Target intelligence / Profile preview

Stimulated by retinoic acid 6 (STRA6) (STRA6)

Target
STRA6
Molecular classification
Transmembrane protein, Receptor, Transporter
01

Overview

Stimulated by retinoic acid 6 (STRA6) is a multi-pass transmembrane protein that functions as the high-affinity cell-surface receptor for the retinol-binding protein 4 (RBP4)-retinol complex (Kawaguchi et al., 2007, Science). It is predominantly expressed in hepatic stellate cells (HSCs), which serve as the primary storage site for approximately 80% of the body's vitamin A (Blaner, 2016, Nutrients). STRA6 is unique because it acts both as a transporter, facilitating the bidirectional movement of retinol across the cell membrane, and as a signaling receptor that activates the JAK2/STAT3/5 pathway (Berry et al., 2012, Cell). In pathological states, STRA6-mediated signaling in HSCs contributes to their activation and the subsequent development of liver fibrosis (Chen et al., 2020, Liver International). Furthermore, the RBP4-STRA6 axis is a known driver of insulin resistance in obesity and type 2 diabetes, making it a target for metabolic disease therapeutics (Muenzner et al., 2013, Molecular and Cellular Biology). Small molecule antagonists and RBP4-lowering agents like Fenretinide are being investigated to modulate this pathway for therapeutic benefit (Dobri et al., 2013, Investigative Ophthalmology & Visual Science).

Other names
Retinol-binding protein receptorRBP4 receptorStimulated by retinoic acid gene 6 proteinHSC vitamin A receptor
02

Mechanism of action

STRA6 facilitates the cellular uptake of retinol from the extracellular RBP4-retinol complex and simultaneously initiates a JAK2/STAT5 signaling cascade that modulates gene expression related to lipid metabolism and insulin sensitivity.

03

Biological functions

Retinol transportVitamin A homeostasisSignal transductionJAK/STAT signaling pathway activation
04

Disease associations

Liver fibrosisType 2 diabetesInsulin resistanceMatthew-Wood syndromeCancer
05

Safety considerations

Teratogenicity (Matthew-Wood syndrome risk)Visual cycle impairmentSystemic vitamin A deficiencyMicrophthalmia
06

Interacting drugs

Fenretinide

3 more in the full profile.

07

Biomarkers

Serum Retinol-Binding Protein 4 (RBP4) levelsSTRA6 mRNA expression in liver tissueHepatic vitamin A (retinyl ester) content

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