CYBB cytochrome b-245, beta polypeptide [Homo sapiens (human)] - Gene

Summary

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Official Symbol: CYBBprovided by HGNC
Official Full Name: cytochrome b-245, beta polypeptideprovided by HGNC
Primary source: HGNC:2578
See related: Ensembl:ENSG00000165168; HPRD:02382; MIM:300481; Vega:OTTHUMG00000033175
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CGD; NOX2; AMCBX2; GP91-1; GP91PHOX; p91-PHOX; GP91-PHOX
Summary: 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]

Genomic context

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Location :: Xp21.1

Sequence :: Chromosome: X; NC_000023.10 (37639270..37672714)

See CYBB in Epigenomics, MapViewer

Chromosome X - NC_000023.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Nox2 regulates lipopolysaccharide-mediated IKK-beta phosphorylation and endothelial activation in human pulmonary microvascular endothelial cells.
Title: LPS-mediated endothelial activation in pulmonary endothelial cells: role of Nox2-dependent IKK-β phosphorylation.
a novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages
Title: NOX2β: A novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages.
findings identified HIF-1 and NOX2 as partners acting in concert to promote angiogenesis in response to U-II
Title: The HIF1 target gene NOX2 promotes angiogenesis through urotensin-II.
The data point to four strategic (87)HEES(90) amino acid residues of the S100A8 C-terminal sequence that are involved directly in the molecular interaction with cytochrome b(558) and then in the phagocyte NADPH oxidase activation.
Title: Molecular interface of S100A8 with cytochrome b558 and NADPH oxidase activation.
Study shows reduced atherosclerotic burden in carriers of NOX2 deficiency, suggesting that oxidative stress generated by this enzymatic pathway is implicated in human atherosclerosis.
Title: Reduced atherosclerotic burden in subjects with genetically determined low oxidative stress.
Eight novel mutations in CYBB and NCF2 genes were identified in patients with chronic granulomatous disease.
Title: Clinical, functional and genetic analysis of twenty-four patients with chronic granulomatous disease - identification of eight novel mutations in CYBB and NCF2 genes.
study reports two rare cases of male X-linked chronic granulomatous disease patients, one caused by a 5.7-kb duplication of a region containing CYBB exons 6 to 8 and the other caused by a deletion of this same region
Title: Rare duplication or deletion of exons 6, 7 and 8 in CYBB leading to X-linked chronic granulomatous disease in two patients from different families.
The study suggests that NOX2-generating oxidative stress may have a pathogenic role in the functional changes of the arterial wall occurring in hypercholesterolemia and obesity.
Title: Obesity and hypercholesterolemia are associated with NOX2 generated oxidative stress and arterial dysfunction.
Data suggest that NOX2 plays a role in pancreatic islets as negative modulator of insulin secretion, reducing cAMP/protein kinase A signaling secondary to generation of reactive oxygen species.
Title: NADPH oxidase NOX2 defines a new antagonistic role for reactive oxygen species and cAMP/PKA in the regulation of insulin secretion.
The data suggest that NOX2/Kv complexes are the predominant O2 sensor in H146 cells and, by inference, in native neuroepithelial bodies.
Title: NOX2 (gp91phox) is a predominant O2 sensor in a human airway chemoreceptor cell line: biochemical, molecular, and electrophysiological evidence.

Submit: New GeneRIF Correction See all (125)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Atypical mycobacteriosis, familial, X-linked 2

MIM: 300645

Genetic Testing Registry

Chronic granulomatous disease, X-linked

MIM: 306400

Genetic Testing Registry

Summary from GeneReviews: Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic oto-sino-pulmonary disease. More than 75% of full-term neonates with PCD have 'neonatal respiratory distress' requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 6%. Approximately 50% of males with PCD are infertile as a result of abnormal sperm motility.

Diagnosis Testing

The diagnosis of PCD requires the presence of the characteristic clinical phenotype and either (1) specific ciliary ultrastructural defects identified by transmission electron microscopy in biopsy samples of the respiratory epithelium or (2) mutation in one of seventeen genes known to be associated with PCD: DNAI1, DNAAF3, DNAH5, HYDIN, NME8, DNAH11, DNAI2, DNAAF2 (C14orf104), RSPH4A, RSPH9, DNAAF1 (LRRC50), CCDC39, CCDC40, DNAL1, CCDC103, HEATR2, and LRRC6. Biallelic mutations in: DNAI1 account for approximately 2%-9% of all PCD; DNAH5 account for approximately 15%-21% of all PCD. Molecular genetic testing of fifteen of the known genes is available on a clinical basis.

Genetic Counseling

PCD is inherited in an autosomal recessive manner. The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes (carriers) are asymptomatic. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.

References

PMID: 20301301

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Inhibition of NRF2 by siRNA results in increased NOX2, NFkappaB (p65/p50), TNF-alpha, and MMP-9 proteins in astrocytes exposed to HIV-1 gp120	PubMed
Tat, p14	tat	Knocking down Nox2 by siRNA decreases HIV-1 Tat-induced NF-KappaB activation as well as activation of MAP kinases including ERK, JNK, and p38	PubMed
	tat	Knocking down oxidase Nox2 blocks Tat-induced cytoskeletal rearrangement	PubMed
	tat	Knocking down Nox2 by siRNA blocks HIV-1 Tat-induced reactive oxygen species (ROS) production, increase of NADPH oxidase activity, and Rac1 activation	PubMed
	tat	HIV-1 Tat-induced up-regulation of VCAM-1/ICAM-1 is blocked by NADPH oxidase (NOX2) inhibitor	PubMed
	tat	HIV-1 Tat-induced glutamate release is mediated through p38 and p42/44 MAPK and through NADPH oxidase and the x(c)(-) cystine-glutamate antiporter (xCT)	PubMed
	tat	Nox2 is involved in HIV-1 Tat-induced NADPH oxidase p65 and IKK phosphorylation	PubMed
capsid	gag	HIV-1 Capsid (p24) inhibits interferon gamma induced increases in HLA-DR and cytochrome B heavy chain mRNA levels in the human monocyte-like cell line THP1	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P04839	P63261	ACTG1	HPRD	PubMed
P04839	P13498	CYBA	HPRD	PubMed
P04839	P46940	IQGAP1	HPRD	PubMed
P04839	P14598	NCF1	HPRD	PubMed
P04839	P19878	NCF2	HPRD	PubMed
P04839	Q15080	NCF4	HPRD	PubMed
P04839	P63000	RAC1	HPRD	PubMed
BioGRID:107916	BioGRID:106575	ACTB	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107916	BioGRID:114353	IQGAP1	BioGRID	PubMed	Affinity Capture-Western; Co-localization
BioGRID:107916	BioGRID:113188	SUMO1	BioGRID	PubMed	Affinity Capture-Western; Co-localization
BioGRID:107916	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Adaptive Immune System, organism-specific biosystem (from REACTOME)
Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
Antigen processing-Cross presentation, organism-specific biosystem (from REACTOME)
Antigen processing-Cross presentation, organism-specific biosystemMHC class I molecules generally present peptide antigens derived from proteins synthesized by the cell itself to CD8+ T cells. However, in some circumstances, antigens from extracellular environment ...
Class I MHC mediated antigen processing & presentation, organism-specific biosystem (from REACTOME)
Class I MHC mediated antigen processing & presentation, organism-specific biosystemMajor histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular b...
Cross-presentation of particulate exogenous antigens (phagosomes), organism-specific biosystem (from REACTOME)
Cross-presentation of particulate exogenous antigens (phagosomes), organism-specific biosystemDendritic cells (DCs) take up and process exogenous particulate or cell-associated antigens such as microbes or tumor cells for MHC-I cross-presentation. Particulate antigens have been reported to be...
Disease, organism-specific biosystem (from REACTOME)
Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
HIF-1 signaling pathway, organism-specific biosystem (from KEGG)
HIF-1 signaling pathway, organism-specific biosystemHypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a c...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Latent infection of Homo sapiens with Mycobacterium tuberculosis, organism-specific biosystem (from REACTOME)
Latent infection of Homo sapiens with Mycobacterium tuberculosis, organism-specific biosystemInfection by Mycobacterium tuberculosis (Mtb) is soon countered by the host's immune system, the organism is however almost never eradicated; ten per cent of infections will develop into "open tuberc...
Leukocyte transendothelial migration, organism-specific biosystem (from KEGG)
Leukocyte transendothelial migration, organism-specific biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
Leukocyte transendothelial migration, conserved biosystem (from KEGG)
Leukocyte transendothelial migration, conserved biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
Osteoclast differentiation, organism-specific biosystem (from KEGG)
Osteoclast differentiation, organism-specific biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
Osteoclast differentiation, conserved biosystem (from KEGG)
Osteoclast differentiation, conserved biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
Phagosomal maturation (early endosomal stage), organism-specific biosystem (from REACTOME)
Phagosomal maturation (early endosomal stage), organism-specific biosystemAlveolar macrophages normally develop their phagosome along the endolysosomal pathway. However, after having internalized Mtb, this development is arrested at an early stage and only includes acidifi...
Phagosome, organism-specific biosystem (from KEGG)
Phagosome, organism-specific biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
Phagosome, conserved biosystem (from KEGG)
Phagosome, conserved biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
RAC1 signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
RAC1 signaling pathway, organism-specific biosystem
RAC1 signaling pathway
Type II interferon signaling (IFNG), organism-specific biosystem (from WikiPathways)
Type II interferon signaling (IFNG), organism-specific biosystemAdapted from Raza et al. (2008). This pathway is initiated by IFNG binding to its receptor and a subsequent phosphorylation cascade involving a number of the JAK and STAT family of proteins. Several ...

General gene information

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Markers

DXS1394 (e-PCR)
- UniSTS:99338

RH35737 (e-PCR)
- UniSTS:68112

GDB:211078 (e-PCR)
- UniSTS:99358

G10525 (e-PCR)
- UniSTS:47405

SHGC-148585 (e-PCR)
- UniSTS:176479

AF020154 (e-PCR)
- UniSTS:42699

SHGC-132083 (e-PCR)
- UniSTS:185048

DXS7487 (e-PCR)
- UniSTS:34020

Genotypes

See CYBB SNP Geneview Report
See CYBB SNP Genotype Report
See CYBB SNP Variation Viewer Report

Homology

Homologs of the CYBB gene: The CYBB gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, M.oryzae, N.crassa, A.thaliana, and rice.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to electron carrier activity	IDA Inferred from Direct Assay more info	PubMed
flavin adenine dinucleotide binding	IMP Inferred from Mutant Phenotype more info	PubMed
heme binding	IMP Inferred from Mutant Phenotype more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
contributes_to superoxide-generating NADPH oxidase activity	IDA Inferred from Direct Assay more info	PubMed
superoxide-generating NADPH oxidase activity	TAS Traceable Author Statement more info	PubMed
voltage-gated ion channel activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
antigen processing and presentation of exogenous peptide antigen via MHC class I	TAS Traceable Author Statement more info
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	TAS Traceable Author Statement more info
antigen processing and presentation of peptide antigen via MHC class I	TAS Traceable Author Statement more info
electron transport chain	IEA Inferred from Electronic Annotation more info
hydrogen peroxide biosynthetic process	IEA Inferred from Electronic Annotation more info
inflammatory response	TAS Traceable Author Statement more info	PubMed
innate immune response	IMP Inferred from Mutant Phenotype more info	PubMed
innate immune response	TAS Traceable Author Statement more info	PubMed
interaction with host	TAS Traceable Author Statement more info
oxidation-reduction process	IDA Inferred from Direct Assay more info	PubMed
oxidation-reduction process	TAS Traceable Author Statement more info	PubMed
phagosome maturation	TAS Traceable Author Statement more info
respiratory burst	IMP Inferred from Mutant Phenotype more info	PubMed
respiratory burst	TAS Traceable Author Statement more info	PubMed
superoxide anion generation	IDA Inferred from Direct Assay more info	PubMed
superoxide anion generation	TAS Traceable Author Statement more info	PubMed
superoxide metabolic process	IDA Inferred from Direct Assay more info	PubMed
superoxide metabolic process	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
NADPH oxidase complex	IDA Inferred from Direct Assay more info	PubMed
NADPH oxidase complex	TAS Traceable Author Statement more info	PubMed
integral to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
mitochondrion	IEA Inferred from Electronic Annotation more info
phagocytic vesicle membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: cytochrome b-245 heavy chain

Names: cytochrome b-245 heavy chain; CGD91-phox; NADPH oxidase 2; p22 phagocyte B-cytochrome; cytochrome b558 subunit beta; cytochrome b(558) subunit beta; neutrophil cytochrome b 91 kDa polypeptide; heme-binding membrane glycoprotein gp91phox; superoxide-generating NADPH oxidase heavy chain subunit

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009065.1 RefSeqGene

Range

5001..38445

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_53

mRNA and Protein(s)

NM_000397.3 → NP_000388.2 cytochrome b-245 heavy chain

Status: REVIEWED

Source sequence(s)

BC032720, DA995835

Consensus CDS

CCDS14242.1

UniProtKB/Swiss-Prot

P04839

Related

ENSP00000367851, OTTHUMP00000031915, ENST00000378588, OTTHUMT00000080881

Conserved Domains (2) summary

cd06186
Location:297 – 570
Blast Score: 413

NOX_Duox_like_FAD_NADP; NADPH oxidase (NOX) catalyzes the generation of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. ROS were originally identified as bactericidal agents in phagocytes, but are now also implicated in cell signaling and metabolism. NOX ...

pfam01794
Location:63 – 220
Blast Score: 118

Ferric_reduct; Ferric reductase like transmembrane component

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 PATCHES

Genomic

NW_003871099.1 Reference GRCh37.p10 PATCHES

Range

491823..521496

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000023.10 Reference GRCh37.p10 Primary Assembly

Range

37639270..37672714

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000155.1 Alternate HuRef

Range

35383460..35418115

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018934.1 Alternate CHM1_1.0

Range

37555817..37589261

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB013904.1	BAA34183.1
genomic	ABBA01047084.1	None
genomic	ABBA01047085.1	None
genomic	ABBA01047086.1	None
genomic	ABBA01047087.1	None
genomic	ABBA01047088.1	None
genomic	ABBA01047089.1	None
genomic	AC233292.3 (156370..186866)	None
genomic	AF469769.1	AAL76082.1
genomic	AL627245.1 (24232..57626)	None
genomic	AMYH01022211.1 (72465..105909)	None
genomic	CH471141.2	EAW59453.1
genomic	DQ314869.1	ABC40728.1
genomic	X05895.1	CAA29327.1
mRNA	AK289753.1	BAF82442.1
mRNA	AK301476.1	BAG62993.1
mRNA	AK301491.1	BAG63002.1
mRNA	AK304033.1	BAG64947.1
mRNA	AK312929.1	None
mRNA	BC032720.1	AAH32720.1
mRNA	DA995835.1	None
mRNA	S67289.1	AAB29151.1
mRNA	X04011.1	CAA27635.1
other-genetic	DQ890878.2	ABM81804.1
other-genetic	DQ894032.2	ABM84958.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P04839.2	GenPept	UniProtKB/Swiss-Prot:P04839

Additional links

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Additional Links

Epigenomics
MIM 300481
CYBBbase: Mutation registry for X-linked chronic granulomatous disease (previously known as X-CDGbase) CYBBbase/
PharmGKB PA27076
Catalogue of Somatic Mutations in Cancer (COSMIC) CYBB
GeneTests for MIM: 300481
GeneTests for MIM: 306400
CYBB homepage - Mendelian genes CYBB
Resource of Asian Primary Immunodeficiency Diseases (RAPID) AGID_51
UCSC UCSC
Integrated X Chromosome Database (IXDB) Integrated X Chromosome Database (IXDB)
UniGene Hs.292356