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Database: UniProt
Entry: Q3TDX8
LinkDB: Q3TDX8
Original site: Q3TDX8 
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   29-OCT-2014, entry version 92.
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). {ECO:0000269|PubMed:15247412}.
CC   -!- CATALYTIC ACTIVITY: NADH + 2 ferricytochrome b5 = NAD(+) + H(+) +
CC       2 ferrocytochrome b5.
CC   -!- COFACTOR: FAD. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum. Note=Soluble protein.
CC       {ECO:0000250}.
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       {ECO:0000269|PubMed:14962668, ECO:0000269|PubMed:16814408}.
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       {ECO:0000269|PubMed:15247412}.
CC   -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide
CC       cytochrome reductase family. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 CS domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00547}.
CC   -!- SIMILARITY: Contains 1 cytochrome b5 heme-binding domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00279}.
CC   -!- SIMILARITY: Contains 1 FAD-binding FR-type domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00716}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH25438.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=BAC41118.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=BAE34044.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=BAE42908.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
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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   CCDS; CCDS40716.2; -. [Q3TDX8-4]
DR   RefSeq; NP_077157.2; NM_024195.2. [Q3TDX8-4]
DR   RefSeq; XP_006511262.1; XM_006511199.1. [Q3TDX8-5]
DR   UniGene; Mm.30166; -.
DR   ProteinModelPortal; Q3TDX8; -.
DR   SMR; Q3TDX8; 51-137, 282-502.
DR   IntAct; Q3TDX8; 1.
DR   PhosphoSite; Q3TDX8; -.
DR   MaxQB; Q3TDX8; -.
DR   PRIDE; Q3TDX8; -.
DR   Ensembl; ENSMUST00000168529; ENSMUSP00000126119; ENSMUSG00000032872. [Q3TDX8-4]
DR   GeneID; 266690; -.
DR   KEGG; mmu:266690; -.
DR   UCSC; uc009qyc.2; mouse. [Q3TDX8-4]
DR   UCSC; uc009qyf.2; mouse. [Q3TDX8-5]
DR   CTD; 51167; -.
DR   MGI; MGI:2386848; Cyb5r4.
DR   eggNOG; COG0543; -.
DR   GeneTree; ENSGT00390000008881; -.
DR   HOVERGEN; HBG108174; -.
DR   InParanoid; Q3TDX8; -.
DR   OMA; KDYHEEK; -.
DR   OrthoDB; EOG718KBZ; -.
DR   TreeFam; TF313874; -.
DR   ChiTaRS; CYB5R4; mouse.
DR   NextBio; 392180; -.
DR   PRO; PR:Q3TDX8; -.
DR   Bgee; Q3TDX8; -.
DR   CleanEx; MM_CYB5R4; -.
DR   ExpressionAtlas; Q3TDX8; baseline.
DR   Genevestigator; Q3TDX8; -.
DR   GO; GO:0005737; C:cytoplasm; ISA:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR   GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; IDA:MGI.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:Ensembl.
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:Ensembl.
DR   GO; GO:0003958; F:NADPH-hemoprotein reductase activity; IEA:Ensembl.
DR   GO; GO:0048468; P:cell development; IMP:MGI.
DR   GO; GO:0006091; P:generation of precursor metabolites and energy; IEA:Ensembl.
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:0006739; P:NADP metabolic process; IEA:Ensembl.
DR   GO; GO:0046677; P:response to antibiotic; IMP:MGI.
DR   GO; GO:0006801; P:superoxide metabolic process; IEA:Ensembl.
DR   Gene3D; 2.60.40.790; -; 1.
DR   Gene3D; 3.10.120.10; -; 1.
DR   InterPro; IPR007052; CS_dom.
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; SSF49764; SSF49764; 1.
DR   SUPFAM; SSF55856; SSF55856; 1.
DR   SUPFAM; SSF63380; SSF63380; 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   Acetylation; Alternative splicing; Complete proteome;
KW   Endoplasmic reticulum; FAD; Flavoprotein; Heme; Iron; Metal-binding;
KW   NAD; Oxidoreductase; Polymorphism; Reference proteome.
FT   CHAIN         1    528       Cytochrome b5 reductase 4.
FT                                /FTId=PRO_0000410469.
FT   DOMAIN       54    130       Cytochrome b5 heme-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00279}.
FT   DOMAIN      172    263       CS. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00547}.
FT   DOMAIN      280    392       FAD-binding FR-type.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00716}.
FT   NP_BIND     372    387       FAD. {ECO:0000250}.
FT   NP_BIND     399    431       FAD. {ECO:0000250}.
FT   METAL        89     89       Iron (heme axial ligand).
FT                                {ECO:0000255|PROSITE-ProRule:PRU00279}.
FT   METAL       112    112       Iron (heme axial ligand).
FT                                {ECO:0000255|PROSITE-ProRule:PRU00279}.
FT   MOD_RES       1      1       N-acetylmethionine. {ECO:0000250}.
FT   VAR_SEQ     326    376       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14962668}.
FT                                /FTId=VSP_041453.
FT   VARIANT     156    156       S -> SDTLPRDVT.
FT                                {ECO:0000269|PubMed:10611283,
FT                                ECO:0000269|PubMed:14962668,
FT                                ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:16141072}.
FT   CONFLICT    171    171       D -> G (in Ref. 1; BAE34044/BAE41470/
FT                                BAE42908, 4; AAK08116 and 5; AAQ83900/
FT                                AAQ83901). {ECO:0000305}.
FT   CONFLICT    216    216       V -> I (in Ref. 3; AAH25438).
FT                                {ECO:0000305}.
FT   CONFLICT    300    300       F -> L (in Ref. 1; BAE34044/BAE41470/
FT                                BAE42908, 3; AAH02170, 4; AAK08116 and 5;
FT                                AAQ83900/AAQ83901). {ECO:0000305}.
FT   CONFLICT    336    336       V -> L (in Ref. 1; BAE34044).
FT                                {ECO:0000305}.
FT   CONFLICT    339    339       S -> P (in Ref. 1; BAE41470).
FT                                {ECO:0000305}.
FT   CONFLICT    356    356       C -> Y (in Ref. 1; BAE34044/BAE41470/
FT                                BAE42908, 3; AAH02170/AAH25438, 4;
FT                                AAK08116 and 5; AAQ83900). {ECO:0000305}.
FT   CONFLICT    388    388       D -> N (in Ref. 1; BAE34044/BAE41470/
FT                                BAE42908, 3; AAH02170/AAH25438, 4;
FT                                AAK08116 and 5; AAQ83900/AAQ83901).
FT                                {ECO:0000305}.
FT   CONFLICT    393    393       K -> T (in Ref. 3; AAH25438).
FT                                {ECO:0000305}.
FT   CONFLICT    438    438       E -> D (in Ref. 1; BAC37357).
FT                                {ECO:0000305}.
FT   CONFLICT    504    504       P -> Q (in Ref. 1; BAE39522).
FT                                {ECO:0000305}.
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
//
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