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Protein

NADPH oxidase 4

Gene

Nox4

Organism
Rattus norvegicus (Rat)
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. Inhibited by plumbagin. Activated by phorbol 12-myristate 13-acetate (PMA) (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

  • aging Source: RGD
  • bone resorption Source: Ensembl
  • cardiac muscle cell differentiation Source: Ensembl
  • 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: Ensembl
  • cellular response to transforming growth factor beta stimulus Source: RGD
  • gene expression Source: Ensembl
  • homocysteine metabolic process Source: Ensembl
  • negative regulation of cell proliferation Source: UniProtKB
  • oxidation-reduction process Source: UniProtKB
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of DNA biosynthetic process Source: Ensembl
  • positive regulation of ERK1 and ERK2 cascade Source: Ensembl
  • positive regulation of MAP kinase activity Source: Ensembl
  • positive regulation of protein kinase B signaling Source: Ensembl
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NADP

Enzyme and pathway databases

BRENDAi1.6.3.1. 5301.
ReactomeiR-RNO-3299685. Detoxification of Reactive Oxygen Species.

Protein family/group databases

PeroxiBasei5409. 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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi620600. Nox4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 16CytoplasmicSequence analysisAdd BLAST16
Transmembranei17 – 37HelicalSequence analysisAdd BLAST21
Topological domaini38 – 62ExtracellularSequence analysisAdd BLAST25
Transmembranei63 – 83HelicalSequence analysisAdd BLAST21
Topological domaini84 – 104CytoplasmicSequence analysisAdd BLAST21
Transmembranei105 – 125HelicalSequence analysisAdd BLAST21
Topological domaini126 – 154ExtracellularSequence analysisAdd BLAST29
Transmembranei155 – 175HelicalSequence analysisAdd BLAST21
Topological domaini176 – 188CytoplasmicSequence analysisAdd BLAST13
Transmembranei189 – 209HelicalSequence analysisAdd BLAST21
Topological domaini210 – 424ExtracellularSequence analysisAdd BLAST215
Transmembranei425 – 445HelicalSequence analysisAdd BLAST21
Topological domaini446 – 578CytoplasmicSequence analysisAdd BLAST133

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell junction, Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi119H → L: Loss of interaction with CYBA/p22phox. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002389831 – 578NADPH oxidase 4Add BLAST578

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi133N-linked (GlcNAc...)Sequence analysis1
Glycosylationi230N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylation is required for the function.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ924V1.
PRIDEiQ924V1.

PTM databases

PhosphoSitePlusiQ924V1.

Expressioni

Tissue specificityi

Expressed in vascular smooth muscle.1 Publication

Inductioni

Up-regulated in diabetic kidney (at protein level).1 Publication

Gene expression databases

BgeeiENSRNOG00000013925.
GenevisibleiQ924V1. RN.

Interactioni

Subunit structurei

Interacts with TLR4 (By similarity). Interacts with, relocalizes and stabilizes CYBA/p22phox. Interacts with protein disulfide isomerase.By similarity2 Publications

Protein-protein interaction databases

BioGridi250101. 2 interactors.
STRINGi10116.ENSRNOP00000018990.

Structurei

3D structure databases

ProteinModelPortaliQ924V1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini58 – 303Ferric oxidoreductaseAdd BLAST246
Domaini304 – 419FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST116

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni248 – 575Mediates interaction with TLR4By similarityAdd BLAST328

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.
InParanoidiQ924V1.
OMAiTDGIQQK.
OrthoDBiEOG091G09RV.

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]

Sequencei

Sequence statusi: Complete.

Q924V1-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:578
Mass (Da):66,469
Last modified:May 30, 2006 - v2
Checksum:i474347299F994D92
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti232T → P in BAB61724 (PubMed:11032835).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY027527 mRNA. Translation: AAK14799.1.
AB044086 mRNA. Translation: BAB61724.1.
RefSeqiNP_445976.1. NM_053524.1.
UniGeneiRn.14744.

Genome annotation databases

EnsembliENSRNOT00000018990; ENSRNOP00000018990; ENSRNOG00000013925.
GeneIDi85431.
KEGGirno:85431.
UCSCiRGD:620600. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY027527 mRNA. Translation: AAK14799.1.
AB044086 mRNA. Translation: BAB61724.1.
RefSeqiNP_445976.1. NM_053524.1.
UniGeneiRn.14744.

3D structure databases

ProteinModelPortaliQ924V1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250101. 2 interactors.
STRINGi10116.ENSRNOP00000018990.

Protein family/group databases

PeroxiBasei5409. RnoNOx04.

PTM databases

PhosphoSitePlusiQ924V1.

Proteomic databases

PaxDbiQ924V1.
PRIDEiQ924V1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000018990; ENSRNOP00000018990; ENSRNOG00000013925.
GeneIDi85431.
KEGGirno:85431.
UCSCiRGD:620600. rat.

Organism-specific databases

CTDi50507.
RGDi620600. Nox4.

Phylogenomic databases

eggNOGiKOG0039. Eukaryota.
ENOG410XNZY. LUCA.
GeneTreeiENSGT00550000074350.
HOGENOMiHOG000216669.
HOVERGENiHBG003760.
InParanoidiQ924V1.
OMAiTDGIQQK.
OrthoDBiEOG091G09RV.

Enzyme and pathway databases

BRENDAi1.6.3.1. 5301.
ReactomeiR-RNO-3299685. Detoxification of Reactive Oxygen Species.

Miscellaneous databases

PROiQ924V1.

Gene expression databases

BgeeiENSRNOG00000013925.
GenevisibleiQ924V1. RN.

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_RAT
AccessioniPrimary (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: November 2, 2016
This is version 85 of the entry and version 2 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. 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.