular permeability
• regulation of meiotic nuclear division
• regulation of ribonuclease activity
• response to xenobiotic stimulus
• positive regulation of oocyte development

Molecular functions

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

Cellular components

• cytosol
• membrane

Protein domainsUniProt · Pfam · InterPro

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

KeywordsUniProt

• cAMP
• cGMP
• Cytoplasm
• Hydrolase
• Isopeptide bond
• Manganese
• Membrane
• Metal-binding
• Phosphoprotein
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of PDE3A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SLFN12
• ARFGEF1
• ARFGEF2