NOX4

Protein identityUniProt · HPA

UniProt accession

Q9NPH5

Gene

NOX4

Ensembl

ENSG00000086991

Chromosome

11

Canonical length

578 aa

Protein class

Predicted membrane proteins, Transporters

OverviewNCBI Gene

This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein have been implicated in numerous biological functions including signal transduction, cell differentiation and tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]

Canonical amino-acid sequenceUniProt

578 residues, UniProt reviewed canonical sequence.

>Q9NPH5|NOX4
     1  MAVSWRSWLA NEGVKHLCLF IWLSMNVLLF WKTFLLYNQG PEYHYLHQML GLGLCLSRAS
    61  ASVLNLNCSL ILLPMCRTLL AYLRGSQKVP SRRTRRLLDK SRTFHITCGV TICIFSGVHV
   121  AAHLVNALNF SVNYSEDFVE LNAARYRDED PRKLLFTTVP GLTGVCMVVV LFLMITASTY
   181  AIRVSNYDIF WYTHNLFFVF YMLLTLHVSG GLLKYQTNLD THPPGCISLN RTSSQNISLP
   241  EYFSEHFHEP FPEGFSKPAE FTQHKFVKIC MEEPRFQANF PQTWLWISGP LCLYCAERLY
   301  RYIRSNKPVT IISVMSHPSD VMEIRMVKEN FKARPGQYIT LHCPSVSALE NHPFTLTMCP
   361  TETKATFGVH LKIVGDWTER FRDLLLPPSS QDSEILPFIQ SRNYPKLYID GPFGSPFEES
   421  LNYEVSLCVA GGIGVTPFAS ILNTLLDDWK PYKLRRLYFI WVCRDIQSFR WFADLLCMLH
   481  NKFWQENRPD YVNIQLYLSQ TDGIQKIIGE KYHALNSRLF IGRPRWKLLF DEIAKYNRGK
   541  TVGVFCCGPN SLSKTLHKLS NQNNSYGTRF EYNKESFS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NOX4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

6

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

129 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.14

gnomAD pLI

0

gnomAD missense Z

-0.9

DepMap mean gene effect

-0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• bone resorption
• cardiac muscle cell differentiation
• cell morphogenesis
• cellular response to glucose stimulus
• defense response
• gene expression
• heart process
• homocysteine metabolic process
• inflammatory response
• intracellular signal transduction
• negative regulation of cell population proliferation
• positive regulation of DNA biosynthetic process
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• reactive oxygen species biosynthetic process
• superoxide anion generation
• superoxide metabolic process

Molecular functions

• electron transfer activity
• flavin adenine dinucleotide binding
• heme binding
• modified amino acid binding
• NAD(P)H oxidase H2O2-forming activity
• nucleotide binding
• oxygen sensor activity
• protein tyrosine kinase binding
• superoxide-generating NAD(P)H oxidase activity
• superoxide-generating NADPH oxidase activity

Cellular components

• endoplasmic reticulum
• endoplasmic reticulum membrane
• focal adhesion
• membrane
• mitochondrion
• NADPH oxidase complex
• nucleolus
• nucleus
• perinuclear endoplasmic reticulum
• perinuclear region of cytoplasm
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Cytochrome b245, heavy chain
• FAD-binding 8
• Ferric reductase, NAD binding domain
• Ferric reductase transmembrane component-like domain
• FAD-binding domain, ferredoxin reductase-type
• Riboflavin synthase-like beta-barrel
• Ferredoxin-NADP reductase (FNR), nucleotide-binding domain
• Respiratory burst oxidase/Ferric reductase
• Ferric reductase like transmembrane component
• FAD-binding domain
• Ferric reductase NAD binding domain

KeywordsUniProt

• Cell junction
• Cell membrane
• Cytoplasm
• Disulfide bond
• Endoplasmic reticulum
• Glycoprotein
• Membrane
• NADP
• Nucleus
• Oxidoreductase
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of NOX4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LRRC8A
• PPP1R15A
• TLR4
• RUBCN
• CYBA