RAB7A
Description
The RAB7A (RAB7A, member RAS oncogene family) is a protein-coding gene located on chromosome 3.
RAB7A is a protein encoded by the RAB7A gene in humans. It is involved in endocytosis, a process that brings substances into cells. RAB7A helps move vesicles into the cell and regulates their trafficking. Mutations in RAB7A are linked to Hereditary sensory neuropathy type 1C (HSN1C), also known as Charcot-Marie-Tooth syndrome type 2B (CMT2B). RAB7A is a member of the RAB family of RAS-related GTP-binding proteins, which are crucial regulators of vesicular transport. RAB7A is localized to late endosomes and is essential for the late endocytic pathway. It plays a fundamental role in cellular vacuolation induced by the cytotoxin VacA of Helicobacter pylori. It is a key regulator in endo-lysosomal trafficking, governs early-to-late endosomal maturation, microtubule minus-end and plus-end directed endosomal migration and positioning, and endosome-lysosome transport through protein-protein interaction cascades.
RAB7A is a small GTPase that switches between an active GTP-bound state and an inactive GDP-bound state. In its active form, it interacts with various effector proteins, playing a key role in regulating endo-lysosomal trafficking. It controls the transition from early to late endosomes, directs endosomal movement towards both the minus and plus ends of microtubules, and manages endosome-lysosome transport through protein-protein interactions. RAB7A is crucial not just in endosomal transport, but also in other cellular and physiological processes such as growth factor signaling, nutrient uptake, neurotrophin transport in neuron axons, and lipid metabolism. It also regulates specific endosomal membrane trafficking, including the maturation of melanosomes, pathogen-induced phagosomes (or vacuoles), and autophagosomes. RAB7A contributes to the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis, and facilitates the fusion of phagosomes with lysosomes. It has significant roles in microbial pathogen infection and survival, and it is involved in the life cycle of viruses. Microbial pathogens have survival strategies that involve RAB7A, sometimes using its function (e.g., Salmonella) and sometimes suppressing it (e.g., Mycobacterium). In collaboration with RAC1, it regulates the formation of ruffled borders in osteoclasts. It governs the endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA. It controls the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation. RAB7A is involved in ADRB2-stimulated lipolysis through lipophagy, a cytosolic lipase-independent autophagic pathway. It is necessary for the exosomal release of SDCBP, CD63, and syndecan. It is required for vesicular trafficking and cell surface expression of ACE2. RAB7A may be involved in PRPH neuronal intermediate filament assembly. The GTP-bound form interacts with RAC1. It interacts with NTRK1/TRKA, C9orf72, CHM (the substrate-binding subunit of the Rab geranylgeranyltransferase complex), RILP, PSMA7, RNF115, FYCO1, the PIK3C3/VPS34-PIK3R4 complex, OSBPL1A, CLN3, CLN5, PLEKHM1 (via N- and C-terminus), RUFY4, PRPH (directly), and VPS13A. The GDP-bound form interacts with RIMOC1. It also interacts with the MON1A-CCZ1B complex, and this interaction is enhanced in the presence of RIMOC1. RAB7A interacts with VPS39 and VPS41.
RAB7A is also known as CMT2B, PRO2706, RAB7.
