Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PDE9A (O76083) - Overview - Molecular Target Synopsis

Protein


PDE9A, High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
Enzyme Classification 3.1.4.35
UniProt O76083

Also Known as PDE9A_HUMAN, PDE9A

Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP (PubMed:9624146, PubMed:18757755, PubMed:21483814). Specifically regulates natriuretic-peptide-dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart (PubMed:25799991). Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein (Probable). In brain, involved in cognitive function, such as learning and long-term memory. Homodimer.

6A3N
CRYSTAL STRUCTURE OF THE PDE9 CATALYTIC DOMAIN IN COMPLEX WITH INHIBITOR 2
RCSB/PDB
Inspect Structure
See all 3D Structures for PDE9A

Isoforms / Transcripts (Protein Coding)


Drugs


PDE9A is targeted by Approved Drug Pentoxifylline. (see details)
Pentoxifylline

Sub-cellular localization


UniProt: PDE9A is active in the following subcellular-locations: cell membrane, cell projection, cytoplasm, endoplasmic reticulum, golgi apparatus, perinuclear region, ruffle membrane, sarcolemma.
GO terms: PDE9A is active in the following subcellular-locations: cytosol, endoplasmic reticulum, Golgi apparatus, perikaryon, perinuclear region of cytoplasm, ruffle membrane, sarcolemma.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PDE9A has gain in 0 cell-lines, loss in 1 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: OVCAR_3, HCT_116, OVCAR_5

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NIH:OVCAR-3, NTERA-2, OvCA 432

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

3D Structures


For PDE9A there are:
22 structures (44 chains) solved
21 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PDE9A has been screened with 312 compounds (376 bioactivities), 142 compounds have bioactivities that show binding affinity of <= 500nM (170 bioactivities). (see details)