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FLASH GENE
Symbol CYBB contributors: mct/shn - updated : 05-09-2017
HGNC name cytochrome b-245, beta polypeptide
HGNC id 2578
Corresponding disease
CGD1 chronic granulomatous disease 1
IMD34 Immunodeficiency 34
Location Xp21.1      Physical location : 37.639.269 - 37.672.714
Synonym name
  • NADPH oxidase 2
  • neutrophil cytochrome b 91 kDa polypeptide
  • heme-binding membrane glycoprotein gp91phox
  • cytochrome b558 subunit beta
  • cytochrome b(558) subunit beta
  • cytochrome b-245, beta polypeptide
  • cytochrome b-245 heavy chain
  • superoxide-generating NADPH oxidase heavy chain subunit
  • chronic granulomatous disease
  • CGD91-phox
  • p22 phagocyte B-cytochrome
  • Synonym symbol(s) CGD, GP91-PHOX, NOX2, GP91-1, AMCBX2, GP91-1, GP91PHOX, p91-PHOX
    EC.number 1.-.-.-
    DNA
    TYPE functioning gene
    STRUCTURE 29.97 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map pter - DXS1049 - DXS8090 - CYBB - DXS1069 - DXS1068 - cen
    Physical map
    FLJ35782 Xp21.1 hypothetical protein FLJ35782 LOC392440 X similar to hypothetical protein MGC33889 LOC340571 Xp21.1 similar to hSIAH1 LOC392441 X similar to melanoma antigen LOC139604 Xp21.1 similar to hypothetical protein MGC33889 MGC34831 Xp21.1 hypothetical protein MGC34831 FLJ36601 Xp21.1 hypothetical protein FLJ36601 LOC158730 Xp21.1 hypothetical LOC158730 PRRG1 Xp21.1 proline-rich Gla (G-carboxyglutamic acid) polypeptide 1 LOC389844 X similar to ferritin, heavy polypeptide-like 17 LOC139249 Xp21.1 similar to hypothetical protein FLJ35782 FLJ42925 Xp21.1 FLJ42925 protein XK Xp21.1 Kell blood group precursor (McLeod phenotype) CYBB Xp21.1 cytochrome b-245, beta polypeptide (chronic granulomatous disease) TCTE1L Xp21.1 t-complex-associated-testis-expressed 1-like SC4MOP Xp21.1 sterol-C4-methyl oxidase pseudogene HYPM Xp21.1 sterol-C4-methyl oxidase pseudogene LOC340549 Xp21.1 similar to RIKEN cDNA 1700113O17 SYTL5 Xp21.1 synaptotagmin-like 5 SRPX Xp21.1 sushi-repeat-containing protein, X chromosome LOC286441 Xp21.1 hypothetical LOC286441 RPGR Xp21.1 retinitis pigmentosa GTPase regulator OTC Xp21.1 ornithine carbamoyltransferase LOC392442 X similar to BAG-family molecular chaperone regulator-1 (BCL-2 binding athanogene-1) (BAG-1) (Glucocorticoid receptor-associated protein RAP46) LOC392443 X similar to ferritin light chain LOC392444 X similar to Nucleolar transcription factor 1 (Upstream binding factor 1) (UBF-1) TM4SF2 Xp11.4-q11 transmembrane 4 superfamily member 2 LOC389845 X LOC389845 STRAIT11499 Xp11.4 hypothetical protein STRAIT11499 LOC389846 X hypothetical gene supported by BC043536 GAPDP1 Xp11.4-p11.23 glyceraldehyde-3-phosphate dehydrogenase pseudogene 1 LOC392445 X similar to 40S ribosomal protein S11 BCOR Xp11.4 BCL6 co-repressor
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - splicing - 12 115 lung, colon 2004 15194196
  • exon downstream from exon III, exon IIIa mapped 6.4 kb downstream of exon III, and 1.6 kb upstream from exon IV
  • playing possibly a role for NOX-2S in the regulation of NADPH oxidase activity
  • 13 - 4353 - 570 - 2005 16179592
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Digestivepharynx   highly
    Endocrineneuroendocrinepituitary  highly
    Lymphoid/Immunelymph node   highly
     spleen   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticplasma   
    Muscularstriatumcardiac   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticneutrophil
    Cardiovascularendothelial cell Homo sapiens
    Lymphoid/Immuneimmunocyte Homo sapiens
    Muscularmyocyte Homo sapiens
    Nervousglia Homo sapiens
    not specificchondrocyte Homo sapiens
    not specificfibroblast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text
  • in developing limb, highly expressed in prehypertrophic and hypertrophic chondrocytes
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • binding sites for NADPH, FAD as well as heme
  • six transmembrane domains
  • C-terminal NADPH and FAD domains
  • conjugated GlycoP , sumoylated
    HOMOLOGY
    interspecies ortholog to Cybb, Mus musculus
    ortholog to Cybb, Rattus norvegicus
    ortholog to cybb, Danio rerio
    Homologene
    FAMILY
  • FRE/CYBB family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nuclear envelope
    basic FUNCTION
  • oxygen dependent mechanism of phagocytosis
  • reduction of oxygen to O-2 at the expense of NADPH, the O2-generated is the precursor of potent oxidants used to kill the invading microorganisms
  • critical for the bactericidal activity of phagocytic cells and plays a major role in innate immunity (
  • its activity participates in the regulation of the phagosomal and endosomal pH in dendritic cells, and is required for efficient antigen cross-presentation (
  • with NOX4 mediate proliferative response in endothelial cells (
  • plays a fundamental role in host defense and innate immunity (
  • plays a fundamental role in conferring macrophages with the ability to respond to extracellular ATP stimulation with robust changes in cellular oxidation
  • plays an important role in the control of afferent arteriole tone and is involved in the contractile responses to ANGPT2 and/or adenosine
  • plays a key role in apoptosis and phagocytosis of hepatocytes inducing activation of hepatic stellate cells and initiation of fibrosis in liver
  • role in the activation of autophagy, a cellular degradative pathway
  • mediating proliferative response in endothelial cells
  • reactive oxygen species generated by NADPH oxidase 2 and 4 (CYBB and NOX4)are required for chondrogenic differentiation
  • implicated as a source of rapid stretch-dependent ROS production at the junctional sarcoplasmic reticulum of cardiomyocytes (X-ROS signaling)
  • plays a role in neuronal cell death during retinal ischemia
  • is a key mediator of insulin resistance in skeletal muscle
  • from both hematopoietic and endothelial cells CYBB is crucial for neutrophil-platelet interactions during TNF-induced venular inflammation
  • is critical for heterotypic neutrophil-platelet interactions during vascular inflammation
  • NOX1 and CYBB play differential roles in different platelet activation pathways and in thrombosis
  • is a critical component of the suppressive machinery of CD8 Tregs, suggesting that repairing CYBB deficiency in these cells may protect older individuals from tissue-destructive inflammatory disease, such as large-vessel vasculitis
  • distinct cell-specific roles for CYBB in blood pressure (BP) regulation
  • CYBB- signaling in macrophages participates in the pathogenesis of obesity, and reinforce a key role for macrophage inflammation in diet-induced metabolic and neurologic decline
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism energetic
    signaling
    superoxide metabolism
    a component
  • membrane bound, heavy component of the NADPH oxidase system cytochrome b- 245
  • component of an intracellular complex, CYBA, NCF1, NCF2, NCF4 in unstimulated endothelial cells
  • component of the phagocyte respiratory burst oxidase
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor, nucleotide,
  • Fa2+
  • FAD
  • protein
  • p22(phox), p47(phox), p67(phox), and p40(phox) (
  • IQGAP1 (
  • Small ubiquitin-like modifier 1, SUMO1 (
  • SLAMF1 recruits a subset of PIK3C3-associated proteins, which is involved in membrane fusion and CYBB regulation
  • CYBB activation requires membrane translocation of the NCF1 subunit and is linked to heart failure
  • CYBB, modulated at least in part by NCF1, mediates early stage compensatory collateral development via a process dependent upon peroxide generation
  • NCF1 is the key regulatory component of the phagocytic NADPH oxidase 2 (CYBB) complex
  • intermittent hypoxia causes reductions and remodeling of atrial GJA5, GJA1, generated in response to reactive oxygen species by CYBB, and likely contributing to the substrate for atrial fibrillation that develops in response to obstructive sleep apnea
  • cell & other
    REGULATION
    activated by HOXA9, in differentiated myeloid cells
    a pathway leading to CYBB activation in which PLA2G6-regulated MAPK14 activity is a key regulator of S100A8/A9 translocation via S100A9 phosphorylation
    repressed by HOXA10
    Other major ROS generator, sumoylated by SUMO1 at plasma membrane and sumoylation modulates NOX activity negatively
    sumoylated by Small ubiquitin-like modifier 1, SUMO1 (
    ASSOCIATED DISORDERS
    corresponding disease(s) CGD1 , IMD34
    related resource X-linked granulomatous disease
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    NOX1 and CYBB deficiency impairs macrophage differentiation and the occurrence of M2-type tumor-associated macrophages (TAMs) during tumor development
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorialvisual 
    therapies targeting Nox2 may have potential for suppressing corneal neovascularization and inflammation in humans
    diabetemetabolic syndrom 
    CYBB inhibition is a potential therapy for heart disease caused by diabetes or obesity
    ANIMAL & CELL MODELS
  • insulin resistance induced by a high fat diet was mitigated in Nox2-null mice compared with wild-type mice after 3 or 9 months on the diet