DENN domain-containing protein 10 (DENND10)

DENN domain-containing protein 10 (DENND10, also known as FAM45A or family with sequence similarity 45 member A) is a member of the DENN domain protein family, which broadly act as guanine nucleotide exchange factors (GEFs) for Rab small GTPases, specialized regulators of membrane trafficking[2]. DENND10 is a component of the Commander complex (comprising COMMD proteins, CCDC22, CCDC93, Retriever subunits, and DENND10), a multi-protein complex essential for endosomal recycling and homeostasis[3][5]. Within this complex, DENND10 tightly associates via direct interaction with CCDC22 and CCDC93 (of the CCC subcomplex), regulating the recycling of transmembrane proteins from endosomes to the plasma membrane[1][3]. Structurally, DENND10 consists of closely packed N- and C-terminal domains characteristic of DENN proteins, but evidence for intrinsic Rab GEF activity is currently lacking, as predicted GTPase binding surfaces may be masked in the complex[1][2][3]. Functionally, DENND10 is necessary for proper endosomal maturation and for the biogenesis and secretion of extracellular vesicles (EVs). Knockdown or loss of DENND10 leads to reduced EV release and alters the proteomic composition of EVs, impairing cancer cell migration and invasion, especially in triple-negative breast cancer[2]. DENND10 expression correlates with worse prognosis in breast cancer, though it is not required for basic cell proliferation[2]. Through its central role in endosomal trafficking and EV biogenesis, DENND10 may contribute to the metastatic potential of tumor cells and impact extracellular matrix (ECM) modulation. DENND10 is broadly conserved from unicellular organisms to vertebrates and is ubiquitously expressed in mammalian tissues[2]. While its structure and participation in the Commander complex are well characterized, direct pharmacologic targeting and associated drugs for DENND10 are not reported as of now, and there are no established clinical biomarkers or known therapeutic safety concerns directly linked to this protein[2][3].

Other names

FAM45AProtein FAM45Afamily with sequence similarity 45 member AANR3