NOX4 Membrane Protein Introduction

Introduction of NOX4

NOX4, encoded by the gene NOX4, belongs to the NOX-family of enzymes and is the catalytic subunit of the NADPH oxidase complex. NOX4 acts as an oxygen sensor and is able to catalyze the molecular oxygen reduced to diverse reactive oxygen species (ROS) in non-phagocytic cells. NOX4 shares only about 40% identity with NOX2. There are several NOX4 splice variants have been reported in humans, but only one NOX4 is found in amphioxus. Except for the strong expression in the kidney, NOX4 mRNA is also found in osteoclasts, endothelial cells, smooth muscle cells, hematopoietic stem cells, fibroblasts, keratinocytes, melanoma cells, and neurons.

Basic Information of NOX4
Protein Name NADPH oxidase 4
Gene Name NOX4
Aliases Kidney oxidase-1, Renal NAD(P)H-oxidase, Kidney superoxide-producing NADPH oxidase
Organism Homo sapiens (Human)
UniProt ID Q9NPH5
Transmembrane Times 6
Length (aa) 578

Function of NOX4 Membrane Protein

NOX4 is a part of NADPH oxidase, which can produce superoxide after the formation of a complex with CYBA/p22phox. Mainly expressed by in endothelial cells and distal tubular cells in the kidney cortex, NOX4 can mediate signaling cascades potentially by phosphatases inhibition. NOX4 may function as an oxygen sensor in the mediation of KCNK3/TASK-1 potassium channel and HIF1A activity. NOX4 is reported to play important roles in bone resorption, apoptosis and lipopolysaccharide-mediated activation of N NF-κB. Besides, NOX4 can protect the vasculature against inflammatory stress. Nox-dependent reactive oxygen species modulation by amino endoperoxides can induce apoptosis in high Nox4-expressing cancer cells. NOX4 can interact with protein disulfide isomerase and TLR4.

Structure of Vascular NADPH oxidases.Fig.1 Structure of Vascular NADPH oxidases. (Schulz, 2008)

Application of NOX4 Membrane Protein in Literature

  1. Guo S and Chen X. The human Nox4: gene, structure, physiological function and pathological significance. J Drug Target. 2015, 23(10): 888-96. PubMed ID: 25950600

    This article gives a detailed description of NOX4 including its gene, structure, pathological significance and physiological function. The introduction of Nox4 is very comprehensive, including cancer, ROS, hydrogen peroxides, cardiovascular diseases and many other aspects of NOX4.

  2. Schürmann C., et al. The NADPH oxidase Nox4 has anti-atherosclerotic functions. Eur Heart J. 2015, 36(48): 3447-56. PubMed ID: 26385958

    This article suggests that the NADPH oxidase Nox4 is an endogenous enzyme which plays a critical role in the anti-atherosclerotic pathway. Additionally, it finds that Nox4 inhibitors may have cardiovascular side-effects.

  3. Nisimoto Y., et al. Nox4: a hydrogen peroxide-generating oxygen sensor. Biochemistry. 2014, 53(31): 5111-20. PubMed ID: 25062272

    This article carries out an in-depth research of Nox4 acting as a hydrogen peroxide-generating oxygen sensor.

  4. Vogel J., et al. Nox4 supports proper capillary growth in exercise and retina neo-vascularization. J Physiol. 2015, 593(9): 2145-54. PubMed ID: 25652847

    This article demonstrates that Nox4 plays a special role in hypoxia- and exercise-induced angiogenesis through a dual mechanism of maintaining vascular endothelial growth factor and preventing angiopoietin 1 expression, suggesting that the developmental angiogenesis is Nox4 independent.

  5. Li J., et al. Tanshinone IIA blocks dexamethasone-induced apoptosis in osteoblasts through inhibiting Nox4-derived ROS production. Int J Clin Exp Pathol. 2015, 8(10): 13695-706. PubMed ID: 26722597

    This article suggests that the inhibition of Nox4 may be a new therapeutic approach of Tanshinone IIA to prevent glucocorticoid-induced osteoporosis and osteoblasts apoptosis.

NOX4 Preparation Options

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  1. Schulz E and Münzel T. (2008). NOX5, a new "radical" player in human atherosclerosis? J Am Coll Cardiol. 52(22): 1810-2.

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