NB5R3_RAT
ID NB5R3_RAT Reviewed; 301 AA.
AC P20070; Q64569; Q64720;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=NADH-cytochrome b5 reductase 3 {ECO:0000305};
DE Short=B5R;
DE Short=Cytochrome b5 reductase;
DE EC=1.6.2.2 {ECO:0000250|UniProtKB:P00387};
DE AltName: Full=Diaphorase-1;
DE Contains:
DE RecName: Full=NADH-cytochrome b5 reductase 3 membrane-bound form;
DE Contains:
DE RecName: Full=NADH-cytochrome b5 reductase 3 soluble form;
GN Name=Cyb5r3 {ECO:0000312|RGD:2502}; Synonyms=Dia1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=2391344; DOI=10.1093/oxfordjournals.jbchem.a123130;
RA Zenno S., Hattori M., Misumi Y., Yubisui T., Sakaki Y.;
RT "Molecular cloning of a cDNA encoding rat NADH-cytochrome b5 reductase and
RT the corresponding gene.";
RL J. Biochem. 107:810-816(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=3174630; DOI=10.1073/pnas.85.19.7246;
RA Pietrini G., Carrera P., Borgese N.;
RT "Two transcripts encode rat cytochrome b5 reductase.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7246-7250(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-37 (ISOFORMS 1; 2 AND 3), AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley, and Wistar; TISSUE=Liver, and Reticulocyte;
RX PubMed=1577871; DOI=10.1083/jcb.117.5.975;
RA Pietrini G., Aggujaro D., Carrera P., Malyszko J., Vitale A., Borgese N.;
RT "A single mRNA, transcribed from an alternative, erythroid-specific,
RT promoter, codes for two non-myristylated forms of NADH-cytochrome b5
RT reductase.";
RL J. Cell Biol. 117:975-986(1992).
RN [5]
RP PROTEIN SEQUENCE OF 2-25, AND MYRISTOYLATION AT GLY-2.
RC TISSUE=Liver;
RX PubMed=2498303; DOI=10.1093/oxfordjournals.jbchem.a122659;
RA Murakami K., Yubisui T., Takeshita M., Miyata T.;
RT "The NH2-terminal structures of human and rat liver microsomal NADH-
RT cytochrome b5 reductases.";
RL J. Biochem. 105:312-317(1989).
RN [6]
RP ALTERNATIVE SPLICING.
RX PubMed=8143727; DOI=10.1111/j.1432-1033.1994.tb18673.x;
RA Mota Vieira L., Kaplan J.-C., Kahn A., Leroux A.;
RT "Heterogeneity of the rat NADH-cytochrome-b5-reductase transcripts
RT resulting from multiple alternative first exons.";
RL Eur. J. Biochem. 220:729-737(1994).
RN [7]
RP ROLE OF MYRISTOYLATION.
RX PubMed=8978818; DOI=10.1083/jcb.135.6.1501;
RA Borgese N., Aggujaro D., Carrera P., Pietrini G., Bassetti M.;
RT "A role for N-myristoylation in protein targeting: NADH-cytochrome b5
RT reductase requires myristic acid for association with outer mitochondrial
RT but not ER membranes.";
RL J. Cell Biol. 135:1501-1513(1996).
RN [8]
RP FAD-BINDING.
RX PubMed=8812833; DOI=10.1006/prep.1996.0072;
RA Barber M.J., Quinn G.B.;
RT "High-level expression in Escherichia coli of the soluble, catalytic domain
RT of rat hepatic cytochrome b5 reductase.";
RL Protein Expr. Purif. 8:41-47(1996).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-301.
RX PubMed=11695905; DOI=10.1021/bi0106336;
RA Bewley M.C., Marohnic C.C., Barber M.J.;
RT "The structure and biochemistry of NADH-dependent cytochrome b5 reductase
RT are now consistent.";
RL Biochemistry 40:13574-13582(2001).
CC -!- FUNCTION: Transfers two electrons from NADH to two molecules of
CC cytochrome b5 through an enzyme-bound FAD. Electrons from the reduced
CC cytochrome b5 are then transferred to various electron acceptors,
CC thereby participating in methemoglobin reduction in red blood cells and
CC in the desaturation and elongation of fatty acids, cholesterol
CC biosynthesis and cytochrome P-450-mediated drug metabolism other
CC tissues. {ECO:0000250|UniProtKB:P00387}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] +
CC H(+) + NAD(+); Xref=Rhea:RHEA:46680, Rhea:RHEA-COMP:10438, Rhea:RHEA-
CC COMP:10439, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.6.2.2;
CC Evidence={ECO:0000250|UniProtKB:P00387};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46681;
CC Evidence={ECO:0000250|UniProtKB:P00387};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:8812833};
CC -!- SUBUNIT: Component of a complex composed of cytochrome b5, NADH-
CC cytochrome b5 reductase (CYB5R3) and MTARC2 (By similarity). Interacts
CC with MTLN; the interaction is required to maintain cellular lipid
CC composition and leads to stimulation of mitochondrial respiratory
CC complex I activity (By similarity). {ECO:0000250|UniProtKB:P83686,
CC ECO:0000250|UniProtKB:Q9DCN2}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane;
CC Lipid-anchor; Cytoplasmic side. Mitochondrion outer membrane; Lipid-
CC anchor; Cytoplasmic side.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm. Note=Produces the soluble
CC form found in erythrocytes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative initiation; Named isoforms=3;
CC Name=1; Synonyms=L-form reticulocyte reductase;
CC IsoId=P20070-1; Sequence=Displayed;
CC Name=2; Synonyms=R-form reticulocyte reductase;
CC IsoId=P20070-2; Sequence=VSP_009661;
CC Name=3; Synonyms=Soluble form;
CC IsoId=P20070-3; Sequence=VSP_009660;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 3 are ubiquitously expressed.
CC Isoform 2 is expressed only in erythroid tissues, reticulocytes and
CC liver. {ECO:0000269|PubMed:1577871}.
CC -!- PTM: Only the isoform 1 is myristoyled.
CC -!- MISCELLANEOUS: [Isoform 1]: Produced by alternative promoter usage.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative initiation.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
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DR EMBL; D00636; BAA00530.1; -; mRNA.
DR EMBL; J03867; AAA41008.1; -; mRNA.
DR EMBL; BC062066; AAH62066.1; -; mRNA.
DR EMBL; X65191; CAA46308.1; -; mRNA.
DR EMBL; X65191; CAA46309.1; -; mRNA.
DR EMBL; X65190; CAA46307.1; -; Genomic_DNA.
DR EMBL; X77117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A40495; RDRTB5.
DR PIR; S23641; S23641.
DR RefSeq; NP_620232.1; NM_138877.1. [P20070-1]
DR RefSeq; XP_006242127.1; XM_006242065.3. [P20070-2]
DR PDB; 1I7P; X-ray; 2.00 A; A=34-301.
DR PDB; 1IB0; X-ray; 2.30 A; A=34-301.
DR PDB; 1QX4; X-ray; 1.80 A; A/B=34-301.
DR PDBsum; 1I7P; -.
DR PDBsum; 1IB0; -.
DR PDBsum; 1QX4; -.
DR AlphaFoldDB; P20070; -.
DR SMR; P20070; -.
DR CORUM; P20070; -.
DR IntAct; P20070; 3.
DR STRING; 10116.ENSRNOP00000012878; -.
DR ChEMBL; CHEMBL4523194; -.
DR iPTMnet; P20070; -.
DR PhosphoSitePlus; P20070; -.
DR SwissPalm; P20070; -.
DR jPOST; P20070; -.
DR PaxDb; P20070; -.
DR PRIDE; P20070; -.
DR Ensembl; ENSRNOT00000102247; ENSRNOP00000077900; ENSRNOG00000009592. [P20070-1]
DR Ensembl; ENSRNOT00000111302; ENSRNOP00000082175; ENSRNOG00000009592. [P20070-2]
DR GeneID; 25035; -.
DR KEGG; rno:25035; -.
DR CTD; 1727; -.
DR RGD; 2502; Cyb5r3.
DR eggNOG; KOG0534; Eukaryota.
DR GeneTree; ENSGT00940000153962; -.
DR HOGENOM; CLU_003827_9_2_1; -.
DR InParanoid; P20070; -.
DR OMA; HAKERCF; -.
DR OrthoDB; 1311668at2759; -.
DR PhylomeDB; P20070; -.
DR TreeFam; TF314333; -.
DR BRENDA; 1.6.2.2; 5301.
DR Reactome; R-RNO-196836; Vitamin C (ascorbate) metabolism.
DR Reactome; R-RNO-211945; Phase I - Functionalization of compounds.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR SABIO-RK; P20070; -.
DR EvolutionaryTrace; P20070; -.
DR PRO; PR:P20070; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000009592; Expressed in lung and 19 other tissues.
DR Genevisible; P20070; RN.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:HGNC-UCL.
DR GO; GO:0005811; C:lipid droplet; ISO:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1903958; C:nitric-oxide synthase complex; ISO:RGD.
DR GO; GO:0043531; F:ADP binding; IDA:RGD.
DR GO; GO:0016208; F:AMP binding; IDA:RGD.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; ISO:RGD.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:RGD.
DR GO; GO:0051287; F:NAD binding; IDA:RGD.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; ISO:RGD.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR001834; CBR-like.
DR InterPro; IPR008333; Cbr1-like_FAD-bd_dom.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR PANTHER; PTHR19370; PTHR19370; 1.
DR Pfam; PF00970; FAD_binding_6; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR PRINTS; PR00371; FPNCR.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation;
KW Alternative promoter usage; Cholesterol biosynthesis;
KW Cholesterol metabolism; Cytoplasm; Direct protein sequencing;
KW Endoplasmic reticulum; FAD; Flavoprotein; Lipid biosynthesis;
KW Lipid metabolism; Lipoprotein; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Myristate; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2498303"
FT CHAIN 2..301
FT /note="NADH-cytochrome b5 reductase 3 membrane-bound form"
FT /id="PRO_0000019401"
FT CHAIN 27..301
FT /note="NADH-cytochrome b5 reductase 3 soluble form"
FT /id="PRO_0000019403"
FT DOMAIN 40..152
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 132..147
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT BINDING 171..206
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT MOD_RES 42
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00387"
FT MOD_RES 43
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P00387"
FT MOD_RES 50
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN2"
FT MOD_RES 120
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN2"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:2498303"
FT VAR_SEQ 1..23
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1577871"
FT /id="VSP_009660"
FT VAR_SEQ 1..7
FT /note="MGAQLST -> MLGPLLWTASLPV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1577871"
FT /id="VSP_009661"
FT CONFLICT 105
FT /note="F -> L (in Ref. 2; AAA41008)"
FT /evidence="ECO:0000305"
FT STRAND 43..52
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 54..63
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 78..85
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 88..94
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:1I7P"
FT HELIX 126..132
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 173..180
FT /evidence="ECO:0007829|PDB:1QX4"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:1QX4"
FT HELIX 184..196
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 203..212
FT /evidence="ECO:0007829|PDB:1QX4"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:1QX4"
FT HELIX 219..228
FT /evidence="ECO:0007829|PDB:1QX4"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 233..241
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:1QX4"
FT HELIX 255..261
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 269..275
FT /evidence="ECO:0007829|PDB:1QX4"
FT HELIX 277..282
FT /evidence="ECO:0007829|PDB:1QX4"
FT HELIX 285..291
FT /evidence="ECO:0007829|PDB:1QX4"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:1QX4"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:1QX4"
SQ SEQUENCE 301 AA; 34175 MW; 45431A644413905F CRC64;
MGAQLSTLSR VVLSPVWFVY SLFMKLFQRS SPAITLENPD IKYPLRLIDK EIISHDTRRF
RFALPSPQHI LGLPIGQHIY LSTRIDGNLV IRPYTPVSSD DDKGFVDLVV KVYFKDTHPK
FPAGGKMSQY LENMNIGDTI EFRGPNGLLV YQGKGKFAIR ADKKSNPVVR TVKSVGMIAG
GTGITPMLQV IRAVLKDPND HTVCYLLFAN QSEKDILLRP ELEELRNEHS SRFKLWYTVD
KAPDAWDYSQ GFVNEEMIRD HLPPPGEETL ILMCGPPPMI QFACLPNLER VGHPKERCFT
F
