ID NB5R4_MOUSE Reviewed; 528 AA.
AC Q3TDX8; E9Q129; Q3TJH3; Q3U012; Q6VXY4; Q6VXY5; Q8BJV8; Q8BTI5;
AC Q8R3H8; Q99LY4; Q99P29;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 3.
DT 01-MAY-2013, entry version 78.
DE RecName: Full=Cytochrome b5 reductase 4;
DE EC=1.6.2.2;
DE AltName: Full=Flavohemoprotein b5/b5R;
DE Short=b5+b5R;
DE AltName: Full=N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein;
DE AltName: Full=cb5/cb5R;
GN Name=Cyb5r4; Synonyms=Ncb5or;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS.
RC STRAIN=C57BL/6J, and NOD; TISSUE=Eye, Liver, Spinal cord, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
RA She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
RA Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
RA Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
RA Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
RA Lindblad-Toh K., Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of
RT the mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS.
RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-528 (ISOFORM 1), AND VARIANT
RP ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS.
RX PubMed=10611283; DOI=10.1073/pnas.96.26.14742;
RA Zhu H., Qiu H., Yoon H.-W., Huang S., Bunn H.F.;
RT "Identification of a cytochrome b-type NAD(P)H oxidoreductase
RT ubiquitously expressed in human cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:14742-14747(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-528 (ISOFORMS 1 AND 2), VARIANT
RP ASP-THR-LEU-PRO-ARG-ASP-VAL-THR-156 INS, AND TISSUE SPECIFICITY.
RC STRAIN=Swiss; TISSUE=Testis;
RX PubMed=14962668; DOI=10.1016/j.ygeno.2003.08.020;
RA Curry B.J., Roman S.D., Wallace C.A., Scott R., Miriami E.,
RA Aitken R.J.;
RT "Identification and characterization of a novel splice variant of
RT mouse and rat cytochrome b5/cytochrome b5 reductase.";
RL Genomics 83:425-438(2004).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15247412; DOI=10.1073/pnas.0404044101;
RA Xie J., Zhu H., Larade K., Ladoux A., Seguritan A., Chu M., Ito S.,
RA Bronson R.T., Leiter E.H., Zhang C.-Y., Rosen E.D., Bunn H.F.;
RT "Absence of a reductase, NCB5OR, causes insulin-deficient diabetes.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10750-10755(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=16814408; DOI=10.1016/j.bbaexp.2006.05.002;
RA Larade K., Bunn H.F.;
RT "Promoter characterization and transcriptional regulation of Ncb5or, a
RT novel reductase necessary for pancreatic beta-cell maintenance.";
RL Biochim. Biophys. Acta 1759:257-262(2006).
CC -!- FUNCTION: NADH-cytochrome b5 reductase involved in endoplasmic
CC reticulum stress response pathway. Plays a critical role in
CC protecting pancreatic beta-cells against oxidant stress, possibly
CC by protecting the cell from excess buildup of reactive oxygen
CC species (ROS).
CC -!- CATALYTIC ACTIVITY: NADH + 2 ferricytochrome b5 = NAD(+) + H(+) +
CC 2 ferrocytochrome b5.
CC -!- COFACTOR: FAD (By similarity).
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum. Note=Soluble protein
CC (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3TDX8-4; Sequence=Displayed;
CC Name=2; Synonyms=cb5/cb5rDelta12;
CC IsoId=Q3TDX8-5; Sequence=VSP_041453;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 2 is expressed
CC in testis, brain, skeletal muscle and in the male germline.
CC -!- DISRUPTION PHENOTYPE: Mice display insulin-deficient diabetes.
CC Embryos and fetus develop normally. At 4 weeks of age, mice show
CC have normal blood glucose levels but impaired glucose tolerance.
CC Isolated islets have markedly impaired glucose- or arginine-
CC stimulated insulin secretion. By 7 weeks of age, they develop
CC severe hyperglycemia with markedly decreased serum insulin levels
CC and nearly normal insulin tolerance. As the animals age, there is
CC a progressive loss of beta cells in pancreatic islets, but there
CC is no loss of alpha, delta, or PP cells. 4 week-old mice have
CC enhanced sensitivity to the diabetogenic agent streptozotocin.
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide
CC cytochrome reductase family.
CC -!- SIMILARITY: Contains 1 CS domain.
CC -!- SIMILARITY: Contains 1 cytochrome b5 heme-binding domain.
CC -!- SIMILARITY: Contains 1 FAD-binding FR-type domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH25438.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAC41118.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAE34044.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAE42908.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AK078682; BAC37357.1; -; mRNA.
DR EMBL; AK090159; BAC41118.1; ALT_INIT; mRNA.
DR EMBL; AK157312; BAE34044.1; ALT_INIT; mRNA.
DR EMBL; AK167436; BAE39522.1; -; mRNA.
DR EMBL; AK169937; BAE41470.1; -; mRNA.
DR EMBL; AK172252; BAE42908.1; ALT_INIT; mRNA.
DR EMBL; AC156793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025438; AAH25438.1; ALT_INIT; mRNA.
DR EMBL; BC002170; AAH02170.1; -; mRNA.
DR EMBL; AF338818; AAK08116.1; -; mRNA.
DR EMBL; AY321368; AAQ83900.1; -; mRNA.
DR EMBL; AY321369; AAQ83901.1; -; mRNA.
DR IPI; IPI00988590; -.
DR IPI; IPI01026790; -.
DR RefSeq; NP_077157.2; NM_024195.2.
DR UniGene; Mm.30166; -.
DR UniGene; Mm.394780; -.
DR HSSP; P00171; 1SH4.
DR ProteinModelPortal; Q3TDX8; -.
DR SMR; Q3TDX8; 51-137, 282-502.
DR PhosphoSite; Q3TDX8; -.
DR PRIDE; Q3TDX8; -.
DR Ensembl; ENSMUST00000168529; ENSMUSP00000126119; ENSMUSG00000032872.
DR Ensembl; ENSMUST00000173126; ENSMUSP00000134460; ENSMUSG00000032872.
DR GeneID; 266690; -.
DR KEGG; mmu:266690; -.
DR UCSC; uc009qyc.2; mouse.
DR UCSC; uc009qyf.2; mouse.
DR CTD; 51167; -.
DR MGI; MGI:2386848; Cyb5r4.
DR eggNOG; COG0543; -.
DR GeneTree; ENSGT00390000008881; -.
DR HOVERGEN; HBG108174; -.
DR InParanoid; Q3TDX8; -.
DR OMA; DSVIVDH; -.
DR OrthoDB; EOG49CQ7B; -.
DR ChiTaRS; CYB5R4; mouse.
DR NextBio; 392180; -.
DR ArrayExpress; Q3TDX8; -.
DR Bgee; Q3TDX8; -.
DR CleanEx; MM_CYB5R4; -.
DR Genevestigator; Q3TDX8; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; IDA:MGI.
DR GO; GO:0020037; F:heme binding; ISA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016174; F:NAD(P)H oxidase activity; IEA:Compara.
DR GO; GO:0048468; P:cell development; IMP:MGI.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; IEA:Compara.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0042168; P:heme metabolic process; ISA:MGI.
DR GO; GO:0030073; P:insulin secretion; IMP:MGI.
DR GO; GO:0046677; P:response to antibiotic; IMP:MGI.
DR GO; GO:0006801; P:superoxide metabolic process; IEA:Compara.
DR Gene3D; 3.10.120.10; -; 1.
DR InterPro; IPR007052; CS-like_domain.
DR InterPro; IPR017447; CS_domain.
DR InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR InterPro; IPR018506; Cyt_B5_heme-BS.
DR InterPro; IPR017927; Fd_Rdtase_FAD-bd.
DR InterPro; IPR008978; HSP20-like_chaperone.
DR InterPro; IPR001834; NADH-Cyt_B5_reductase.
DR InterPro; IPR008333; OxRdtase_FAD-bd_dom.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR Pfam; PF04969; CS; 1.
DR Pfam; PF00173; Cyt-b5; 1.
DR Pfam; PF00970; FAD_binding_6; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR PRINTS; PR00406; CYTB5RDTASE.
DR PRINTS; PR00363; CYTOCHROMEB5.
DR SUPFAM; SSF55856; Cyt_B5; 1.
DR SUPFAM; SSF49764; HSP20_chap; 1.
DR SUPFAM; SSF63380; Riboflavin_synthase_like_b-brl; 1.
DR PROSITE; PS51203; CS; 1.
DR PROSITE; PS00191; CYTOCHROME_B5_1; 1.
DR PROSITE; PS50255; CYTOCHROME_B5_2; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Complete proteome; Endoplasmic reticulum; FAD;
KW Flavoprotein; Heme; Iron; Metal-binding; NAD; Oxidoreductase;
KW Polymorphism; Reference proteome.
FT CHAIN 1 528 Cytochrome b5 reductase 4.
FT /FTId=PRO_0000410469.
FT DOMAIN 54 130 Cytochrome b5 heme-binding.
FT DOMAIN 172 263 CS.
FT DOMAIN 280 392 FAD-binding FR-type.
FT NP_BIND 372 387 FAD (By similarity).
FT NP_BIND 399 431 FAD (By similarity).
FT METAL 89 89 Iron (heme axial ligand) (By similarity).
FT METAL 112 112 Iron (heme axial ligand) (By similarity).
FT VAR_SEQ 326 376 Missing (in isoform 2).
FT /FTId=VSP_041453.
FT VARIANT 156 156 S -> SDTLPRDVT.
FT CONFLICT 171 171 D -> G (in Ref. 1; BAE34044/BAE41470/
FT BAE42908, 4; AAK08116 and 5; AAQ83900/
FT AAQ83901).
FT CONFLICT 216 216 V -> I (in Ref. 3; AAH25438).
FT CONFLICT 300 300 F -> L (in Ref. 1; BAE34044/BAE41470/
FT BAE42908, 3; AAH02170, 4; AAK08116 and 5;
FT AAQ83900/AAQ83901).
FT CONFLICT 336 336 V -> L (in Ref. 1; BAE34044).
FT CONFLICT 339 339 S -> P (in Ref. 1; BAE41470).
FT CONFLICT 356 356 C -> Y (in Ref. 1; BAE34044/BAE41470/
FT BAE42908, 3; AAH02170/AAH25438, 4;
FT AAK08116 and 5; AAQ83900).
FT CONFLICT 388 388 D -> N (in Ref. 1; BAE34044/BAE41470/
FT BAE42908, 3; AAH02170/AAH25438, 4;
FT AAK08116 and 5; AAQ83900/AAQ83901).
FT CONFLICT 393 393 K -> T (in Ref. 3; AAH25438).
FT CONFLICT 438 438 E -> D (in Ref. 1; BAC37357).
FT CONFLICT 504 504 P -> Q (in Ref. 1; BAE39522).
SQ SEQUENCE 528 AA; 59716 MW; 8CF34CE865980A66 CRC64;
MLNVPSQAFP APGSQQRVSS QGRSKVPLKQ GRSLMDWIRL TKSGKDLTGL KGGLIEVTEE
ELKKHNKKED CWICIRGFVY NVSPYMEYHP GGEDELMRAA GADGTDLFNE VHRWVNYESM
LKECLVGRMA VKPAVPKDCH EGKRVLNGML PKSQMSDTLP RDVTDTLPRE DLSSPSYDWF
QTESSVTIVV YTKQKNISLD SVIVDLQDDS LRAEAVIKDH SYLVHVGLSH EVQENFSVRV
IENVGKIEIV LQKKESVSWQ CLGDHLEKHD SFIPKKDTGL YYRRCQLISK EDVTHDTRLF
CLMLPPSTHL QVPVGQHVYL KLSVTGAEIV KPYTPVSDSL LSDFKEPVLS PNKYICFLIK
IYPAGLFTPE LDRLQIGDFI SVSGPEGDFK VSKLQEVEDL FLLAAGTGFT PMVTVLNYAL
SHMSSLRKVK LMFFNKTEDD IIWRCQLEKL ALREKRFDVE FVLSAPSPEW NGKQGHISRA
LLSEFLQRSS ENSRAFLCIC GPTPFTDEGI RLLHDLNFSD DEIHGFTA
//
