CYBB

Protein identityUniProt · HPA

UniProt accession

P04839

Gene

CYBB

Ensembl

ENSG00000165168

Chromosome

X

Canonical length

570 aa

Protein class

Disease related genes, Human disease related genes, Potential drug targets, Predicted membrane proteins, Transporters

OverviewNCBI Gene

Cytochrome b (-245) is composed of cytochrome b alpha (CYBA) and beta (CYBB) chain. It has been proposed as a primary component of the microbicidal oxidase system of phagocytes. CYBB deficiency is one of five described biochemical defects associated with chronic granulomatous disease (CGD). In this disorder, there is decreased activity of phagocyte NADPH oxidase; neutrophils are able to phagocytize bacteria but cannot kill them in the phagocytic vacuoles. The cause of the killing defect is an inability to increase the cell's respiration and consequent failure to deliver activated oxygen into the phagocytic vacuole. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

570 residues, UniProt reviewed canonical sequence.

>P04839|CYBB
     1  MGNWAVNEGL SIFVILVWLG LNVFLFVWYY RVYDIPPKFF YTRKLLGSAL ALARAPAACL
    61  NFNCMLILLP VCRNLLSFLR GSSACCSTRV RRQLDRNLTF HKMVAWMIAL HSAIHTIAHL
   121  FNVEWCVNAR VNNSDPYSVA LSELGDRQNE SYLNFARKRI KNPEGGLYLA VTLLAGITGV
   181  VITLCLILII TSSTKTIRRS YFEVFWYTHH LFVIFFIGLA IHGAERIVRG QTAESLAVHN
   241  ITVCEQKISE WGKIKECPIP QFAGNPPMTW KWIVGPMFLY LCERLVRFWR SQQKVVITKV
   301  VTHPFKTIEL QMKKKGFKME VGQYIFVKCP KVSKLEWHPF TLTSAPEEDF FSIHIRIVGD
   361  WTEGLFNACG CDKQEFQDAW KLPKIAVDGP FGTASEDVFS YEVVMLVGAG IGVTPFASIL
   421  KSVWYKYCNN ATNLKLKKIY FYWLCRDTHA FEWFADLLQL LESQMQERNN AGFLSYNIYL
   481  TGWDESQANH FAVHHDEEKD VITGLKQKTL YGRPNWDNEF KTIASQHPNT RIGVFLCGPE
   541  ALAETLSKQS ISNSESGPRG VHFIFNKENF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CYBB 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)

0.26

Highest tissue expression

150 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CYBB.

Disease | AllUniProt

Conditions CYBB is implicated in, by any mechanism.

• Granulomatous disease, chronic, X-linked (CGDX) MIM:306400
• Immunodeficiency 34 (IMD34) MIM:300645

Disease | GeneticClinVar

209 pathogenic / likely-pathogenic of 906 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Granulomatous disease, chronic, X-linked
• Chronic granulomatous disease
• Granulomatous disease, chronic, X-linked, variant
• X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency
• Thyroid cancer, nonmedullary, 1

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)

0.19

gnomAD pLI

1

gnomAD missense Z

2.19

DepMap mean gene effect

0.12

DepMap dependency class

none

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

• cellular response to cadmium ion
• cellular response to ethanol
• cellular response to L-glutamine
• defense response
• hydrogen peroxide biosynthetic process
• hypoxia-inducible factor-1alpha signaling pathway
• inflammatory response
• innate immune response
• monoatomic ion transmembrane transport
• positive regulation of angiogenesis
• positive regulation of tumor necrosis factor production
• respiratory burst
• response to aldosterone
• response to angiotensin
• response to nutrient
• response to xenobiotic stimulus
• superoxide anion generation
• superoxide metabolic process

Molecular functions

• FAD binding
• flavin adenine dinucleotide binding
• heme binding
• metal ion binding
• NAD(P)H oxidase H2O2-forming activity
• NADPH binding
• protein heterodimerization activity
• superoxide-generating NAD(P)H oxidase activity
• superoxide-generating NADPH oxidase activity

Cellular components

• dendrite
• endoplasmic reticulum membrane
• monoatomic ion channel complex
• NADPH oxidase complex
• neuronal cell body
• nuclear envelope
• perinuclear endoplasmic reticulum
• phagocytic vesicle membrane
• plasma membrane
• specific granule membrane
• tertiary granule 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 membrane
• Chronic granulomatous disease
• Electron transport
• FAD
• Flavoprotein
• Glycoprotein
• Heme
• Ion channel
• Ion transport
• Iron
• Isopeptide bond
• Membrane
• Metal-binding
• NADP
• Oxidoreductase
• Phosphoprotein
• Transmembrane
• Transmembrane helix
• Transport
• Ubl conjugation
• Voltage-gated channel

InteractionsUniProt · HPA

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

• CYBC1
• GBP7
• NCF1
• NCF2
• NRROS
• RAC1
• RAC2
• RUBCN
• S100A8
• S100A9