NOX5 Membrane Protein Introduction

Introduction of NOX5

NOX5 is a calcium-dependent NADPH oxidase, encoded by NOX5 gene. NOX5 is mainly expressed in the testis and also found in lymphocyte-rich areas of spleen and lymph nodes. NOX5 can generate superoxide and may mediate redox-dependent processes in spermatozoa and lymphocytes as a calcium-dependent proton channel. There are six alternatively spliced transcript variants been reported for this gene.

Basic Information of NOX5
Protein Name	NADPH oxidase 5
Gene Name	NOX5
Aliases	NA
Organism	Homo sapiens (Human)
UniProt ID	Q96PH1
Transmembrane Times	7
Length (aa)	765
Sequence	MNTSGDPAQTGPEGCRGTMSAEEDARWLRWVTQQFKTIAGEDGEISLQEFKAALHVKESFFAERFFALFDSDRSGTITLQELQEALTLLIHGSPMDKLKFLFQVYDIDVCARQGASAGTEWGAGAGPHWASSPLGTGSGSIDPDELRTVLQSCLRESAISLPDEKLDQLTLALFESADADGNGAITFEELRDELQRFPGVMENLTISAAHWLTAPAPRPRPRRPRQLTRAYWHNHRSQLFCLATYAGLHVLLFGLAASAHRDLGASVMVAKGCGQCLNFDCSFIAVLMLRRCLTWLRATWLAQVLPLDQNIQFHQLMGYVVVGLSLVHTVAHTVNFVLQAQAEASPFQFWELLLTTRPGIGWVHGSASPTGVALLLLLLLMFICSSSCIRRSGHFEVFYWTHLSYLLVWLLLIFHGPNFWKWLLVPGILFFLEKAIGLAVSRMAAVCIMEVNLLPSKVTHLLIKRPPFFHYRPGDYLYLNIPTIARYEWHPFTISSAPEQKDTIWLHIRSQGQWTNRLYESFKASDPLGRGSKRLSRSVTMRKSQRSSKGSEILLEKHKFCNIKCYIDGPYGTPTRRIFASEHAVLIGAGIGITPFASILQSIMYRHQKRKHTCPSCQHSWIEGVQDNMKLHKVDFIWINRDQRSFEWFVSLLTKLEMDQAEEAQYGRFLELHMYMTSALGKNDMKAIGLQMALDLLANKEKKDSITGLQTRTQPGRPDWSKVFQKVAAEKKGKVQVFFCGSPALAKVLKGHCEKFGFRFFQENF

Function of NOX5 Membrane Protein

As a calcium-dependent NADPH oxidase, NOX5 can generate superoxide and regulate redox-dependent processes, functioning as a proton channel. In addition, NOX5 may play a role in apoptosis and cell growth. NOX5 can be activated by calcium, which induces changes of conformational and interaction between the C-terminal catalytic region and the N-terminal regulatory region, and can be repressed by diphenylene iodonium. It is documented that silencing of Nox5 in human mesangial cells is associated with attenuation of the hyperglycemia and TGF-β1-induced enhanced ROS production, increased expression of profibrotic and proinflammatory mediators, suggesting the role for Nox5 and its derived ROS in promoting progression of diabetic nephropathy. NOX5 is shown to play a role in the generation ROS, angiogenesis, and proliferation and contribute to the endothelial response to thrombin.

Fig.1 The role of NADPH oxidase NOX5 in vascular disease. (Jha, 2016)

Application of NOX5 Membrane Protein in Literature

Chen F., et al. Nox5 stability and superoxide production is regulated by C-terminal binding of Hsp90 and Co-chaperones. Free Radic Biol Med. 2015, 89: 793-805. PubMed ID: 26456056

This article shows that NOX5 interacts with the M domain of Hsp90 through its C-terminal region, and this interaction facilitates oligomerization and the productive efficiency of superoxide.
Dho S.H., et al. NOX5-L can stimulate proliferation and apoptosis depending on its levels and cellular context, determining cancer cell susceptibility to cisplatin. Oncotarget. 2015, 6(36): 39235-46. PubMed ID: 26513170

This article indicates that the long form of NOX5 (NOX5-L) determines cellular responses in a context- and concentration-dependent manner, and determines the balance of death and proliferation, in lung cancer, breast and skin cells.
Carnesecchi S., et al. The NADPH oxidase NOX5 protects against apoptosis in ALK-positive anaplastic large-cell lymphoma cell lines. Free Radic Biol Med. 2015, 84: 22-29. PubMed ID: 25797883

This article indicates that NOX5-derived ROS is associated with apoptosis blockage in ALK (+) ALCL cell lines and suggests that NOX5 may be a potential pharmaceutical target to promote apoptosis and thus to repress the progression of tumor and prevent relapse in pediatric ALK (+) ALCL patients that have resistance against classical therapeutic approaches.
Chen F., et al. Enzymatic regulation and functional relevance of NOX5. Curr Pharm Des. 2015, 21(41): 5999-6008. PubMed ID: 26510438

This review summarizes accumulated and recent knowledge of the enzymatic and genetic regulation of NOX5 and the importance of NOX5 in human pathophysiology and physiology.
Wang Y., et al. Impact of Nox5 polymorphisms on basal and stimulus-dependent ROS generation. PLoS One. 2014, 9(7): e100102. PubMed ID: 24992705

This article identifies a number of exonic SNPs in Nox5 that have influence in its activity and 7 missense mutations in Nox5 that lead to little or no enzyme activity.

NOX5 Preparation Options

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Reference

Jha J C, et al. (2017). The emerging role of NADPH oxidase NOX5 in vascular disease. Clin Sci (Lond). 131(10): 981-990.

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