RAB7A Human
Description
Gene and Protein Overview
The RAB7A gene (HGNC:9788) is located on chromosome 3q21.3 (GRCh38: 3:128,693,669–128,825,942) and encodes a 207-amino acid protein . Key features include:
| Transcript ID | Protein Length | Biotype | Key Isoforms |
|---|---|---|---|
| ENST00000265062.8 | 207 aa | Protein coding | Canonical (MANE Select) |
| ENST00000675864.1 | 217 aa | Protein coding | Alternative splicing variant |
| ENST00000482525.5 | 160 aa | Protein coding | Truncated isoform |
The protein contains conserved Rab family GTPase domains and a C-terminal CXC prenylation motif critical for membrane localization .
Molecular Functions
RAB7A governs:
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Endosomal maturation: Mediates early-to-late endosome transitions and lysosomal fusion via interactions with RILP (Rab-interacting lysosomal protein) and the retromer complex .
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Autophagy regulation: Binds Rubicon to suppress autophagosome-lysosome fusion in nutrient-rich conditions .
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Vesicle trafficking: Coordinates microtubule-dependent transport of signaling endosomes in neurons and phagosomes in immune cells .
Regulatory Mechanisms
RAB7A activity is modulated by:
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GTP/GDP cycling: GTP-bound RAB7A recruits effectors like FYCO1 for plus-end-directed vesicle transport, while GDP-bound forms are inactive .
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Transcriptional control: Expression is regulated by SOX10 (neuroectodermal development) and MYC (oncogenic signaling), independent of MITF in melanoma .
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Post-translational modifications: Phosphorylation at Tyr183 alters effector binding and subcellular localization .
Neurodegenerative Disorders
Mutations in RAB7A cause Charcot-Marie-Tooth type 2B (CMT2B), characterized by peripheral neuropathy due to impaired retrograde axonal transport .
Cancer Dynamics
RAB7A exhibits dual roles in tumor progression:
In PAAD, high RAB7A expression predicts reduced survival (HR = 1.67, P < 0.05), particularly in males and patients aged ≤65 years .
Tissue Distribution and Expression
RAB7A is ubiquitously expressed, with elevated levels in:
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Skeletal muscle: Facilitates retrograde transport in axons .
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Immune cells: Regulates phagolysosome formation in macrophages .
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Cancer tissues: Overexpressed in melanoma, breast, and pancreatic tumors .
| High-Expression Tissues | Functional Relevance |
|---|---|
| Neurons | Axonal transport of neurotrophic signals |
| Osteoclasts | Lysosomal acidification |
| Tumor cells | Metastasis and chemoresistance |
Therapeutic Implications
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Melanoma: Targeting RAB7A-SOX10/MYC axis may reduce metastatic risk .
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Breast cancer: Knockdown suppresses xenograft tumor growth by 60% (P < 0.01) via apoptosis induction and cell cycle arrest .
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Pancreatic cancer: RAB7A-associated pathways (e.g., mTOR, ROS) are potential biomarkers for adjuvant therapy .
Product Specs
NVEQAFQTIA RNALKQETEV ELYNEFPEPI KLDKNDRAKA SAESCSC.
Product Science Overview
RAB7A, a member of the RAS oncogene family, is a small GTPase that plays a crucial role in the regulation of vesicular transport. This protein is encoded by the RAB7A gene and is involved in various cellular processes, including endo-lysosomal trafficking, cell signaling, and lipid metabolism.
The RAB7A gene is located on chromosome 3 and encodes a protein that consists of 207 amino acids. The protein belongs to the RAB family of small GTPases, which are known for their role in vesicle trafficking. RAB7A cycles between an active GTP-bound state and an inactive GDP-bound state, interacting with various effector proteins to regulate endosomal and lysosomal transport .
RAB7A is primarily involved in the regulation of endo-lysosomal trafficking. It governs early-to-late endosomal maturation, endosome-lysosome transport, and endosomal positioning. The protein plays a central role in several cellular and physiological events, such as:
Mutations in the RAB7A gene have been associated with Charcot-Marie-Tooth disease type 2B (CMT2B), a hereditary neuropathy characterized by progressive muscle weakness and atrophy. These mutations often occur at highly conserved amino acid residues, leading to altered protein function and disease manifestation .
RAB7A has been identified as a potential drug target and biomarker for various diseases, including cancer. Its role in vesicular trafficking and cell signaling makes it a critical player in tumorigenesis. Targeting RAB7A and its family members has become a focus of clinical research, with the aim of developing novel therapeutic strategies for cancer treatment .
