NOX4_HUMAN
ID NOX4_HUMAN Reviewed; 578 AA.
AC Q9NPH5; A8K715; B7Z520; E7EMD7; Q5K3R4; Q5K3R5; Q5K3R6; Q5K3R8; Q7Z7G3;
AC Q86V92;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=NADPH oxidase 4;
DE EC=1.6.3.-;
DE AltName: Full=Kidney oxidase-1;
DE Short=KOX-1;
DE AltName: Full=Kidney superoxide-producing NADPH oxidase;
DE AltName: Full=Renal NAD(P)H-oxidase;
GN Name=NOX4; Synonyms=RENOX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE, AND VARIANT
RP ILE-315.
RC TISSUE=Kidney;
RX PubMed=10869423; DOI=10.1073/pnas.130135897;
RA Geiszt M., Kopp J.B., Varnai P., Leto T.L.;
RT "Identification of renox, an NAD(P)H oxidase in kidney.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8010-8014(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND VARIANT ILE-315.
RC TISSUE=Fetal kidney;
RX PubMed=11376945; DOI=10.1016/s0378-1119(01)00449-8;
RA Cheng G., Cao Z., Xu X., van Meir E.G., Lambeth J.D.;
RT "Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and
RT Nox5.";
RL Gene 269:131-140(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND VARIANT ILE-315.
RC TISSUE=Kidney;
RX PubMed=11032835; DOI=10.1074/jbc.m007597200;
RA Shiose A., Kuroda J., Tsuruya K., Hirai M., Hirakata H., Naito S.,
RA Hattori M., Sakaki Y., Sumimoto H.;
RT "A novel superoxide-producing NAD(P)H oxidase in kidney.";
RL J. Biol. Chem. 276:1417-1423(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), TISSUE SPECIFICITY, AND VARIANT
RP ILE-315.
RX PubMed=15210697; DOI=10.1074/jbc.m404983200;
RA Schwarzer C., Machen T.E., Illek B., Fischer H.;
RT "NADPH oxidase-dependent acid production in airway epithelial cells.";
RL J. Biol. Chem. 279:36454-36461(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4; 5 AND 6), FUNCTION,
RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND VARIANT ILE-315.
RC TISSUE=Lung;
RX PubMed=15721269; DOI=10.1016/j.bbrc.2005.01.089;
RA Goyal P., Weissmann N., Rose F., Grimminger F., Schaefers H.J., Seeger W.,
RA Haenze J.;
RT "Identification of novel Nox4 splice variants with impact on ROS levels in
RT A549 cells.";
RL Biochem. Biophys. Res. Commun. 329:32-39(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 6 AND 9), AND VARIANT
RP ILE-315.
RC TISSUE=Pulmonary artery;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 7), AND VARIANT
RP ILE-315.
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION.
RX PubMed=15155719; DOI=10.1074/jbc.m400078200;
RA Vaquero E.C., Edderkaoui M., Pandol S.J., Gukovsky I., Gukovskaya A.S.;
RT "Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in
RT pancreatic cancer cells.";
RL J. Biol. Chem. 279:34643-34654(2004).
RN [10]
RP FUNCTION, AND INTERACTION WITH TLR4.
RX PubMed=15356101; DOI=10.4049/jimmunol.173.6.3589;
RA Park H.S., Jung H.Y., Park E.Y., Kim J., Lee W.J., Bae Y.S.;
RT "Direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for
RT lipopolysaccharide-induced production of reactive oxygen species and
RT activation of NF-kappa B.";
RL J. Immunol. 173:3589-3593(2004).
RN [11]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=14966267; DOI=10.1128/mcb.24.5.1844-1854.2004;
RA Mahadev K., Motoshima H., Wu X., Ruddy J.M., Arnold R.S., Cheng G.,
RA Lambeth J.D., Goldstein B.J.;
RT "The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation
RT of H2O2 and plays an integral role in insulin signal transduction.";
RL Mol. Cell. Biol. 24:1844-1854(2004).
RN [12]
RP FUNCTION, INDUCTION, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=15572675; DOI=10.1128/mcb.24.24.10703-10717.2004;
RA Pedruzzi E., Guichard C., Ollivier V., Driss F., Fay M., Prunet C.,
RA Marie J.-C., Pouzet C., Samadi M., Elbim C., O'dowd Y., Bens M.,
RA Vandewalle A., Gougerot-Pocidalo M.-A., Lizard G., Ogier-Denis E.;
RT "NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic
RT reticulum stress and apoptosis in human aortic smooth muscle cells.";
RL Mol. Cell. Biol. 24:10703-10717(2004).
RN [13]
RP FUNCTION.
RX PubMed=16230378; DOI=10.1158/0008-5472.can-05-2105;
RA Maranchie J.K., Zhan Y.;
RT "Nox4 is critical for hypoxia-inducible factor 2-alpha transcriptional
RT activity in von Hippel-Lindau-deficient renal cell carcinoma.";
RL Cancer Res. 65:9190-9193(2005).
RN [14]
RP FUNCTION.
RX PubMed=16179589; DOI=10.1161/01.res.0000187457.24338.3d;
RA Cucoranu I., Clempus R., Dikalova A., Phelan P.J., Ariyan S., Dikalov S.,
RA Sorescu D.;
RT "NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced
RT differentiation of cardiac fibroblasts into myofibroblasts.";
RL Circ. Res. 97:900-907(2005).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND ACTIVITY
RP REGULATION.
RX PubMed=16324151; DOI=10.1111/j.1365-2443.2005.00907.x;
RA Kuroda J., Nakagawa K., Yamasaki T., Nakamura K., Takeya R.,
RA Kuribayashi F., Imajoh-Ohmi S., Igarashi K., Shibata Y., Sueishi K.,
RA Sumimoto H.;
RT "The superoxide-producing NAD(P)H oxidase Nox4 in the nucleus of human
RT vascular endothelial cells.";
RL Genes Cells 10:1139-1151(2005).
RN [16]
RP FUNCTION, INTERACTION WITH CYBA, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ARG-304 AND 575-GLU--SER-578.
RX PubMed=15927447; DOI=10.1016/j.cellsig.2005.03.023;
RA Martyn K.D., Frederick L.M., von Loehneysen K., Dinauer M.C., Knaus U.G.;
RT "Functional analysis of Nox4 reveals unique characteristics compared to
RT other NADPH oxidases.";
RL Cell. Signal. 18:69-82(2006).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=16019190; DOI=10.1016/j.cellsig.2005.05.025;
RA Lee Y.-M., Kim B.-J., Chun Y.-S., So I., Choi H., Kim M.-S., Park J.-W.;
RT "NOX4 as an oxygen sensor to regulate TASK-1 activity.";
RL Cell. Signal. 18:499-507(2006).
RN [18]
RP FUNCTION (ISOFORM 4), AND SUBCELLULAR LOCATION (ISOFORM 4).
RX PubMed=23393389; DOI=10.1161/atvbaha.112.300956;
RA Anilkumar N., San Jose G., Sawyer I., Santos C.X., Sand C., Brewer A.C.,
RA Warren D., Shah A.M.;
RT "A 28-kDa splice variant of NADPH oxidase-4 is nuclear-localized and
RT involved in redox signaling in vascular cells.";
RL Arterioscler. Thromb. Vasc. Biol. 33:E104-E112(2013).
RN [19]
RP INTERACTION WITH PPP1R15A, AND SUBCELLULAR LOCATION.
RX PubMed=26742780; DOI=10.15252/embj.201592394;
RA Santos C.X., Hafstad A.D., Beretta M., Zhang M., Molenaar C., Kopec J.,
RA Fotinou D., Murray T.V., Cobb A.M., Martin D., Zeh Silva M., Anilkumar N.,
RA Schroeder K., Shanahan C.M., Brewer A.C., Brandes R.P., Blanc E.,
RA Parsons M., Belousov V., Cammack R., Hider R.C., Steiner R.A., Shah A.M.;
RT "Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates
RT eIF2alpha-mediated stress signaling.";
RL EMBO J. 35:319-334(2016).
CC -!- FUNCTION: Constitutive NADPH oxidase which generates superoxide
CC intracellularly upon formation of a complex with CYBA/p22phox.
CC Regulates signaling cascades probably through phosphatases inhibition.
CC May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium
CC channel and HIF1A activity. May regulate insulin signaling cascade. May
CC play a role in apoptosis, bone resorption and lipolysaccharide-mediated
CC activation of NFKB. May produce superoxide in the nucleus and play a
CC role in regulating gene expression upon cell stimulation. Isoform 3 is
CC not functional. Isoform 5 and isoform 6 display reduced activity.
CC -!- FUNCTION: [Isoform 4]: Involved in redox signaling in vascular cells.
CC Constitutively and NADPH-dependently generates reactive oxygen species
CC (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1
CC transcription factor, and is capable of inducing nuclear DNA damage.
CC Displays an increased activity relative to isoform 1.
CC -!- ACTIVITY REGULATION: Inhibited by plumbagin (By similarity). Activated
CC by phorbol 12-myristate 13-acetate (PMA). Activated by insulin.
CC Inhibited by diphenylene iodonium. {ECO:0000250,
CC ECO:0000269|PubMed:14966267, ECO:0000269|PubMed:15572675,
CC ECO:0000269|PubMed:16019190, ECO:0000269|PubMed:16324151}.
CC -!- SUBUNIT: Interacts with protein disulfide isomerase (By similarity).
CC Interacts with, relocalizes and stabilizes CYBA/p22phox. Interacts with
CC TLR4. Interacts with PPP1R15A (PubMed:26742780). {ECO:0000250,
CC ECO:0000269|PubMed:15356101, ECO:0000269|PubMed:15927447}.
CC -!- INTERACTION:
CC Q9NPH5; O00206: TLR4; NbExp=4; IntAct=EBI-11301574, EBI-528701;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:26742780}; Multi-pass membrane protein. Cell
CC membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. Cell
CC junction, focal adhesion {ECO:0000305}. Note=May localize to plasma
CC membrane and focal adhesions. According to PubMed:15927447, may also
CC localize to the nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Nucleus
CC {ECO:0000269|PubMed:23393389}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:23393389}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=1;
CC IsoId=Q9NPH5-1; Sequence=Displayed;
CC Name=2; Synonyms=Nox4A;
CC IsoId=Q9NPH5-2; Sequence=VSP_019052;
CC Name=3; Synonyms=Nox4E;
CC IsoId=Q9NPH5-3; Sequence=VSP_019053, VSP_019058;
CC Name=4; Synonyms=28 kDa, Nox4D;
CC IsoId=Q9NPH5-4; Sequence=VSP_019053;
CC Name=5; Synonyms=Nox4C;
CC IsoId=Q9NPH5-5; Sequence=VSP_019056, VSP_019057;
CC Name=6; Synonyms=Nox4B;
CC IsoId=Q9NPH5-6; Sequence=VSP_019058;
CC Name=7;
CC IsoId=Q9NPH5-7; Sequence=VSP_019054, VSP_019055;
CC Name=8;
CC IsoId=Q9NPH5-8; Sequence=VSP_053826;
CC Name=9;
CC IsoId=Q9NPH5-9; Sequence=VSP_053826, VSP_019058;
CC -!- TISSUE SPECIFICITY: Expressed by distal tubular cells in kidney cortex
CC and in endothelial cells (at protein level). Widely expressed. Strongly
CC expressed in kidney and to a lower extent in heart, adipocytes,
CC hepatoma, endothelial cells, skeletal muscle, brain, several brain
CC tumor cell lines and airway epithelial cells.
CC {ECO:0000269|PubMed:11032835, ECO:0000269|PubMed:11376945,
CC ECO:0000269|PubMed:15210697, ECO:0000269|PubMed:16324151}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal kidney and fetal liver.
CC {ECO:0000269|PubMed:10869423, ECO:0000269|PubMed:11032835,
CC ECO:0000269|PubMed:11376945}.
CC -!- INDUCTION: By 7-ketocholesterol (at protein level).
CC {ECO:0000269|PubMed:15572675}.
CC -!- PTM: Isoform 3 and isoform 4 are N-glycosylated. Isoform 4
CC glycosylation is required for its proper function.
CC {ECO:0000269|PubMed:15721269}.
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DR EMBL; AF261943; AAF87572.1; -; mRNA.
DR EMBL; AF254621; AAF68973.1; -; mRNA.
DR EMBL; AB041035; BAA95695.1; -; mRNA.
DR EMBL; AY288918; AAP41109.1; -; mRNA.
DR EMBL; AJ704725; CAG28807.1; -; mRNA.
DR EMBL; AJ704726; CAG28808.1; -; mRNA.
DR EMBL; AJ704727; CAG28809.1; -; mRNA.
DR EMBL; AJ704728; CAG28810.1; -; mRNA.
DR EMBL; AJ704729; CAG28811.1; -; mRNA.
DR EMBL; AK291830; BAF84519.1; -; mRNA.
DR EMBL; AK298323; BAH12756.1; -; mRNA.
DR EMBL; AP003400; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001815; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002404; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC040105; AAH40105.1; -; mRNA.
DR EMBL; BC051371; AAH51371.1; -; mRNA.
DR CCDS; CCDS44695.1; -. [Q9NPH5-6]
DR CCDS; CCDS44696.1; -. [Q9NPH5-8]
DR CCDS; CCDS73361.1; -. [Q9NPH5-9]
DR CCDS; CCDS8285.1; -. [Q9NPH5-1]
DR RefSeq; NP_001137308.1; NM_001143836.2. [Q9NPH5-6]
DR RefSeq; NP_001137309.1; NM_001143837.1. [Q9NPH5-8]
DR RefSeq; NP_001278855.1; NM_001291926.1. [Q9NPH5-2]
DR RefSeq; NP_001278856.1; NM_001291927.1.
DR RefSeq; NP_001287924.1; NM_001300995.1. [Q9NPH5-9]
DR RefSeq; NP_058627.1; NM_016931.4. [Q9NPH5-1]
DR RefSeq; XP_011541159.1; XM_011542857.2. [Q9NPH5-8]
DR AlphaFoldDB; Q9NPH5; -.
DR SMR; Q9NPH5; -.
DR BioGRID; 119078; 23.
DR IntAct; Q9NPH5; 3.
DR STRING; 9606.ENSP00000263317; -.
DR BindingDB; Q9NPH5; -.
DR ChEMBL; CHEMBL1250375; -.
DR DrugCentral; Q9NPH5; -.
DR GuidetoPHARMACOLOGY; 3004; -.
DR PeroxiBase; 5967; HsNOx04.
DR TCDB; 5.B.1.1.2; the phagocyte (gp91(phox)) nadph oxidase family.
DR GlyGen; Q9NPH5; 2 sites.
DR iPTMnet; Q9NPH5; -.
DR PhosphoSitePlus; Q9NPH5; -.
DR BioMuta; NOX4; -.
DR DMDM; 212276447; -.
DR MassIVE; Q9NPH5; -.
DR PaxDb; Q9NPH5; -.
DR PeptideAtlas; Q9NPH5; -.
DR PRIDE; Q9NPH5; -.
DR ProteomicsDB; 16922; -.
DR ProteomicsDB; 82003; -. [Q9NPH5-1]
DR ProteomicsDB; 82004; -. [Q9NPH5-2]
DR ProteomicsDB; 82005; -. [Q9NPH5-3]
DR ProteomicsDB; 82006; -. [Q9NPH5-4]
DR ProteomicsDB; 82008; -. [Q9NPH5-6]
DR Antibodypedia; 17747; 640 antibodies from 38 providers.
DR DNASU; 50507; -.
DR Ensembl; ENST00000263317.9; ENSP00000263317.4; ENSG00000086991.13. [Q9NPH5-1]
DR Ensembl; ENST00000343727.9; ENSP00000344747.5; ENSG00000086991.13. [Q9NPH5-8]
DR Ensembl; ENST00000375979.7; ENSP00000365146.3; ENSG00000086991.13. [Q9NPH5-4]
DR Ensembl; ENST00000393282.2; ENSP00000376961.2; ENSG00000086991.13. [Q9NPH5-7]
DR Ensembl; ENST00000424319.5; ENSP00000412446.1; ENSG00000086991.13. [Q9NPH5-8]
DR Ensembl; ENST00000527956.5; ENSP00000433797.1; ENSG00000086991.13. [Q9NPH5-8]
DR Ensembl; ENST00000529343.5; ENSP00000435474.1; ENSG00000086991.13. [Q9NPH5-5]
DR Ensembl; ENST00000531342.5; ENSP00000435039.1; ENSG00000086991.13. [Q9NPH5-3]
DR Ensembl; ENST00000532825.5; ENSP00000434924.1; ENSG00000086991.13. [Q9NPH5-9]
DR Ensembl; ENST00000534731.5; ENSP00000436892.1; ENSG00000086991.13. [Q9NPH5-6]
DR GeneID; 50507; -.
DR KEGG; hsa:50507; -.
DR MANE-Select; ENST00000263317.9; ENSP00000263317.4; NM_016931.5; NP_058627.2.
DR UCSC; uc001pct.4; human. [Q9NPH5-1]
DR CTD; 50507; -.
DR DisGeNET; 50507; -.
DR GeneCards; NOX4; -.
DR HGNC; HGNC:7891; NOX4.
DR HPA; ENSG00000086991; Tissue enriched (kidney).
DR MIM; 605261; gene.
DR neXtProt; NX_Q9NPH5; -.
DR OpenTargets; ENSG00000086991; -.
DR PharmGKB; PA31692; -.
DR VEuPathDB; HostDB:ENSG00000086991; -.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000159621; -.
DR HOGENOM; CLU_005646_3_1_1; -.
DR InParanoid; Q9NPH5; -.
DR OMA; FIRGTHV; -.
DR OrthoDB; 936110at2759; -.
DR PhylomeDB; Q9NPH5; -.
DR TreeFam; TF105354; -.
DR PathwayCommons; Q9NPH5; -.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-HSA-9702518; STAT5 activation downstream of FLT3 ITD mutants.
DR Reactome; R-HSA-9703465; Signaling by FLT3 fusion proteins.
DR SignaLink; Q9NPH5; -.
DR SIGNOR; Q9NPH5; -.
DR BioGRID-ORCS; 50507; 12 hits in 1076 CRISPR screens.
DR ChiTaRS; NOX4; human.
DR GeneWiki; NOX4; -.
DR GenomeRNAi; 50507; -.
DR Pharos; Q9NPH5; Tchem.
DR PRO; PR:Q9NPH5; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9NPH5; protein.
DR Bgee; ENSG00000086991; Expressed in calcaneal tendon and 117 other tissues.
DR ExpressionAtlas; Q9NPH5; baseline and differential.
DR Genevisible; Q9NPH5; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; TAS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:ARUK-UCL.
DR GO; GO:0043020; C:NADPH oxidase complex; IBA:GO_Central.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:ARUK-UCL.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; ISS:ARUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; TAS:UniProtKB.
DR GO; GO:0020037; F:heme binding; TAS:UniProtKB.
DR GO; GO:0072341; F:modified amino acid binding; IDA:UniProtKB.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; TAS:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; TAS:UniProtKB.
DR GO; GO:0019826; F:oxygen sensor activity; TAS:UniProtKB.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISS:ARUK-UCL.
DR GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IBA:GO_Central.
DR GO; GO:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0000902; P:cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0006952; P:defense response; IBA:GO_Central.
DR GO; GO:0010467; P:gene expression; IMP:CACAO.
DR GO; GO:0003015; P:heart process; IGI:ARUK-UCL.
DR GO; GO:0050667; P:homocysteine metabolic process; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISS:ARUK-UCL.
DR GO; GO:1903409; P:reactive oxygen species biosynthetic process; NAS:ARUK-UCL.
DR GO; GO:0042554; P:superoxide anion generation; ISS:UniProtKB.
DR GO; GO:0006801; P:superoxide metabolic process; IDA:CACAO.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR000778; Cyt_b245_heavy_chain.
DR InterPro; IPR013112; FAD-bd_8.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR013130; Fe3_Rdtase_TM_dom.
DR InterPro; IPR013121; Fe_red_NAD-bd_6.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR Pfam; PF08022; FAD_binding_8; 1.
DR Pfam; PF01794; Ferric_reduct; 1.
DR Pfam; PF08030; NAD_binding_6; 1.
DR PRINTS; PR00466; GP91PHOX.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Membrane; NADP; Nucleus;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..578
FT /note="NADPH oxidase 4"
FT /id="PRO_0000238980"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..62
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 84..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 125..154
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 176..188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 210..424
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 425..445
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 446..578
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 58..303
FT /note="Ferric oxidoreductase"
FT DOMAIN 304..419
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 248..575
FT /note="Mediates interaction with TLR4"
FT /evidence="ECO:0000269|PubMed:15356101"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..74
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15721269"
FT /id="VSP_019052"
FT VAR_SEQ 1..24
FT /note="Missing (in isoform 8 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053826"
FT VAR_SEQ 52..358
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15721269"
FT /id="VSP_019053"
FT VAR_SEQ 52..54
FT /note="LGL -> ELS (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019054"
FT VAR_SEQ 55..578
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019055"
FT VAR_SEQ 211..224
FT /note="GLLKYQTNLDTHPP -> VQLKPKQHLGFILK (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15721269"
FT /id="VSP_019056"
FT VAR_SEQ 225..578
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15721269"
FT /id="VSP_019057"
FT VAR_SEQ 407..446
FT /note="Missing (in isoform 3, isoform 6 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15210697, ECO:0000303|PubMed:15721269"
FT /id="VSP_019058"
FT VARIANT 315
FT /note="M -> I (in dbSNP:rs317139)"
FT /evidence="ECO:0000269|PubMed:10869423,
FT ECO:0000269|PubMed:11032835, ECO:0000269|PubMed:11376945,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15210697,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15721269"
FT /id="VAR_047114"
FT MUTAGEN 304
FT /note="R->RGT: Partial loss of catalytic activity. No
FT effect on CYBA localization."
FT /evidence="ECO:0000269|PubMed:15927447"
FT MUTAGEN 575..578
FT /note="Missing: Partial loss of catalytic activity. No
FT effect on CYBA localization."
FT /evidence="ECO:0000269|PubMed:15927447"
FT CONFLICT 286
FT /note="W -> C (in Ref. 6; BAH12756)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 578 AA; 66932 MW; D150A92CC71DD40D CRC64;
MAVSWRSWLA NEGVKHLCLF IWLSMNVLLF WKTFLLYNQG PEYHYLHQML GLGLCLSRAS
ASVLNLNCSL ILLPMCRTLL AYLRGSQKVP SRRTRRLLDK SRTFHITCGV TICIFSGVHV
AAHLVNALNF SVNYSEDFVE LNAARYRDED PRKLLFTTVP GLTGVCMVVV LFLMITASTY
AIRVSNYDIF WYTHNLFFVF YMLLTLHVSG GLLKYQTNLD THPPGCISLN RTSSQNISLP
EYFSEHFHEP FPEGFSKPAE FTQHKFVKIC MEEPRFQANF PQTWLWISGP LCLYCAERLY
RYIRSNKPVT IISVMSHPSD VMEIRMVKEN FKARPGQYIT LHCPSVSALE NHPFTLTMCP
TETKATFGVH LKIVGDWTER FRDLLLPPSS QDSEILPFIQ SRNYPKLYID GPFGSPFEES
LNYEVSLCVA GGIGVTPFAS ILNTLLDDWK PYKLRRLYFI WVCRDIQSFR WFADLLCMLH
NKFWQENRPD YVNIQLYLSQ TDGIQKIIGE KYHALNSRLF IGRPRWKLLF DEIAKYNRGK
TVGVFCCGPN SLSKTLHKLS NQNNSYGTRF EYNKESFS
