InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NOX4

Summary

InnateDB Protein

IDBP-243926.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NOX4

Protein Name

NADPH oxidase 4

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000376961

InnateDB Gene

IDBG-67316 (NOX4)

Protein Structure

UniProt Annotation

Function

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.

Subcellular Localization

Endoplasmic reticulum membrane; Multi-pass membrane protein. Cell membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. Cell junction, focal adhesion {ECO:0000305}. Note=May localize to plasma membrane and focal adhesions. According to PubMed:15927447, may also localize to the nucleus.Isoform 4: Nucleus {ECO:0000269PubMed:23393389}. Nucleus, nucleolus {ECO:0000269PubMed:23393389}.

Disease Associations

Tissue Specificity

Expressed by distal tubular cells in kidney cortex and in endothelial cells (at protein level). Widely expressed. Strongly expressed in kidney and to a lower extent in heart, adipocytes, hepatoma, endothelial cells, skeletal muscle, brain, several brain tumor cell lines and airway epithelial cells. {ECO:0000269PubMed:11032835, ECO:0000269PubMed:11376945, ECO:0000269PubMed:15210697, ECO:0000269PubMed:16324151}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 5 experimentally validated interaction(s) in this database.

Experimentally validated
Total	5 [view]
Protein-Protein	2 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0009055	electron carrier activity
GO:0016174	NAD(P)H oxidase activity
GO:0019826	oxygen sensor activity
GO:0020037	heme binding
GO:0050660	flavin adenine dinucleotide binding
GO:0072341	modified amino acid binding

Biological Process

GO:0000902	cell morphogenesis
GO:0006954	inflammatory response
GO:0007569	cell aging
GO:0008285	negative regulation of cell proliferation
GO:0042554	superoxide anion generation
GO:0045087	innate immune response (InnateDB)
GO:0050667	homocysteine metabolic process
GO:0055114	oxidation-reduction process
GO:0072593	reactive oxygen species metabolic process