Human Gene CYB5R4 (ENST00000369681.10_4) from GENCODE V47lift37
  Description: RIPPLY2-CYB5R4 readthrough, transcript variant 4 (from RefSeq NR_174605.1)
Gencode Transcript: ENST00000369681.10_4
Gencode Gene: ENSG00000065615.14_7
Transcript (Including UTRs)
   Position: hg19 chr6:84,569,408-84,677,142 Size: 107,735 Total Exon Count: 16 Strand: +
Coding Region
   Position: hg19 chr6:84,569,502-84,669,597 Size: 100,096 Coding Exon Count: 16 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:84,569,408-84,677,142)mRNA (may differ from genome)Protein (521 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblExonPrimerGeneCardsHGNC
MalacardsMGIPubMedReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: NB5R4_HUMAN
DESCRIPTION: RecName: Full=Cytochrome b5 reductase 4; EC=1.6.2.2; AltName: Full=Flavohemoprotein b5/b5R; Short=b5+b5R; AltName: Full=N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein; AltName: Full=cb5/cb5R;
FUNCTION: NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway. Plays a critical role in protecting pancreatic beta-cells against oxidant stress, possibly by protecting the cell from excess buildup of reactive oxygen species (ROS). Reduces a variety of substrates in vitro, such as cytochrome c, feericyanide and methemoglobin.
CATALYTIC ACTIVITY: NADH + 2 ferricytochrome b5 = NAD(+) + H(+) + 2 ferrocytochrome b5.
COFACTOR: FAD.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=25 mM for O(2); Redox potential: E(0) is -108 mV;
SUBCELLULAR LOCATION: Endoplasmic reticulum. Note=Soluble protein.
TISSUE SPECIFICITY: Widely expressed.
POLYMORPHISM: Variants Arg-187 and Arg-223 do not influence the pathogenesis of non-autoimmune diabetes.
SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
SIMILARITY: Contains 1 CS domain.
SIMILARITY: Contains 1 cytochrome b5 heme-binding domain.
SIMILARITY: Contains 1 FAD-binding FR-type domain.
SEQUENCE CAUTION: Sequence=AAF04812.1; Type=Erroneous initiation; Sequence=CAI19905.1; Type=Erroneous gene model prediction; Sequence=CAI22326.1; Type=Erroneous gene model prediction;
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/cyb5r4/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: CYB5R4
Diseases sorted by gene-association score: maturity-onset diabetes of the young (2)

-  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: 6.72 RPKM in Whole Blood
Total median expression: 97.58 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 -49.2094-0.523 Picture PostScript Text
3' UTR -2089.007545-0.277 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
IPR007052 - CS-like_domain
IPR017447 - CS_domain
IPR001199 - Cyt_B5
IPR018506 - Cyt_B5_heme-BS
IPR017927 - Fd_Rdtase_FAD-bd
IPR008978 - HSP20-like_chaperone
IPR001834 - NADH-Cyt_B5_reductase
IPR008333 - OxRdtase_FAD-bd_dom
IPR001433 - OxRdtase_FAD/NAD-bd
IPR017938 - Riboflavin_synthase-like_b-brl

Pfam Domains:
PF00173 - Cytochrome b5-like Heme/Steroid binding domain
PF00175 - Oxidoreductase NAD-binding domain
PF00970 - Oxidoreductase FAD-binding domain
PF04969 - CS domain

SCOP Domains:
49764 - HSP20-like chaperones
63380 - Riboflavin synthase domain-like
52343 - Ferredoxin reductase-like, C-terminal NADP-linked domain
55856 - Cytochrome b5-like heme/steroid binding domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3LF5 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q7L1T6
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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 orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details Gene Details  
Gene SorterGene Sorter Gene Sorter  
 RGDEnsembl   
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004128 cytochrome-b5 reductase activity, acting on NAD(P)H
GO:0016174 NAD(P)H oxidase activity
GO:0016491 oxidoreductase activity
GO:0016653 oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor
GO:0020037 heme binding
GO:0046872 metal ion binding

Biological Process:
GO:0003032 detection of oxygen
GO:0006091 generation of precursor metabolites and energy
GO:0006801 superoxide metabolic process
GO:0015701 bicarbonate transport
GO:0030073 insulin secretion
GO:0042593 glucose homeostasis
GO:0046677 response to antibiotic
GO:0048468 cell development
GO:0055114 oxidation-reduction process

Cellular Component:
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  LP895546 - Sequence 410 from Patent EP3253886.
AK313146 - Homo sapiens cDNA, FLJ93638, Homo sapiens NADPH cytochrome B5 oxidoreductase (NCB5OR), mRNA.
BC025380 - Homo sapiens cytochrome b5 reductase 4, mRNA (cDNA clone MGC:26107 IMAGE:4829042), complete cds.
AL832113 - Homo sapiens mRNA; cDNA DKFZp686A20103 (from clone DKFZp686A20103).
AB527313 - Synthetic construct DNA, clone: pF1KE0012, Homo sapiens CYB5R4 gene for cytochrome b5 reductase 4, without stop codon, in Flexi system.
AM393033 - Synthetic construct Homo sapiens clone IMAGE:100002223 for hypothetical protein (CYB5R4 gene).
JD122309 - Sequence 103333 from Patent EP1572962.
JD125314 - Sequence 106338 from Patent EP1572962.
AF169803 - Homo sapiens flavohemoprotein b5+b5R mRNA, complete cds.
CU692982 - Synthetic construct Homo sapiens gateway clone IMAGE:100020704 5' read CYB5R4 mRNA.
KJ902565 - Synthetic construct Homo sapiens clone ccsbBroadEn_11959 CYB5R4 gene, encodes complete protein.
DQ895260 - Synthetic construct Homo sapiens clone IMAGE:100009720; FLH182840.01L; RZPDo839C11139D cytochrome b5 reductase 4 (CYB5R4) gene, encodes complete protein.
DQ892067 - Synthetic construct Homo sapiens clone IMAGE:100004697; FLH263499.01X; RZPDo839C11140D cytochrome b5 reductase 4 (CYB5R4) gene, encodes complete protein.
LF353926 - JP 2014500723-A/161429: Polycomb-Associated Non-Coding RNAs.
LF353925 - JP 2014500723-A/161428: Polycomb-Associated Non-Coding RNAs.
BC029339 - Homo sapiens cytochrome b5 reductase 4, mRNA (cDNA clone IMAGE:4705478).
LF353924 - JP 2014500723-A/161427: Polycomb-Associated Non-Coding RNAs.
LF206396 - JP 2014500723-A/13899: Polycomb-Associated Non-Coding RNAs.
LF353923 - JP 2014500723-A/161426: Polycomb-Associated Non-Coding RNAs.
JD251373 - Sequence 232397 from Patent EP1572962.
JD507043 - Sequence 488067 from Patent EP1572962.
JD304730 - Sequence 285754 from Patent EP1572962.
JD486167 - Sequence 467191 from Patent EP1572962.
JD047113 - Sequence 28137 from Patent EP1572962.
LF353922 - JP 2014500723-A/161425: Polycomb-Associated Non-Coding RNAs.
JD490755 - Sequence 471779 from Patent EP1572962.
JD503128 - Sequence 484152 from Patent EP1572962.
JD034879 - Sequence 15903 from Patent EP1572962.
MA589503 - JP 2018138019-A/161429: Polycomb-Associated Non-Coding RNAs.
MA589502 - JP 2018138019-A/161428: Polycomb-Associated Non-Coding RNAs.
MA589501 - JP 2018138019-A/161427: Polycomb-Associated Non-Coding RNAs.
MA441973 - JP 2018138019-A/13899: Polycomb-Associated Non-Coding RNAs.
MA589500 - JP 2018138019-A/161426: Polycomb-Associated Non-Coding RNAs.
MA589499 - JP 2018138019-A/161425: Polycomb-Associated Non-Coding RNAs.
AK124658 - Homo sapiens cDNA FLJ42667 fis, clone BRAMY2020058.
JD296941 - Sequence 277965 from Patent EP1572962.
JD397540 - Sequence 378564 from Patent EP1572962.
JD166827 - Sequence 147851 from Patent EP1572962.
JD396027 - Sequence 377051 from Patent EP1572962.
JD219182 - Sequence 200206 from Patent EP1572962.
JD076853 - Sequence 57877 from Patent EP1572962.
JD496434 - Sequence 477458 from Patent EP1572962.
JD455091 - Sequence 436115 from Patent EP1572962.
JD537352 - Sequence 518376 from Patent EP1572962.
JD194754 - Sequence 175778 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q7L1T6 (Reactome details) participates in the following event(s):

R-HSA-6806831 CYB5Rs reduce MetHb to HbA
R-HSA-1237044 Erythrocytes take up carbon dioxide and release oxygen
R-HSA-1480926 O2/CO2 exchange in erythrocytes
R-HSA-382551 Transport of small molecules

-  Other Names for This Gene
  Alternate Gene Symbols: B1AEM2, CYB5R4 , ENST00000369681.1, ENST00000369681.2, ENST00000369681.3, ENST00000369681.4, ENST00000369681.5, ENST00000369681.6, ENST00000369681.7, ENST00000369681.8, ENST00000369681.9, NB5R4_HUMAN, NCB5OR, NR_174605, Q5TGI9, Q7L1T6, Q9NUE4, Q9UHI9, uc318htj.1, uc318htj.2
UCSC ID: ENST00000369681.10_4
RefSeq Accession: NM_016230.4
Protein: Q7L1T6 (aka NB5R4_HUMAN)

-  Gene Model Information
  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.