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Protein

NADPH oxidase 4

Gene

NOX4

Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

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

Keywordsi

Molecular functionOxidoreductase
LigandNADP

Names & Taxonomyi

Protein namesi
Recommended name:
NADPH oxidase 4 (EC:1.6.3.-)
Gene namesi
Name:NOX4
OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Taxonomic identifieri9601 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
Proteomesi
  • UP000001595 Componenti: Chromosome 11

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 – 103CytoplasmicSequence analysisAdd BLAST20
Transmembranei104 – 124HelicalSequence analysisAdd BLAST21
Topological domaini125 – 154ExtracellularSequence analysisAdd BLAST30
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

Keywords - Cellular componenti

Cell junction, Cell membrane, Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002389821 – 578NADPH oxidase 4Add BLAST578

Amino acid modifications

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

Post-translational modificationi

N-glycosylation is required for the function.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

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

STRINGi9601.ENSPPYP00000004298.

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0039. Eukaryota.
ENOG410XNZY. LUCA.
GeneTreeiENSGT00550000074350.
HOVERGENiHBG003760.
InParanoidiQ5R5C5.
OMAiFCCGPNS.
OrthoDBiEOG091G09RV.
TreeFamiTF105354.

Family and domain databases

InterProiView protein in 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.
PfamiView protein in Pfam
PF08022. FAD_binding_8. 1 hit.
PF01794. Ferric_reduct. 1 hit.
PF08030. NAD_binding_6. 1 hit.
PRINTSiPR00466. GP91PHOX.
SUPFAMiSSF63380. SSF63380. 1 hit.
PROSITEiView protein in PROSITE
PS51384. FAD_FR. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5R5C5-1) [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 NEGVKHLCLF IWLSMNVLLF WKTFLLYNQG PEYHYLHQML
60 70 80 90 100
GLGLCLSRAS ASVLNLNCSL ILLPMCRTLL AYLRGSQKVP SRRTRRLLDK
110 120 130 140 150
SRTFHITCGV TICIFSGVHV AAHLVNALNF SVNYSEDFVE LNAARYRDED
160 170 180 190 200
PRKLLFTTVP GLTGVCMVVV LFLMITASTY AIRVSNYDIF WYTHNLFFVF
210 220 230 240 250
YMLLTLHVSG GLLKYQTNLD THPPGCISLN RTSSQNISLP EYFSEHFHEP
260 270 280 290 300
FPEGFSKPEE FTQNTFVKIC MEEPRFQANF PQTWLWISGP LCLYCAERLY
310 320 330 340 350
RYIRSNKPVT IISVISHPSD VMEIRMVKEN FKARPGQYIT LHCPSVSALE
360 370 380 390 400
NHPFTLTMCP TETKATFGVH LKIVGDWTER FRDLLLPPSS QDSEILPFIQ
410 420 430 440 450
SRNYPKLYID GPFGSPFEES LNYEVSLCVA GGIGVTPFAS ILNTLLDDWK
460 470 480 490 500
PYKLRRLYFI WVCRDIQSFR WFADLLCMLH NKFWQENRPD YVNIQLYLSQ
510 520 530 540 550
TDGIQKIIGE KYHALNSRLF IGRPRWKLLF DEIAKYNRGK TVGVFCCGPN
560 570
SLSKTLHKLS NQINSYGTRF EYNKESFS
Length:578
Mass (Da):66,921
Last modified:May 30, 2006 - v2
Checksum:iC4D5C2839D617571
GO
Isoform 2 (identifier: Q5R5C5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MAVSWRSWLANEGVKHLCL → MGEEVWRKREEVIFSEHSFSFYPLNIFAPFVLFPDYFCLLE

Note: No experimental confirmation available.
Show »
Length:600
Mass (Da):69,754
Checksum:iFA6FA6977ACA6ABC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti246H → R in CAH90544 (Ref. 1) Curated1
Sequence conflicti246H → R in CAH89946 (Ref. 1) Curated1
Sequence conflicti306N → D in CAH93041 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0190651 – 19MAVSW…KHLCL → MGEEVWRKREEVIFSEHSFS FYPLNIFAPFVLFPDYFCLL E in isoform 2. 1 PublicationAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR857676 mRNA. Translation: CAH89946.1.
CR858307 mRNA. Translation: CAH90544.1.
CR860937 mRNA. Translation: CAH93041.1.
RefSeqiNP_001124912.1. NM_001131440.1.
NP_001128890.1. NM_001135418.1.
XP_009245205.1. XM_009246930.1. [Q5R5C5-1]
UniGeneiPab.19389.

Genome annotation databases

EnsembliENSPPYT00000004472; ENSPPYP00000004298; ENSPPYG00000003756. [Q5R5C5-1]
GeneIDi100171782.
100189825.
KEGGipon:100171782.
pon:100189825.

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNOX4_PONAB
AccessioniPrimary (citable) accession number: Q5R5C5
Secondary accession number(s): Q5RCG3, Q5RE61
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: May 30, 2006
Last modified: June 7, 2017
This is version 73 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome