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

PDE4D (Q08499) - Overview - Molecular Target Synopsis

Protein


PDE4D, cAMP-specific 3',5'-cyclic phosphodiesterase 4D
Enzyme Classification 3.1.4.53
UniProt Q08499

Also Known as PDE4D_HUMAN, PDE4D, DPDE3

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Isoform 3 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9. Interacts with PDE4DIP. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity). Isoform 5, isoform N3 and isoform 12 bind RACK1 via their unique N-terminus. Binds ARRB2. Interacts (via N-terminal region) with SHANK2 (via proline-rich region); the interaction is increased in a PKA-dependent manner.

6NJH
CRYSTAL STRUCTURE OF THE PDE4D CATALYTIC DOMAIN AND UCR2 REGULATORY HELIX WITH T-48
RCSB/PDB
Inspect Structure
See all 3D Structures for PDE4D

Isoforms / Transcripts (Protein Coding)


Drugs


PDE4D is targeted by Approved Drugs Roflumilast, Amlexanox, Crisaborole, Apremilast, Pentoxifylline. (see details)
Roflumilast
Amlexanox
Crisaborole
Apremilast
Pentoxifylline

Sub-cellular localization


UniProt: PDE4D is active in the following subcellular-locations: apical cell membrane, centrosome, cytoplasm, cytoskeleton, membrane, microtubule organizing center.
GO terms: PDE4D is active in the following subcellular-locations: apical plasma membrane, calcium channel complex, centrosome, cytosol, membrane, nuclear membrane, plasma membrane, voltage-gated calcium channel complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PDE4D has gain in 2 cell-lines, loss in 3 cell-lines and no signal in 1000 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: NCI_H460, SR, A549

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC-15, NCI-H1355, SW 527

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: HeLa-S3, A549, SK-N-SH_RA

(see details)

3D Structures


For PDE4D there are:
65 structures (209 chains) solved
64 are solved in complex with at least one small molecule ligand
5 are solved with an approved drug

PDE4D is solved in complex with the approved drug(s):

AMP/ADENOSINE PHOSPHATE (1PTW_A, 1PTW_B, 1PTW_C, 1PTW_D, 1TB7_A, 1TB7_B),
ROF/ROFLUMILAST (1XOQ_A, 1XOQ_B, 3G4L_A, 3G4L_B, 3G4L_C, 3G4L_D),
EV1/PAPAVERINE (3IAK_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PDE4D has been screened with 3227 compounds (5033 bioactivities), 1190 compounds have bioactivities that show binding affinity of <= 500nM (1828 bioactivities). (see details)