Full text data of BLVRB
BLVRB
(FLR)
[Confidence: high (present in two of the MS resources)]
Flavin reductase (NADPH); FR; 1.5.1.30 (Biliverdin reductase B; BVR-B; 1.3.1.24; Biliverdin-IX beta-reductase; Green heme-binding protein; GHBP; NADPH-dependent diaphorase; NADPH-flavin reductase; FLR)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Flavin reductase (NADPH); FR; 1.5.1.30 (Biliverdin reductase B; BVR-B; 1.3.1.24; Biliverdin-IX beta-reductase; Green heme-binding protein; GHBP; NADPH-dependent diaphorase; NADPH-flavin reductase; FLR)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00219910
IPI00219910 Flavin reductase Flavin reductase membrane n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a 1 cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00219910 Flavin reductase Flavin reductase membrane n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a 1 cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P30043
ID BLVRB_HUMAN Reviewed; 206 AA.
AC P30043; A6NKD8; B2R5C6; P32078; P53005; Q32LZ2;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 140.
DE RecName: Full=Flavin reductase (NADPH);
DE Short=FR;
DE EC=1.5.1.30;
DE AltName: Full=Biliverdin reductase B;
DE Short=BVR-B;
DE EC=1.3.1.24;
DE AltName: Full=Biliverdin-IX beta-reductase;
DE AltName: Full=Green heme-binding protein;
DE Short=GHBP;
DE AltName: Full=NADPH-dependent diaphorase;
DE AltName: Full=NADPH-flavin reductase;
DE Short=FLR;
GN Name=BLVRB; Synonyms=FLR;
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 [MRNA], AND PROTEIN SEQUENCE OF 2-34; 63-87 AND
RP 98-206.
RC TISSUE=Erythrocyte, and Reticulocyte;
RX PubMed=8117274; DOI=10.1006/bbrc.1994.1165;
RA Chikuba K., Yubisui T., Shirabe K., Takeshita M.;
RT "Cloning and nucleotide sequence of a cDNA of the human erythrocyte
RT NADPH-flavin reductase.";
RL Biochem. Biophys. Res. Commun. 198:1170-1176(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8799475;
RA Komuro A., Tobe T., Hashimoto K., Nakano Y., Yamaguchi T.,
RA Nakajima H., Tomita M.;
RT "Molecular cloning and expression of human liver biliverdin-IXbeta
RT reductase.";
RL Biol. Pharm. Bull. 19:796-804(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-46.
RG NIEHS SNPs program;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [8]
RP PROTEIN SEQUENCE OF 2-205.
RC TISSUE=Liver;
RX PubMed=8280170; DOI=10.1006/bbrc.1993.2649;
RA Yamaguchi T., Komuro A., Nakano Y., Tomita M., Nakajima H.;
RT "Complete amino acid sequence of biliverdin-IX beta reductase from
RT human liver.";
RL Biochem. Biophys. Res. Commun. 197:1518-1523(1993).
RN [9]
RP PROTEIN SEQUENCE OF 2-21, SUBUNIT, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=7929092;
RA Yamaguchi T., Komoda Y., Nakajima H.;
RT "Biliverdin-IX alpha reductase and biliverdin-IX beta reductase from
RT human liver. Purification and characterization.";
RL J. Biol. Chem. 269:24343-24348(1994).
RN [10]
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [11]
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Erythrocyte;
RX PubMed=8313871; DOI=10.1002/elps.11501401183;
RA Golaz O., Hughes G.J., Frutiger S., Paquet N., Bairoch A.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Appel R.D., Walzer C.,
RA Balant L., Hochstrasser D.F.;
RT "Plasma and red blood cell protein maps: update 1993.";
RL Electrophoresis 14:1223-1231(1993).
RN [12]
RP PROTEIN SEQUENCE OF 40-92; 64-78; 106-124 AND 146-170, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [13]
RP IDENTITY OF FR AND BVR-B.
RX PubMed=8687377;
RA Shalloe F., Elliott G., Ennis O., Mantle T.J.;
RT "Evidence that biliverdin-IX beta reductase and flavin reductase are
RT identical.";
RL Biochem. J. 316:385-387(1996).
RN [14]
RP FUNCTION, ENZYME REGULATION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10620517; DOI=10.1042/0264-6021:3450393;
RA Cunningham O., Gore M.G., Mantle T.J.;
RT "Initial-rate kinetics of the flavin reductase reaction catalysed by
RT human biliverdin-IXbeta reductase (BVR-B).";
RL Biochem. J. 345:393-399(2000).
RN [15]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-153.
RX PubMed=18241201; DOI=10.1042/BJ20071495;
RA Smith L.J., Browne S., Mulholland A.J., Mantle T.J.;
RT "Computational and experimental studies on the catalytic mechanism of
RT biliverdin-IXbeta reductase.";
RL Biochem. J. 411:475-484(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) IN COMPLEXES WITH
RP MESOBILIVERDIN; BILIVERDIN; FLAVIN MONONUCLEOTIDE; LUMICHROME AND
RP NADP, AND SUBUNIT.
RX PubMed=11224564; DOI=10.1038/84948;
RA Pereira P.J., Macedo-Ribeiro S., Parraga A., Perez-Luque R.,
RA Cunningham O., Darcy K., Mantle T.J., Coll M.;
RT "Structure of human biliverdin IXbeta reductase, an early fetal
RT bilirubin IXbeta producing enzyme.";
RL Nat. Struct. Biol. 8:215-220(2001).
CC -!- FUNCTION: Broad specificity oxidoreductase that catalyzes the
CC NADPH-dependent reduction of a variety of flavins, such as
CC riboflavin, FAD or FMN, biliverdins, methemoglobin and PQQ
CC (pyrroloquinoline quinone). Contributes to heme catabolism and
CC metabolizes linear tetrapyrroles. Can also reduce the complexed
CC Fe(3+) iron to Fe(2+) in the presence of FMN and NADPH. In the
CC liver, converts biliverdin to bilirubin.
CC -!- CATALYTIC ACTIVITY: Reduced riboflavin + NADP(+) = riboflavin +
CC NADPH.
CC -!- CATALYTIC ACTIVITY: Bilirubin + NAD(P)(+) = biliverdin + NAD(P)H.
CC -!- ENZYME REGULATION: Mesobiliverdin acts as competitve inhibitor for
CC flavin reduction, indicating that flavin and tetrapyrrole
CC substrates compete for the same site.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=36 uM for NADP;
CC KM=5.6 mM for NADH;
CC KM=0.3 uM for biliverdin IX-beta;
CC KM=52 uM for FMN;
CC KM=125 uM for FAD;
CC KM=53 uM for riboflavin;
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in liver and
CC erythrocytes. At lower levels in heart, lung, adrenal gland and
CC cerebrum.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/blvrb/";
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DR EMBL; D26308; BAA05370.1; -; mRNA.
DR EMBL; D32143; BAA06874.1; -; mRNA.
DR EMBL; AK312137; BAG35073.1; -; mRNA.
DR EMBL; AY340485; AAP88933.1; -; Genomic_DNA.
DR EMBL; AC010271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471126; EAW56969.1; -; Genomic_DNA.
DR EMBL; BC109371; AAI09372.1; -; mRNA.
DR PIR; JC2070; JC2070.
DR RefSeq; NP_000704.1; NM_000713.2.
DR UniGene; Hs.515785; -.
DR PDB; 1HDO; X-ray; 1.15 A; A=1-206.
DR PDB; 1HE2; X-ray; 1.20 A; A=1-206.
DR PDB; 1HE3; X-ray; 1.40 A; A=1-206.
DR PDB; 1HE4; X-ray; 1.40 A; A=1-206.
DR PDB; 1HE5; X-ray; 1.50 A; A=1-206.
DR PDBsum; 1HDO; -.
DR PDBsum; 1HE2; -.
DR PDBsum; 1HE3; -.
DR PDBsum; 1HE4; -.
DR PDBsum; 1HE5; -.
DR ProteinModelPortal; P30043; -.
DR SMR; P30043; 1-205.
DR IntAct; P30043; 5.
DR MINT; MINT-5001335; -.
DR STRING; 9606.ENSP00000263368; -.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00140; Riboflavin.
DR PhosphoSite; P30043; -.
DR DMDM; 1706870; -.
DR DOSAC-COBS-2DPAGE; P30043; -.
DR REPRODUCTION-2DPAGE; IPI00783862; -.
DR SWISS-2DPAGE; P30043; -.
DR UCD-2DPAGE; P30043; -.
DR PaxDb; P30043; -.
DR PRIDE; P30043; -.
DR Ensembl; ENST00000263368; ENSP00000263368; ENSG00000090013.
DR GeneID; 645; -.
DR KEGG; hsa:645; -.
DR UCSC; uc002onw.2; human.
DR CTD; 645; -.
DR GeneCards; GC19M040953; -.
DR HGNC; HGNC:1063; BLVRB.
DR HPA; HPA041698; -.
DR HPA; HPA041937; -.
DR MIM; 600941; gene.
DR neXtProt; NX_P30043; -.
DR PharmGKB; PA25374; -.
DR eggNOG; NOG239698; -.
DR HOGENOM; HOG000262432; -.
DR HOVERGEN; HBG050695; -.
DR InParanoid; P30043; -.
DR KO; K05901; -.
DR OMA; TDEYNGH; -.
DR Reactome; REACT_111217; Metabolism.
DR EvolutionaryTrace; P30043; -.
DR GenomeRNAi; 645; -.
DR NextBio; 2618; -.
DR PRO; PR:P30043; -.
DR ArrayExpress; P30043; -.
DR Bgee; P30043; -.
DR CleanEx; HS_BLVRB; -.
DR Genevestigator; P30043; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0004074; F:biliverdin reductase activity; IDA:UniProtKB.
DR GO; GO:0042602; F:riboflavin reductase (NADPH) activity; IDA:UniProtKB.
DR GO; GO:0042167; P:heme catabolic process; IDA:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR016040; NAD(P)-bd_dom.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Direct protein sequencing;
KW NADP; Oxidoreductase; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 206 Flavin reductase (NADPH).
FT /FTId=PRO_0000064948.
FT NP_BIND 10 15 NADP.
FT NP_BIND 54 55 NADP.
FT NP_BIND 75 78 NADP.
FT BINDING 35 35 NADP.
FT BINDING 132 132 NADP.
FT BINDING 153 153 Substrate.
FT BINDING 154 154 NADP; via amide nitrogen.
FT VARIANT 46 46 R -> Q (in dbSNP:rs11547746).
FT /FTId=VAR_019168.
FT MUTAGEN 153 153 H->A: Reduced affinity for biliverdin.
FT CONFLICT 16 16 G -> C (in Ref. 9; AA sequence).
FT STRAND 5 10
FT HELIX 14 25
FT STRAND 29 35
FT HELIX 37 39
FT STRAND 42 44
FT STRAND 48 53
FT HELIX 58 65
FT STRAND 69 73
FT HELIX 86 101
FT STRAND 105 109
FT HELIX 112 114
FT HELIX 118 120
FT HELIX 123 125
FT HELIX 126 141
FT STRAND 144 149
FT STRAND 152 155
FT STRAND 164 169
FT STRAND 174 177
FT HELIX 178 187
FT HELIX 188 190
FT TURN 193 196
FT STRAND 198 202
SQ SEQUENCE 206 AA; 22119 MW; 3057E6D69A9F9F9F CRC64;
MAVKKIAIFG ATGQTGLTTL AQAVQAGYEV TVLVRDSSRL PSEGPRPAHV VVGDVLQAAD
VDKTVAGQDA VIVLLGTRND LSPTTVMSEG ARNIVAAMKA HGVDKVVACT SAFLLWDPTK
VPPRLQAVTD DHIRMHKVLR ESGLKYVAVM PPHIGDQPLT GAYTVTLDGR GPSRVISKHD
LGHFMLRCLT TDEYDGHSTY PSHQYQ
//
ID BLVRB_HUMAN Reviewed; 206 AA.
AC P30043; A6NKD8; B2R5C6; P32078; P53005; Q32LZ2;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 140.
DE RecName: Full=Flavin reductase (NADPH);
DE Short=FR;
DE EC=1.5.1.30;
DE AltName: Full=Biliverdin reductase B;
DE Short=BVR-B;
DE EC=1.3.1.24;
DE AltName: Full=Biliverdin-IX beta-reductase;
DE AltName: Full=Green heme-binding protein;
DE Short=GHBP;
DE AltName: Full=NADPH-dependent diaphorase;
DE AltName: Full=NADPH-flavin reductase;
DE Short=FLR;
GN Name=BLVRB; Synonyms=FLR;
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 [MRNA], AND PROTEIN SEQUENCE OF 2-34; 63-87 AND
RP 98-206.
RC TISSUE=Erythrocyte, and Reticulocyte;
RX PubMed=8117274; DOI=10.1006/bbrc.1994.1165;
RA Chikuba K., Yubisui T., Shirabe K., Takeshita M.;
RT "Cloning and nucleotide sequence of a cDNA of the human erythrocyte
RT NADPH-flavin reductase.";
RL Biochem. Biophys. Res. Commun. 198:1170-1176(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8799475;
RA Komuro A., Tobe T., Hashimoto K., Nakano Y., Yamaguchi T.,
RA Nakajima H., Tomita M.;
RT "Molecular cloning and expression of human liver biliverdin-IXbeta
RT reductase.";
RL Biol. Pharm. Bull. 19:796-804(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-46.
RG NIEHS SNPs program;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [8]
RP PROTEIN SEQUENCE OF 2-205.
RC TISSUE=Liver;
RX PubMed=8280170; DOI=10.1006/bbrc.1993.2649;
RA Yamaguchi T., Komuro A., Nakano Y., Tomita M., Nakajima H.;
RT "Complete amino acid sequence of biliverdin-IX beta reductase from
RT human liver.";
RL Biochem. Biophys. Res. Commun. 197:1518-1523(1993).
RN [9]
RP PROTEIN SEQUENCE OF 2-21, SUBUNIT, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=7929092;
RA Yamaguchi T., Komoda Y., Nakajima H.;
RT "Biliverdin-IX alpha reductase and biliverdin-IX beta reductase from
RT human liver. Purification and characterization.";
RL J. Biol. Chem. 269:24343-24348(1994).
RN [10]
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [11]
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Erythrocyte;
RX PubMed=8313871; DOI=10.1002/elps.11501401183;
RA Golaz O., Hughes G.J., Frutiger S., Paquet N., Bairoch A.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Appel R.D., Walzer C.,
RA Balant L., Hochstrasser D.F.;
RT "Plasma and red blood cell protein maps: update 1993.";
RL Electrophoresis 14:1223-1231(1993).
RN [12]
RP PROTEIN SEQUENCE OF 40-92; 64-78; 106-124 AND 146-170, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [13]
RP IDENTITY OF FR AND BVR-B.
RX PubMed=8687377;
RA Shalloe F., Elliott G., Ennis O., Mantle T.J.;
RT "Evidence that biliverdin-IX beta reductase and flavin reductase are
RT identical.";
RL Biochem. J. 316:385-387(1996).
RN [14]
RP FUNCTION, ENZYME REGULATION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10620517; DOI=10.1042/0264-6021:3450393;
RA Cunningham O., Gore M.G., Mantle T.J.;
RT "Initial-rate kinetics of the flavin reductase reaction catalysed by
RT human biliverdin-IXbeta reductase (BVR-B).";
RL Biochem. J. 345:393-399(2000).
RN [15]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-153.
RX PubMed=18241201; DOI=10.1042/BJ20071495;
RA Smith L.J., Browne S., Mulholland A.J., Mantle T.J.;
RT "Computational and experimental studies on the catalytic mechanism of
RT biliverdin-IXbeta reductase.";
RL Biochem. J. 411:475-484(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) IN COMPLEXES WITH
RP MESOBILIVERDIN; BILIVERDIN; FLAVIN MONONUCLEOTIDE; LUMICHROME AND
RP NADP, AND SUBUNIT.
RX PubMed=11224564; DOI=10.1038/84948;
RA Pereira P.J., Macedo-Ribeiro S., Parraga A., Perez-Luque R.,
RA Cunningham O., Darcy K., Mantle T.J., Coll M.;
RT "Structure of human biliverdin IXbeta reductase, an early fetal
RT bilirubin IXbeta producing enzyme.";
RL Nat. Struct. Biol. 8:215-220(2001).
CC -!- FUNCTION: Broad specificity oxidoreductase that catalyzes the
CC NADPH-dependent reduction of a variety of flavins, such as
CC riboflavin, FAD or FMN, biliverdins, methemoglobin and PQQ
CC (pyrroloquinoline quinone). Contributes to heme catabolism and
CC metabolizes linear tetrapyrroles. Can also reduce the complexed
CC Fe(3+) iron to Fe(2+) in the presence of FMN and NADPH. In the
CC liver, converts biliverdin to bilirubin.
CC -!- CATALYTIC ACTIVITY: Reduced riboflavin + NADP(+) = riboflavin +
CC NADPH.
CC -!- CATALYTIC ACTIVITY: Bilirubin + NAD(P)(+) = biliverdin + NAD(P)H.
CC -!- ENZYME REGULATION: Mesobiliverdin acts as competitve inhibitor for
CC flavin reduction, indicating that flavin and tetrapyrrole
CC substrates compete for the same site.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=36 uM for NADP;
CC KM=5.6 mM for NADH;
CC KM=0.3 uM for biliverdin IX-beta;
CC KM=52 uM for FMN;
CC KM=125 uM for FAD;
CC KM=53 uM for riboflavin;
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in liver and
CC erythrocytes. At lower levels in heart, lung, adrenal gland and
CC cerebrum.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/blvrb/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; D26308; BAA05370.1; -; mRNA.
DR EMBL; D32143; BAA06874.1; -; mRNA.
DR EMBL; AK312137; BAG35073.1; -; mRNA.
DR EMBL; AY340485; AAP88933.1; -; Genomic_DNA.
DR EMBL; AC010271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471126; EAW56969.1; -; Genomic_DNA.
DR EMBL; BC109371; AAI09372.1; -; mRNA.
DR PIR; JC2070; JC2070.
DR RefSeq; NP_000704.1; NM_000713.2.
DR UniGene; Hs.515785; -.
DR PDB; 1HDO; X-ray; 1.15 A; A=1-206.
DR PDB; 1HE2; X-ray; 1.20 A; A=1-206.
DR PDB; 1HE3; X-ray; 1.40 A; A=1-206.
DR PDB; 1HE4; X-ray; 1.40 A; A=1-206.
DR PDB; 1HE5; X-ray; 1.50 A; A=1-206.
DR PDBsum; 1HDO; -.
DR PDBsum; 1HE2; -.
DR PDBsum; 1HE3; -.
DR PDBsum; 1HE4; -.
DR PDBsum; 1HE5; -.
DR ProteinModelPortal; P30043; -.
DR SMR; P30043; 1-205.
DR IntAct; P30043; 5.
DR MINT; MINT-5001335; -.
DR STRING; 9606.ENSP00000263368; -.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00140; Riboflavin.
DR PhosphoSite; P30043; -.
DR DMDM; 1706870; -.
DR DOSAC-COBS-2DPAGE; P30043; -.
DR REPRODUCTION-2DPAGE; IPI00783862; -.
DR SWISS-2DPAGE; P30043; -.
DR UCD-2DPAGE; P30043; -.
DR PaxDb; P30043; -.
DR PRIDE; P30043; -.
DR Ensembl; ENST00000263368; ENSP00000263368; ENSG00000090013.
DR GeneID; 645; -.
DR KEGG; hsa:645; -.
DR UCSC; uc002onw.2; human.
DR CTD; 645; -.
DR GeneCards; GC19M040953; -.
DR HGNC; HGNC:1063; BLVRB.
DR HPA; HPA041698; -.
DR HPA; HPA041937; -.
DR MIM; 600941; gene.
DR neXtProt; NX_P30043; -.
DR PharmGKB; PA25374; -.
DR eggNOG; NOG239698; -.
DR HOGENOM; HOG000262432; -.
DR HOVERGEN; HBG050695; -.
DR InParanoid; P30043; -.
DR KO; K05901; -.
DR OMA; TDEYNGH; -.
DR Reactome; REACT_111217; Metabolism.
DR EvolutionaryTrace; P30043; -.
DR GenomeRNAi; 645; -.
DR NextBio; 2618; -.
DR PRO; PR:P30043; -.
DR ArrayExpress; P30043; -.
DR Bgee; P30043; -.
DR CleanEx; HS_BLVRB; -.
DR Genevestigator; P30043; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0004074; F:biliverdin reductase activity; IDA:UniProtKB.
DR GO; GO:0042602; F:riboflavin reductase (NADPH) activity; IDA:UniProtKB.
DR GO; GO:0042167; P:heme catabolic process; IDA:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR016040; NAD(P)-bd_dom.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Direct protein sequencing;
KW NADP; Oxidoreductase; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 206 Flavin reductase (NADPH).
FT /FTId=PRO_0000064948.
FT NP_BIND 10 15 NADP.
FT NP_BIND 54 55 NADP.
FT NP_BIND 75 78 NADP.
FT BINDING 35 35 NADP.
FT BINDING 132 132 NADP.
FT BINDING 153 153 Substrate.
FT BINDING 154 154 NADP; via amide nitrogen.
FT VARIANT 46 46 R -> Q (in dbSNP:rs11547746).
FT /FTId=VAR_019168.
FT MUTAGEN 153 153 H->A: Reduced affinity for biliverdin.
FT CONFLICT 16 16 G -> C (in Ref. 9; AA sequence).
FT STRAND 5 10
FT HELIX 14 25
FT STRAND 29 35
FT HELIX 37 39
FT STRAND 42 44
FT STRAND 48 53
FT HELIX 58 65
FT STRAND 69 73
FT HELIX 86 101
FT STRAND 105 109
FT HELIX 112 114
FT HELIX 118 120
FT HELIX 123 125
FT HELIX 126 141
FT STRAND 144 149
FT STRAND 152 155
FT STRAND 164 169
FT STRAND 174 177
FT HELIX 178 187
FT HELIX 188 190
FT TURN 193 196
FT STRAND 198 202
SQ SEQUENCE 206 AA; 22119 MW; 3057E6D69A9F9F9F CRC64;
MAVKKIAIFG ATGQTGLTTL AQAVQAGYEV TVLVRDSSRL PSEGPRPAHV VVGDVLQAAD
VDKTVAGQDA VIVLLGTRND LSPTTVMSEG ARNIVAAMKA HGVDKVVACT SAFLLWDPTK
VPPRLQAVTD DHIRMHKVLR ESGLKYVAVM PPHIGDQPLT GAYTVTLDGR GPSRVISKHD
LGHFMLRCLT TDEYDGHSTY PSHQYQ
//
MIM
600941
*RECORD*
*FIELD* NO
600941
*FIELD* TI
*600941 BILIVERDIN REDUCTASE B; BLVRB
;;BVRB;;
NADPH-FLAVIN REDUCTASE; FLR;;
METHEMOGLOBIN REDUCTASE;;
read moreNADPH REDUCTASE
*FIELD* TX
DESCRIPTION
The final step in heme metabolism in mammals is catalyzed by the
cytosolic biliverdin reductase enzymes A and B (EC 1.3.1.24).
CLONING
Yamaguchi et al. (1993) isolated 2 biliverdin reductases. BLVRB, which
they called biliverdin-IX beta-reductase, is found predominantly in
fetal liver. BLVRA (109750), which they called biliverdin-IX
alpha-reductase, is a major component of human adult liver and is
identical to the enzyme previously reported as biliverdin reductase.
Chikuba et al. (1994) isolated a cDNA encoding human erythrocyte
NADPH-flavin reductase (FLR) from a human reticulocyte library. The FLR
cDNA, which appeared to be identical to the BLVRB cDNA, encodes a
deduced 206-amino acid protein. Western blot analysis of rat tissues
showed highest levels of FLR in the erythrocytes and liver. Northern
blot analysis detected a 1.1-kb transcript in human tissues. FLR had
previously been isolated as an NADPH-dependent diaphorase, designated
diaphorase-2 (DIA2), by Fisher et al. (1977) and has also been called
methemoglobin reductase and NADPH reductase. Yubisui et al. (1977, 1979)
found that flavins are the effective electron acceptor of the enzyme and
purified FLR to homogeneity.
Quandt and Hultquist (1994) cloned bovine liver NADPH-flavin reductase.
The deduced bovine FLR protein shares 91% sequence homology with human
BLVRB.
Komuro et al. (1994) confirmed the identity of the human BLVRB and FLR
proteins. Northern blot analysis detected highest expression of BLVRB in
fetal liver and adult skeletal muscle and liver.
MAPPING
By fluorescence in situ hybridization using a 0.76-kb cDNA fragment as a
probe, Saito et al. (1995) mapped the BLVRB gene to chromosome
19q13.13-q13.2. The BLVRA gene maps to 7p14-cen.
*FIELD* RF
1. Chikuba, K.; Yubisui, T.; Shirabe, K.; Takeshita, M.: Cloning
and nucleotide sequence of a cDNA of the human erythrocyte NADPH-flavin
reductase. Biochem. Biophys. Res. Commun. 198: 1170-1176, 1994.
2. Fisher, R. A.; Edwards, Y. H.; Putt, W.; Potter, J.: An interpretation
of human diaphorase isozymes in terms of three gene loci DIA-1, DIA-2,
and DIA-3. Ann. Hum. Genet. 41: 139-149, 1977.
3. Komuro, A.; Tobe, T.; Hashimoto, K.; Nakano, Y.; Yamaguchi, T.;
Nakajima, H.; Tomita, M.: Molecular cloning and expression of human
liver biliverdin-IX-beta reductase. Biol. Pharm. Bull. 19: 796-804,
1994.
4. Quandt, K. S.; Hultquist, D. E.: Flavin reductase: sequence of
cDNA from bovine liver and tissue distribution. Proc. Nat. Acad.
Sci. 91: 9322-9326, 1994.
5. Saito, F.; Yamaguchi, T.; Komuro, A.; Tobe, T.; Ikeuchi, T.; Tomita,
M.; Nakajima, H.: Mapping of the newly identified biliverdin-IX beta-reductase
gene (BLVRB) to human chromosome 19q13.13-q13.2 by fluorescence in
situ hybridization. Cytogenet. Cell Genet. 71: 179-181, 1995.
6. Yamaguchi, T.; Komuro, A.; Nakano, Y.; Tomita, M.; Nakajima, H.
: Complete amino acid sequence of biliverdin-IX beta reductase from
human liver. Biochem. Biophys. Res. Commun. 197: 1518-1523, 1993.
7. Yubisui, T.; Matsuki, T.; Takeshita, M.; Yoneyama, Y.: Characterization
of the purified NADPH-flavin reductase of human erythrocytes. J.
Biochem. 85: 719-728, 1979.
8. Yubisui, T.; Matsuki, T.; Tanishima, K.; Takeshita, M.; Yoneyama,
Y.: NADPH-flavin reductase in human erythrocytes and the reduction
of methemoglobin through flavin by the enzyme. Biochem. Biophys.
Res. Commun. 76: 174-182, 1977.
*FIELD* CN
Carol A. Bocchini - updated: 07/09/2009
*FIELD* CD
Victor A. McKusick: 11/13/1995
*FIELD* ED
carol: 07/09/2009
terry: 7/1/2009
carol: 6/30/2009
cwells: 1/16/2003
terry: 1/15/2003
carol: 4/8/1999
terry: 2/6/1996
mark: 11/13/1995
*RECORD*
*FIELD* NO
600941
*FIELD* TI
*600941 BILIVERDIN REDUCTASE B; BLVRB
;;BVRB;;
NADPH-FLAVIN REDUCTASE; FLR;;
METHEMOGLOBIN REDUCTASE;;
read moreNADPH REDUCTASE
*FIELD* TX
DESCRIPTION
The final step in heme metabolism in mammals is catalyzed by the
cytosolic biliverdin reductase enzymes A and B (EC 1.3.1.24).
CLONING
Yamaguchi et al. (1993) isolated 2 biliverdin reductases. BLVRB, which
they called biliverdin-IX beta-reductase, is found predominantly in
fetal liver. BLVRA (109750), which they called biliverdin-IX
alpha-reductase, is a major component of human adult liver and is
identical to the enzyme previously reported as biliverdin reductase.
Chikuba et al. (1994) isolated a cDNA encoding human erythrocyte
NADPH-flavin reductase (FLR) from a human reticulocyte library. The FLR
cDNA, which appeared to be identical to the BLVRB cDNA, encodes a
deduced 206-amino acid protein. Western blot analysis of rat tissues
showed highest levels of FLR in the erythrocytes and liver. Northern
blot analysis detected a 1.1-kb transcript in human tissues. FLR had
previously been isolated as an NADPH-dependent diaphorase, designated
diaphorase-2 (DIA2), by Fisher et al. (1977) and has also been called
methemoglobin reductase and NADPH reductase. Yubisui et al. (1977, 1979)
found that flavins are the effective electron acceptor of the enzyme and
purified FLR to homogeneity.
Quandt and Hultquist (1994) cloned bovine liver NADPH-flavin reductase.
The deduced bovine FLR protein shares 91% sequence homology with human
BLVRB.
Komuro et al. (1994) confirmed the identity of the human BLVRB and FLR
proteins. Northern blot analysis detected highest expression of BLVRB in
fetal liver and adult skeletal muscle and liver.
MAPPING
By fluorescence in situ hybridization using a 0.76-kb cDNA fragment as a
probe, Saito et al. (1995) mapped the BLVRB gene to chromosome
19q13.13-q13.2. The BLVRA gene maps to 7p14-cen.
*FIELD* RF
1. Chikuba, K.; Yubisui, T.; Shirabe, K.; Takeshita, M.: Cloning
and nucleotide sequence of a cDNA of the human erythrocyte NADPH-flavin
reductase. Biochem. Biophys. Res. Commun. 198: 1170-1176, 1994.
2. Fisher, R. A.; Edwards, Y. H.; Putt, W.; Potter, J.: An interpretation
of human diaphorase isozymes in terms of three gene loci DIA-1, DIA-2,
and DIA-3. Ann. Hum. Genet. 41: 139-149, 1977.
3. Komuro, A.; Tobe, T.; Hashimoto, K.; Nakano, Y.; Yamaguchi, T.;
Nakajima, H.; Tomita, M.: Molecular cloning and expression of human
liver biliverdin-IX-beta reductase. Biol. Pharm. Bull. 19: 796-804,
1994.
4. Quandt, K. S.; Hultquist, D. E.: Flavin reductase: sequence of
cDNA from bovine liver and tissue distribution. Proc. Nat. Acad.
Sci. 91: 9322-9326, 1994.
5. Saito, F.; Yamaguchi, T.; Komuro, A.; Tobe, T.; Ikeuchi, T.; Tomita,
M.; Nakajima, H.: Mapping of the newly identified biliverdin-IX beta-reductase
gene (BLVRB) to human chromosome 19q13.13-q13.2 by fluorescence in
situ hybridization. Cytogenet. Cell Genet. 71: 179-181, 1995.
6. Yamaguchi, T.; Komuro, A.; Nakano, Y.; Tomita, M.; Nakajima, H.
: Complete amino acid sequence of biliverdin-IX beta reductase from
human liver. Biochem. Biophys. Res. Commun. 197: 1518-1523, 1993.
7. Yubisui, T.; Matsuki, T.; Takeshita, M.; Yoneyama, Y.: Characterization
of the purified NADPH-flavin reductase of human erythrocytes. J.
Biochem. 85: 719-728, 1979.
8. Yubisui, T.; Matsuki, T.; Tanishima, K.; Takeshita, M.; Yoneyama,
Y.: NADPH-flavin reductase in human erythrocytes and the reduction
of methemoglobin through flavin by the enzyme. Biochem. Biophys.
Res. Commun. 76: 174-182, 1977.
*FIELD* CN
Carol A. Bocchini - updated: 07/09/2009
*FIELD* CD
Victor A. McKusick: 11/13/1995
*FIELD* ED
carol: 07/09/2009
terry: 7/1/2009
carol: 6/30/2009
cwells: 1/16/2003
terry: 1/15/2003
carol: 4/8/1999
terry: 2/6/1996
mark: 11/13/1995