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Q3TDX8 (NB5R4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Cyb5r4
Synonyms:Ncb5or
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length528 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

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). Ref.6

Catalytic activity

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

Cofactor

FAD By similarity.

Subcellular location

Endoplasmic reticulum. Note: Soluble protein By similarity.

Tissue specificity

Ubiquitously expressed. Isoform 2 is expressed in testis, brain, skeletal muscle and in the male germline. Ref.5 Ref.7

Disruption phenotype

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. Ref.6

Sequence similarities

Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.

Contains 1 CS domain.

Contains 1 cytochrome b5 heme-binding domain.

Contains 1 FAD-binding FR-type domain.

Sequence caution

The sequence AAH25438.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAC41118.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAE34044.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAE42908.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandFAD
Flavoprotein
Heme
Iron
Metal-binding
NAD
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNADP metabolic process

Inferred from electronic annotation. Source: Ensembl

cell development

Inferred from mutant phenotype Ref.6. Source: MGI

generation of precursor metabolites and energy

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from mutant phenotype Ref.6. Source: MGI

heme metabolic process

Inferred from sequence alignment Ref.4. Source: MGI

insulin secretion

Inferred from mutant phenotype Ref.6. Source: MGI

response to antibiotic

Inferred from mutant phenotype PubMed 17343567. Source: MGI

superoxide metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from sequence alignment Ref.4. Source: MGI

endoplasmic reticulum

Inferred from direct assay PubMed 15131110. Source: MGI

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionNAD(P)H oxidase activity

Inferred from electronic annotation. Source: Ensembl

NADPH-hemoprotein reductase activity

Inferred from electronic annotation. Source: Ensembl

cytochrome-b5 reductase activity, acting on NAD(P)H

Inferred from direct assay PubMed 15131110. Source: MGI

flavin adenine dinucleotide binding

Inferred from electronic annotation. Source: Ensembl

heme binding

Inferred from sequence alignment Ref.4. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q3TDX8-4)

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.
Isoform 2 (identifier: Q3TDX8-5)

Also known as: cb5/cb5rDelta12;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 528528Cytochrome b5 reductase 4
PRO_0000410469

Regions

Domain54 – 13077Cytochrome b5 heme-binding
Domain172 – 26392CS
Domain280 – 392113FAD-binding FR-type
Nucleotide binding372 – 38716FAD By similarity
Nucleotide binding399 – 43133FAD By similarity

Sites

Metal binding891Iron (heme axial ligand) By similarity
Metal binding1121Iron (heme axial ligand) By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity

Natural variations

Alternative sequence326 – 37651Missing in isoform 2.
VSP_041453
Natural variant1561S → SDTLPRDVT.

Experimental info

Sequence conflict1711D → G in BAE34044. Ref.1
Sequence conflict1711D → G in BAE41470. Ref.1
Sequence conflict1711D → G in BAE42908. Ref.1
Sequence conflict1711D → G in AAK08116. Ref.4
Sequence conflict1711D → G in AAQ83900. Ref.5
Sequence conflict1711D → G in AAQ83901. Ref.5
Sequence conflict2161V → I in AAH25438. Ref.3
Sequence conflict3001F → L in BAE34044. Ref.1
Sequence conflict3001F → L in BAE41470. Ref.1
Sequence conflict3001F → L in BAE42908. Ref.1
Sequence conflict3001F → L in AAH02170. Ref.3
Sequence conflict3001F → L in AAK08116. Ref.4
Sequence conflict3001F → L in AAQ83900. Ref.5
Sequence conflict3001F → L in AAQ83901. Ref.5
Sequence conflict3361V → L in BAE34044. Ref.1
Sequence conflict3391S → P in BAE41470. Ref.1
Sequence conflict3561C → Y in BAE34044. Ref.1
Sequence conflict3561C → Y in BAE41470. Ref.1
Sequence conflict3561C → Y in BAE42908. Ref.1
Sequence conflict3561C → Y in AAH02170. Ref.3
Sequence conflict3561C → Y in AAH25438. Ref.3
Sequence conflict3561C → Y in AAK08116. Ref.4
Sequence conflict3561C → Y in AAQ83900. Ref.5
Sequence conflict3881D → N in BAE34044. Ref.1
Sequence conflict3881D → N in BAE41470. Ref.1
Sequence conflict3881D → N in BAE42908. Ref.1
Sequence conflict3881D → N in AAH02170. Ref.3
Sequence conflict3881D → N in AAH25438. Ref.3
Sequence conflict3881D → N in AAK08116. Ref.4
Sequence conflict3881D → N in AAQ83900. Ref.5
Sequence conflict3881D → N in AAQ83901. Ref.5
Sequence conflict3931K → T in AAH25438. Ref.3
Sequence conflict4381E → D in BAC37357. Ref.1
Sequence conflict5041P → Q in BAE39522. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 28, 2011. Version 3.
Checksum: 8CF34CE865980A66

FASTA52859,716
        10         20         30         40         50         60 
MLNVPSQAFP APGSQQRVSS QGRSKVPLKQ GRSLMDWIRL TKSGKDLTGL KGGLIEVTEE 

        70         80         90        100        110        120 
ELKKHNKKED CWICIRGFVY NVSPYMEYHP GGEDELMRAA GADGTDLFNE VHRWVNYESM 

       130        140        150        160        170        180 
LKECLVGRMA VKPAVPKDCH EGKRVLNGML PKSQMSDTLP RDVTDTLPRE DLSSPSYDWF 

       190        200        210        220        230        240 
QTESSVTIVV YTKQKNISLD SVIVDLQDDS LRAEAVIKDH SYLVHVGLSH EVQENFSVRV 

       250        260        270        280        290        300 
IENVGKIEIV LQKKESVSWQ CLGDHLEKHD SFIPKKDTGL YYRRCQLISK EDVTHDTRLF 

       310        320        330        340        350        360 
CLMLPPSTHL QVPVGQHVYL KLSVTGAEIV KPYTPVSDSL LSDFKEPVLS PNKYICFLIK 

       370        380        390        400        410        420 
IYPAGLFTPE LDRLQIGDFI SVSGPEGDFK VSKLQEVEDL FLLAAGTGFT PMVTVLNYAL 

       430        440        450        460        470        480 
SHMSSLRKVK LMFFNKTEDD IIWRCQLEKL ALREKRFDVE FVLSAPSPEW NGKQGHISRA 

       490        500        510        520 
LLSEFLQRSS ENSRAFLCIC GPTPFTDEGI RLLHDLNFSD DEIHGFTA 

« Hide

Isoform 2 (cb5/cb5rDelta12) [UniParc].

Checksum: 4F809037109F6B5D
Show »

FASTA47753,994

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS.
Strain: C57BL/6J and NOD.
Tissue: Eye, Liver, Spinal cord and Spleen.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS.
Strain: Czech II and FVB/N.
Tissue: Mammary tumor.
[4]"Identification of a cytochrome b-type NAD(P)H oxidoreductase ubiquitously expressed in human cells."
Zhu H., Qiu H., Yoon H.-W., Huang S., Bunn H.F.
Proc. Natl. Acad. Sci. U.S.A. 96:14742-14747(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-528 (ISOFORM 1), VARIANT ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS.
[5]"Identification and characterization of a novel splice variant of mouse and rat cytochrome b5/cytochrome b5 reductase."
Curry B.J., Roman S.D., Wallace C.A., Scott R., Miriami E., Aitken R.J.
Genomics 83:425-438(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-528 (ISOFORMS 1 AND 2), VARIANT ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS, TISSUE SPECIFICITY.
Strain: Swiss.
Tissue: Testis.
[6]"Absence of a reductase, NCB5OR, causes insulin-deficient diabetes."
Xie J., Zhu H., Larade K., Ladoux A., Seguritan A., Chu M., Ito S., Bronson R.T., Leiter E.H., Zhang C.-Y., Rosen E.D., Bunn H.F.
Proc. Natl. Acad. Sci. U.S.A. 101:10750-10755(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]"Promoter characterization and transcriptional regulation of Ncb5or, a novel reductase necessary for pancreatic beta-cell maintenance."
Larade K., Bunn H.F.
Biochim. Biophys. Acta 1759:257-262(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_077157.2. NM_024195.2.
XP_006511262.1. XM_006511199.1.
UniGeneMm.30166.

3D structure databases

ProteinModelPortalQ3TDX8.
SMRQ3TDX8. Positions 51-137, 174-263, 282-502.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ3TDX8. 1 interaction.

PTM databases

PhosphoSiteQ3TDX8.

Proteomic databases

PRIDEQ3TDX8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000168529; ENSMUSP00000126119; ENSMUSG00000032872. [Q3TDX8-4]
ENSMUST00000173126; ENSMUSP00000134460; ENSMUSG00000032872. [Q3TDX8-5]
GeneID266690.
KEGGmmu:266690.
UCSCuc009qyc.2. mouse. [Q3TDX8-4]
uc009qyf.2. mouse. [Q3TDX8-5]

Organism-specific databases

CTD51167.
MGIMGI:2386848. Cyb5r4.

Phylogenomic databases

eggNOGCOG0543.
GeneTreeENSGT00390000008881.
HOVERGENHBG108174.
InParanoidQ3TDX8.
OMADSVIVDH.
OrthoDBEOG718KBZ.
TreeFamTF313874.

Gene expression databases

BgeeQ3TDX8.
CleanExMM_CYB5R4.
GenevestigatorQ3TDX8.

Family and domain databases

Gene3D2.60.40.790. 1 hit.
3.10.120.10. 1 hit.
InterProIPR007052. CS_dom.
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]
PfamPF04969. CS. 1 hit.
PF00173. Cyt-b5. 1 hit.
PF00970. FAD_binding_6. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSPR00406. CYTB5RDTASE.
PR00363. CYTOCHROMEB5.
SUPFAMSSF49764. SSF49764. 1 hit.
SSF55856. SSF55856. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEPS51203. CS. 1 hit.
PS00191. CYTOCHROME_B5_1. 1 hit.
PS50255. CYTOCHROME_B5_2. 1 hit.
PS51384. FAD_FR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCYB5R4. mouse.
NextBio392180.
PROQ3TDX8.
SOURCESearch...

Entry information

Entry nameNB5R4_MOUSE
AccessionPrimary (citable) accession number: Q3TDX8
Secondary accession number(s): E9Q129 expand/collapse secondary AC list , Q3TJH3, Q3U012, Q6VXY4, Q6VXY5, Q8BJV8, Q8BTI5, Q8R3H8, Q99LY4, Q99P29
Entry history
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: June 28, 2011
Last modified: April 16, 2014
This is version 87 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot