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Protein

NADPH oxidase 4

Gene

Nox4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 Publications

Enzyme regulationi

Activated by insulin. Inhibited by diphenylene iodonium (By similarity). Inhibited by plumbagin. Activated by phorbol 12-myristate 13-acetate (PMA).By similarity2 Publications

GO - Molecular functioni

  • modified amino acid binding Source: MGI
  • NAD(P)H oxidase activity Source: Ensembl
  • superoxide-generating NADPH oxidase activity Source: UniProtKB

GO - Biological processi

  • bone resorption Source: MGI
  • cardiac muscle cell differentiation Source: MGI
  • cell aging Source: UniProtKB
  • cell morphogenesis Source: UniProtKB
  • cellular response to cAMP Source: Ensembl
  • cellular response to gamma radiation Source: Ensembl
  • cellular response to glucose stimulus Source: UniProtKB
  • cellular response to transforming growth factor beta stimulus Source: Ensembl
  • gene expression Source: MGI
  • homocysteine metabolic process Source: MGI
  • negative regulation of cell proliferation Source: UniProtKB
  • oxidation-reduction process Source: UniProtKB
  • positive regulation of apoptotic process Source: Ensembl
  • positive regulation of DNA biosynthetic process Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of MAP kinase activity Source: UniProtKB
  • positive regulation of protein kinase B signaling Source: UniProtKB
  • positive regulation of reactive oxygen species metabolic process Source: Ensembl
  • positive regulation of smooth muscle cell migration Source: Ensembl
  • positive regulation of stress fiber assembly Source: Ensembl
  • reactive oxygen species metabolic process Source: UniProtKB
  • response to hypoxia Source: Ensembl
  • superoxide anion generation Source: UniProtKB
  • superoxide metabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NADP

Enzyme and pathway databases

ReactomeiR-MMU-3299685. Detoxification of Reactive Oxygen Species.

Protein family/group databases

PeroxiBasei5966. MmNOx04.

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
Renal NAD(P)H-oxidase
Superoxide-generating NADPH oxidase 4
Gene namesi
Name:Nox4
Synonyms:Renox
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1354184. Nox4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1616CytoplasmicSequence analysisAdd
BLAST
Transmembranei17 – 3721HelicalSequence analysisAdd
BLAST
Topological domaini38 – 6225ExtracellularSequence analysisAdd
BLAST
Transmembranei63 – 8321HelicalSequence analysisAdd
BLAST
Topological domaini84 – 10421CytoplasmicSequence analysisAdd
BLAST
Transmembranei105 – 12521HelicalSequence analysisAdd
BLAST
Topological domaini126 – 15429ExtracellularSequence analysisAdd
BLAST
Transmembranei155 – 17521HelicalSequence analysisAdd
BLAST
Topological domaini176 – 18813CytoplasmicSequence analysisAdd
BLAST
Transmembranei189 – 20921HelicalSequence analysisAdd
BLAST
Topological domaini210 – 424215ExtracellularSequence analysisAdd
BLAST
Transmembranei425 – 44521HelicalSequence analysisAdd
BLAST
Topological domaini446 – 578133CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • cell periphery Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • focal adhesion Source: UniProtKB-SubCell
  • mitochondrion Source: Ensembl
  • NADPH oxidase complex Source: Ensembl
  • nucleus Source: MGI
  • perinuclear region of cytoplasm Source: UniProtKB
  • stress fiber Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 578578NADPH oxidase 4PRO_0000238981Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi133 – 1331N-linked (GlcNAc...)Sequence analysis
Glycosylationi230 – 2301N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

N-glycosylation is required for the function.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9JHI8.
PaxDbiQ9JHI8.
PRIDEiQ9JHI8.

PTM databases

iPTMnetiQ9JHI8.
PhosphoSiteiQ9JHI8.

Expressioni

Tissue specificityi

EXpressed in brain, in all layers of the cerebellum, in pyramidal cells of the Ammon horn and in Purkinje cells (at protein level). Expressed in osteoclasts, leukocytes, kidney, liver and lung.3 Publications

Inductioni

Upon brain ischemia it is up-regulated in ischemic tissues and more specially in neocapillaries (at protein level). Up-regulated upon hypoxia.2 Publications

Gene expression databases

BgeeiENSMUSG00000030562.
CleanExiMM_NOX4.
ExpressionAtlasiQ9JHI8. baseline and differential.
GenevisibleiQ9JHI8. MM.

Interactioni

Subunit structurei

Interacts with, relocalizes and stabilizes CYBA/p22phox. Interacts with TLR4. Interacts with protein disulfide isomerase (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000032781.

Structurei

3D structure databases

ProteinModelPortaliQ9JHI8.
SMRiQ9JHI8. Positions 409-577.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini58 – 303246Ferric oxidoreductaseAdd
BLAST
Domaini304 – 419116FAD-binding FR-typePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni248 – 575328Mediates interaction with TLR4By similarityAdd
BLAST

Sequence similaritiesi

Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation
Contains 1 ferric oxidoreductase domain.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0039. Eukaryota.
ENOG410XNZY. LUCA.
GeneTreeiENSGT00550000074350.
HOGENOMiHOG000216669.
HOVERGENiHBG003760.
InParanoidiQ9JHI8.
OMAiEADEQRI.
OrthoDBiEOG091G09RV.
PhylomeDBiQ9JHI8.
TreeFamiTF105354.

Family and domain databases

InterProiIPR000778. 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]
PfamiPF08022. FAD_binding_8. 1 hit.
PF01794. Ferric_reduct. 1 hit.
PF08030. NAD_binding_6. 1 hit.
[Graphical view]
PRINTSiPR00466. GP91PHOX.
SUPFAMiSSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9JHI8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAVSWRSWLA NEGVKHLCLL IWLSLNVLLF WKTFLLYNQG PEYYYIHQML
60 70 80 90 100
GLGLCLSRAS ASVLNLNCSL ILLPMCRTVL AYLRGSQKVP SRRTRRLLDK
110 120 130 140 150
SKTLHITCGV TICIFSGVHV AAHLVNALNF SVNYSEDFLE LNAARYQNED
160 170 180 190 200
PRKLLFTTIP GLTGVCMVVV LFLMVTASTY AIRVSNYDIF WYTHNLFFVF
210 220 230 240 250
YMLLLLHVSG GLLKYQTNVD THPPGCISLN QTSSQNMSIP DYVSEHFHGS
260 270 280 290 300
LPRGFSKLED RYQKTLVKIC LEEPKFQAHF PQTWIWISGP LCLYCAERLY
310 320 330 340 350
RCIRSNKPVT IISVINHPSD VMELRMIKEN FKARPGQYII LHCPSVSALE
360 370 380 390 400
NHPFTLTMCP TETKATFGVH FKVVGDWTER FRDLLLPPSS QDSEILPFIH
410 420 430 440 450
SRNYPKLYID GPFGSPFEES LNYEVSLCVA GGIGVTPFAS ILNTLLDDWK
460 470 480 490 500
PYKLRRLYFI WVCRDIQSFQ WFADLLCVLH NKFWQENRPD FVNIQLYLSQ
510 520 530 540 550
TDGIQKIIGE KYHTLNSRLF IGRPRWKLLF DEIAKCNRGK TVGVFCCGPS
560 570
SISKTLHSLS NRNNSYGTKF EYNKESFS
Length:578
Mass (Da):66,519
Last modified:October 1, 2000 - v1
Checksum:i7887ADD40599A3D1
GO
Isoform 2 (identifier: Q9JHI8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     150-164: DPRKLLFTTIPGLTG → VGGVCFSIFCSLVIR
     165-578: Missing.

Note: No experimental confirmation available.
Show »
Length:164
Mass (Da):18,575
Checksum:iC66ACDA0C48753A8
GO
Isoform 3 (identifier: Q9JHI8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     540-540: K → FEDQGQDFVPARKQHLHRGAPKALSFFSNGKGYLHFTIMTLKKCCFHGSPLIF
     541-578: Missing.

Note: No experimental confirmation available.
Show »
Length:592
Mass (Da):68,254
Checksum:iD4FD3BA5134AF5F2
GO
Isoform 4 (identifier: Q9JHI8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     358-358: M → MLCQKRWQPWHSRVWIYSFFVCSDAACHEDTSKMNHAFLL

Note: No experimental confirmation available.
Show »
Length:617
Mass (Da):71,244
Checksum:iDACA3D02C0A3D569
GO

Sequence cautioni

The sequence BC021378 differs from that shown. Reason: Frameshift at position 52. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti298 – 2981R → G in BAC39460 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei150 – 16415DPRKL…PGLTG → VGGVCFSIFCSLVIR in isoform 2. 1 PublicationVSP_019060Add
BLAST
Alternative sequencei165 – 578414Missing in isoform 2. 1 PublicationVSP_019061Add
BLAST
Alternative sequencei358 – 3581M → MLCQKRWQPWHSRVWIYSFF VCSDAACHEDTSKMNHAFLL in isoform 4. 1 PublicationVSP_019062
Alternative sequencei540 – 5401K → FEDQGQDFVPARKQHLHRGA PKALSFFSNGKGYLHFTIMT LKKCCFHGSPLIF in isoform 3. 1 PublicationVSP_019063
Alternative sequencei541 – 57838Missing in isoform 3. 1 PublicationVSP_019064Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF261944 mRNA. Translation: AAF87573.1.
AB041034 mRNA. Translation: BAA95682.1.
AB042745 mRNA. Translation: BAB18134.1.
AF218723 mRNA. Translation: AAF43142.1.
AF276957 mRNA. Translation: AAK69443.1.
AK050371 mRNA. Translation: BAC34215.1.
AK085509 mRNA. Translation: BAC39460.1.
AK169304 mRNA. Translation: BAE41059.1.
BC021378 mRNA. No translation available.
CCDSiCCDS21437.1. [Q9JHI8-1]
RefSeqiNP_056575.1. NM_015760.5. [Q9JHI8-1]
XP_006508075.1. XM_006508012.1. [Q9JHI8-4]
UniGeneiMm.31748.

Genome annotation databases

EnsembliENSMUST00000032781; ENSMUSP00000032781; ENSMUSG00000030562. [Q9JHI8-1]
ENSMUST00000068829; ENSMUSP00000070039; ENSMUSG00000030562. [Q9JHI8-3]
GeneIDi50490.
KEGGimmu:50490.
UCSCiuc009ifj.2. mouse. [Q9JHI8-2]
uc009ifl.2. mouse. [Q9JHI8-1]
uc009ifm.2. mouse. [Q9JHI8-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF261944 mRNA. Translation: AAF87573.1.
AB041034 mRNA. Translation: BAA95682.1.
AB042745 mRNA. Translation: BAB18134.1.
AF218723 mRNA. Translation: AAF43142.1.
AF276957 mRNA. Translation: AAK69443.1.
AK050371 mRNA. Translation: BAC34215.1.
AK085509 mRNA. Translation: BAC39460.1.
AK169304 mRNA. Translation: BAE41059.1.
BC021378 mRNA. No translation available.
CCDSiCCDS21437.1. [Q9JHI8-1]
RefSeqiNP_056575.1. NM_015760.5. [Q9JHI8-1]
XP_006508075.1. XM_006508012.1. [Q9JHI8-4]
UniGeneiMm.31748.

3D structure databases

ProteinModelPortaliQ9JHI8.
SMRiQ9JHI8. Positions 409-577.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000032781.

Protein family/group databases

PeroxiBasei5966. MmNOx04.

PTM databases

iPTMnetiQ9JHI8.
PhosphoSiteiQ9JHI8.

Proteomic databases

MaxQBiQ9JHI8.
PaxDbiQ9JHI8.
PRIDEiQ9JHI8.

Protocols and materials databases

DNASUi50490.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000032781; ENSMUSP00000032781; ENSMUSG00000030562. [Q9JHI8-1]
ENSMUST00000068829; ENSMUSP00000070039; ENSMUSG00000030562. [Q9JHI8-3]
GeneIDi50490.
KEGGimmu:50490.
UCSCiuc009ifj.2. mouse. [Q9JHI8-2]
uc009ifl.2. mouse. [Q9JHI8-1]
uc009ifm.2. mouse. [Q9JHI8-4]

Organism-specific databases

CTDi50507.
MGIiMGI:1354184. Nox4.

Phylogenomic databases

eggNOGiKOG0039. Eukaryota.
ENOG410XNZY. LUCA.
GeneTreeiENSGT00550000074350.
HOGENOMiHOG000216669.
HOVERGENiHBG003760.
InParanoidiQ9JHI8.
OMAiEADEQRI.
OrthoDBiEOG091G09RV.
PhylomeDBiQ9JHI8.
TreeFamiTF105354.

Enzyme and pathway databases

ReactomeiR-MMU-3299685. Detoxification of Reactive Oxygen Species.

Miscellaneous databases

PROiQ9JHI8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030562.
CleanExiMM_NOX4.
ExpressionAtlasiQ9JHI8. baseline and differential.
GenevisibleiQ9JHI8. MM.

Family and domain databases

InterProiIPR000778. 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]
PfamiPF08022. FAD_binding_8. 1 hit.
PF01794. Ferric_reduct. 1 hit.
PF08030. NAD_binding_6. 1 hit.
[Graphical view]
PRINTSiPR00466. GP91PHOX.
SUPFAMiSSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNOX4_MOUSE
AccessioniPrimary (citable) accession number: Q9JHI8
Secondary accession number(s): Q3TF39, Q8C3M1, Q8VCA3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: October 1, 2000
Last modified: September 7, 2016
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.