Rab-like protein 3 (RABL3)

Rab-like protein 3 (RABL3) is a highly conserved small GTPase, structurally and phylogenetically related to, but distinct from, canonical Rab proteins within the Ras superfamily[1][2][4]. It features conserved GTP/GDP-binding motifs (G1–G5) without the typical Rab C-terminal prenylation site, instead possessing a unique C-terminal membrane-targeting motif[1]. RABL3 forms homodimers, displaying a conventional small G protein fold, and has direct roles in regulating KRAS signaling and other small GTPase prenylation events[3]. It is essential for normal lymphocyte development, as deficiency or mutation in RABL3 leads to significant impairment in B cell, T cell, and natural killer cell differentiation and function, with implications for immune deficiencies and cancer, particularly pancreatic cancer[1][3][4]. RABL3 interacts directly with and stabilizes GPR89, a putative GPCR or ion channel, highlighting its role in signal transduction pathways important for hematopoiesis and immune function[1][4]. Homozygous knockout in mice is embryonic lethal, and hypomorphic mutations result in profound immunological defects without affecting myeloid lineages[1][4].

Other names

RAB, member of RAS oncogene family like 3RABL3Rab-like protein 3MGC23920PNCA5

Not applicable; no direct drugs known to target RABL3[3].