NOX4

This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein have been implicated in numerous biological functions including signal transduction, cell differentiation and tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]

NADPH Oxidase 4

Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.
Isoform 4
Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.

Bone resorptionIEA:Ensembl
Cardiac muscle cell differentiationIEA:Ensembl
Cell agingBy SimilarityISS:UniProtKB
Cell morphogenesisBy SimilarityISS:UniProtKB
Cellular response to glucose stimulusIEA:Ensembl
Defense responseManual Assertion Based On ExperimentIBA:GO_Central
Gene expressionManual Assertion Based On ExperimentIMP:CACAO
Heart processManual Assertion Based On ExperimentIGI:ARUK-UCL
Homocysteine metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Inflammatory responseManual Assertion Based On ExperimentTAS:UniProtKB
Negative regulation of cell population proliferationBy SimilarityISS:UniProtKB
Positive regulation of DNA biosynthetic processIEA:Ensembl
Positive regulation of ERK1 and ERK2 cascadeIEA:Ensembl
Positive regulation of MAP kinase activityIEA:Ensembl
Positive regulation of protein kinase B signalingIEA:Ensembl
Positive regulation of protein tyrosine kinase activityBy SimilarityISS:ARUK-UCL
Reactive oxygen species biosynthetic process1 PublicationNAS:ARUK-UCL
Reactive oxygen species metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Superoxide anion generationBy SimilarityISS:UniProtKB
Superoxide metabolic processManual Assertion Based On ExperimentIDA:CACAO

Endoplasmic reticulum membrane
Cell membrane
Cell junction, focal adhesion
May localize to plasma membrane and focal adhesions. According to PubMed:15927447, may also localize to the nucleus.
Isoform 4
Nucleus
Nucleus, nucleolus

Cytoplasmic: 1-16
Helical: 17-37
Extracellular: 38-62
Helical: 63-83
Cytoplasmic: 84-103
Helical: 104-124
Extracellular: 125-154
Helical: 155-175
Cytoplasmic: 176-188
Helical: 189-209
Extracellular: 210-424
Helical: 425-445
Cytoplasmic: 446-578

Isoform 3 and isoform 4 are N-glycosylated. Isoform 4 glycosylation is required for its proper function.