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

Summary

Official Symbol: CYBBprovided by HGNC
Official Full Name: cytochrome b-245 beta chainprovided by HGNC
Primary source: HGNC:HGNC:2578
See related: Ensembl:ENSG00000165168 MIM:300481; AllianceGenome:HGNC:2578
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; CGDX; NOX2; IMD34; 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]
Expression: Broad expression in appendix (RPKM 106.7), bone marrow (RPKM 63.5) and 15 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xp21.1-p11.4

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (37780059..37813461)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (37183630..37217034)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (37639312..37672714)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.
Title: The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.
Structural basis for EROS binding to human phagocyte NADPH oxidase NOX2.
Title: Structural basis for EROS binding to human phagocyte NADPH oxidase NOX2.
CYBB-Mediated Ferroptosis Associated with Immunosuppression in Mycobacterium leprae-Infected Monocyte-Derived Macrophages.
Title: CYBB-Mediated Ferroptosis Associated with Immunosuppression in Mycobacterium leprae-Infected Monocyte-Derived Macrophages.
Nox2 inhibition reduces trophoblast ferroptosis in preeclampsia via the STAT3/GPX4 pathway.
Title: Nox2 inhibition reduces trophoblast ferroptosis in preeclampsia via the STAT3/GPX4 pathway.
Structure of human phagocyte NADPH oxidase in the activated state.
Title: Structure of human phagocyte NADPH oxidase in the activated state.
Association Between Serum Levels of Nicotinamide-Adenine Dinucleotide Phosphate Oxidase 2 and the Development of Atrial Fibrillation After Isolated Coronary Artery Bypass Grafting: A Prospective Pilot Study.
Title: Association Between Serum Levels of Nicotinamide-Adenine Dinucleotide Phosphate Oxidase 2 and the Development of Atrial Fibrillation After Isolated Coronary Artery Bypass Grafting: A Prospective Pilot Study.
Activated SIRT1 contributes to DPT-induced glioma cell parthanatos by upregulation of NOX2 and NAT10.
Title: Activated SIRT1 contributes to DPT-induced glioma cell parthanatos by upregulation of NOX2 and NAT10.
Ang II Promotes ET-1 Production by Regulating NOX2 Activity Through Transcription Factor Oct-1.
Title: Ang II Promotes ET-1 Production by Regulating NOX2 Activity Through Transcription Factor Oct-1.
Novel mutations in CYBB Gene Cause X-linked chronic Granulomatous Disease in Pakistani patients.
Title: Novel mutations in CYBB Gene Cause X-linked chronic Granulomatous Disease in Pakistani patients.
The Expression and Role of NADPH Oxidase 2 in Colon Cancer.
Title: The Expression and Role of NADPH Oxidase 2 in Colon Cancer.

Submit: New GeneRIF Correction See all GeneRIFs (298)

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

Associated conditions

Description	Tests
Granulomatous disease, chronic, X-linked MedGen: C1844376 OMIM: 306400 GeneReviews: Chronic Granulomatous Disease	not available
X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency MedGen: C1970859 OMIM: 300645 GeneReviews: Not available	not available

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-05-27) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-05-27) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of cytochrome b-245, beta polypeptide (CYBB) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Knockdown of NOX2 and NOX4 by siRNA abrogates HIV-1 gp120-induced reactive oxygen species (ROS), suggesting that NOX2 and NOX4 are involved in ROS production through CYP2E1 in astrocytes	PubMed
	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
Nef	nef	NADPH oxidase is required for HIV-1 Nef-induced ROS production and endothelial apoptosis in human coronary arterial endothelial cells	PubMed
Tat	tat	HIV-1 Tat C downregulates the expression of miR-17 to increase the expression of NOX2 and NOX4; overexpression of miR-17 inhibits NOX2 and NOX4 expression in human microglial cells	PubMed
	tat	HIV-1 Tat C upregulates NOX2 and NOX4 expression and increases ROS production in human brain cells	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 downregulates the expression of cytochrome b-245, beta polypeptide (CYBB; NOX2) in human primary T cells	PubMed
	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	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 Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to electron transfer activity	IDA Inferred from Direct Assay more info	PubMed
enables flavin adenine dinucleotide binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables heme binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
contributes_to superoxide-generating NAD(P)H oxidase activity	IDA Inferred from Direct Assay more info	PubMed
enables superoxide-generating NAD(P)H oxidase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular response to L-glutamine	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cadmium ion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in defense response	IBA Inferred from Biological aspect of Ancestor more info
involved_in hydrogen peroxide biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in hypoxia-inducible factor-1alpha signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in innate immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in innate immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in innate immune response	TAS Traceable Author Statement more info	PubMed
involved_in monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of tumor necrosis factor production	IEA Inferred from Electronic Annotation more info
involved_in respiratory burst	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in respiratory burst	NAS Non-traceable Author Statement more info	PubMed
involved_in respiratory burst	TAS Traceable Author Statement more info	PubMed
involved_in response to aldosterone	IEA Inferred from Electronic Annotation more info
involved_in response to angiotensin	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in superoxide anion generation	IBA Inferred from Biological aspect of Ancestor more info
involved_in superoxide anion generation	IDA Inferred from Direct Assay more info	PubMed
involved_in superoxide anion generation	TAS Traceable Author Statement more info	PubMed
involved_in superoxide metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in superoxide metabolic process	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of NADPH oxidase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of NADPH oxidase complex	IDA Inferred from Direct Assay more info	PubMed
part_of NADPH oxidase complex	NAS Non-traceable Author Statement more info	PubMed
part_of NADPH oxidase complex	TAS Traceable Author Statement more info	PubMed
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in nuclear envelope	IEA Inferred from Electronic Annotation more info
located_in perinuclear endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in phagocytic vesicle membrane	TAS Traceable Author Statement more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in specific granule membrane	TAS Traceable Author Statement more info
located_in tertiary granule membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: cytochrome b-245 heavy chain

Names: CGD91-phox; NADPH oxidase 2; cytochrome b(558) subunit beta; cytochrome b-245 beta polypeptide; cytochrome b558 subunit beta; heme-binding membrane glycoprotein gp91phox; neutrophil cytochrome b 91 kDa polypeptide; p22 phagocyte B-cytochrome; 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_000397.4 → NP_000388.2 cytochrome b-245 heavy chain

See identical proteins and their annotated locations for NP_000388.2

Status: REVIEWED

Source sequence(s)

BC032720

Consensus CDS

CCDS14242.1

UniProtKB/Swiss-Prot

A8K138, P04839, Q2PP16

UniProtKB/TrEMBL

A0A0S2Z3S6, A0A8Q3SIJ1

Related

ENSP00000367851.4, ENST00000378588.5

Conserved Domains (3) summary

cd06186
Location:297 → 570

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 ...

PLN02844
Location:165 → 423

PLN02844; oxidoreductase/ferric-chelate reductase

pfam01794
Location:66 → 219

Ferric_reduct; Ferric reductase like transmembrane component