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

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019477	hsa-miR-148b-3p	Microarray	17612493
MIRT437922	rno-miR-25-3p	Luciferase reporter assay	23722270
MIRT437922	rno-miR-25-3p	Luciferase reporter assay	23722270
MIRT756008	hsa-miR-99a-5p	Luciferase reporter assay, qRT-PCR, Western blot	26986073
MIRT734718	hsa-miR-214-3p	Western blotting, Immunohistochemistry (IHC), Immunofluorescence, qRT-PCR	32051833
MIRT755591	hsa-miR-182-5p	Western blotting, qRT-PCR, Immunohistochemistry (IHC), Immunofluorescence, ELISA	37737899
MIRT756008	hsa-miR-99a-5p	Luciferase reporter assay, Western blotting, qRT-PCR	35135443
MIRT1190255	hsa-miR-34b	CLIP-seq
MIRT1190256	hsa-miR-34c-3p	CLIP-seq
MIRT1190257	hsa-miR-3545-3p	CLIP-seq
MIRT1190258	hsa-miR-4256	CLIP-seq
MIRT1190259	hsa-miR-4635	CLIP-seq
MIRT1190260	hsa-miR-4680-5p	CLIP-seq
MIRT1190261	hsa-miR-4714-5p	CLIP-seq
MIRT1190262	hsa-miR-548g	CLIP-seq
MIRT1190263	hsa-miR-640	CLIP-seq
MIRT1190257	hsa-miR-3545-3p	CLIP-seq
MIRT1190264	hsa-miR-3663-5p	CLIP-seq
MIRT1190258	hsa-miR-4256	CLIP-seq
MIRT1190265	hsa-miR-4273	CLIP-seq
MIRT1190266	hsa-miR-4303	CLIP-seq
MIRT1190267	hsa-miR-4517	CLIP-seq
MIRT1190259	hsa-miR-4635	CLIP-seq
MIRT1190268	hsa-miR-4677-5p	CLIP-seq
MIRT1190260	hsa-miR-4680-5p	CLIP-seq
MIRT1190261	hsa-miR-4714-5p	CLIP-seq
MIRT1190263	hsa-miR-640	CLIP-seq
MIRT1190269	hsa-miR-1271	CLIP-seq
MIRT1190270	hsa-miR-182	CLIP-seq
MIRT1190271	hsa-miR-3622a-5p	CLIP-seq
MIRT1190272	hsa-miR-375	CLIP-seq
MIRT1190273	hsa-miR-4258	CLIP-seq
MIRT1190274	hsa-miR-4423-3p	CLIP-seq
MIRT1190275	hsa-miR-4428	CLIP-seq
MIRT1190276	hsa-miR-4642	CLIP-seq
MIRT1190277	hsa-miR-4775	CLIP-seq
MIRT1190278	hsa-miR-498	CLIP-seq
MIRT1190279	hsa-miR-590-3p	CLIP-seq
MIRT1190280	hsa-miR-9	CLIP-seq
MIRT1190281	hsa-miR-96	CLIP-seq
MIRT1922287	hsa-miR-122	CLIP-seq
MIRT1922288	hsa-miR-24	CLIP-seq
MIRT1922289	hsa-miR-3135b	CLIP-seq
MIRT1922290	hsa-miR-3652	CLIP-seq
MIRT1922291	hsa-miR-4284	CLIP-seq
MIRT1922292	hsa-miR-4430	CLIP-seq
MIRT1922293	hsa-miR-4772-3p	CLIP-seq
MIRT1190275	hsa-miR-4428	CLIP-seq
MIRT1922287	hsa-miR-122	CLIP-seq
MIRT2055110	hsa-miR-1237	CLIP-seq
MIRT2055111	hsa-miR-1248	CLIP-seq
MIRT2055112	hsa-miR-1303	CLIP-seq
MIRT1922288	hsa-miR-24	CLIP-seq
MIRT1922289	hsa-miR-3135b	CLIP-seq
MIRT1922290	hsa-miR-3652	CLIP-seq
MIRT2055113	hsa-miR-370	CLIP-seq
MIRT2055114	hsa-miR-3977	CLIP-seq
MIRT1190273	hsa-miR-4258	CLIP-seq
MIRT1922291	hsa-miR-4284	CLIP-seq
MIRT1922292	hsa-miR-4430	CLIP-seq
MIRT1922293	hsa-miR-4772-3p	CLIP-seq
MIRT1922288	hsa-miR-24	CLIP-seq
MIRT1922291	hsa-miR-4284	CLIP-seq
MIRT1922293	hsa-miR-4772-3p	CLIP-seq
MIRT2284061	hsa-miR-935	CLIP-seq
MIRT2055110	hsa-miR-1237	CLIP-seq
MIRT2055111	hsa-miR-1248	CLIP-seq
MIRT2055112	hsa-miR-1303	CLIP-seq
MIRT2055113	hsa-miR-370	CLIP-seq
MIRT2055114	hsa-miR-3977	CLIP-seq
MIRT2439047	hsa-miR-129-5p	CLIP-seq
MIRT2439047	hsa-miR-129-5p	CLIP-seq
MIRT1922287	hsa-miR-122	CLIP-seq
MIRT1922288	hsa-miR-24	CLIP-seq
MIRT1922289	hsa-miR-3135b	CLIP-seq
MIRT1922290	hsa-miR-3652	CLIP-seq
MIRT1922291	hsa-miR-4284	CLIP-seq
MIRT1922292	hsa-miR-4430	CLIP-seq
MIRT1922293	hsa-miR-4772-3p	CLIP-seq
MIRT1922287	hsa-miR-122	CLIP-seq
MIRT1922288	hsa-miR-24	CLIP-seq
MIRT1922289	hsa-miR-3135b	CLIP-seq
MIRT1922290	hsa-miR-3652	CLIP-seq
MIRT1922291	hsa-miR-4284	CLIP-seq
MIRT1922292	hsa-miR-4430	CLIP-seq
MIRT1922293	hsa-miR-4772-3p	CLIP-seq

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 1.6.3.1) (Kidney oxidase-1) (KOX-1) (Kidney superoxide-producing NADPH oxidase) (Renal NAD(P)H-oxidase)
• Protein function: NADPH oxidase that catalyzes predominantly the reduction of oxygen to H2O2 (PubMed:14966267, PubMed:15356101, PubMed:15927447, PubMed:21343298, PubMed:25062272). Can also catalyze to a smaller extent, the reduction of oxygen to superoxide (PubMe
• 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

Pathways

KEGG:

AGE-RAGE signaling pathway in diabetic complications
Alcoholic liver disease
Alzheimer disease
Pathways of neurodegeneration - multiple diseases
Chemical carcinogenesis - reactive oxygen species

Reactome:

Detoxification of Reactive Oxygen Species

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Colonic neoplasms	Malignant tumor of colon, Colonic Neoplasms	rs267607789, rs774277300, rs781222233, rs1060502734, rs1060503333, rs1339238483	20715105
Diabetes mellitus	Diabetes Mellitus, Non-Insulin-Dependent	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs1553638903, rs1553638909, rs948820149, rs371977235, rs1553784995, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261	30178632
Hypertension	Hypertensive disease	rs13306026, rs13333226	27659729, 27847271
Myocardial infarction	Myocardial Failure	rs12316150, rs41303970, rs909253, rs7291467, rs2234693	20304815
Narcolepsy	Narcolepsy	rs104894574, rs387906655	19629137
Renal insufficiency	Renal Insufficiency	rs1596536873	23325087

Unknown
Disease name	Disease term	dbSNP ID	References
Congestive heart failure	Congestive heart failure	rs2301610, rs3833910, rs12301951, rs201674674, rs186741807, rs150140412, rs786205727, rs757840030, rs552050895, rs759465783, rs201978086, rs572757800, rs1572143354, rs749160569	20304815
Diabetic retinopathy	Diabetic Retinopathy		30178632
Heart failure	Heart failure, Left-Sided Heart Failure, Heart Failure, Right-Sided	rs121918074, rs142027794, rs148791216, rs72648927, rs71578935, rs142416150, rs199830512, rs755445214, rs150102469, rs779568205, rs907992794, rs1202130741	20304815
Kidney failure	Kidney Failure, Chronic, Kidney Failure		19420110, 23325087