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FLASH GENE
Symbol NOX5 contributors: mct/pgu - updated : 17-12-2013
HGNC name NADPH oxidase, EF hand calcium-binding domain 5
HGNC id 14874
Location 15q23      Physical location : 69.222.838 - 69.349.500
Synonym name NOX5 variant lacking EF hands
Synonym symbol(s) NOX5A, NOX5B, MGC149776, MGC149777
EC.number 1.6.3.-
DNA
TYPE functioning gene
STRUCTURE 126.66 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
16 splicing 2809 - 765 spleen only 2012 22427510
  • NOX5 gamma
  • - splicing 2900 - 719 in endothelial cells 2012 22427510
  • Nox5-epsilon that can inhibit NOX5 activity and activate ERK and HVSMC proliferation
  • lacking calcium-binding domains
  • short, calcium-independent splice form, NOX5S, that may function as an endogenous inhibitor of calcium-stimulated ROS generation by full-length NOX5
  • 16 - 2852 - 730 - 2012 22427510
    16 - 2725 - 737 - 2012 22427510
  • Nox5-alpha
  • major isoform that are expressed and the only variant capable of ROS production
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
     vessel     Homo sapiens
    Reproductivemale systemtestis    Homo sapiens
    Respiratorylung   moderately
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    Lymphoid/Immunelymphocyte
    Muscularmyocyte Homo sapiens
    Reproductivespermatozoa Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three N terminal EF hand motifs
  • two conserved polybasic regions: one N-terminal (PBR-N), located between the fourth EF-hand and the first transmembrane region (Arg197 a key residue to regulate subcellular localization of Nox5 and its interaction with PIB5PA)
  • one C-terminal (PBR-C), between the first and second NADPH-binding subregions, also containing putative phosphorylation sites, and a consensus calmodulin-binding domain (CaMBD)
  • mono polymer octamer
    HOMOLOGY
    Homologene
    FAMILY NOX family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • can be found intracellularly and at the cell surface, at the plasma membrane
  • found in the endoplasmic reticulum of human microvascular endothelial cells (HMEC-1) and in the vascular wall
  • basic FUNCTION
  • ROS-generating NADPH oxidase which contains an N-terminal EF-hand region and can be activated by cytosolic Ca(2+) elevations
  • play an important role in PDGF-induced JAK/STAT activation and human aortic smooth muscle cell (HASMC) proliferation
  • being functional, promoting endothelial ROS production, proliferation, and the formation of capillary-like structures and contributing to the endothelial response to thrombin
  • is the main source of superoxide and is implicated in human spermatozoa motility
  • role for NOX5-dependent ROS generation in human spermatozoa motility
  • is the predominant NOX family NADPH oxidase in human spermatozoa
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms a catalytically active oligomer in the membrane that is mediated by its dehydrogenase domain
  • functional complex between NOX5 and ABL1 exist in human spermatozoa
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with and is regulated by calmodulin
  • ABL1 plays a central role in the induction of NOX5 activity in response to H2O2
  • H2O2-NOX5 regulation in human spermatozoa is mediated through a ABL1-dependent signaling pathway
  • cell & other
    REGULATION
    activated by protein kinase C, in addition to its Ca(2+) activation
    by the coordinated phosphorylation of both MAPK and PKC pathways
    Other regulated by Ca(2+) through intramolecular activation of the C-terminal catalytic domain by the EF-hand-containing N-terminal regulatory domain
    phosphorylation at key AAs facilitates enzyme activation at lower levels of intracellular calcium and may provide an avenue for enzyme activation in response to a greater variety of extracellular stimuli
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in teratozoospermic semen
    constitutional     --over  
    in intramyocardial blood vessels and cardiomyocytes after acute myocardial infarction
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    reproductioncontraception 
    NOX5 and the proteins regulating its activity represent new therapeutic targets for male contraception (if NOX5 is physiologically active)
    reproductionfertility 
    NOX5 and the proteins regulating its activity represent new therapeutic targets for male infertility (if NOX5 is hyperactive)
    ANIMAL & CELL MODELS