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Target intelligence / Profile preview
DENN domain-containing protein 2A (DENND2A)
- Target
- DENND2A
- Molecular classification
- Guanine nucleotide exchange factor (GEF), DENN domain-containing protein, Regulator of Rab GTPases, Other
01
Overview
DENN domain-containing protein 2A (DENND2A) is a guanine nucleotide exchange factor (GEF) belonging to the DENN domain protein family. It enables GDP-to-GTP exchange on Rab9a/b GTPases, promoting retrograde transport from late endosomes to the trans-Golgi network and regulating cellular vesicle trafficking. DENND2A localizes with the actin cytoskeleton and plays a role in modulating immune signaling, suppressing NF-κB-driven transcription and cytokine production. It may also interact functionally with scaffold proteins such as SASH1. DENND2A is important for maintenance of hepatitis B virus (HBV) in infected cells, making it a potential therapeutic target for viral clearance strategies. Pathogenic variants have been associated with rare syndromic disorders, emphasizing its essential cellular roles.
- Other names
- DENND2AKIAA1277FAM31DDENN/MADD domain containing 2ADENN domain containing protein 2A
02
Mechanism of action
For hypothetical drugs: Modulation of GEF activity for Rab GTPases (e.g., inhibition or disruption of DENND2A-Rab9 interaction). Disruption of DENND2A-protein interactions (e.g., via peptide inhibitors blocking DENND2A-SASH1 interaction).
03
Biological functions
Guanine nucleotide exchange activity, specifically for Rab9a and Rab9b GTPasesPromotes retrograde trafficking from late endosomes to the trans-Golgi networkInteracts with the actin cytoskeletonRegulation of NF-κB transcriptional activity and cytokine production
04
Disease associations
Hepatitis B virus (HBV) maintenance and possible viral immune evasionPotential roles in rare genetic syndromes such as Martsolf syndrome 1 and Warburg Micro syndrome 1Broader roles in vesicle trafficking-related disorders (inferred from Rab GTPase regulation)
05
Safety considerations
Potentially essential gene for vesicle trafficking, suggesting that broad inhibition may disrupt critical cellular trafficking and immune regulatory pathwaysPossible risk for impaired immune function if DENND2A is broadly inhibited, due to its regulation of NF-κB and cytokine production
06
Biomarkers
Altered DENND2A expression or function in hepatocytes (implications for HBV infection and inflammation, but not yet a validated biomarker)
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