ARF5 Human
Description
Introduction to ARF5 Human
ARF5 (ADP-ribosylation factor 5) is a small GTP-binding protein belonging to the ARF gene family, part of the RAS superfamily. It participates in vesicular trafficking, Golgi membrane dynamics, and signaling pathways critical for cellular processes. As a class II ARF protein, ARF5 shares structural and functional similarities with ARF4 but exhibits distinct regulatory roles. Below is a detailed analysis of its structure, function, clinical relevance, and research findings.
Structure and Gene Organization
Genomic and Protein Characteristics
| Feature | Description |
|---|---|
| Gene Location | Chromosome 7 (Homo sapiens) |
| Gene Span | ~3.2 kb (6 exons, 5 introns) |
| Protein Length | 180 amino acids (ARF5_HUMAN) |
| Molecular Weight | ~22.8–23 kDa (recombinant His-tagged variant) |
| Sequence Similarity | Class II ARF (closest to ARF4) |
| Key Domains | GTP-binding domain, Golgi localization signals |
ARF5’s gene structure is conserved with other ARF family members, though its promoter and regulatory elements differ. The protein’s N-terminal domain directs Golgi localization, while the C-terminal effector-binding region interacts with downstream targets .
Vesicular Trafficking and Membrane Dynamics
ARF5 regulates vesicle budding and uncoating at the Golgi apparatus, modulating protein secretion and lipid metabolism. Key interactions include:
ARF5 also interacts with mTORC1 at plasma membrane ruffles, enabling nutrient-sensing and growth signaling .
3.2.1 Cancer Progression
ARF5 overexpression is linked to poor prognosis in hepatocellular carcinoma (HCC) and breast cancer:
| Cancer Type | Clinical Correlation | Survival Impact | Source |
|---|---|---|---|
| HCC | Elevated expression in 29 cancers | Negative OS, DFI, DSS | |
| Breast Cancer | Associated with reduced DMFS and RFS | Shorter recurrence-free survival |
ARF5 may promote tumor immune evasion and metabolic reprogramming, as evidenced by WGCNA analysis showing associations with ribosome biogenesis and lipid synthesis pathways .
3.2.2 Viral Replication
ARF5 binds RNA and modulates Foot-and-Mouth Disease Virus (FMDV) internal ribosome entry site (IRES) activity, inhibiting translation initiation. This highlights a novel RNA-binding function distinct from its GTPase activity .
Protein Production and Experimental Applications
ARF5 is frequently produced as a recombinant protein for biochemical studies:
| Parameter | Details |
|---|---|
| Expression Host | E. coli (His-tagged at N-terminus) |
| Purity | >95% (SDS-PAGE validated) |
| Formulation | 20 mM Tris-HCl (pH 8.0), 1 mM DTT, 20% glycerol, 0.1 M NaCl |
| Applications | GTPase activity assays, interaction studies, structural analysis |
Recombinant ARF5 retains functional GTP-binding capacity and interacts with effector proteins like Raptor (mTORC1 subunit) .
Novel Regulatory Pathways
-
mTORC1 Recruitment: ARF5-GTP recruits mTORC1 to plasma membrane ruffles, enabling nutrient-responsive signaling. This contrasts with lysosomal mTORC1 activation mediated by Rag GTPases .
-
RNA-Binding Function: ARF5 binds viral RNA elements, suggesting roles in pathogen-host interactions beyond GTPase activity .
Therapeutic Potential
Product Specs
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Product Science Overview
The ARF gene family consists of six ARF proteins and eleven ARF-like proteins, all of which belong to the RAS superfamily. The ARF proteins are categorized into three classes:
- Class I: ARF1, ARF2, ARF3
- Class II: ARF4, ARF5
- Class III: ARF6
Each class shares a common gene organization, and the ARF5 gene spans approximately 3.2 kb of genomic DNA, containing six exons and five introns .
ARF5 is involved in protein trafficking, particularly in modulating vesicle budding and uncoating within the Golgi apparatus. It functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase . This activation is crucial for the toxin’s ability to modify host cell proteins, leading to various cellular responses.
ARF5 interacts with several proteins, including ARFIP2, and is involved in multiple cellular pathways such as:
- Vesicle-mediated transport
- Golgi-to-ER retrograde transport
- Intracellular protein transport
These interactions and pathways highlight the importance of ARF5 in maintaining cellular homeostasis and facilitating efficient protein trafficking .
Mutations or dysregulation of ARF5 have been associated with diseases such as cholera and congenital myasthenic syndrome . Understanding the function and regulation of ARF5 can provide insights into the molecular mechanisms underlying these conditions and potentially lead to the development of targeted therapies.
