InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NOX4

Summary

InnateDB Protein

IDBP-67318.6

Last Modified

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

Gene Symbol

NOX4

Protein Name

NADPH oxidase 4

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000263317

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:0005515	protein binding
GO:0009055	electron carrier activity
GO:0016174	NAD(P)H oxidase activity
GO:0016175	superoxide-generating NADPH oxidase activity
GO:0016491	oxidoreductase activity
GO:0019826	oxygen sensor activity
GO:0020037	heme binding
GO:0050660	flavin adenine dinucleotide binding
GO:0050664	oxidoreductase activity, acting on NADH or NADPH, oxygen as acceptor
GO:0072341	modified amino acid binding

Biological Process

GO:0000902	cell morphogenesis
GO:0001666	response to hypoxia
GO:0006801	superoxide metabolic process
GO:0006954	inflammatory response
GO:0007568	aging
GO:0007569	cell aging
GO:0008285	negative regulation of cell proliferation
GO:0014911	positive regulation of smooth muscle cell migration
GO:0042554	superoxide anion generation
GO:0043065	positive regulation of apoptotic process
GO:0043406	positive regulation of MAP kinase activity
GO:0045087	innate immune response (InnateDB)
GO:0045453	bone resorption
GO:0050667	homocysteine metabolic process
GO:0051496	positive regulation of stress fiber assembly
GO:0051897	positive regulation of protein kinase B signaling
GO:0055007	cardiac muscle cell differentiation
GO:0055114	oxidation-reduction process
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0071320	cellular response to cAMP
GO:0071333	cellular response to glucose stimulus
GO:0071480	cellular response to gamma radiation
GO:0071560	cellular response to transforming growth factor beta stimulus
GO:0072593	reactive oxygen species metabolic process
GO:2000379	positive regulation of reactive oxygen species metabolic process
GO:2000573	positive regulation of DNA biosynthetic process

Cellular Component

GO:0001725	stress fiber
GO:0005730	nucleolus
GO:0005739	mitochondrion
GO:0005789	endoplasmic reticulum membrane
GO:0005925	focal adhesion
GO:0016021	integral component of membrane
GO:0016324	apical plasma membrane
GO:0043020	NADPH oxidase complex
GO:0048471	perinuclear region of cytoplasm
GO:0071944	cell periphery

Protein Structure and Domains

PDB ID

InterPro

IPR000778 Cytochrome b245, heavy chain
IPR013112 FAD-binding 8
IPR013121 Ferric reductase, NAD binding
IPR013130 Ferric reductase transmembrane component-like domain
IPR017938 Riboflavin synthase-like beta-barrel

PFAM

PF08022
PF08030
PF01794

PRINTS

PR00466

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9NPH5