RAB7A

RAB family members are small, RAS-related GTP-binding proteins that are important regulators of vesicular transport. Each RAB protein targets multiple proteins that act in exocytic / endocytic pathways. This gene encodes a RAB family member that regulates vesicle traffic in the late endosomes and also from late endosomes to lysosomes. This encoded protein is also involved in the cellular vacuolation of the VacA cytotoxin of Helicobacter pylori. Mutations at highly conserved amino acid residues in this gene have caused some forms of Charcot-Marie-Tooth (CMT) type 2 neuropathies.

RAB7A, member RAS oncogene family

Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins playing a key role in the regulation of endo-lysosomal trafficking. Governs early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. Plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as growth-factor-mediated cell signaling, nutrient-transportor mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism. Also involved in regulation of some specialized endosomal membrane trafficking, such as maturation of melanosomes, pathogen-induced phagosomes (or vacuoles) and autophagosomes. Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays a role in the fusion of phagosomes with lysosomes. Plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses. Microbial pathogens possess survival strategies governed by RAB7A, sometimes by employing RAB7A function (e.g. Salmonella) and sometimes by excluding RAB7A function (e.g. Mycobacterium). In concert with RAC1, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. Controls the endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA (PubMed:11179213, PubMed:12944476, PubMed:14617358, PubMed:20028791, PubMed:21255211).
Regulates the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation. Involved in the ADRB2-stimulated lipolysis through lipophagy, a cytosolic lipase-independent autophagic pathway (By similarity).
Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).
Required for vesicular trafficking and cell surface expression of ACE2 (PubMed:33147445).
May play a role in PRPH neuronal intermediate filament assembly (By similarity).

Biological Process autophagosome assemblyManual Assertion Based On ExperimentIMP:GO_Central
Biological Process bone resorptionIEA:Ensembl
Biological Process early endosome to late endosome transportManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process endocytosisManual Assertion Based On ExperimentTAS:ProtInc
Biological Process endosome to lysosome transportManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process endosome to plasma membrane protein transportManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process epidermal growth factor catabolic processManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process establishment of vesicle localizationIEA:Ensembl
Biological Process intracellular transportManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process lipid catabolic processIEA:UniProtKB-KW
Biological Process lipophagyISS:GO_Central
Biological Process negative regulation of exosomal secretionManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process negative regulation of intralumenal vesicle formationManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Biological Process phagosome acidificationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process phagosome maturationManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process phagosome-lysosome fusionManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of exosomal secretionManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of protein catabolic processManual Assertion Based On ExperimentIMP:CACAO
Biological Process positive regulation of viral processManual Assertion Based On ExperimentIMP:CACAO
Biological Process protein targeting to lysosomeManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process protein to membrane dockingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein transportManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process response to bacteriumManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process retrograde transport, endosome to GolgiManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process viral release from host cellManual Assertion Based On ExperimentIMP:CACAO

Cytoplasmic vesicle, phagosome membrane
Late endosome membrane
Lysosome membrane
Melanosome membrane
Cytoplasmic vesicle, autophagosome membrane
Lipid droplet
Endosome membrane
Cytoplasmic vesicle
Mitochondrion membrane
Colocalizes with OSBPL1A at the late endosome (PubMed:16176980).
Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts. Recruited to phagosomes containing S.aureus or Mycobacterium (PubMed:21255211).
Lipid droplet localization is increased upon ADRB2 stimulation (By similarity).
Recruited to damaged mitochondria during mitophagy in a RIMOC1-dependent manner (PubMed:34432599).

Charcot-Marie-Tooth disease 2B (CMT2B):
A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.