Cyb5r4 cytochrome b5 reductase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Cyb5r4provided by MGI
Official Full Name: cytochrome b5 reductase 4provided by MGI
Primary source: MGI:MGI:2386848
See related: Ensembl:ENSMUSG00000032872 AllianceGenome:MGI:2386848
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: b5b5r; B5+B5R; Ncb5or; b5/b5r; Cb5cb5r; 2810034J18Rik
Summary: Enables cytochrome-b5 reductase activity, acting on NAD(P)H. Acts upstream of or within several processes, including glucose homeostasis; insulin secretion; and response to antibiotic. Located in endoplasmic reticulum. Is expressed in metanephros; nervous system; sensory organ; submandibular gland primordium; and thymus primordium. Used to study type 2 diabetes mellitus. Human ortholog(s) of this gene implicated in type 2 diabetes mellitus. Orthologous to human CYB5R4 (cytochrome b5 reductase 4). [provided by Alliance of Genome Resources, Apr 2025]
Expression: Ubiquitous expression in CNS E11.5 (RPKM 10.7), bladder adult (RPKM 10.6) and 28 other tissues See more
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Genomic context

Location:: 9 E3.1; 9 46.69 cM

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (86904082..86959827)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (87022008..87077774)

Chromosome 9 - NC_000075.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

the findings of this study suggest altered feeding response post starvation as a result of NCB5OR deficiency in the cerebellum.
Title: NCB5OR Deficiency in the Cerebellum and Midbrain Leads to Dehydration and Alterations in Thirst Response, Fasted Feeding Behavior, and Voluntary Exercise in Mice.
Our findings suggest an essential role for NCB5OR in maintaining both iron homeostasis and the proper functioning of various locomotor pathways in the mouse cerebellum and midbrain.
Title: Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice.
In livers of HRN mice Cyp1a1, cytochrome b5 and mEH can effectively activate BaP to DNA binding species, even in the presence of very low amounts of P450 oxidoreductase.
Title: Cytochrome b5 and epoxide hydrolase contribute to benzo[a]pyrene-DNA adduct formation catalyzed by cytochrome P450 1A1 under low NADPH:P450 oxidoreductase conditions.
FFA accumulation and catabolism and oxidative stress are major consequences of Ncb5or deficiency in liver.
Title: Ncb5or deficiency increases fatty acid catabolism and oxidative stress.
Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain.
Title: Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain.
Onset of hyperglycemia in the Chop(-/-);Ncb5or(-/-) mice was delayed two weeks beyond that observed in Chop(+/+);Ncb5or(-/-) mice.
Title: The flavoheme reductase Ncb5or protects cells against endoplasmic reticulum stress-induced lipotoxicity.
Ncb5or loss results in impaired fatty acid desaturation, lipoatrophy, and diabetes
Title: Loss of Ncb5or results in impaired fatty acid desaturation, lipoatrophy, and diabetes.
Data suggest that NCB5OR does not appear to be involved in ER stress, although it may be involved in maintaining or regulating the redox status in beta-cells.
Title: The reductase NCB5OR is responsive to the redox status in beta-cells and is not involved in the ER stress response.
The data presented here identify and characterize the previously unknown promoter of Ncb5or, a reductase critical for beta-cell survival.
Title: Promoter characterization and transcriptional regulation of Ncb5or, a novel reductase necessary for pancreatic beta-cell maintenance.
NCB5OR is a novel soluble NAD(P)H reductase localized in the endoplasmic reticulum
Title: NCB5OR is a novel soluble NAD(P)H reductase localized in the endoplasmic reticulum.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (4)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

g3 (e-PCR), detects polymorphism
- UniSTS:258307

px-15e7 (e-PCR)
- UniSTS:257310

px-30g2 (e-PCR)
- UniSTS:257568

px-64d8 (e-PCR)
- UniSTS:258095

px-16g2 (e-PCR)
- UniSTS:257336

RH126727 (e-PCR)
- UniSTS:209732

px-35d10 (e-PCR)
- UniSTS:257631

px-1e5 (e-PCR)
- UniSTS:257384

px-45f3 (e-PCR)
- UniSTS:258415

px-5f4 (e-PCR)
- UniSTS:258430

px-72g5 (e-PCR)
- UniSTS:258181

AU046641 (e-PCR)
- UniSTS:111260

px-24c2 (e-PCR)
- UniSTS:257448

px-24g4 (e-PCR)
- UniSTS:257458

NoName (e-PCR)
- UniSTS:236215

px-9h2 (e-PCR)
- UniSTS:258246

g2 (e-PCR), detects polymorphism
- UniSTS:257242

Readthrough Gm57850

Readthrough gene: Gm57850, Included gene: Ripply2

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables NAD(P)H oxidase H2O2-forming activity	IEA Inferred from Electronic Annotation more info
enables NAD(P)H oxidase H2O2-forming activity	ISO Inferred from Sequence Orthology more info
enables NADPH-hemoprotein reductase activity	ISO Inferred from Sequence Orthology more info
enables cytochrome-b5 reductase activity, acting on NAD(P)H	IBA Inferred from Biological aspect of Ancestor more info
enables cytochrome-b5 reductase activity, acting on NAD(P)H	IDA Inferred from Direct Assay more info	PubMed
enables cytochrome-b5 reductase activity, acting on NAD(P)H	ISO Inferred from Sequence Orthology more info	PubMed
enables flavin adenine dinucleotide binding	ISO Inferred from Sequence Orthology more info
enables heme binding	IBA Inferred from Biological aspect of Ancestor more info
enables heme binding	ISO Inferred from Sequence Orthology more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in NADP metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within glucose homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within heme metabolic process	ISO Inferred from Sequence Orthology more info	PubMed
acts_upstream_of_or_within insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in reactive oxygen species metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to antibiotic	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in superoxide metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in superoxide metabolic process	IEA Inferred from Electronic Annotation more info
involved_in superoxide metabolic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info	PubMed
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: cytochrome b5 reductase 4

Names: N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein; NADPH cytochrome B5 oxidoreductase; cb5/cb5R; cytochrome b-type NAD(P)H oxidoreductase; flavohemoprotein b5/b5R

NP_001346891.1

EC 1.6.2.2

NP_077157.2

EC 1.6.2.2

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.

mRNA and Protein(s)

NM_001359962.1 → NP_001346891.1 cytochrome b5 reductase 4 isoform 2

Status: VALIDATED

Source sequence(s)

AC156793, CO801035

Conserved Domains (3) summary

cd06183
Location:285 → 475

cyt_b5_reduct_like; Cytochrome b5 reductase catalyzes the reduction of 2 molecules of cytochrome b5 using NADH as an electron donor. Like ferredoxin reductases, these proteins have an N-terminal FAD binding subdomain and a C-terminal NADH binding subdomain, separated by a ...

cd06490
Location:177 → 263

p23_NCB5OR; p23_like domain found in NAD(P)H cytochrome b5 (NCB5) oxidoreductase (OR) and similar proteins. NCB5OR is widely expressed in human organs and tissues and is localized in the ER (endoplasmic reticulum). It appears to play a critical role in maintaining ...

pfam00173
Location:58 → 130

Cyt-b5; Cytochrome b5-like Heme/Steroid binding domain
NM_024195.2 → NP_077157.2 cytochrome b5 reductase 4 isoform 1

See identical proteins and their annotated locations for NP_077157.2

Status: VALIDATED

Source sequence(s)

AK090159, CO801035

Consensus CDS

CCDS40716.2

UniProtKB/Swiss-Prot

E9Q129, Q3TDX8, Q3TJH3, Q3U012, Q6VXY4, Q6VXY5, Q8BJV8, Q8BTI5, Q8R3H8, Q99LY4, Q99P29

Related

ENSMUSP00000126119.3, ENSMUST00000168529.9

Conserved Domains (3) summary

cd06183
Location:285 → 526

cyt_b5_reduct_like; Cytochrome b5 reductase catalyzes the reduction of 2 molecules of cytochrome b5 using NADH as an electron donor. Like ferredoxin reductases, these proteins have an N-terminal FAD binding subdomain and a C-terminal NADH binding subdomain, separated by a ...

cd06490
Location:177 → 263

p23_NCB5OR; p23_like domain found in NAD(P)H cytochrome b5 (NCB5) oxidoreductase (OR) and similar proteins. NCB5OR is widely expressed in human organs and tissues and is localized in the ER (endoplasmic reticulum). It appears to play a critical role in maintaining ...

pfam00173
Location:56 → 128

Cyt-b5; Cytochrome b5-like Heme/Steroid binding domain