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MGP005059

UniProt Annotations

Entry Information
Gene NameNADPH oxidase 4
Protein EntryNOX4_HUMAN
UniProt IDQ9NPH5
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=9; Name=1; IsoId=Q9NPH5-1; Sequence=Displayed; Name=2; Synonyms=Nox4A; IsoId=Q9NPH5-2; Sequence=VSP_019052; Name=3; Synonyms=Nox4E; IsoId=Q9NPH5-3; Sequence=VSP_019053, VSP_019058; Name=4; Synonyms=28 kDa, Nox4D; IsoId=Q9NPH5-4; Sequence=VSP_019053; Name=5; Synonyms=Nox4C; IsoId=Q9NPH5-5; Sequence=VSP_019056, VSP_019057; Name=6; Synonyms=Nox4B; IsoId=Q9NPH5-6; Sequence=VSP_019058; Name=7; IsoId=Q9NPH5-7; Sequence=VSP_019054, VSP_019055; Name=8; IsoId=Q9NPH5-8; Sequence=VSP_053826; Name=9; IsoId=Q9NPH5-9; Sequence=VSP_053826, VSP_019058;
Developmental StageExpressed in fetal kidney and fetal liver. {ECO:0000269|PubMed:10869423, ECO:0000269|PubMed:11032835, ECO:0000269|PubMed:11376945}.
Enzyme RegulationInhibited by plumbagin (By similarity). Activated by phorbol 12-myristate 13-acetate (PMA). Activated by insulin. Inhibited by diphenylene iodonium. {ECO:0000250, ECO:0000269|PubMed:14966267, ECO:0000269|PubMed:15572675, ECO:0000269|PubMed:16019190, ECO:0000269|PubMed:16324151}.
FunctionConstitutive 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.
FunctionIsoform 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.
InductionBy 7-ketocholesterol (at protein level). {ECO:0000269|PubMed:15572675}.
PtmIsoform 3 and isoform 4 are N-glycosylated. Isoform 4 glycosylation is required for its proper function. {ECO:0000269|PubMed:15721269}.
SimilarityContains 1 FAD-binding FR-type domain. {ECO:0000255|PROSITE-ProRule:PRU00716}.
SimilarityContains 1 ferric oxidoreductase domain. {ECO:0000305}.
Subcellular LocationEndoplasmic 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.
Subcellular LocationIsoform 4: Nucleus {ECO:0000269|PubMed:23393389}. Nucleus, nucleolus {ECO:0000269|PubMed:23393389}.
SubunitInteracts with protein disulfide isomerase (By similarity). Interacts with, relocalizes and stabilizes CYBA/p22phox. Interacts with TLR4. {ECO:0000250, ECO:0000269|PubMed:15356101, ECO:0000269|PubMed:15927447}.
Tissue SpecificityExpressed 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:0000269|PubMed:11032835, ECO:0000269|PubMed:11376945, ECO:0000269|PubMed:15210697, ECO:0000269|PubMed:16324151}.
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