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Protein

Cytochrome b5 reductase 4

Gene

Cyb5r4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionOxidoreductase
LigandFAD, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:2386848 Cyb5r4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

iPTMnetiQ3TDX8
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 Expressed in 35 organ(s), highest expression level in bone marrow macrophage
CleanExiMM_CYB5R4
ExpressionAtlasiQ3TDX8 baseline and differential
GenevisibleiQ3TDX8 MM

Interactioni

Protein-protein interaction databases

IntActiQ3TDX8, 1 interactor
MINTiQ3TDX8
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

Phylogenomic databases

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

Family and domain databases

CDDicd06490 p23_NCB5OR, 1 hit
Gene3Di2.60.40.790, 1 hit
3.10.120.10, 1 hit
3.40.50.80, 1 hit
InterProiView protein in InterPro
IPR008333 Cbr1-like_FAD-bd_dom
IPR007052 CS_dom
IPR001199 Cyt_B5-like_heme/steroid-bd
IPR036400 Cyt_B5-like_heme/steroid_sf
IPR018506 Cyt_B5_heme-BS
IPR017927 FAD-bd_FR_type
IPR039261 FNR_nucleotide-bd
IPR008978 HSP20-like_chaperone
IPR001834 NADH-Cyt_B5_reductase
IPR001433 OxRdtase_FAD/NAD-bd
IPR037908 p23_NCB5OR
IPR017938 Riboflavin_synthase-like_b-brl
PfamiView protein in Pfam
PF04969 CS, 1 hit
PF00173 Cyt-b5, 1 hit
PF00970 FAD_binding_6, 1 hit
PF00175 NAD_binding_1, 1 hit
PRINTSiPR00406 CYTB5RDTASE
PR00363 CYTOCHROMEB5
SMARTiView protein in SMART
SM01117 Cyt-b5, 1 hit
SUPFAMiSSF49764 SSF49764, 1 hit
SSF52343 SSF52343, 1 hit
SSF55856 SSF55856, 1 hit
SSF63380 SSF63380, 1 hit
PROSITEiView protein in PROSITE
PS51203 CS, 1 hit
PS00191 CYTOCHROME_B5_1, 1 hit
PS50255 CYTOCHROME_B5_2, 1 hit
PS51384 FAD_FR, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3UY26G3UY26_MOUSE
Cytochrome b5 reductase 4
Cyb5r4
89Annotation score:

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 → SDTLPRDVT4 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
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

Similar proteinsi

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
UniGeneiMm.30166
Mm.317460

3D structure databases

ProteinModelPortaliQ3TDX8
SMRiQ3TDX8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ3TDX8, 1 interactor
MINTiQ3TDX8
STRINGi10090.ENSMUSP00000126119

PTM databases

iPTMnetiQ3TDX8
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
OMAiRNKCALK
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
PROiPR:Q3TDX8
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032872 Expressed in 35 organ(s), highest expression level in bone marrow macrophage
CleanExiMM_CYB5R4
ExpressionAtlasiQ3TDX8 baseline and differential
GenevisibleiQ3TDX8 MM

Family and domain databases

CDDicd06490 p23_NCB5OR, 1 hit
Gene3Di2.60.40.790, 1 hit
3.10.120.10, 1 hit
3.40.50.80, 1 hit
InterProiView protein in InterPro
IPR008333 Cbr1-like_FAD-bd_dom
IPR007052 CS_dom
IPR001199 Cyt_B5-like_heme/steroid-bd
IPR036400 Cyt_B5-like_heme/steroid_sf
IPR018506 Cyt_B5_heme-BS
IPR017927 FAD-bd_FR_type
IPR039261 FNR_nucleotide-bd
IPR008978 HSP20-like_chaperone
IPR001834 NADH-Cyt_B5_reductase
IPR001433 OxRdtase_FAD/NAD-bd
IPR037908 p23_NCB5OR
IPR017938 Riboflavin_synthase-like_b-brl
PfamiView protein in Pfam
PF04969 CS, 1 hit
PF00173 Cyt-b5, 1 hit
PF00970 FAD_binding_6, 1 hit
PF00175 NAD_binding_1, 1 hit
PRINTSiPR00406 CYTB5RDTASE
PR00363 CYTOCHROMEB5
SMARTiView protein in SMART
SM01117 Cyt-b5, 1 hit
SUPFAMiSSF49764 SSF49764, 1 hit
SSF52343 SSF52343, 1 hit
SSF55856 SSF55856, 1 hit
SSF63380 SSF63380, 1 hit
PROSITEiView protein in PROSITE
PS51203 CS, 1 hit
PS00191 CYTOCHROME_B5_1, 1 hit
PS50255 CYTOCHROME_B5_2, 1 hit
PS51384 FAD_FR, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: June 28, 2011
Last modified: October 10, 2018
This is version 121 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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