E3 ubiquitin-protein ligase Praja-2 (PJA2)

E3 ubiquitin-protein ligase Praja-2 (PJA2) is an enzyme encoded by the PJA2 gene on chromosome 5 in humans and belongs to the RING finger family of E3 ubiquitin ligases[1][2][4]. PJA2 catalyzes the transfer of ubiquitin to specific substrate proteins, targeting them for proteasomal degradation, notably including the regulatory subunits of cAMP-dependent protein kinase A (PKA)[1][2][5][6]. Through substrate ubiquitination, PJA2 regulates cellular processes such as long-term memory formation (via PKA) and innate immunity (via TLR2 pathway modulation), as well as promoting pro-inflammatory macrophage polarization and ciliogenesis through additional targets such as OFD1 and MFHAS1[1][2][5][6]. Dysregulation or altered expression of PJA2 has been associated with a variety of diseases, including neurodegenerative disorders (notably Alzheimer’s disease, where PJA2 modulates amyloid and tau gene expression), numerous kidney diseases, and potentially cancer[3][1]. No drugs are currently known to directly target PJA2, but its central role in key ubiquitin-mediated signaling pathways positions it as an emerging focus for therapeutic research in neurodegeneration, immune modulation, and oncology[3][1][2].

Other names

Praja2KIAA0438RNF131Neurodap1praja ring finger ubiquitin ligase 2praja ring finger 2ring finger protein 131RING-type E3 ubiquitin transferase Praja-2E3 ubiquitin protein ligaseRING-H2 motif containing

Induces ubiquitination and proteasomal degradation of target proteins, especially components of the PKA complex Modulates innate immune and inflammatory signaling by ubiquitinating pathway regulators