General Information of Drug Therapeutic Target (DTT) (ID: TTF6WAQ)

DTT Name Ras-related protein Rab-7a (RAB7A)
Synonyms RAB7
Gene Name RAB7A
DTT Type
Literature-reported target
[1]
BioChemical Class
Small GTPase
UniProt ID
RAB7A_HUMAN
TTD ID
T14030
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MTSRKKVLLKVIILGDSGVGKTSLMNQYVNKKFSNQYKATIGADFLTKEVMVDDRLVTMQ
IWDTAGQERFQSLGVAFYRGADCCVLVFDVTAPNTFKTLDSWRDEFLIQASPRDPENFPF
VVLGNKIDLENRQVATKRAQAWCYSKNNIPYFETSAKEAINVEQAFQTIARNALKQETEV
ELYNEFPEPIKLDKNDRAKASAESCSC
Function
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. 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. Required for the exosomal release of SDCBP, CD63 and syndecan. Key regulator in endo-lysosomal trafficking.
KEGG Pathway
Mitophagy - animal (hsa04137 )
Autophagy - animal (hsa04140 )
Endocytosis (hsa04144 )
Phagosome (hsa04145 )
Salmonella infection (hsa05132 )
Amoebiasis (hsa05146 )
Tuberculosis (hsa05152 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
TBC/RABGAPs (R-HSA-8854214 )
RAB geranylgeranylation (R-HSA-8873719 )
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )
CDC42 GTPase cycle (R-HSA-9013148 )
RAC1 GTPase cycle (R-HSA-9013149 )
RAC2 GTPase cycle (R-HSA-9013404 )
RHOD GTPase cycle (R-HSA-9013405 )
RHOQ GTPase cycle (R-HSA-9013406 )
RHOH GTPase cycle (R-HSA-9013407 )
RHOG GTPase cycle (R-HSA-9013408 )
RHOJ GTPase cycle (R-HSA-9013409 )
RAC3 GTPase cycle (R-HSA-9013423 )
RHOF GTPase cycle (R-HSA-9035034 )
Prevention of phagosomal-lysosomal fusion (R-HSA-9636383 )
Suppression of autophagy (R-HSA-9636569 )
MHC class II antigen presentation (R-HSA-2132295 )

References

1 Modulation of RAB7A Protein Expression Determines Resistance to Cisplatin through Late Endocytic Pathway Impairment and Extracellular Vesicular Sec... Cancers (Basel). 2019 Jan 8;11(1). pii: E52.