DENN domain-containing protein 2C (DENND2C)

DENN domain-containing protein 2C (DENND2C) is a guanine nucleotide exchange factor (GEF) for Rab GTPases and functions primarily to regulate intracellular trafficking and cellular signaling[1][3][4]. It contains a DENN domain, which confers GEF activity and is part of a larger family of Rab GEFs. DENND2C is expressed in the nucleoplasm and, by regulating the activity and localization of small GTPases such as RHOA, contributes to the maintenance of stem cell pluripotency and blocks cell differentiation in embryonic stem cells[3][2]. It also negatively regulates multinucleation and differentiation of osteoclasts through effects on actin polymerization and protrusion formation in monocyte/macrophage-derived cells[2]. DENND2C is implicated in cancer biology due to regulation by p53, associating it with cell cycle and apoptosis control[1]. It is conserved across vertebrates, with closely related paralogs DENND2A, DENND2B, and DENND2D[1]. In disease, genetic studies have suggested a role in rotator cuff degeneration, Noonan syndrome, and some cancers[5][3]. Interacting drugs and biomarkers for therapeutic use are not established, but its multifaceted role in cellular signaling and differentiation underpins interest in DENND2C as a candidate for targeted therapy or as a disease biomarker[1][2][3][5].

Other names

DENND2CDENN domain containing 2CDENN/MADD domain containing 2CdJ1156J9.1DJ1156J9.1FLJ37099DKFZp686G0351DKFZp779P1149RP5-1156J9.1

Not established; experimental manipulation involves inhibition of actin polymerization (latrunculin B), Cdc42, and Rac1 pathways to reverse DENND2C-driven effects on cytoskeletal dynamics and differentiation