Q9NPH5 (NOX4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NADPH oxidase 4
EC=1.6.3.-

Alternative name(s):
Kidney oxidase-1
Short name=KOX-1
Kidney superoxide-producing NADPH oxidase
Renal NAD(P)H-oxidase

Gene names

Name:	NOX4
Synonyms:	RENOX

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	578 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 4 displays an increased activity. Isoform 5 and isoform 6 display reduced activity. Ref.3 Ref.5 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Enzyme regulation	Inhibited by plumbagin By similarity. Activated by phorbol 12-myristate 13-acetate (PMA). Activated by insulin. Inhibited by diphenylene iodonium. Ref.11 Ref.12 Ref.15 Ref.17
Subunit structure	Interacts with protein disulfide isomerase By similarity. Interacts with, relocalizes and stabilizes CYBA/p22phox. Interacts with TLR4. Ref.10 Ref.16
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein Probable. Cell junction › focal adhesion Probable. Nucleus Probable. Note: May localize to plasma membrane and focal adhesions. According to Ref.16, may also localize to the nucleus. Ref.5 Ref.12 Ref.15 Ref.16 Ref.17
Tissue specificity	Expressed 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. Ref.2 Ref.3 Ref.4 Ref.15
Developmental stage	Expressed in fetal kidney and fetal liver. Ref.1 Ref.2 Ref.3
Induction	By 7-ketocholesterol (at protein level). Ref.11 Ref.12 Ref.15 Ref.17
Post-translational modification	Isoform 3 and isoform 4 are N-glycosylated. Isoform 4 glycosylation is required for its proper function. Ref.5
Sequence similarities	Contains 1 FAD-binding FR-type domain. Contains 1 ferric oxidoreductase domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bone resorption Inferred from electronic annotation. Source: Compara cardiocyte differentiation Inferred from electronic annotation. Source: Compara cell aging Inferred from sequence or structural similarity Ref.1. Source: UniProtKB cell morphogenesis Inferred from sequence or structural similarity Ref.1. Source: UniProtKB cellular response to cAMP Inferred from electronic annotation. Source: Compara cellular response to gamma radiation Inferred from electronic annotation. Source: Compara cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara cellular response to transforming growth factor beta stimulus Inferred from electronic annotation. Source: Compara homocysteine metabolic process Inferred from direct assay PubMed 20031578. Source: UniProtKB inflammatory response Traceable author statement Ref.1. Source: UniProtKB negative regulation of cell proliferation Inferred from sequence or structural similarity Ref.1. Source: UniProtKB positive regulation of DNA biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara positive regulation of reactive oxygen species metabolic process Inferred from electronic annotation. Source: Compara positive regulation of smooth muscle cell migration Inferred from electronic annotation. Source: Compara positive regulation of stress fiber assembly Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara superoxide anion generation Inferred from sequence or structural similarity Ref.1. Source: UniProtKB
Cellular_component	NADPH oxidase complex Inferred from electronic annotation. Source: Compara apical plasma membrane Inferred from electronic annotation. Source: Compara endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell focal adhesion Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Traceable author statement Ref.1. Source: UniProtKB mitochondrion Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara
Molecular_function	NAD(P)H oxidase activity Traceable author statement Ref.1. Source: UniProtKB electron carrier activity Traceable author statement Ref.1. Source: UniProtKB flavin adenine dinucleotide binding Traceable author statement Ref.1. Source: UniProtKB heme binding Traceable author statement Ref.1. Source: UniProtKB modified amino acid binding Inferred from direct assay PubMed 20031578. Source: UniProtKB oxygen sensor activity Traceable author statement Ref.1. Source: UniProtKB superoxide-generating NADPH oxidase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NPH5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NPH5-2)

Also known as: Nox4A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-74: Missing.

Isoform 3 (identifier: Q9NPH5-3)

Also known as: Nox4E;

The sequence of this isoform differs from the canonical sequence as follows:
     52-358: Missing.
     407-446: Missing.

Isoform 4 (identifier: Q9NPH5-4)

Also known as: Nox4D;

The sequence of this isoform differs from the canonical sequence as follows:
     52-358: Missing.

Isoform 5 (identifier: Q9NPH5-5)

Also known as: Nox4C;

The sequence of this isoform differs from the canonical sequence as follows:
     211-224: GLLKYQTNLDTHPP → VQLKPKQHLGFILK
     225-578: Missing.

Isoform 6 (identifier: Q9NPH5-6)

Also known as: Nox4B;

The sequence of this isoform differs from the canonical sequence as follows:
     407-446: Missing.

Isoform 7 (identifier: Q9NPH5-7)

The sequence of this isoform differs from the canonical sequence as follows:
     52-54: LGL → ELS
     55-578: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 578	578	NADPH oxidase 4		PRO_0000238980
Regions
	Topological domain	1 – 16	16	Cytoplasmic Potential
	Transmembrane	17 – 37	21	Helical; Potential
	Topological domain	38 – 62	25	Extracellular Potential
	Transmembrane	63 – 83	21	Helical; Potential
	Topological domain	84 – 103	20	Cytoplasmic Potential
	Transmembrane	104 – 124	21	Helical; Potential
	Topological domain	125 – 154	30	Extracellular Potential
	Transmembrane	155 – 175	21	Helical; Potential
	Topological domain	176 – 188	13	Cytoplasmic Potential
	Transmembrane	189 – 209	21	Helical; Potential
	Topological domain	210 – 424	215	Extracellular Potential
	Transmembrane	425 – 445	21	Helical; Potential
	Topological domain	446 – 578	133	Cytoplasmic Potential
	Domain	58 – 303	246	Ferric oxidoreductase
	Domain	304 – 419	116	FAD-binding FR-type
	Region	248 – 575	328	Mediates interaction with TLR4
Amino acid modifications
	Glycosylation	133	1	N-linked (GlcNAc...) Potential
	Glycosylation	230	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 74	74	Missing in isoform 2.		VSP_019052
	Alternative sequence	52 – 358	307	Missing in isoform 3 and isoform 4.		VSP_019053
	Alternative sequence	52 – 54	3	LGL → ELS in isoform 7.		VSP_019054
	Alternative sequence	55 – 578	524	Missing in isoform 7.		VSP_019055
	Alternative sequence	211 – 224	14	GLLKY…DTHPP → VQLKPKQHLGFILK in isoform 5.		VSP_019056
	Alternative sequence	225 – 578	354	Missing in isoform 5.		VSP_019057
	Alternative sequence	407 – 446	40	Missing in isoform 3 and isoform 6.		VSP_019058
	Natural variant	315	1	M → I. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.8 Corresponds to variant rs317139 [ dbSNP | Ensembl ].		VAR_047114
Experimental info
	Mutagenesis	304	1	R → RGT: Partial loss of catalytic activity. No effect on CYBA localization. Ref.16
	Mutagenesis	575 – 578	4	Missing: Partial loss of catalytic activity. No effect on CYBA localization. Ref.16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 4, 2008. Version 2. Checksum: D150A92CC71DD40D	FASTA	578	66,932
	10 20 30 40 50 60 MAVSWRSWLA NEGVKHLCLF IWLSMNVLLF WKTFLLYNQG PEYHYLHQML GLGLCLSRAS 70 80 90 100 110 120 ASVLNLNCSL ILLPMCRTLL AYLRGSQKVP SRRTRRLLDK SRTFHITCGV TICIFSGVHV 130 140 150 160 170 180 AAHLVNALNF SVNYSEDFVE LNAARYRDED PRKLLFTTVP GLTGVCMVVV LFLMITASTY 190 200 210 220 230 240 AIRVSNYDIF WYTHNLFFVF YMLLTLHVSG GLLKYQTNLD THPPGCISLN RTSSQNISLP 250 260 270 280 290 300 EYFSEHFHEP FPEGFSKPAE FTQHKFVKIC MEEPRFQANF PQTWLWISGP LCLYCAERLY 310 320 330 340 350 360 RYIRSNKPVT IISVMSHPSD VMEIRMVKEN FKARPGQYIT LHCPSVSALE NHPFTLTMCP 370 380 390 400 410 420 TETKATFGVH LKIVGDWTER FRDLLLPPSS QDSEILPFIQ SRNYPKLYID GPFGSPFEES 430 440 450 460 470 480 LNYEVSLCVA GGIGVTPFAS ILNTLLDDWK PYKLRRLYFI WVCRDIQSFR WFADLLCMLH 490 500 510 520 530 540 NKFWQENRPD YVNIQLYLSQ TDGIQKIIGE KYHALNSRLF IGRPRWKLLF DEIAKYNRGK 550 560 570 TVGVFCCGPN SLSKTLHKLS NQNNSYGTRF EYNKESFS
	Isoform 2 (Nox4A) [UniParc]. Checksum: 5D1ECB62CB23ED47	FASTA	504	58,410
	10 20 30 40 50 60 MCRTLLAYLR GSQKVPSRRT RRLLDKSRTF HITCGVTICI FSGVHVAAHL VNALNFSVNY 70 80 90 100 110 120 SEDFVELNAA RYRDEDPRKL LFTTVPGLTG VCMVVVLFLM ITASTYAIRV SNYDIFWYTH 130 140 150 160 170 180 NLFFVFYMLL TLHVSGGLLK YQTNLDTHPP GCISLNRTSS QNISLPEYFS EHFHEPFPEG 190 200 210 220 230 240 FSKPAEFTQH KFVKICMEEP RFQANFPQTW LWISGPLCLY CAERLYRYIR SNKPVTIISV 250 260 270 280 290 300 MSHPSDVMEI RMVKENFKAR PGQYITLHCP SVSALENHPF TLTMCPTETK ATFGVHLKIV 310 320 330 340 350 360 GDWTERFRDL LLPPSSQDSE ILPFIQSRNY PKLYIDGPFG SPFEESLNYE VSLCVAGGIG 370 380 390 400 410 420 VTPFASILNT LLDDWKPYKL RRLYFIWVCR DIQSFRWFAD LLCMLHNKFW QENRPDYVNI 430 440 450 460 470 480 QLYLSQTDGI QKIIGEKYHA LNSRLFIGRP RWKLLFDEIA KYNRGKTVGV FCCGPNSLSK 490 500 TLHKLSNQNN SYGTRFEYNK ESFS
	Isoform 3 (Nox4E) [UniParc]. Checksum: 548F872E16DC4D37	FASTA	231	27,625
	10 20 30 40 50 60 MAVSWRSWLA NEGVKHLCLF IWLSMNVLLF WKTFLLYNQG PEYHYLHQML GCPTETKATF 70 80 90 100 110 120 GVHLKIVGDW TERFRDLLLP PSSQDSEILP FIQSRNYPKD DWKPYKLRRL YFIWVCRDIQ 130 140 150 160 170 180 SFRWFADLLC MLHNKFWQEN RPDYVNIQLY LSQTDGIQKI IGEKYHALNS RLFIGRPRWK 190 200 210 220 230 LLFDEIAKYN RGKTVGVFCC GPNSLSKTLH KLSNQNNSYG TRFEYNKESF S
	Isoform 4 (Nox4D) [UniParc]. Checksum: 9C889BAAB7E531A2	FASTA	271	31,812
	10 20 30 40 50 60 MAVSWRSWLA NEGVKHLCLF IWLSMNVLLF WKTFLLYNQG PEYHYLHQML GCPTETKATF 70 80 90 100 110 120 GVHLKIVGDW TERFRDLLLP PSSQDSEILP FIQSRNYPKL YIDGPFGSPF EESLNYEVSL 130 140 150 160 170 180 CVAGGIGVTP FASILNTLLD DWKPYKLRRL YFIWVCRDIQ SFRWFADLLC MLHNKFWQEN 190 200 210 220 230 240 RPDYVNIQLY LSQTDGIQKI IGEKYHALNS RLFIGRPRWK LLFDEIAKYN RGKTVGVFCC 250 260 270 GPNSLSKTLH KLSNQNNSYG TRFEYNKESF S
	Isoform 5 (Nox4C) [UniParc]. Checksum: 27E3A0B6890E2A67	FASTA	224	25,761
	10 20 30 40 50 60 MAVSWRSWLA NEGVKHLCLF IWLSMNVLLF WKTFLLYNQG PEYHYLHQML GLGLCLSRAS 70 80 90 100 110 120 ASVLNLNCSL ILLPMCRTLL AYLRGSQKVP SRRTRRLLDK SRTFHITCGV TICIFSGVHV 130 140 150 160 170 180 AAHLVNALNF SVNYSEDFVE LNAARYRDED PRKLLFTTVP GLTGVCMVVV LFLMITASTY 190 200 210 220 AIRVSNYDIF WYTHNLFFVF YMLLTLHVSG VQLKPKQHLG FILK
	Isoform 6 (Nox4B) [UniParc]. Checksum: 2E541C48425EF25B	FASTA	538	62,745
	10 20 30 40 50 60 MAVSWRSWLA NEGVKHLCLF IWLSMNVLLF WKTFLLYNQG PEYHYLHQML GLGLCLSRAS 70 80 90 100 110 120 ASVLNLNCSL ILLPMCRTLL AYLRGSQKVP SRRTRRLLDK SRTFHITCGV TICIFSGVHV 130 140 150 160 170 180 AAHLVNALNF SVNYSEDFVE LNAARYRDED PRKLLFTTVP GLTGVCMVVV LFLMITASTY 190 200 210 220 230 240 AIRVSNYDIF WYTHNLFFVF YMLLTLHVSG GLLKYQTNLD THPPGCISLN RTSSQNISLP 250 260 270 280 290 300 EYFSEHFHEP FPEGFSKPAE FTQHKFVKIC MEEPRFQANF PQTWLWISGP LCLYCAERLY 310 320 330 340 350 360 RYIRSNKPVT IISVMSHPSD VMEIRMVKEN FKARPGQYIT LHCPSVSALE NHPFTLTMCP 370 380 390 400 410 420 TETKATFGVH LKIVGDWTER FRDLLLPPSS QDSEILPFIQ SRNYPKDDWK PYKLRRLYFI 430 440 450 460 470 480 WVCRDIQSFR WFADLLCMLH NKFWQENRPD YVNIQLYLSQ TDGIQKIIGE KYHALNSRLF 490 500 510 520 530 IGRPRWKLLF DEIAKYNRGK TVGVFCCGPN SLSKTLHKLS NQNNSYGTRF EYNKESFS
	Isoform 7 [UniParc]. Checksum: 2392A10568021769	FASTA	54	6,516
	10 20 30 40 50 MAVSWRSWLA NEGVKHLCLF IWLSMNVLLF WKTFLLYNQG PEYHYLHQML GELS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of renox, an NAD(P)H oxidase in kidney." Geiszt M., Kopp J.B., Varnai P., Leto T.L. Proc. Natl. Acad. Sci. U.S.A. 97:8010-8014(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE, VARIANT ILE-315. Tissue: Kidney.
[2]	"Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5." Cheng G., Cao Z., Xu X., van Meir E.G., Lambeth J.D. Gene 269:131-140(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, VARIANT ILE-315. Tissue: Fetal kidney.
[3]	"A novel superoxide-producing NAD(P)H oxidase in kidney." Shiose A., Kuroda J., Tsuruya K., Hirai M., Hirakata H., Naito S., Hattori M., Sakaki Y., Sumimoto H. J. Biol. Chem. 276:1417-1423(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, VARIANT ILE-315. Tissue: Kidney.
[4]	"NADPH oxidase-dependent acid production in airway epithelial cells." Schwarzer C., Machen T.E., Illek B., Fischer H. J. Biol. Chem. 279:36454-36461(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), TISSUE SPECIFICITY, VARIANT ILE-315.
[5]	"Identification of novel Nox4 splice variants with impact on ROS levels in A549 cells." Goyal P., Weissmann N., Rose F., Grimminger F., Schaefers H.J., Seeger W., Haenze J. Biochem. Biophys. Res. Commun. 329:32-39(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4; 5 AND 6), FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, VARIANT ILE-315. Tissue: Lung.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6). Tissue: Pulmonary artery.
[7]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 7), VARIANT ILE-315. Tissue: Ovary.
[9]	"Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in pancreatic cancer cells." Vaquero E.C., Edderkaoui M., Pandol S.J., Gukovsky I., Gukovskaya A.S. J. Biol. Chem. 279:34643-34654(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B." Park H.S., Jung H.Y., Park E.Y., Kim J., Lee W.J., Bae Y.S. J. Immunol. 173:3589-3593(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TLR4.
[11]	"The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction." Mahadev K., Motoshima H., Wu X., Ruddy J.M., Arnold R.S., Cheng G., Lambeth J.D., Goldstein B.J. Mol. Cell. Biol. 24:1844-1854(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[12]	"NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells." Pedruzzi E., Guichard C., Ollivier V., Driss F., Fay M., Prunet C., Marie J.-C., Pouzet C., Samadi M., Elbim C., O'dowd Y., Bens M., Vandewalle A., Gougerot-Pocidalo M.-A., Lizard G., Ogier-Denis E. Mol. Cell. Biol. 24:10703-10717(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
[13]	"Nox4 is critical for hypoxia-inducible factor 2-alpha transcriptional activity in von Hippel-Lindau-deficient renal cell carcinoma." Maranchie J.K., Zhan Y. Cancer Res. 65:9190-9193(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts." Cucoranu I., Clempus R., Dikalova A., Phelan P.J., Ariyan S., Dikalov S., Sorescu D. Circ. Res. 97:900-907(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"The superoxide-producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells." Kuroda J., Nakagawa K., Yamasaki T., Nakamura K., Takeya R., Kuribayashi F., Imajoh-Ohmi S., Igarashi K., Shibata Y., Sueishi K., Sumimoto H. Genes Cells 10:1139-1151(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ENZYME REGULATION.
[16]	"Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases." Martyn K.D., Frederick L.M., von Loehneysen K., Dinauer M.C., Knaus U.G. Cell. Signal. 18:69-82(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CYBA, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-304 AND 575-GLU--SER-578.
[17]	"NOX4 as an oxygen sensor to regulate TASK-1 activity." Lee Y.-M., Kim B.-J., Chun Y.-S., So I., Choi H., Kim M.-S., Park J.-W. Cell. Signal. 18:499-507(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF261943 mRNA. Translation: AAF87572.1. AF254621 mRNA. Translation: AAF68973.1. AB041035 mRNA. Translation: BAA95695.1. AY288918 mRNA. Translation: AAP41109.1. AJ704725 mRNA. Translation: CAG28807.1. AJ704726 mRNA. Translation: CAG28808.1. AJ704727 mRNA. Translation: CAG28809.1. AJ704728 mRNA. Translation: CAG28810.1. AJ704729 mRNA. Translation: CAG28811.1. AK291830 mRNA. Translation: BAF84519.1. AP001815 Genomic DNA. No translation available. AP002404 Genomic DNA. No translation available. BC040105 mRNA. Translation: AAH40105.1. BC051371 mRNA. Translation: AAH51371.1.
IPI	IPI00385546. IPI00552918. IPI00553065. IPI00759550. IPI00759558. IPI00978411. IPI01016002.
RefSeq	NP_001137308.1. NM_001143836.1. NP_058627.1. NM_016931.3.
UniGene	Hs.371036.
3D structure databases
ProteinModelPortal	Q9NPH5.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000263317.
Protein family/group databases
PeroxiBase	5967. HsNOx04.
TCDB	5.B.1.1.2. phagocyte (gp91phox) NADPH oxidase family.
PTM databases
PhosphoSite	Q9NPH5.
Polymorphism databases
DMDM	212276447.
Proteomic databases
PaxDb	Q9NPH5.
PRIDE	Q9NPH5.
Protocols and materials databases
DNASU	50507.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263317; ENSP00000263317; ENSG00000086991. ENST00000375979; ENSP00000365146; ENSG00000086991. ENST00000393282; ENSP00000376961; ENSG00000086991. ENST00000529343; ENSP00000435474; ENSG00000086991. ENST00000531342; ENSP00000435039; ENSG00000086991. ENST00000534731; ENSP00000436892; ENSG00000086991.
GeneID	50507.
KEGG	hsa:50507.
UCSC	uc001pcu.3. human. uc001pcv.3. human. uc001pcw.3. human. uc001pcx.3. human.
Organism-specific databases
CTD	50507.
GeneCards	GC11M089057.
HGNC	HGNC:7891. NOX4.
HPA	HPA015475.
MIM	605261. gene.
neXtProt	NX_Q9NPH5.
PharmGKB	PA31692.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG265816.
HOVERGEN	HBG003760.
InParanoid	Q9NPH5.
OrthoDB	EOG4FR0R6.
PhylomeDB	Q9NPH5.
Enzyme and pathway databases
Pathway_Interaction_DB	ptp1bpathway. Signaling events mediated by PTP1B.
Gene expression databases
ArrayExpress	Q9NPH5.
Bgee	Q9NPH5.
CleanEx	HS_NOX4.
Genevestigator	Q9NPH5.
GermOnline	ENSG00000086991. Homo sapiens.
Family and domain databases
InterPro	IPR000778. Cyt_b245_heavy_chain. IPR013112. FAD-bd_8. IPR017927. Fd_Rdtase_FAD-bd. IPR013130. Fe3_Rdtase_TM_dom. IPR013121. Fe_red_NAD-bd_6. IPR017938. Riboflavin_synthase-like_b-brl. [Graphical view]
Pfam	PF08022. FAD_binding_8. 1 hit. PF01794. Ferric_reduct. 1 hit. PF08030. NAD_binding_6. 1 hit. [Graphical view]
PRINTS	PR00466. GP91PHOX.
SUPFAM	SSF63380. Riboflavin_synthase_like_b-brl. 1 hit.
PROSITE	PS51384. FAD_FR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9NPH5.
ChEMBL	CHEMBL1250375.
GenomeRNAi	50507.
NextBio	53070.
SOURCE	Search...

Entry information

Entry name

NOX4_HUMAN

Accession

Primary (citable) accession number: Q9NPH5
Secondary accession number(s): A8K715 , Q5K3R4, Q5K3R5, Q5K3R6, Q5K3R8, Q7Z7G3, Q86V92

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2006
Last sequence update:	November 4, 2008
Last modified:	May 1, 2013
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.