UniProtKB - Q924V1 (NOX4_RAT)
NADPH oxidase 4
Nox4
Functioni
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.
2 PublicationsActivity regulationi
GO - Molecular functioni
- modified amino acid binding Source: RGD
- NAD(P)H oxidase H2O2-forming activity Source: RGD
- oxidoreductase activity, acting on NAD(P)H, oxygen as acceptor Source: RGD
- protein tyrosine kinase binding Source: RGD
- superoxide-generating NAD(P)H oxidase activity Source: RGD
GO - Biological processi
- aging Source: RGD
- bone resorption Source: RGD
- cardiac muscle cell differentiation Source: RGD
- cell aging Source: UniProtKB
- cell morphogenesis Source: UniProtKB
- cellular response to cAMP Source: RGD
- cellular response to gamma radiation Source: RGD
- cellular response to glucose stimulus Source: RGD
- cellular response to transforming growth factor beta stimulus Source: RGD
- defense response Source: GO_Central
- gene expression Source: RGD
- heart process Source: RGD
- homocysteine metabolic process Source: RGD
- negative regulation of cell population proliferation Source: UniProtKB
- positive regulation of apoptotic process Source: RGD
- positive regulation of DNA biosynthetic process Source: RGD
- positive regulation of ERK1 and ERK2 cascade Source: RGD
- positive regulation of MAP kinase activity Source: RGD
- positive regulation of protein kinase B signaling Source: RGD
- positive regulation of protein tyrosine kinase activity Source: RGD
- positive regulation of reactive oxygen species metabolic process Source: RGD
- positive regulation of smooth muscle cell migration Source: RGD
- positive regulation of stress fiber assembly Source: RGD
- reactive oxygen species metabolic process Source: UniProtKB
- response to hypoxia Source: RGD
- superoxide anion generation Source: UniProtKB
- superoxide metabolic process Source: RGD
Keywordsi
Molecular function | Oxidoreductase |
Ligand | NADP |
Enzyme and pathway databases
BRENDAi | 1.6.3.1, 5301 |
Reactomei | R-RNO-3299685, Detoxification of Reactive Oxygen Species |
Protein family/group databases
PeroxiBasei | 5409, RnoNOx04 |
Names & Taxonomyi
Protein namesi | Recommended name: NADPH oxidase 4 (EC:1.6.3.-)Alternative name(s): Kidney oxidase-1 Short name: KOX-1 Kidney superoxide-producing NADPH oxidase |
Gene namesi | Name:Nox4 Synonyms:Kox |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 620600, Nox4 |
Subcellular locationi
Endoplasmic reticulum
Plasma membrane
- Cell membrane Curated; Multi-pass membrane protein Curated
Other locations
- focal adhesion Curated
Note: May localize to plasma membrane and focal adhesions.
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
- perinuclear endoplasmic reticulum Source: ARUK-UCL
Mitochondrion
- mitochondrion Source: ARUK-UCL
Nucleus
- nucleus Source: ARUK-UCL
Plasma Membrane
- apical plasma membrane Source: RGD
- NADPH oxidase complex Source: RGD
- plasma membrane Source: GO_Central
Other locations
- cell periphery Source: RGD
- focal adhesion Source: RGD
- perinuclear region of cytoplasm Source: ARUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 16 | CytoplasmicSequence analysisAdd BLAST | 16 | |
Transmembranei | 17 – 37 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 38 – 62 | ExtracellularSequence analysisAdd BLAST | 25 | |
Transmembranei | 63 – 83 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 84 – 104 | CytoplasmicSequence analysisAdd BLAST | 21 | |
Transmembranei | 105 – 125 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 126 – 154 | ExtracellularSequence analysisAdd BLAST | 29 | |
Transmembranei | 155 – 175 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 176 – 188 | CytoplasmicSequence analysisAdd BLAST | 13 | |
Transmembranei | 189 – 209 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 210 – 424 | ExtracellularSequence analysisAdd BLAST | 215 | |
Transmembranei | 425 – 445 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 446 – 578 | CytoplasmicSequence analysisAdd BLAST | 133 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Endoplasmic reticulum, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 119 | H → L: Loss of interaction with CYBA/p22phox. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000238983 | 1 – 578 | NADPH oxidase 4Add BLAST | 578 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 133 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
PaxDbi | Q924V1 |
PTM databases
GlyGeni | Q924V1, 1 site |
PhosphoSitePlusi | Q924V1 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSRNOG00000013925, Expressed in adult mammalian kidney and 17 other tissues |
Genevisiblei | Q924V1, RN |
Interactioni
Subunit structurei
Interacts with TLR4 (By similarity).
Interacts with, relocalizes and stabilizes CYBA/p22phox.
Interacts with protein disulfide isomerase.
By similarity2 PublicationsGO - Molecular functioni
- protein tyrosine kinase binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 250101, 3 interactors |
STRINGi | 10116.ENSRNOP00000018990 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 58 – 303 | Ferric oxidoreductaseAdd BLAST | 246 | |
Domaini | 304 – 419 | FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST | 116 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 248 – 575 | Mediates interaction with TLR4By similarityAdd BLAST | 328 |
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0039, Eukaryota |
GeneTreei | ENSGT00940000159621 |
HOGENOMi | CLU_005646_3_1_1 |
InParanoidi | Q924V1 |
OMAi | CKEDAHF |
OrthoDBi | 936110at2759 |
Family and domain databases
Gene3Di | 3.40.50.80, 1 hit |
InterProi | View protein in InterPro IPR000778, Cyt_b245_heavy_chain IPR013112, FAD-bd_8 IPR017927, FAD-bd_FR_type IPR013130, Fe3_Rdtase_TM_dom IPR013121, Fe_red_NAD-bd_6 IPR039261, FNR_nucleotide-bd IPR017938, Riboflavin_synthase-like_b-brl |
Pfami | View protein in Pfam PF08022, FAD_binding_8, 1 hit PF01794, Ferric_reduct, 1 hit PF08030, NAD_binding_6, 1 hit |
PRINTSi | PR00466, GP91PHOX |
SUPFAMi | SSF52343, SSF52343, 1 hit SSF63380, SSF63380, 1 hit |
PROSITEi | View protein in PROSITE PS51384, FAD_FR, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MALSWRSWLA NEGVKHLCLL VWLSLNVLLF WKTFLLYNQG PEYYYIHQML
60 70 80 90 100
GLGLCLSRAS ASVLNLNCSL ILLPMCRTVL AYLRGSQKVP SRRTRRLLDK
110 120 130 140 150
SKTLHITCGI TICIFSGVHV AAHLVNALNF SVNYSEHFLA LNAARYQNED
160 170 180 190 200
PRKLLFTTVP GLTGVCMVVV LFLMVTASTY AIRVSNYDIF WYTHNLFFVF
210 220 230 240 250
YMLLLLHVSG GLLKYQTNLD THPPGCISLN RTPSQNMSIA DYVSEHFHGS
260 270 280 290 300
LPGGFSKLED HYQKTLVKIC LEEPKFQAHF PQTWIWISGP LCLYCAERLY
310 320 330 340 350
RCIRSNKPVT IISVINHPSD VMELRMIKEN FKARPGQYII LHCPSVSALE
360 370 380 390 400
NHPFTLTMCP TETKATFGVH FKVVGDWTER FRDLLLPPSS QDSEILPFIQ
410 420 430 440 450
SRNYPKLYID GPFGSPFEES LNYEVSLCVA GGIGVTPFAS ILNTLLDDWK
460 470 480 490 500
PYKLRRLYFI WVCRDIQSFQ WFADLLYVLH NKFWQENRPD FVNIQLYLSQ
510 520 530 540 550
TDGIQKIIGE KYHTLNSRLF IGRPRWKLLF DEIAKCNRGK TVGVFCCGPS
560 570
SISKTLHNLS NRNNSYGTKF EYNKESFS
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 232 | T → P in BAB61724 (PubMed:11032835).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY027527 mRNA Translation: AAK14799.1 AB044086 mRNA Translation: BAB61724.1 |
RefSeqi | NP_445976.1, NM_053524.1 |
Genome annotation databases
Ensembli | ENSRNOT00000018990; ENSRNOP00000018990; ENSRNOG00000013925 |
GeneIDi | 85431 |
KEGGi | rno:85431 |
UCSCi | RGD:620600, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY027527 mRNA Translation: AAK14799.1 AB044086 mRNA Translation: BAB61724.1 |
RefSeqi | NP_445976.1, NM_053524.1 |
3D structure databases
SMRi | Q924V1 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 250101, 3 interactors |
STRINGi | 10116.ENSRNOP00000018990 |
Protein family/group databases
PeroxiBasei | 5409, RnoNOx04 |
PTM databases
GlyGeni | Q924V1, 1 site |
PhosphoSitePlusi | Q924V1 |
Proteomic databases
PaxDbi | Q924V1 |
Genome annotation databases
Ensembli | ENSRNOT00000018990; ENSRNOP00000018990; ENSRNOG00000013925 |
GeneIDi | 85431 |
KEGGi | rno:85431 |
UCSCi | RGD:620600, rat |
Organism-specific databases
CTDi | 50507 |
RGDi | 620600, Nox4 |
Phylogenomic databases
eggNOGi | KOG0039, Eukaryota |
GeneTreei | ENSGT00940000159621 |
HOGENOMi | CLU_005646_3_1_1 |
InParanoidi | Q924V1 |
OMAi | CKEDAHF |
OrthoDBi | 936110at2759 |
Enzyme and pathway databases
BRENDAi | 1.6.3.1, 5301 |
Reactomei | R-RNO-3299685, Detoxification of Reactive Oxygen Species |
Miscellaneous databases
PROi | PR:Q924V1 |
Gene expression databases
Bgeei | ENSRNOG00000013925, Expressed in adult mammalian kidney and 17 other tissues |
Genevisiblei | Q924V1, RN |
Family and domain databases
Gene3Di | 3.40.50.80, 1 hit |
InterProi | View protein in InterPro IPR000778, Cyt_b245_heavy_chain IPR013112, FAD-bd_8 IPR017927, FAD-bd_FR_type IPR013130, Fe3_Rdtase_TM_dom IPR013121, Fe_red_NAD-bd_6 IPR039261, FNR_nucleotide-bd IPR017938, Riboflavin_synthase-like_b-brl |
Pfami | View protein in Pfam PF08022, FAD_binding_8, 1 hit PF01794, Ferric_reduct, 1 hit PF08030, NAD_binding_6, 1 hit |
PRINTSi | PR00466, GP91PHOX |
SUPFAMi | SSF52343, SSF52343, 1 hit SSF63380, SSF63380, 1 hit |
PROSITEi | View protein in PROSITE PS51384, FAD_FR, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NOX4_RAT | |
Accessioni | Q924V1Primary (citable) accession number: Q924V1 Secondary accession number(s): Q99M78 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2006 |
Last sequence update: | May 30, 2006 | |
Last modified: | February 23, 2022 | |
This is version 113 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |