NOX4 (NADPH oxidase 4)

Gene

• Entrez ID: 50507
• Gene name: NADPH oxidase 4
• Gene symbol: NOX4
• Synonyms: KOX, KOX-1, RENOX
• Chromosome: 11
• Chromosome location: 11q14.3
• Summary: 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]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019477	hsa-miR-148b-3p	Microarray	17612493
MIRT732472	hsa-miR-99b-5p	ELISA, qRT-PCR, In situ hybridization, Immunofluorescence	25378491
MIRT732993	hsa-miR-99a-5p	Luciferase reporter assay, qRT-PCR, Western blot	26986073
MIRT733403	hsa-miR-182-3p	Luciferase reporter assay, qRT-PCR, Western blot	27207535
MIRT734064	hsa-miR-9-5p	Luciferase reporter assay, qRT-PCR, Western blot	26315535

Transcription factors

Transcription factor	Regulation	Reference
E2F1	Activation	18554521
NFKB1	Activation	20622120
RELA	Activation	20622120
SP3	Activation	21235713
STAT1	Unknown	19834108
STAT3	Unknown	19834108
STAT4	Unknown	19834108

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	TAS	10869423
GO:0000902	Process	Cell morphogenesis	ISS	10869423
GO:0001666	Process	Response to hypoxia	IEA
GO:0001725	Component	Stress fiber	IEA
GO:0003015	Process	Heart process	IGI	27525436
GO:0005515	Function	Protein binding	IPI	15356101, 17064675
GO:0005634	Component	Nucleus	ISS	27525436
GO:0005654	Component	Nucleoplasm	IDA
GO:0005730	Component	Nucleolus	IEA
GO:0005739	Component	Mitochondrion	ISS	27525436
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005925	Component	Focal adhesion	IEA
GO:0006801	Process	Superoxide metabolic process	IDA	18760347
GO:0006952	Process	Defense response	IBA	21873635
GO:0006954	Process	Inflammatory response	TAS	10869423
GO:0007569	Process	Cell aging	ISS	10869423
GO:0008285	Process	Negative regulation of cell population proliferation	ISS	10869423
GO:0009055	Function	Electron transfer activity	TAS	10869423
GO:0010467	Process	Gene expression	IMP	23144758
GO:0014911	Process	Positive regulation of smooth muscle cell migration	IEA
GO:0016021	Component	Integral component of membrane	TAS	10869423
GO:0016174	Function	NAD(P)H oxidase H2O2-forming activity	TAS	10869423
GO:0016175	Function	Superoxide-generating NAD(P)H oxidase activity	IBA	21873635
GO:0016324	Component	Apical plasma membrane	IEA
GO:0019826	Function	Oxygen sensor activity	TAS	10869423
GO:0020037	Function	Heme binding	TAS	10869423
GO:0022900	Process	Electron transport chain	IEA
GO:0034599	Process	Cellular response to oxidative stress	TAS
GO:0042554	Process	Superoxide anion generation	IBA	21873635
GO:0042554	Process	Superoxide anion generation	ISS	10869423
GO:0043020	Component	NADPH oxidase complex	IBA	21873635
GO:0043065	Process	Positive regulation of apoptotic process	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	ISS	27525436
GO:0050660	Function	Flavin adenine dinucleotide binding	TAS	10869423
GO:0050667	Process	Homocysteine metabolic process	IDA	20031578
GO:0051496	Process	Positive regulation of stress fiber assembly	IEA
GO:0061098	Process	Positive regulation of protein tyrosine kinase activity	ISS	27525436
GO:0071320	Process	Cellular response to cAMP	IEA
GO:0071480	Process	Cellular response to gamma radiation	IEA
GO:0071560	Process	Cellular response to transforming growth factor beta stimulus	IEA
GO:0072341	Function	Modified amino acid binding	IDA	20031578
GO:0072593	Process	Reactive oxygen species metabolic process	IDA	10869423
GO:0097038	Component	Perinuclear endoplasmic reticulum	ISS	27525436
GO:1903409	Process	Reactive oxygen species biosynthetic process	NAS	27525436
GO:1990782	Function	Protein tyrosine kinase binding	ISS	27525436
GO:2000379	Process	Positive regulation of reactive oxygen species metabolic process	IEA

Other IDs

• MIM: 605261
• HGNC: 7891
• e!Ensembl: ENSG00000086991

Protein

• UniProt ID: Q9NPH5
• Protein name: NADPH oxidase 4 (EC 1.6.3.-) (Kidney oxidase-1) (KOX-1) (Kidney superoxide-producing NADPH oxidase) (Renal NAD(P)H-oxidase)
• Protein 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.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01794	Ferric_reduct	58 → 205	Ferric reductase like transmembrane component	Family
  PF08022	FAD_binding_8	306 → 417	FAD-binding domain	Domain
  PF08030	NAD_binding_6	423 → 561	Ferric reductase NAD binding domain	Domain

• Sequence:

  MAVSWRSWLANEGVKHLCLFIWLSMNVLLFWKTFLLYNQGPEYHYLHQMLGLGLCLSRAS
  ASVLNLNCSLILLPMCRTLLAYLRGSQKVPSRRTRRLLDKSRTFHITCGVTICIFSGVHV
  AAHLVNALNFSVNYSEDFVELNAARYRDEDPRKLLFTTVPGLTGVCMVVVLFLMITASTY
  AIRVSNYDIFWYTHNLFFVFYMLLTLHVSGGLLKYQTNLDTHPPGCISLNRTSSQNISLP
  EYFSEHFHEPFPEGFSKPAEFTQHKFVKICMEEPRFQANFPQTWLWISGPLCLYCAERLY
  RYIRSNKPVTIISVMSHPSDVMEIRMVKENFKARPGQYITLHCPSVSALENHPFTLTMCP
  TETKATFGVHLKIVGDWTERFRDLLLPPSSQDSEILPFIQSRNYPKLYIDGPFGSPFEES
  LNYEVSLCVAGGIGVTPFASILNTLLDDWKPYKLRRLYFIWVCRDIQSFRWFADLLCMLH
  NKFWQENRPDYVNIQLYLSQTDGIQKIIGEKYHALNSRLFIGRPRWKLLFDEIAKYNRGK
  TVGVFCCGPNSLSKTLHKLSNQNNSYGTRFEYNKESFS

• Sequence length: 578