Human Gene CYBA (uc002flb.4) Description and Page Index
  Description: Homo sapiens cytochrome b-245, alpha polypeptide (CYBA), mRNA.
RefSeq Summary (NM_000101): Cytochrome b is comprised of a light chain (alpha) and a heavy chain (beta). This gene encodes the light, alpha subunit which has been proposed as a primary component of the microbicidal oxidase system of phagocytes. Mutations in this gene are associated with autosomal recessive chronic granulomatous disease (CGD), that is characterized by the failure of activated phagocytes to generate superoxide, which is important for the microbicidal activity of these cells. [provided by RefSeq, Jul 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: CA311054.1, CA311071.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1968540, SAMEA1970526 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000261623.8/ ENSP00000261623.3 RefSeq Select criteria :: based on conservation, expression ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr16:88,709,697-88,717,492 Size: 7,796 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg19 chr16:88,709,761-88,717,421 Size: 7,661 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:88,709,697-88,717,492)mRNA (may differ from genome)Protein (195 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCEUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: CY24A_HUMAN
DESCRIPTION: RecName: Full=Cytochrome b-245 light chain; AltName: Full=Cytochrome b(558) alpha chain; AltName: Full=Cytochrome b558 subunit alpha; AltName: Full=Neutrophil cytochrome b 22 kDa polypeptide; AltName: Full=Superoxide-generating NADPH oxidase light chain subunit; AltName: Full=p22 phagocyte B-cytochrome; AltName: Full=p22-phox; Short=p22phox;
FUNCTION: Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide.
SUBUNIT: Composed of a heavy chain (beta) and a light chain (alpha). Interacts with SH3PXD2A (By similarity). Interacts with DUOX1, DUOX2 and TPO. Interacts with NOX3 and NOX4. Interacts with calprotectin (S100A8/9).
INTERACTION: P14598:NCF1; NbExp=6; IntAct=EBI-986058, EBI-395044;
SUBCELLULAR LOCATION: Cell membrane.
PTM: The heme prosthetic group could be coordinated with residues of the light chain, the heavy chain, or both, and it is possible that more than one heme is present per cytochrome b-245.
PTM: Phosphorylation at Thr-147 enhances NADPH oxidase activity by promoting p47phox binding (By similarity).
DISEASE: Defects in CYBA are a cause of chronic granulomatous disease autosomal recessive cytochrome-b-negative (ARCGD) [MIM:233690]. Chronic granulomatous disease is a genetically heterogeneous disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.
SIMILARITY: Belongs to the p22phox family.
WEB RESOURCE: Name=CYBAbase; Note=CYBA mutation db; URL="http://bioinf.uta.fi/CYBAbase/";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CYBA";
WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=C&genename=CYBB+%40+GP91-PHOX";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CYBA
CDC HuGE Published Literature: CYBA
Positive Disease Associations: atherosclerosis , atherosclerosis, coronary , cardiac death cardiovascular disease oxidative stress , cardiovascular , Cell Adhesion Molecules , cerebrovascular disease , cervical intraepithelial neoplasia grade 3 , cholesterol , coronary artery disease , coronary endothelial vasodilator function , coronary heart disease in younger individuals. , hypertension , hypertension NADPH oxidase activity , hypertension vascular aging , Insulin Resistance|Obesity , kidney failure, acute , NADPH Oxidase , oxidative stress , periodontitis , vascular NAD(P)H oxidase activity , vasodilation, flow-mediated
Related Studies:
  1. atherosclerosis
    Hayaishi-Okano, R. et al. 2003, Association of NAD(P)H Oxidase p22 phox Gene Variation With Advanced Carotid Atherosclerosis in Japanese Type 2 Diabetes, Diabetes care. 2003 Feb;26(2):458-63. [PubMed 12547880]
    These results show that the C242T mutation in the p22 phox gene is associated with progression of asymptomatic atherosclerosis in the subjects with type 2 diabetes and is also associated with insulin resistance in nondiabetic subjects.
  2. atherosclerosis, coronary
    He, M. et al. 2004, [Study on the relationship between the polymorphism of P22phox C242T, vitamin E and coronary heart disease], Wei sheng yan jiu. 2004 Jul;33(4):443-6. [PubMed 15461271]
    The polymorphism of P22phox C242T is associated with CHD in Chinese. Vitamin E is protective against CHD and there is effect on the progress of CHD in the interaction of the polymorphism of P22phox C242T and vitamin E.
  3. atherosclerosis, coronary
    Nasti, S. et al. 2006, C242T Polymorphism in CYBA gene (p22;{phox}) and risk of coronary artery disease in a population of Caucasian Italians, Dis Markers 2006 22(3) 167-73. [PubMed 16788250]
    these results support the increased risk of developing early CAD and of having rapid progression of coronary stenosis in subjects carrying the C242T nucleotide transition among the Italian population.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: CYBA
Diseases sorted by gene-association score: chronic granulomatous disease, autosomal, due to deficiency of cyba* (1300), chronic granulomatous disease* (467), phagocyte bactericidal dysfunction (9), diabetic polyneuropathy (7), atherosclerosis (6), tetralogy of fallot (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 187.27 RPKM in Whole Blood
Total median expression: 1115.53 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -36.8071-0.518 Picture PostScript Text
3' UTR -23.0964-0.361 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007732 - Cyt_b558_asu

Pfam Domains:
PF05038 - Cytochrome Cytochrome b558 alpha-subunit

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1WLP
- NMR MuPIT


ModBase Predicted Comparative 3D Structure on P13498
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0009055 electron carrier activity
GO:0016175 superoxide-generating NADPH oxidase activity
GO:0016491 oxidoreductase activity
GO:0017124 SH3 domain binding
GO:0020037 heme binding
GO:0046872 metal ion binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0001666 response to hypoxia
GO:0001938 positive regulation of endothelial cell proliferation
GO:0003106 negative regulation of glomerular filtration by angiotensin
GO:0006801 superoxide metabolic process
GO:0006954 inflammatory response
GO:0008217 regulation of blood pressure
GO:0014823 response to activity
GO:0014895 smooth muscle hypertrophy
GO:0017004 cytochrome complex assembly
GO:0022900 electron transport chain
GO:0030307 positive regulation of cell growth
GO:0031667 response to nutrient levels
GO:0032755 positive regulation of interleukin-6 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0032930 positive regulation of superoxide anion generation
GO:0033864 positive regulation of NAD(P)H oxidase activity
GO:0034137 positive regulation of toll-like receptor 2 signaling pathway
GO:0034599 cellular response to oxidative stress
GO:0042493 response to drug
GO:0042554 superoxide anion generation
GO:0043312 neutrophil degranulation
GO:0045087 innate immune response
GO:0045730 respiratory burst
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0050665 hydrogen peroxide biosynthetic process
GO:0050766 positive regulation of phagocytosis
GO:0051279 regulation of release of sequestered calcium ion into cytosol
GO:0055114 oxidation-reduction process
GO:0070257 positive regulation of mucus secretion
GO:0070555 response to interleukin-1
GO:0071230 cellular response to amino acid stimulus
GO:0071260 cellular response to mechanical stimulus
GO:0071310 cellular response to organic substance
GO:0071333 cellular response to glucose stimulus
GO:0071356 cellular response to tumor necrosis factor
GO:0071407 cellular response to organic cyclic compound
GO:0071480 cellular response to gamma radiation
GO:0072593 reactive oxygen species metabolic process
GO:1900426 positive regulation of defense response to bacterium
GO:1903428 positive regulation of reactive oxygen species biosynthetic process
GO:1904044 response to aldosterone
GO:1904385 cellular response to angiotensin
GO:1904845 cellular response to L-glutamine

Cellular Component:
GO:0001725 stress fiber
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005789 endoplasmic reticulum membrane
GO:0005794 Golgi apparatus
GO:0005886 plasma membrane
GO:0005925 focal adhesion
GO:0016020 membrane
GO:0016324 apical plasma membrane
GO:0030141 secretory granule
GO:0030425 dendrite
GO:0030670 phagocytic vesicle membrane
GO:0035579 specific granule membrane
GO:0043020 NADPH oxidase complex
GO:0043025 neuronal cell body
GO:0070821 tertiary granule membrane
GO:0097038 perinuclear endoplasmic reticulum


-  Descriptions from all associated GenBank mRNAs
  BC006465 - Homo sapiens cytochrome b-245, alpha polypeptide, mRNA (cDNA clone MGC:2279 IMAGE:3502788), complete cds.
M21186 - Human neutrophil cytochrome b light chain p22 phagocyte b-cytochrome mRNA, complete cds.
HH837079 - Sequence 6 from Patent EP2231168.
HI214720 - Sequence 6 from Patent EP2076526.
HV601522 - JP 2011500003-A/6: Novel siRNA Structures.
HV708913 - JP 2012506450-A/11: Methods for treating eye disorders.
HV856595 - JP 2010507387-A/6: Novel siRNAs and Methods of Use Thereof.
HW061133 - JP 2012529430-A/8: METHODS FOR TREATING CHRONIC KIDNEY DISEASE.
HW165082 - JP 2013102767-A/6: Novel siRNA's and Use Thereof.
HW675590 - JP 2014210789-A/6: Novel siRNA Structures.
HW835278 - JP 2015051004-A/6: Novel siRNA's and Use Thereof.
JA482091 - Sequence 74 from Patent WO2011072091.
JA538121 - Sequence 6 from Patent EP2371958.
JB251941 - Sequence 8 from Patent EP2440214.
JE980383 - Sequence 74 from Patent EP2862929.
LF384486 - JP 2014500723-A/191989: Polycomb-Associated Non-Coding RNAs.
LP764840 - Sequence 8 from Patent EP3276004.
MS836043 - Sequence 7 from Patent EP3112469.
AK097127 - Homo sapiens cDNA FLJ39808 fis, clone SPLEN2009081.
AK300049 - Homo sapiens cDNA FLJ57889 complete cds, highly similar to Cytochrome b-245 light chain.
BT006861 - Homo sapiens cytochrome b-245, alpha polypeptide mRNA, complete cds.
DQ893235 - Synthetic construct clone IMAGE:100005865; FLH195484.01X; RZPDo839C12152D cytochrome b-245, alpha polypeptide (CYBA) gene, encodes complete protein.
DQ896565 - Synthetic construct Homo sapiens clone IMAGE:100011025; FLH195480.01L; RZPDo839C12151D cytochrome b-245, alpha polypeptide (CYBA) gene, encodes complete protein.
AB590173 - Synthetic construct DNA, clone: pFN21AE1371, Homo sapiens CYBA gene for cytochrome b-245, alpha polypeptide, without stop codon, in Flexi system.
LF375074 - JP 2014500723-A/182577: Polycomb-Associated Non-Coding RNAs.
BC033739 - Homo sapiens cytochrome b-245, alpha polypeptide, mRNA (cDNA clone IMAGE:5179916), with apparent retained intron.
BC028224 - Homo sapiens cytochrome b-245, alpha polypeptide, mRNA (cDNA clone IMAGE:5217162), with apparent retained intron.
BC048338 - Homo sapiens mRNA similar to cytochrome b-245, alpha polypeptide (cDNA clone IMAGE:5212219).
AK309030 - Homo sapiens cDNA, FLJ99071.
BC011565 - Homo sapiens cytochrome b-245, alpha polypeptide, mRNA (cDNA clone IMAGE:4563468), with apparent retained intron.
AK125578 - Homo sapiens cDNA FLJ43590 fis, clone SMINT2001818.
KJ901368 - Synthetic construct Homo sapiens clone ccsbBroadEn_10762 CYBA gene, encodes complete protein.
LF375076 - JP 2014500723-A/182579: Polycomb-Associated Non-Coding RNAs.
MA421964 - JP 2018519830-A/7: UTRs increasing the translation efficiency of RNA molecules.
MA620063 - JP 2018138019-A/191989: Polycomb-Associated Non-Coding RNAs.
MA610651 - JP 2018138019-A/182577: Polycomb-Associated Non-Coding RNAs.
MA610653 - JP 2018138019-A/182579: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04670 - Leukocyte transendothelial migration
hsa05140 - Leishmaniasis

Reactome (by CSHL, EBI, and GO)

Protein P13498 (Reactome details) participates in the following event(s):

R-HSA-5668714 RAC1:GTP binds NOX1 complex
R-HSA-5668735 RAC1:GTP binds NOX3 complex
R-HSA-6799350 Exocytosis of specific granule membrane proteins
R-HSA-6798747 Exocytosis of tertiary granule membrane proteins
R-HSA-5668605 RAC2:GTP binds NOX2 complex
R-HSA-5218827 NADPH oxidase 2 (NOX2) complex binds RAC1
R-HSA-1222376 NOX2 generates superoxide from oxygen
R-HSA-1236967 Alkalization of the phagosomal lumen by NOX2
R-HSA-5668718 NOX1 complex:RAC1:GTP generates superoxide from oxygen
R-HSA-5668731 NOX3 complex:RAC1:GTP generates superoxide from oxygen
R-HSA-6807557 NOX4, NOX5 reduce O2 to O2.-
R-HSA-5668629 Production of phagocyte oxygen radicals by NOX2 complex bound to RAC2:GTP
R-HSA-5218841 NADPH oxidase 2 generates superoxide from oxygen
R-HSA-5668599 RHO GTPases Activate NADPH Oxidases
R-HSA-6798695 Neutrophil degranulation
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-195258 RHO GTPase Effectors
R-HSA-168249 Innate Immune System
R-HSA-1222556 ROS, RNS production in phagocytes
R-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-1236973 Cross-presentation of particulate exogenous antigens (phagosomes)
R-HSA-194138 Signaling by VEGF
R-HSA-194315 Signaling by Rho GTPases
R-HSA-168256 Immune System
R-HSA-2262752 Cellular responses to stress
R-HSA-1236975 Antigen processing-Cross presentation
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-162582 Signal Transduction
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-1280218 Adaptive Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: CY24A_HUMAN, NM_000101, NP_000092, P13498, Q14090, Q9BR72, uc002flb.3
UCSC ID: uc002flb.4
RefSeq Accession: NM_000101
Protein: P13498 (aka CY24A_HUMAN or C24A_HUMAN)
CCDS: CCDS32504.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene CYBA:
cgd (Chronic Granulomatous Disease)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000101.3
exon count: 6CDS single in 3' UTR: no RNA size: 778
ORF size: 588CDS single in intron: no Alignment % ID: 99.86
txCdsPredict score: 1184.00frame shift in genome: no % Coverage: 92.93
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.