Full text data of CYBRD1
CYBRD1
(DCYTB, FRRS3)
[Confidence: high (present in two of the MS resources)]
Cytochrome b reductase 1; 1.-.-.- (Duodenal cytochrome b; Ferric-chelate reductase 3)
Cytochrome b reductase 1; 1.-.-.- (Duodenal cytochrome b; Ferric-chelate reductase 3)
hRBCD
IPI00432050
IPI00432050 Duodenal cytochrome b sequence coverage:10 percentage Duodenal cytochrome b sequence coverage:10 percentage membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a Integral membrane protein n/a found at its expected molecular weight found at molecular weight
IPI00432050 Duodenal cytochrome b sequence coverage:10 percentage Duodenal cytochrome b sequence coverage:10 percentage membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a Integral membrane protein n/a found at its expected molecular weight found at molecular weight
UniProt
Q53TN4
ID CYBR1_HUMAN Reviewed; 286 AA.
AC Q53TN4; B2RE79; B4DWD7; Q6KC16; Q6KC17; Q6P147; Q6ZR51; Q9H0Q8;
read moreAC Q9H5G5;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 22-JAN-2014, entry version 76.
DE RecName: Full=Cytochrome b reductase 1;
DE EC=1.-.-.-;
DE AltName: Full=Duodenal cytochrome b;
DE AltName: Full=Ferric-chelate reductase 3;
GN Name=CYBRD1; Synonyms=DCYTB, FRRS3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ASN-266.
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND
RP VARIANT THR-156.
RC TISSUE=Placenta, Small intestine, Synovium, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-266.
RG NIEHS SNPs program;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-266.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ASN-266.
RC TISSUE=Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 65-134 AND 187-285, AND VARIANT
RP HIS-226.
RX PubMed=15338274; DOI=10.1007/s00439-004-1166-y;
RA Zaahl M.G., Merryweather-Clarke A.T., Kotze M.J., van der Merwe S.,
RA Warnich L., Robson K.J.H.;
RT "Analysis of genes implicated in iron regulation in individuals
RT presenting with primary iron overload.";
RL Hum. Genet. 115:409-417(2004).
RN [8]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=12949720; DOI=10.1016/S0016-5085(03)01063-1;
RA Zoller H., Theurl I., Koch R.O., McKie A.T., Vogel W., Weiss G.;
RT "Duodenal cytochrome b and hephaestin expression in patients with iron
RT deficiency and hemochromatosis.";
RL Gastroenterology 125:746-754(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-285, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP POLYMORPHISM, AND ROLE IN HEREDITARY HEMOCHROMATOSIS.
RX PubMed=19673882; DOI=10.1111/j.1365-2141.2009.07843.x;
RA Constantine C.C., Anderson G.J., Vulpe C.D., McLaren C.E., Bahlo M.,
RA Yeap H.L., Gertig D.M., Osborne N.J., Bertalli N.A., Beckman K.B.,
RA Chen V., Matak P., McKie A.T., Delatycki M.B., Olynyk J.K.,
RA English D.R., Southey M.C., Giles G.G., Hopper J.L., Allen K.J.,
RA Gurrin L.C.;
RT "A novel association between a SNP in CYBRD1 and serum ferritin levels
RT in a cohort study of HFE hereditary haemochromatosis.";
RL Br. J. Haematol. 147:140-149(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-285, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-285, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP VARIANT HIS-226.
RX PubMed=16521301;
RA Zaahl M.G., Merryweather-Clarke A.T., Kotze M.J., van der Merwe S.,
RA Warnich L., Robson K.J.;
RT "Gene symbol: DCYTB/CYBRD1. Disease: primary iron overload.";
RL Hum. Genet. 118:546-546(2005).
RN [16]
RP ROLE IN HEREDITARY HEMOCHROMATOSIS.
RX PubMed=16521311;
RA Zaahl M.G., Merryweather-Clarke A.T., Kotze M.J., van der Merwe S.,
RA Warnich L., Robson K.J.;
RT "Gene symbol: DCYTB/CYBRD1. Disease: primary iron overload.";
RL Hum. Genet. 118:548-549(2005).
RN [17]
RP ROLE IN HEREDITARY HEMOCHROMATOSIS.
RX PubMed=16521312;
RA Zaahl M.G., Merryweather-Clarke A.T., Kotze M.J., van der Merwe S.,
RA Warnich L., Robson K.J.;
RT "Gene symbol: DCYTB/CYBRD1. Disease: primary iron overload.";
RL Hum. Genet. 118:549-549(2005).
RN [18]
RP INDUCTION.
RX PubMed=17087784; DOI=10.1111/j.1365-2362.2006.01732.x;
RA Li A.C.Y., Warley A., Thoree V., Simpson R.J., McKie A.T.,
RA Kodjabashia K., Thompson R.P.H., Powell J.J.;
RT "Immunolocalization of duodenal cytochrome B: a relationship with
RT circulating markers of iron status.";
RL Eur. J. Clin. Invest. 36:890-898(2006).
RN [19]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17068337; DOI=10.1074/jbc.M606543200;
RA Su D., May J.M., Koury M.J., Asard H.;
RT "Human erythrocyte membranes contain a cytochrome b561 that may be
RT involved in extracellular ascorbate recycling.";
RL J. Biol. Chem. 281:39852-39859(2006).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=16510471; DOI=10.1152/ajplung.00342.2005;
RA Turi J.L., Wang X., McKie A.T., Nozik-Grayck E., Mamo L.B.,
RA Crissman K., Piantadosi C.A., Ghio A.J.;
RT "Duodenal cytochrome b: a novel ferrireductase in airway epithelial
RT cells.";
RL Am. J. Physiol. 291:L272-L280(2006).
CC -!- FUNCTION: Ferric-chelate reductase that reduces Fe(3+) to Fe(2+).
CC Present at the brush border of duodenal enterocytes where it
CC probably reduces dietary Fe(3+) thereby facilitating its transport
CC into the mucosal cells. Uses ascorbate as electron donor. May be
CC involved in extracellular ascorbate recycling in erythrocyte
CC membranes. May also act as a ferrireductase in airway epithelial
CC cells.
CC -!- COFACTOR: Binds 2 heme groups non-covalently (By similarity).
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q53TN4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q53TN4-2; Sequence=VSP_042039;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q53TN4-3; Sequence=VSP_044945;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Present in erythrocyte membranes (at protein
CC level). Also expressed in respiratory epithelium.
CC -!- INDUCTION: By iron deficiency (at protein level).
CC -!- POLYMORPHISM: Genetic variations in CYBRD1 may act as modifier of
CC iron overload expression and account for the variance observed in
CC serum ferritin levels in patients with hereditary hemochromatosis.
CC -!- SIMILARITY: Contains 1 cytochrome b561 domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAG29366.1; Type=Erroneous gene model prediction;
CC Sequence=CAG29367.1; Type=Erroneous gene model prediction;
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DR EMBL; AL136693; CAB66628.1; -; mRNA.
DR EMBL; AK027115; BAB15661.1; -; mRNA.
DR EMBL; AK128495; BAC87466.1; -; mRNA.
DR EMBL; AK291731; BAF84420.1; -; mRNA.
DR EMBL; AK301485; BAG62999.1; -; mRNA.
DR EMBL; AK316588; BAG38176.1; -; mRNA.
DR EMBL; DQ496101; ABF47090.1; -; Genomic_DNA.
DR EMBL; AC007969; AAY14730.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11210.1; -; Genomic_DNA.
DR EMBL; BC065290; AAH65290.1; -; mRNA.
DR EMBL; AJ715523; CAG29366.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AJ715524; CAG29367.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_001120855.1; NM_001127383.1.
DR RefSeq; NP_001243838.1; NM_001256909.1.
DR RefSeq; NP_079119.3; NM_024843.3.
DR UniGene; Hs.221941; -.
DR ProteinModelPortal; Q53TN4; -.
DR IntAct; Q53TN4; 1.
DR STRING; 9606.ENSP00000319141; -.
DR TCDB; 5.B.2.1.3; the eukaryotic cytochrome b561 (cytb561) family.
DR PhosphoSite; Q53TN4; -.
DR DMDM; 74726934; -.
DR PaxDb; Q53TN4; -.
DR PRIDE; Q53TN4; -.
DR DNASU; 79901; -.
DR Ensembl; ENST00000321348; ENSP00000319141; ENSG00000071967.
DR Ensembl; ENST00000375252; ENSP00000364401; ENSG00000071967.
DR Ensembl; ENST00000409484; ENSP00000386739; ENSG00000071967.
DR GeneID; 79901; -.
DR KEGG; hsa:79901; -.
DR UCSC; uc031rqa.1; human.
DR CTD; 79901; -.
DR GeneCards; GC02P172378; -.
DR H-InvDB; HIX0002588; -.
DR HGNC; HGNC:20797; CYBRD1.
DR HPA; HPA014757; -.
DR MIM; 605745; gene.
DR neXtProt; NX_Q53TN4; -.
DR PharmGKB; PA134970061; -.
DR eggNOG; NOG259716; -.
DR HOGENOM; HOG000143632; -.
DR HOVERGEN; HBG054164; -.
DR InParanoid; Q53TN4; -.
DR KO; K08370; -.
DR OMA; MEGYRGF; -.
DR OrthoDB; EOG7SJD5W; -.
DR PhylomeDB; Q53TN4; -.
DR BioCyc; MetaCyc:HS01046-MONOMER; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; CYBRD1; human.
DR GenomeRNAi; 79901; -.
DR NextBio; 69747; -.
DR PRO; PR:Q53TN4; -.
DR ArrayExpress; Q53TN4; -.
DR Bgee; Q53TN4; -.
DR CleanEx; HS_CYBRD1; -.
DR Genevestigator; Q53TN4; -.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0000293; F:ferric-chelate reductase activity; IDA:HGNC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006879; P:cellular iron ion homeostasis; TAS:Reactome.
DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR InterPro; IPR006593; Cyt_b561/ferric_Rdtase_TM.
DR InterPro; IPR004877; Cyt_b561_euk.
DR Pfam; PF03188; Cytochrom_B561; 1.
DR SMART; SM00665; B561; 1.
DR PROSITE; PS50939; CYTOCHROME_B561; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Electron transport;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Oxidoreductase;
KW Phosphoprotein; Polymorphism; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 286 Cytochrome b reductase 1.
FT /FTId=PRO_0000314830.
FT TRANSMEM 12 32 Helical; Name=1; (Potential).
FT TRANSMEM 49 69 Helical; Name=2; (Potential).
FT TRANSMEM 85 105 Helical; Name=3; (Potential).
FT TRANSMEM 123 143 Helical; Name=4; (Potential).
FT TRANSMEM 158 178 Helical; Name=5; (Potential).
FT TRANSMEM 199 219 Helical; Name=6; (Potential).
FT DOMAIN 15 220 Cytochrome b561.
FT METAL 50 50 Iron (heme axial ligand) (Potential).
FT METAL 86 86 Iron (heme axial ligand) (Potential).
FT METAL 108 108 Iron (heme axial ligand) (Potential).
FT METAL 120 120 Iron (heme axial ligand) (Potential).
FT METAL 159 159 Iron (heme axial ligand) (Potential).
FT MOD_RES 285 285 Phosphothreonine.
FT CARBOHYD 231 231 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 1 64 MAMEGYWRFLALLGSALLVGFLSVIFALVWVLHYREGLGWD
FT GSALEFNWHPVLMVTGFVFIQGI -> MLDEGE (in
FT isoform 3).
FT /FTId=VSP_044945.
FT VAR_SEQ 66 286 IIVYRLPWTWKCSKLLMKSIHAGLNAVAAILAIISVVAVFE
FT NHNVNNIANMYSLHSWVGLIAVICYLLQLLSGFSVFLLPWA
FT PLSLRAFLMPIHVYSGIVIFGTVIATALMGLTEKLIFSLRD
FT PAYSTFPPEGVFVNTLGLLILVFGALIFWIVTRPQWKRPKE
FT PNSTILHPNGGTEQGARGSMPAYSGNNMDKSDSELNSEVAA
FT RKRNLALDEAGQRSTM -> SFRFFSLSASMGSAFSPSISH
FT AHTCLFWNCHLWNSDCNSTYGIDRETDFFPERSCIQYIPAR
FT RCFRKYAWPSDPGVRGPHFLDSHQTAMETS (in
FT isoform 2).
FT /FTId=VSP_042039.
FT VARIANT 156 156 M -> T (in dbSNP:rs16859487).
FT /FTId=VAR_038065.
FT VARIANT 226 226 R -> H (in some patients with hereditary
FT hemochromatosis; dbSNP:rs62181680).
FT /FTId=VAR_038066.
FT VARIANT 266 266 S -> N (in dbSNP:rs10455).
FT /FTId=VAR_038067.
FT CONFLICT 7 7 W -> R (in Ref. 1; CAB66628).
SQ SEQUENCE 286 AA; 31641 MW; 09AA921925A077F7 CRC64;
MAMEGYWRFL ALLGSALLVG FLSVIFALVW VLHYREGLGW DGSALEFNWH PVLMVTGFVF
IQGIAIIVYR LPWTWKCSKL LMKSIHAGLN AVAAILAIIS VVAVFENHNV NNIANMYSLH
SWVGLIAVIC YLLQLLSGFS VFLLPWAPLS LRAFLMPIHV YSGIVIFGTV IATALMGLTE
KLIFSLRDPA YSTFPPEGVF VNTLGLLILV FGALIFWIVT RPQWKRPKEP NSTILHPNGG
TEQGARGSMP AYSGNNMDKS DSELNSEVAA RKRNLALDEA GQRSTM
//
ID CYBR1_HUMAN Reviewed; 286 AA.
AC Q53TN4; B2RE79; B4DWD7; Q6KC16; Q6KC17; Q6P147; Q6ZR51; Q9H0Q8;
read moreAC Q9H5G5;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 22-JAN-2014, entry version 76.
DE RecName: Full=Cytochrome b reductase 1;
DE EC=1.-.-.-;
DE AltName: Full=Duodenal cytochrome b;
DE AltName: Full=Ferric-chelate reductase 3;
GN Name=CYBRD1; Synonyms=DCYTB, FRRS3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ASN-266.
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND
RP VARIANT THR-156.
RC TISSUE=Placenta, Small intestine, Synovium, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-266.
RG NIEHS SNPs program;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-266.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ASN-266.
RC TISSUE=Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 65-134 AND 187-285, AND VARIANT
RP HIS-226.
RX PubMed=15338274; DOI=10.1007/s00439-004-1166-y;
RA Zaahl M.G., Merryweather-Clarke A.T., Kotze M.J., van der Merwe S.,
RA Warnich L., Robson K.J.H.;
RT "Analysis of genes implicated in iron regulation in individuals
RT presenting with primary iron overload.";
RL Hum. Genet. 115:409-417(2004).
RN [8]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=12949720; DOI=10.1016/S0016-5085(03)01063-1;
RA Zoller H., Theurl I., Koch R.O., McKie A.T., Vogel W., Weiss G.;
RT "Duodenal cytochrome b and hephaestin expression in patients with iron
RT deficiency and hemochromatosis.";
RL Gastroenterology 125:746-754(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-285, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP POLYMORPHISM, AND ROLE IN HEREDITARY HEMOCHROMATOSIS.
RX PubMed=19673882; DOI=10.1111/j.1365-2141.2009.07843.x;
RA Constantine C.C., Anderson G.J., Vulpe C.D., McLaren C.E., Bahlo M.,
RA Yeap H.L., Gertig D.M., Osborne N.J., Bertalli N.A., Beckman K.B.,
RA Chen V., Matak P., McKie A.T., Delatycki M.B., Olynyk J.K.,
RA English D.R., Southey M.C., Giles G.G., Hopper J.L., Allen K.J.,
RA Gurrin L.C.;
RT "A novel association between a SNP in CYBRD1 and serum ferritin levels
RT in a cohort study of HFE hereditary haemochromatosis.";
RL Br. J. Haematol. 147:140-149(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-285, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-285, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP VARIANT HIS-226.
RX PubMed=16521301;
RA Zaahl M.G., Merryweather-Clarke A.T., Kotze M.J., van der Merwe S.,
RA Warnich L., Robson K.J.;
RT "Gene symbol: DCYTB/CYBRD1. Disease: primary iron overload.";
RL Hum. Genet. 118:546-546(2005).
RN [16]
RP ROLE IN HEREDITARY HEMOCHROMATOSIS.
RX PubMed=16521311;
RA Zaahl M.G., Merryweather-Clarke A.T., Kotze M.J., van der Merwe S.,
RA Warnich L., Robson K.J.;
RT "Gene symbol: DCYTB/CYBRD1. Disease: primary iron overload.";
RL Hum. Genet. 118:548-549(2005).
RN [17]
RP ROLE IN HEREDITARY HEMOCHROMATOSIS.
RX PubMed=16521312;
RA Zaahl M.G., Merryweather-Clarke A.T., Kotze M.J., van der Merwe S.,
RA Warnich L., Robson K.J.;
RT "Gene symbol: DCYTB/CYBRD1. Disease: primary iron overload.";
RL Hum. Genet. 118:549-549(2005).
RN [18]
RP INDUCTION.
RX PubMed=17087784; DOI=10.1111/j.1365-2362.2006.01732.x;
RA Li A.C.Y., Warley A., Thoree V., Simpson R.J., McKie A.T.,
RA Kodjabashia K., Thompson R.P.H., Powell J.J.;
RT "Immunolocalization of duodenal cytochrome B: a relationship with
RT circulating markers of iron status.";
RL Eur. J. Clin. Invest. 36:890-898(2006).
RN [19]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17068337; DOI=10.1074/jbc.M606543200;
RA Su D., May J.M., Koury M.J., Asard H.;
RT "Human erythrocyte membranes contain a cytochrome b561 that may be
RT involved in extracellular ascorbate recycling.";
RL J. Biol. Chem. 281:39852-39859(2006).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=16510471; DOI=10.1152/ajplung.00342.2005;
RA Turi J.L., Wang X., McKie A.T., Nozik-Grayck E., Mamo L.B.,
RA Crissman K., Piantadosi C.A., Ghio A.J.;
RT "Duodenal cytochrome b: a novel ferrireductase in airway epithelial
RT cells.";
RL Am. J. Physiol. 291:L272-L280(2006).
CC -!- FUNCTION: Ferric-chelate reductase that reduces Fe(3+) to Fe(2+).
CC Present at the brush border of duodenal enterocytes where it
CC probably reduces dietary Fe(3+) thereby facilitating its transport
CC into the mucosal cells. Uses ascorbate as electron donor. May be
CC involved in extracellular ascorbate recycling in erythrocyte
CC membranes. May also act as a ferrireductase in airway epithelial
CC cells.
CC -!- COFACTOR: Binds 2 heme groups non-covalently (By similarity).
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q53TN4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q53TN4-2; Sequence=VSP_042039;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q53TN4-3; Sequence=VSP_044945;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Present in erythrocyte membranes (at protein
CC level). Also expressed in respiratory epithelium.
CC -!- INDUCTION: By iron deficiency (at protein level).
CC -!- POLYMORPHISM: Genetic variations in CYBRD1 may act as modifier of
CC iron overload expression and account for the variance observed in
CC serum ferritin levels in patients with hereditary hemochromatosis.
CC -!- SIMILARITY: Contains 1 cytochrome b561 domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAG29366.1; Type=Erroneous gene model prediction;
CC Sequence=CAG29367.1; Type=Erroneous gene model prediction;
CC -----------------------------------------------------------------------
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DR EMBL; AL136693; CAB66628.1; -; mRNA.
DR EMBL; AK027115; BAB15661.1; -; mRNA.
DR EMBL; AK128495; BAC87466.1; -; mRNA.
DR EMBL; AK291731; BAF84420.1; -; mRNA.
DR EMBL; AK301485; BAG62999.1; -; mRNA.
DR EMBL; AK316588; BAG38176.1; -; mRNA.
DR EMBL; DQ496101; ABF47090.1; -; Genomic_DNA.
DR EMBL; AC007969; AAY14730.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11210.1; -; Genomic_DNA.
DR EMBL; BC065290; AAH65290.1; -; mRNA.
DR EMBL; AJ715523; CAG29366.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AJ715524; CAG29367.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_001120855.1; NM_001127383.1.
DR RefSeq; NP_001243838.1; NM_001256909.1.
DR RefSeq; NP_079119.3; NM_024843.3.
DR UniGene; Hs.221941; -.
DR ProteinModelPortal; Q53TN4; -.
DR IntAct; Q53TN4; 1.
DR STRING; 9606.ENSP00000319141; -.
DR TCDB; 5.B.2.1.3; the eukaryotic cytochrome b561 (cytb561) family.
DR PhosphoSite; Q53TN4; -.
DR DMDM; 74726934; -.
DR PaxDb; Q53TN4; -.
DR PRIDE; Q53TN4; -.
DR DNASU; 79901; -.
DR Ensembl; ENST00000321348; ENSP00000319141; ENSG00000071967.
DR Ensembl; ENST00000375252; ENSP00000364401; ENSG00000071967.
DR Ensembl; ENST00000409484; ENSP00000386739; ENSG00000071967.
DR GeneID; 79901; -.
DR KEGG; hsa:79901; -.
DR UCSC; uc031rqa.1; human.
DR CTD; 79901; -.
DR GeneCards; GC02P172378; -.
DR H-InvDB; HIX0002588; -.
DR HGNC; HGNC:20797; CYBRD1.
DR HPA; HPA014757; -.
DR MIM; 605745; gene.
DR neXtProt; NX_Q53TN4; -.
DR PharmGKB; PA134970061; -.
DR eggNOG; NOG259716; -.
DR HOGENOM; HOG000143632; -.
DR HOVERGEN; HBG054164; -.
DR InParanoid; Q53TN4; -.
DR KO; K08370; -.
DR OMA; MEGYRGF; -.
DR OrthoDB; EOG7SJD5W; -.
DR PhylomeDB; Q53TN4; -.
DR BioCyc; MetaCyc:HS01046-MONOMER; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; CYBRD1; human.
DR GenomeRNAi; 79901; -.
DR NextBio; 69747; -.
DR PRO; PR:Q53TN4; -.
DR ArrayExpress; Q53TN4; -.
DR Bgee; Q53TN4; -.
DR CleanEx; HS_CYBRD1; -.
DR Genevestigator; Q53TN4; -.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0000293; F:ferric-chelate reductase activity; IDA:HGNC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006879; P:cellular iron ion homeostasis; TAS:Reactome.
DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR InterPro; IPR006593; Cyt_b561/ferric_Rdtase_TM.
DR InterPro; IPR004877; Cyt_b561_euk.
DR Pfam; PF03188; Cytochrom_B561; 1.
DR SMART; SM00665; B561; 1.
DR PROSITE; PS50939; CYTOCHROME_B561; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Electron transport;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Oxidoreductase;
KW Phosphoprotein; Polymorphism; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 286 Cytochrome b reductase 1.
FT /FTId=PRO_0000314830.
FT TRANSMEM 12 32 Helical; Name=1; (Potential).
FT TRANSMEM 49 69 Helical; Name=2; (Potential).
FT TRANSMEM 85 105 Helical; Name=3; (Potential).
FT TRANSMEM 123 143 Helical; Name=4; (Potential).
FT TRANSMEM 158 178 Helical; Name=5; (Potential).
FT TRANSMEM 199 219 Helical; Name=6; (Potential).
FT DOMAIN 15 220 Cytochrome b561.
FT METAL 50 50 Iron (heme axial ligand) (Potential).
FT METAL 86 86 Iron (heme axial ligand) (Potential).
FT METAL 108 108 Iron (heme axial ligand) (Potential).
FT METAL 120 120 Iron (heme axial ligand) (Potential).
FT METAL 159 159 Iron (heme axial ligand) (Potential).
FT MOD_RES 285 285 Phosphothreonine.
FT CARBOHYD 231 231 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 1 64 MAMEGYWRFLALLGSALLVGFLSVIFALVWVLHYREGLGWD
FT GSALEFNWHPVLMVTGFVFIQGI -> MLDEGE (in
FT isoform 3).
FT /FTId=VSP_044945.
FT VAR_SEQ 66 286 IIVYRLPWTWKCSKLLMKSIHAGLNAVAAILAIISVVAVFE
FT NHNVNNIANMYSLHSWVGLIAVICYLLQLLSGFSVFLLPWA
FT PLSLRAFLMPIHVYSGIVIFGTVIATALMGLTEKLIFSLRD
FT PAYSTFPPEGVFVNTLGLLILVFGALIFWIVTRPQWKRPKE
FT PNSTILHPNGGTEQGARGSMPAYSGNNMDKSDSELNSEVAA
FT RKRNLALDEAGQRSTM -> SFRFFSLSASMGSAFSPSISH
FT AHTCLFWNCHLWNSDCNSTYGIDRETDFFPERSCIQYIPAR
FT RCFRKYAWPSDPGVRGPHFLDSHQTAMETS (in
FT isoform 2).
FT /FTId=VSP_042039.
FT VARIANT 156 156 M -> T (in dbSNP:rs16859487).
FT /FTId=VAR_038065.
FT VARIANT 226 226 R -> H (in some patients with hereditary
FT hemochromatosis; dbSNP:rs62181680).
FT /FTId=VAR_038066.
FT VARIANT 266 266 S -> N (in dbSNP:rs10455).
FT /FTId=VAR_038067.
FT CONFLICT 7 7 W -> R (in Ref. 1; CAB66628).
SQ SEQUENCE 286 AA; 31641 MW; 09AA921925A077F7 CRC64;
MAMEGYWRFL ALLGSALLVG FLSVIFALVW VLHYREGLGW DGSALEFNWH PVLMVTGFVF
IQGIAIIVYR LPWTWKCSKL LMKSIHAGLN AVAAILAIIS VVAVFENHNV NNIANMYSLH
SWVGLIAVIC YLLQLLSGFS VFLLPWAPLS LRAFLMPIHV YSGIVIFGTV IATALMGLTE
KLIFSLRDPA YSTFPPEGVF VNTLGLLILV FGALIFWIVT RPQWKRPKEP NSTILHPNGG
TEQGARGSMP AYSGNNMDKS DSELNSEVAA RKRNLALDEA GQRSTM
//
MIM
605745
*RECORD*
*FIELD* NO
605745
*FIELD* TI
*605745 CYTOCHROME b REDUCTASE 1; CYBRD1
;;DUODENAL CYTOCHROME b; DCYTB
*FIELD* TX
read more
CLONING
The ability of intestinal mucosa to absorb dietary ferric iron is
attributed to the presence of a brush-border membrane reductase activity
that displays adaptive responses to iron status. McKie et al. (2001)
isolated a cDNA, which they called Dcytb for 'duodenal cytochrome b,'
that encodes a putative plasma membrane di-heme protein in mouse
duodenal mucosa. By searching EST databases, the authors also found a
fully sequenced cDNA clone from a human small intestine library
containing the full-length human DCYTB cDNA (GenBank GENBANK AK027115).
DCYTB encodes a protein with 6 predicted transmembrane domains and 4
conserved histidine residues which are proposed heme ligands. DCYTB
shares 45 to 50% similarity with the cytochrome b561 (600019) family of
plasma membrane reductases, is highly expressed in the brush-border
membrane of duodenal enterocytes, and induces ferric reductase activity
when expressed in Xenopus oocytes and cultured cells. Duodenal
expression levels of DCYTB mRNA and protein were regulated by changes in
physiologic modulators of iron absorption, including chronic anemia,
iron deficiency, and hypoxia. Three major transcripts of 1, 4, and
greater than 5 kb were detectable by Northern blot analysis, indicative
of alternative splicing or the presence of unprocessed pre-mRNA species.
DCYTB appears to lack any conventional NADH-, NADPH-, or flavin-binding
motifs that would allow these cofactors to act as intracellular electron
donors. Cytochrome b561 receives an electron from ascorbate and does not
appear to require other components. McKie et al. (2001) speculated that
DCYTB may also use ascorbate or, like gp91-phox (300481), associate with
several other proteins to form an active complex.
GENE FUNCTION
Zoller et al. (2003) studied the mRNA and protein expression and
activity of DCYTB in duodenal biopsies of patients with iron deficiency
anemia, hereditary hemochromatosis (235200), and controls. They found
that DCYTB activity in iron deficiency is stimulated via enhanced
protein expression, whereas in hemochromatosis due to mutations in the
HFE gene (613609) it is upregulated posttranslationally. Hemochromatosis
patients with no mutations in HFE did not have increased DCYTB activity.
Zoller et al. (2003) concluded that there are different kinetics of
intestinal iron uptake between iron deficiency and hemochromatosis due
to mutations in HFE, and that duodenal iron accumulation in hereditary
hemochromatosis due to mutations in HFE and hereditary hemochromatosis
due to mutations in other genes is pathophysiologically different.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the CYBRD1
gene to chromosome 2 (TMAP RH46529).
*FIELD* RF
1. McKie, A. T.; Barrow, D.; Latunde-Dada, G. O.; Rolfs, A.; Sager,
G.; Mudaly, E.; Mudaly, M.; Richardson, C.; Barlow, D.; Bomford, A.;
Peters, T. J.; Raja, K. B.; Shirali, S.; Hediger, M. A.; Farzaneh,
F.; Simpson, R. J.: An iron-regulated ferric reductase associated
with the absorption of dietary iron. Science 291: 1755-1759, 2001.
2. Zoller, H.; Theurl, I.; Koch, R. O.; McKie, A. T.; Vogel, W.; Weiss,
G.: Duodenal cytochrome b and hephaestin expression in patients with
iron deficiency and hemochromatosis. Gastroenterology 123: 746-754,
2003.
*FIELD* CN
Marla J. F. O'Neill - updated: 4/25/2005
*FIELD* CD
Ada Hamosh: 3/20/2001
*FIELD* ED
carol: 10/21/2010
carol: 7/19/2005
alopez: 7/15/2005
wwang: 4/29/2005
wwang: 4/27/2005
terry: 4/25/2005
ckniffin: 3/12/2004
alopez: 4/25/2003
alopez: 3/20/2001
*RECORD*
*FIELD* NO
605745
*FIELD* TI
*605745 CYTOCHROME b REDUCTASE 1; CYBRD1
;;DUODENAL CYTOCHROME b; DCYTB
*FIELD* TX
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CLONING
The ability of intestinal mucosa to absorb dietary ferric iron is
attributed to the presence of a brush-border membrane reductase activity
that displays adaptive responses to iron status. McKie et al. (2001)
isolated a cDNA, which they called Dcytb for 'duodenal cytochrome b,'
that encodes a putative plasma membrane di-heme protein in mouse
duodenal mucosa. By searching EST databases, the authors also found a
fully sequenced cDNA clone from a human small intestine library
containing the full-length human DCYTB cDNA (GenBank GENBANK AK027115).
DCYTB encodes a protein with 6 predicted transmembrane domains and 4
conserved histidine residues which are proposed heme ligands. DCYTB
shares 45 to 50% similarity with the cytochrome b561 (600019) family of
plasma membrane reductases, is highly expressed in the brush-border
membrane of duodenal enterocytes, and induces ferric reductase activity
when expressed in Xenopus oocytes and cultured cells. Duodenal
expression levels of DCYTB mRNA and protein were regulated by changes in
physiologic modulators of iron absorption, including chronic anemia,
iron deficiency, and hypoxia. Three major transcripts of 1, 4, and
greater than 5 kb were detectable by Northern blot analysis, indicative
of alternative splicing or the presence of unprocessed pre-mRNA species.
DCYTB appears to lack any conventional NADH-, NADPH-, or flavin-binding
motifs that would allow these cofactors to act as intracellular electron
donors. Cytochrome b561 receives an electron from ascorbate and does not
appear to require other components. McKie et al. (2001) speculated that
DCYTB may also use ascorbate or, like gp91-phox (300481), associate with
several other proteins to form an active complex.
GENE FUNCTION
Zoller et al. (2003) studied the mRNA and protein expression and
activity of DCYTB in duodenal biopsies of patients with iron deficiency
anemia, hereditary hemochromatosis (235200), and controls. They found
that DCYTB activity in iron deficiency is stimulated via enhanced
protein expression, whereas in hemochromatosis due to mutations in the
HFE gene (613609) it is upregulated posttranslationally. Hemochromatosis
patients with no mutations in HFE did not have increased DCYTB activity.
Zoller et al. (2003) concluded that there are different kinetics of
intestinal iron uptake between iron deficiency and hemochromatosis due
to mutations in HFE, and that duodenal iron accumulation in hereditary
hemochromatosis due to mutations in HFE and hereditary hemochromatosis
due to mutations in other genes is pathophysiologically different.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the CYBRD1
gene to chromosome 2 (TMAP RH46529).
*FIELD* RF
1. McKie, A. T.; Barrow, D.; Latunde-Dada, G. O.; Rolfs, A.; Sager,
G.; Mudaly, E.; Mudaly, M.; Richardson, C.; Barlow, D.; Bomford, A.;
Peters, T. J.; Raja, K. B.; Shirali, S.; Hediger, M. A.; Farzaneh,
F.; Simpson, R. J.: An iron-regulated ferric reductase associated
with the absorption of dietary iron. Science 291: 1755-1759, 2001.
2. Zoller, H.; Theurl, I.; Koch, R. O.; McKie, A. T.; Vogel, W.; Weiss,
G.: Duodenal cytochrome b and hephaestin expression in patients with
iron deficiency and hemochromatosis. Gastroenterology 123: 746-754,
2003.
*FIELD* CN
Marla J. F. O'Neill - updated: 4/25/2005
*FIELD* CD
Ada Hamosh: 3/20/2001
*FIELD* ED
carol: 10/21/2010
carol: 7/19/2005
alopez: 7/15/2005
wwang: 4/29/2005
wwang: 4/27/2005
terry: 4/25/2005
ckniffin: 3/12/2004
alopez: 4/25/2003
alopez: 3/20/2001