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Protein

Cytochrome b5 reductase 4

Gene

Cyb5r4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).1 Publication

Catalytic activityi

NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5.

Cofactori

FADBy similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi89Iron (heme axial ligand)PROSITE-ProRule annotation1
Metal bindingi112Iron (heme axial ligand)PROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi372 – 387FADBy similarityAdd BLAST16
Nucleotide bindingi399 – 431FADBy similarityAdd BLAST33

GO - Molecular functioni

GO - Biological processi

  • cell development Source: MGI
  • generation of precursor metabolites and energy Source: MGI
  • glucose homeostasis Source: MGI
  • heme metabolic process Source: MGI
  • insulin secretion Source: MGI
  • oxidation-reduction process Source: MGI
  • response to antibiotic Source: MGI
  • superoxide metabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

FAD, Flavoprotein, Heme, Iron, Metal-binding, NAD

Enzyme and pathway databases

BRENDAi1.6.2.2. 3474.
ReactomeiR-MMU-1237044. Erythrocytes take up carbon dioxide and release oxygen.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome b5 reductase 4 (EC:1.6.2.2)
Alternative name(s):
Flavohemoprotein b5/b5R
Short name:
b5+b5R
N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein
cb5/cb5R
Gene namesi
Name:Cyb5r4
Synonyms:Ncb5or
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:2386848. Cyb5r4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • endoplasmic reticulum Source: MGI
  • perinuclear region of cytoplasm Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Disruption phenotypei

Mice display insulin-deficient diabetes. Embryos and fetus develop normally. At 4 weeks of age, mice show have normal blood glucose levels but impaired glucose tolerance. Isolated islets have markedly impaired glucose- or arginine-stimulated insulin secretion. By 7 weeks of age, they develop severe hyperglycemia with markedly decreased serum insulin levels and nearly normal insulin tolerance. As the animals age, there is a progressive loss of beta cells in pancreatic islets, but there is no loss of alpha, delta, or PP cells. 4 week-old mice have enhanced sensitivity to the diabetogenic agent streptozotocin.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004104691 – 528Cytochrome b5 reductase 4Add BLAST528

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ3TDX8.
MaxQBiQ3TDX8.
PaxDbiQ3TDX8.
PeptideAtlasiQ3TDX8.
PRIDEiQ3TDX8.

PTM databases

PhosphoSitePlusiQ3TDX8.

Expressioni

Tissue specificityi

Ubiquitously expressed. Isoform 2 is expressed in testis, brain, skeletal muscle and in the male germline.2 Publications

Gene expression databases

BgeeiENSMUSG00000032872.
CleanExiMM_CYB5R4.
ExpressionAtlasiQ3TDX8. baseline and differential.
GenevisibleiQ3TDX8. MM.

Interactioni

Protein-protein interaction databases

IntActiQ3TDX8. 1 interactor.
STRINGi10090.ENSMUSP00000126119.

Structurei

3D structure databases

ProteinModelPortaliQ3TDX8.
SMRiQ3TDX8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 130Cytochrome b5 heme-bindingPROSITE-ProRule annotationAdd BLAST77
Domaini172 – 263CSPROSITE-ProRule annotationAdd BLAST92
Domaini280 – 392FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST113

Sequence similaritiesi

Contains 1 CS domain.PROSITE-ProRule annotation
Contains 1 cytochrome b5 heme-binding domain.PROSITE-ProRule annotation
Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0534. Eukaryota.
KOG0536. Eukaryota.
COG0543. LUCA.
COG5274. LUCA.
GeneTreeiENSGT00390000008881.
HOVERGENiHBG108174.
InParanoidiQ3TDX8.
KOiK00326.
OMAiKDYHEEK.
OrthoDBiEOG091G05LX.
TreeFamiTF313874.

Family and domain databases

Gene3Di2.60.40.790. 1 hit.
3.10.120.10. 1 hit.
InterProiIPR007052. CS_dom.
IPR033566. CYB5R4.
IPR001199. Cyt_B5-like_heme/steroid-bd.
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.
[Graphical view]
PANTHERiPTHR19370:SF122. PTHR19370:SF122. 2 hits.
PfamiPF04969. CS. 1 hit.
PF00173. Cyt-b5. 1 hit.
PF00970. FAD_binding_6. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSiPR00406. CYTB5RDTASE.
PR00363. CYTOCHROMEB5.
SMARTiSM01117. Cyt-b5. 1 hit.
[Graphical view]
SUPFAMiSSF49764. SSF49764. 1 hit.
SSF55856. SSF55856. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEiPS51203. CS. 1 hit.
PS00191. CYTOCHROME_B5_1. 1 hit.
PS50255. CYTOCHROME_B5_2. 1 hit.
PS51384. FAD_FR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q3TDX8-4) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLNVPSQAFP APGSQQRVSS QGRSKVPLKQ GRSLMDWIRL TKSGKDLTGL
60 70 80 90 100
KGGLIEVTEE ELKKHNKKED CWICIRGFVY NVSPYMEYHP GGEDELMRAA
110 120 130 140 150
GADGTDLFNE VHRWVNYESM LKECLVGRMA VKPAVPKDCH EGKRVLNGML
160 170 180 190 200
PKSQMSDTLP RDVTDTLPRE DLSSPSYDWF QTESSVTIVV YTKQKNISLD
210 220 230 240 250
SVIVDLQDDS LRAEAVIKDH SYLVHVGLSH EVQENFSVRV IENVGKIEIV
260 270 280 290 300
LQKKESVSWQ CLGDHLEKHD SFIPKKDTGL YYRRCQLISK EDVTHDTRLF
310 320 330 340 350
CLMLPPSTHL QVPVGQHVYL KLSVTGAEIV KPYTPVSDSL LSDFKEPVLS
360 370 380 390 400
PNKYICFLIK IYPAGLFTPE LDRLQIGDFI SVSGPEGDFK VSKLQEVEDL
410 420 430 440 450
FLLAAGTGFT PMVTVLNYAL SHMSSLRKVK LMFFNKTEDD IIWRCQLEKL
460 470 480 490 500
ALREKRFDVE FVLSAPSPEW NGKQGHISRA LLSEFLQRSS ENSRAFLCIC
510 520
GPTPFTDEGI RLLHDLNFSD DEIHGFTA
Length:528
Mass (Da):59,716
Last modified:June 28, 2011 - v3
Checksum:i8CF34CE865980A66
GO
Isoform 2 (identifier: Q3TDX8-5) [UniParc]FASTAAdd to basket
Also known as: cb5/cb5rDelta12

The sequence of this isoform differs from the canonical sequence as follows:
     326-376: Missing.

Show »
Length:477
Mass (Da):53,994
Checksum:i4F809037109F6B5D
GO

Sequence cautioni

The sequence AAH25438 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC41118 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAE34044 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAE42908 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti171D → G in BAE34044 (PubMed:16141072).Curated1
Sequence conflicti171D → G in BAE41470 (PubMed:16141072).Curated1
Sequence conflicti171D → G in BAE42908 (PubMed:16141072).Curated1
Sequence conflicti171D → G in AAK08116 (PubMed:10611283).Curated1
Sequence conflicti171D → G in AAQ83900 (PubMed:14962668).Curated1
Sequence conflicti171D → G in AAQ83901 (PubMed:14962668).Curated1
Sequence conflicti216V → I in AAH25438 (PubMed:15489334).Curated1
Sequence conflicti300F → L in BAE34044 (PubMed:16141072).Curated1
Sequence conflicti300F → L in BAE41470 (PubMed:16141072).Curated1
Sequence conflicti300F → L in BAE42908 (PubMed:16141072).Curated1
Sequence conflicti300F → L in AAH02170 (PubMed:15489334).Curated1
Sequence conflicti300F → L in AAK08116 (PubMed:10611283).Curated1
Sequence conflicti300F → L in AAQ83900 (PubMed:14962668).Curated1
Sequence conflicti300F → L in AAQ83901 (PubMed:14962668).Curated1
Sequence conflicti336V → L in BAE34044 (PubMed:16141072).Curated1
Sequence conflicti339S → P in BAE41470 (PubMed:16141072).Curated1
Sequence conflicti356C → Y in BAE34044 (PubMed:16141072).Curated1
Sequence conflicti356C → Y in BAE41470 (PubMed:16141072).Curated1
Sequence conflicti356C → Y in BAE42908 (PubMed:16141072).Curated1
Sequence conflicti356C → Y in AAH02170 (PubMed:15489334).Curated1
Sequence conflicti356C → Y in AAH25438 (PubMed:15489334).Curated1
Sequence conflicti356C → Y in AAK08116 (PubMed:10611283).Curated1
Sequence conflicti356C → Y in AAQ83900 (PubMed:14962668).Curated1
Sequence conflicti388D → N in BAE34044 (PubMed:16141072).Curated1
Sequence conflicti388D → N in BAE41470 (PubMed:16141072).Curated1
Sequence conflicti388D → N in BAE42908 (PubMed:16141072).Curated1
Sequence conflicti388D → N in AAH02170 (PubMed:15489334).Curated1
Sequence conflicti388D → N in AAH25438 (PubMed:15489334).Curated1
Sequence conflicti388D → N in AAK08116 (PubMed:10611283).Curated1
Sequence conflicti388D → N in AAQ83900 (PubMed:14962668).Curated1
Sequence conflicti388D → N in AAQ83901 (PubMed:14962668).Curated1
Sequence conflicti393K → T in AAH25438 (PubMed:15489334).Curated1
Sequence conflicti438E → D in BAC37357 (PubMed:16141072).Curated1
Sequence conflicti504P → Q in BAE39522 (PubMed:16141072).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti156S → SDTLPRDVT.4 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041453326 – 376Missing in isoform 2. 1 PublicationAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK078682 mRNA. Translation: BAC37357.1.
AK090159 mRNA. Translation: BAC41118.1. Different initiation.
AK157312 mRNA. Translation: BAE34044.1. Different initiation.
AK167436 mRNA. Translation: BAE39522.1.
AK169937 mRNA. Translation: BAE41470.1.
AK172252 mRNA. Translation: BAE42908.1. Different initiation.
AC156793 Genomic DNA. No translation available.
BC025438 mRNA. Translation: AAH25438.1. Different initiation.
BC002170 mRNA. Translation: AAH02170.1.
AF338818 mRNA. Translation: AAK08116.1.
AY321368 mRNA. Translation: AAQ83900.1.
AY321369 mRNA. Translation: AAQ83901.1.
CCDSiCCDS40716.2. [Q3TDX8-4]
RefSeqiNP_077157.2. NM_024195.2. [Q3TDX8-4]
XP_006511262.1. XM_006511199.1. [Q3TDX8-5]
UniGeneiMm.30166.
Mm.317460.

Genome annotation databases

EnsembliENSMUST00000168529; ENSMUSP00000126119; ENSMUSG00000032872. [Q3TDX8-4]
GeneIDi266690.
KEGGimmu:266690.
UCSCiuc009qyc.2. mouse. [Q3TDX8-4]
uc009qyf.2. mouse. [Q3TDX8-5]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK078682 mRNA. Translation: BAC37357.1.
AK090159 mRNA. Translation: BAC41118.1. Different initiation.
AK157312 mRNA. Translation: BAE34044.1. Different initiation.
AK167436 mRNA. Translation: BAE39522.1.
AK169937 mRNA. Translation: BAE41470.1.
AK172252 mRNA. Translation: BAE42908.1. Different initiation.
AC156793 Genomic DNA. No translation available.
BC025438 mRNA. Translation: AAH25438.1. Different initiation.
BC002170 mRNA. Translation: AAH02170.1.
AF338818 mRNA. Translation: AAK08116.1.
AY321368 mRNA. Translation: AAQ83900.1.
AY321369 mRNA. Translation: AAQ83901.1.
CCDSiCCDS40716.2. [Q3TDX8-4]
RefSeqiNP_077157.2. NM_024195.2. [Q3TDX8-4]
XP_006511262.1. XM_006511199.1. [Q3TDX8-5]
UniGeneiMm.30166.
Mm.317460.

3D structure databases

ProteinModelPortaliQ3TDX8.
SMRiQ3TDX8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ3TDX8. 1 interactor.
STRINGi10090.ENSMUSP00000126119.

PTM databases

PhosphoSitePlusiQ3TDX8.

Proteomic databases

EPDiQ3TDX8.
MaxQBiQ3TDX8.
PaxDbiQ3TDX8.
PeptideAtlasiQ3TDX8.
PRIDEiQ3TDX8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000168529; ENSMUSP00000126119; ENSMUSG00000032872. [Q3TDX8-4]
GeneIDi266690.
KEGGimmu:266690.
UCSCiuc009qyc.2. mouse. [Q3TDX8-4]
uc009qyf.2. mouse. [Q3TDX8-5]

Organism-specific databases

CTDi51167.
MGIiMGI:2386848. Cyb5r4.

Phylogenomic databases

eggNOGiKOG0534. Eukaryota.
KOG0536. Eukaryota.
COG0543. LUCA.
COG5274. LUCA.
GeneTreeiENSGT00390000008881.
HOVERGENiHBG108174.
InParanoidiQ3TDX8.
KOiK00326.
OMAiKDYHEEK.
OrthoDBiEOG091G05LX.
TreeFamiTF313874.

Enzyme and pathway databases

BRENDAi1.6.2.2. 3474.
ReactomeiR-MMU-1237044. Erythrocytes take up carbon dioxide and release oxygen.

Miscellaneous databases

ChiTaRSiCyb5r4. mouse.
PROiQ3TDX8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032872.
CleanExiMM_CYB5R4.
ExpressionAtlasiQ3TDX8. baseline and differential.
GenevisibleiQ3TDX8. MM.

Family and domain databases

Gene3Di2.60.40.790. 1 hit.
3.10.120.10. 1 hit.
InterProiIPR007052. CS_dom.
IPR033566. CYB5R4.
IPR001199. Cyt_B5-like_heme/steroid-bd.
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.
[Graphical view]
PANTHERiPTHR19370:SF122. PTHR19370:SF122. 2 hits.
PfamiPF04969. CS. 1 hit.
PF00173. Cyt-b5. 1 hit.
PF00970. FAD_binding_6. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSiPR00406. CYTB5RDTASE.
PR00363. CYTOCHROMEB5.
SMARTiSM01117. Cyt-b5. 1 hit.
[Graphical view]
SUPFAMiSSF49764. SSF49764. 1 hit.
SSF55856. SSF55856. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEiPS51203. CS. 1 hit.
PS00191. CYTOCHROME_B5_1. 1 hit.
PS50255. CYTOCHROME_B5_2. 1 hit.
PS51384. FAD_FR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNB5R4_MOUSE
AccessioniPrimary (citable) accession number: Q3TDX8
Secondary accession number(s): E9Q129
, Q3TJH3, Q3U012, Q6VXY4, Q6VXY5, Q8BJV8, Q8BTI5, Q8R3H8, Q99LY4, Q99P29
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: June 28, 2011
Last modified: November 2, 2016
This is version 110 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.