Protein: Ras-related protein Rab-7a (EC 3.6.5.2) (P51150)
Organism: Mus musculus (Mouse)
Function: 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-transporter-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 Mycobacteria. 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. Regulates the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation (By similarity). Involved in the ADRB2-stimulated lipolysis through lipophagy, a cytosolic lipase-independent autophagic pathway. Required for the exosomal release of SDCBP, CD63 and syndecan (By similarity). Required for vesicular trafficking and cell surface expression of ACE2 (By similarity). May play a role in PRPH neuronal intermediate filament assembly.
Subcellular location: Cytoplasmic vesicle, phagosome membrane {ECO:0000250|UniProtKB:P51149}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Late endosome membrane {ECO:0000250|UniProtKB:P51149}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Lysosome membrane {ECO:0000269|PubMed:28063257}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Melanosome membrane {ECO:0000250|UniProtKB:P51149}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000250|UniProtKB:P51149}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Lipid droplet {ECO:0000269|PubMed:23708524}. Endosome membrane {ECO:0000250|UniProtKB:P51149}. Cytoplasmic vesicle {ECO:0000269|PubMed:23179371}. Mitochondrion membrane {ECO:0000250|UniProtKB:P51149}; Peripheral membrane protein {ECO:0000305}. Note=Colocalizes with OSBPL1A at the late endosome (By similarity). Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts (By similarity). Recruited to phagosomes containing S.aureus or Mycobacterium (By similarity). Lipid droplet localization is increased upon ADRB2 stimulation (PubMed:23708524). Recruited to damaged mitochondria during mitophagy in a RIMOC1-dependent manner (By similarity). {ECO:0000250|UniProtKB:P51149, ECO:0000269|PubMed:23708524}.
Sequence: MTSRKKVLLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQIWDTAGQERFQSLGVAFYRGADCCVLVFDVTAPNTFKTLDSWRDEFLIQASPRDPENFPFVVLGNKIDLENRQVATKRAQAWCYSKNNIPYFETSAKEAINVEQAFQTIARNALKQETEVELYNEFPEPIKLDKNDRAKASAESCSC
InterPro domains: - IPR001806: Small GTPase (family) [1-207]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [1-190]
- IPR005225: Small GTP-binding domain (domain) [10-169]
Interaction partners: - Rab-interacting lysosomal protein
- FYVE and coiled-coil domain-containing protein 1
- Oxysterol-binding protein-related protein 1
- Rab proteins geranylgeranyltransferase component A 1
- Vacuolar protein sorting-associated protein 35
- TBC1 domain family member 15
- Vacuolar protein sorting-associated protein 26A
- Vacuolar protein sorting-associated protein 29
- Vacuolar fusion protein CCZ1 homolog
- TBC1 domain family member 17
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0097367 (carbohydrate derivative binding), GO:0036094 (small molecule binding), GO:1901363 (heterocyclic compound binding), GO:0016787 (hydrolase activity), GO:0044877 (protein-containing complex binding), GO:0043167 (ion binding), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0016817 (hydrolase activity, acting on acid anhydrides), GO:1901265 (nucleoside phosphate binding), GO:0043168 (anion binding), GO:0000166 (nucleotide binding), GO:0032553 (ribonucleotide binding), GO:0035639 (purine ribonucleoside triphosphate binding), GO:0019003 (GDP binding), GO:0032555 (purine ribonucleotide binding), GO:0016818 (hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides), GO:0017076 (purine nucleotide binding), GO:0016462 (pyrophosphatase activity), GO:0005525 (GTP binding), GO:0019001 (guanyl nucleotide binding), GO:0032561 (guanyl ribonucleotide binding), GO:0017111 (ribonucleoside triphosphate phosphatase activity), GO:0003924 (GTPase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0051179 (localization), GO:0051234 (establishment of localization), GO:0051641 (cellular localization), GO:0046907 (intracellular transport), GO:0051649 (establishment of localization in cell), GO:0006810 (transport), GO:0007034 (vacuolar transport), GO:0016192 (vesicle-mediated transport), GO:0007041 (lysosomal transport), GO:0008333 (endosome to lysosome transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0005773 (vacuole), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0000323 (lytic vacuole), GO:0043231 (intracellular membrane-bounded organelle), GO:0005764 (lysosome)