DENN domain-containing protein 2D (DENND2D)

DENN domain-containing protein 2D (DENND2D) is a member of the DENND2 protein family, characterized by the presence of a C-terminal DENN domain that confers guanine nucleotide exchange factor (GEF) activity toward Rab GTPases, primarily Rab9a/b[3][4]. DENND2D is implicated in the regulation of endosomal membrane trafficking and vesicle transport, processes essential for cell signaling and homeostasis[3][4]. Functionally, DENND2D acts as a tumor suppressor gene, with its reduced expression—often by promoter hypermethylation—being reported in several human cancers, including lung, gastric, colon, hepatocellular, bladder, and esophageal squamous cell carcinomas[2][4]. In cancer, loss of DENND2D function is associated with increased proliferation, metastasis, and poor prognosis[2][4]. Its value as a therapeutic target stems from its regulatory role in cell trafficking and tumorigenesis, though no drugs are currently known to interact directly with DENND2D, and its mechanisms in chemoresistance or other pathways remain under investigation[2][4].

Other names

FLJ22457RP5-1180E21.2DENN/MADD domain containing 2D

Guanine nucleotide exchange on Rab GTPases (especially Rab9a/b)