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NADPH oxidase 4; kidney oxidase-1; KOX-1; kidney superoxide-producing NADPH oxidase; renal NADPH-oxidase (NOX4, RENOX)
Function:
1) constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox
2) regulates signaling cascades via phosphatase inhibition
3) oxygen sensor regulating the KCNK3/TASK-1 K+ channel & HIF1A activity (putative)
4) regulation of insulin signaling cascade role in apoptosis, bone resorption & lipolysaccharide-mediated activation of NFKB
5) may produce superoxide in the nucleus & play a role in regulating gene expression upon cell stimulation
6) interacts with protein disulfide isomerase
7) interacts with, relocalizes & stabilizes CYBA/p22phox
8) interacts with TLR4, residues 248-575
9) contains 1 ferric oxidoreductase domain, residues 58-561
10) inhibited by plumbagin, diphenylene iodonium
11) activated by phorbol 12-myristate 13-acetate, insulin
Structure:
- contains 1 FAD-binding FR-type domain
- contains 1 ferric oxidoreductase domain
Compartment:
- endoplasmic reticulum
- cell junction, focal adhesion (probable).
- nucleus (probable)
Alternative splicing: named isoforms=7; isoform 3 is not functional; isoform 4 displays an increased activity; isoform 3 & isoform 4 are N-glycosylated; isoform 4 glycosylation required for function; isoform 5 & isoform 6 display reduced activity;
Expression:
- expressed by distal tubular cells in kidney cortex & in endothelial cells
- widely expressed
- expressed in kidney > heart, adipocytes, hepatoma, endothelial cells, skeletal muscle, brain, airway epithelial cells
- expressed in fetal kidney & fetal liver
- induced by 7-ketocholesterol
Pathology:
- expressed in several brain tumor cell lines
General
glycoprotein
oxidoreductase
transmembrane 6 protein
Properties
SIZE: MW = 67 kD
entity length = 578 aa
COMPARTMENT: endoplasmic reticulum
MOTIF: cytoplasmic domain {1-16}
transmembrane domain {17-37}
exoplasmic loop {38-62}
transmembrane domain {63-83}
cytoplasmic loop {84-103}
transmembrane domain {104-124}
exoplasmic loop {125-154}
MOTIF: N-glycosylation site {N133}
transmembrane domain {155-175}
cytoplasmic loop {176-188}
transmembrane domain {189-209}
exoplasmic loop {210-424}
MOTIF: N-glycosylation site {N230}
transmembrane domain {425-445}
cytoplasmic domain {446-578}
Database Correlations
OMIM 605261
UniProt Q9NPH5
PFAM correlations
Entrez Gene 50507
Kegg hsa:50507
References
UniProt :accession Q9NPH5