ARL6 Human
Description
Introduction to ARL6 Human
ARL6 Human refers to the protein encoded by the ARL6 gene (ADP-ribosylation factor-like 6), a member of the ARF family of GTP-binding proteins. This protein plays critical roles in membrane trafficking, ciliary function, and cellular signaling. Mutations in ARL6 are associated with Bardet-Biedl Syndrome (BBS3) and retinitis pigmentosa, while its overexpression is implicated in hepatocellular carcinoma (HCC) progression and prognosis .
Gene Information
| Feature | Detail |
|---|---|
| Chromosomal Location | 3p12.3 |
| Aliases | BBS3, RP55, MGC32934 |
| Molecular Weight | 23.2 kDa |
| Amino Acids | 186 residues (full-length isoform) |
| Key Domains | GTP-binding domain, ciliary trafficking motifs |
Protein Structure and Production
ARL6 Human is produced recombinantly in E. coli with a 20-amino acid His-tag for purification. Its sequence includes motifs critical for GTP binding and ciliary transport :
Amino Acid Sequence Excerpt
MGSSHHHHHHSSGLVPRGSHMGLLDRLSVLLGLKKKEVHVLLCLGLDNSGKT...
Cellular Trafficking and Cilia Assembly
ARL6 facilitates primary cilia formation by recruiting the BBSome complex, essential for ciliary membrane protein trafficking. It interacts with pathways like sonic hedgehog (SHH) signaling and regulates organelle localization .
Disease Associations
Expression and Prognosis
Immune Microenvironment Impact
ARL6 expression correlates with tumor-infiltrating immune cells:
| Cell Type | Correlation (Spearman) | p-value |
|---|---|---|
| Neutrophils | 0.457 | 3.22e−19 |
| CD4+ T cells | 0.304 | 8.60e−9 |
| Macrophages | 0.401 | 1.31e−14 |
| Myeloid Dendritic Cells | 0.292 | 1.95e−8 |
Data from TIMER and TCGA-HCC databases .
Pathway Analysis
Metascape analysis of ARL6-co-expressed genes highlights:
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Primary cilium development
-
Rho GTPase signaling
-
Intraflagellar transport
-
Protein dephosphorylation
Key Co-Expressed Genes
| Gene | Function |
|---|---|
| ARL6IP6 | Binds ARL6, regulates ciliary trafficking |
| ATL2 | Modulates ciliary localization of proteins |
| IQCB1 | Involved in ciliopathy-associated signaling |
Biomarker Potential
ARL6 serves as a prognostic biomarker in HCC, with ROC-AUC values of 0.646 (1-year survival) and 0.586 (5-year survival) .
Targeted Therapy
Knockdown of ARL6 via siRNA reduces HCC cell proliferation and invasion (p < 0.001), suggesting potential therapeutic strategies .
Product Specs
Product Science Overview
ARL6 is a small GTPase that plays a crucial role in cellular functions by cycling between an active GTP-bound state and an inactive GDP-bound state. This cycling is essential for its role in regulating intracellular traffic and other cellular processes . ARL6 is particularly known for its involvement in the regulation of ciliary membrane biogenesis and maintenance .
ARL6 is involved in several critical cellular pathways, including:
Mutations in the ARL6 gene can lead to severe clinical manifestations, including vision loss, obesity, polydactyly, and kidney abnormalities, which are characteristic of Bardet-Biedl Syndrome . Understanding the function and regulation of ARL6 is therefore critical for developing therapeutic strategies for these conditions.
Research on ARL6 has significant implications for understanding the molecular mechanisms underlying ciliary function and related disorders. The human recombinant form of ARL6 is used in various research applications to study its function and interactions with other proteins. This research is vital for developing potential therapeutic interventions for diseases associated with ARL6 dysfunction.
