NB5R3_BOVIN
ID NB5R3_BOVIN Reviewed; 301 AA.
AC P07514; A6H7G0;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 3.
DT 03-AUG-2022, entry version 166.
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; Synonyms=DIA1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 2-301.
RC STRAIN=Black Angus; TISSUE=Liver;
RX PubMed=3900065; DOI=10.1016/s0021-9258(17)38970-6;
RA Ozols J., Korza G., Heinemann F.S., Hediger M.A., Strittmatter P.;
RT "Complete amino acid sequence of steer liver microsomal NADH-cytochrome b5
RT reductase.";
RL J. Biol. Chem. 260:11953-11961(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-301, AND MUTAGENESIS.
RX PubMed=1370824; DOI=10.1016/s0021-9258(18)45910-8;
RA Strittmatter P., Kittler J.M., Coghill J.E., Ozols J.;
RT "Characterization of lysyl residues of NADH-cytochrome b5 reductase
RT implicated in charge-pairing with active-site carboxyl residues of
RT cytochrome b5 by site-directed mutagenesis of an expression vector for the
RT flavoprotein.";
RL J. Biol. Chem. 267:2519-2523(1992).
RN [4]
RP PROTEIN SEQUENCE OF 27-53.
RX PubMed=3654589; DOI=10.1093/oxfordjournals.jbchem.a121979;
RA Tamura M., Yubisui T., Takeshita M., Kawabata S., Miyata T., Iwanaga S.;
RT "Structural comparison of bovine erythrocyte, brain, and liver NADH-
RT cytochrome b5 reductase by HPLC mapping.";
RL J. Biochem. 101:1147-1159(1987).
RN [5]
RP PROTEIN SEQUENCE OF 2-37, AND MYRISTOYLATION AT GLY-2.
RX PubMed=6436247; DOI=10.1016/s0021-9258(18)90701-5;
RA Ozols J., Carr S.A., Strittmatter P.;
RT "Identification of the NH2-terminal blocking group of NADH-cytochrome b5
RT reductase as myristic acid and the complete amino acid sequence of the
RT membrane-binding domain.";
RL J. Biol. Chem. 259:13349-13354(1984).
RN [6]
RP PROTEIN SEQUENCE OF 17-44.
RX PubMed=6643503; DOI=10.1016/s0021-9258(17)43913-5;
RA Kensil C.R., Hediger M.A., Ozols J., Strittmatter P.;
RT "Isolation and partial characterization of the NH2-terminal membrane-
RT binding domain of NADH-cytochrome b5 reductase.";
RL J. Biol. Chem. 258:14656-14663(1983).
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:0000250|UniProtKB:P00387};
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: [NADH-cytochrome b5 reductase 3 membrane-bound
CC form]: Endoplasmic reticulum membrane; Lipid-anchor; Cytoplasmic side.
CC Mitochondrion outer membrane; Lipid-anchor; Cytoplasmic side. Note=The
CC enzyme exists in two forms, a membrane-bound form on the cytoplasmic
CC side of the endoplasmic reticulum and also on the mitochondrial outer
CC membrane and in soluble form in erythrocytes.
CC -!- SUBCELLULAR LOCATION: [NADH-cytochrome b5 reductase 3 soluble form]:
CC Cytoplasm.
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
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DR EMBL; BC146232; AAI46233.1; -; mRNA.
DR EMBL; M83104; AAA30483.1; -; mRNA.
DR PIR; A42328; RDBOB5.
DR RefSeq; NP_001096720.1; NM_001103250.1.
DR AlphaFoldDB; P07514; -.
DR SMR; P07514; -.
DR STRING; 9913.ENSBTAP00000040254; -.
DR iPTMnet; P07514; -.
DR PaxDb; P07514; -.
DR PeptideAtlas; P07514; -.
DR PRIDE; P07514; -.
DR Ensembl; ENSBTAT00000079355; ENSBTAP00000071053; ENSBTAG00000016516.
DR GeneID; 515773; -.
DR KEGG; bta:515773; -.
DR CTD; 1727; -.
DR VEuPathDB; HostDB:ENSBTAG00000016516; -.
DR VGNC; VGNC:49054; CYB5R3.
DR eggNOG; KOG0534; Eukaryota.
DR GeneTree; ENSGT00940000153962; -.
DR InParanoid; P07514; -.
DR OMA; HAKERCF; -.
DR OrthoDB; 1311668at2759; -.
DR BRENDA; 1.6.2.2; 908.
DR SABIO-RK; P07514; -.
DR Proteomes; UP000009136; Chromosome 5.
DR Bgee; ENSBTAG00000016516; Expressed in subcutaneous adipose tissue and 109 other tissues.
DR ExpressionAtlas; P07514; baseline and differential.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; IEA:UniProtKB-EC.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
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 Acetylation; Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm;
KW Direct protein sequencing; Endoplasmic reticulum; FAD; Flavoprotein;
KW Lipid biosynthesis; 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:3900065,
FT ECO:0000269|PubMed:6436247"
FT CHAIN 2..301
FT /note="NADH-cytochrome b5 reductase 3 membrane-bound form"
FT /id="PRO_0000019389"
FT CHAIN 27..301
FT /note="NADH-cytochrome b5 reductase 3 soluble form"
FT /id="PRO_0000019391"
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 /evidence="ECO:0000250"
FT BINDING 171..206
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
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:6436247"
FT MUTAGEN 42
FT /note="K->E: Decrease of activity."
FT /evidence="ECO:0000269|PubMed:1370824"
FT MUTAGEN 126
FT /note="K->E: Decrease of activity."
FT /evidence="ECO:0000269|PubMed:1370824"
FT MUTAGEN 164
FT /note="K->E: Decrease of activity."
FT /evidence="ECO:0000269|PubMed:1370824"
FT CONFLICT 16
FT /note="V -> L (in Ref. 2; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="K -> G (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="K -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="N -> D (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 301 AA; 34122 MW; 435229B893B2A3DA CRC64;
MGAQLSTLGH VVLSPVWFLY SLIMKLFQRS TPAITLENPD IKYPLRLIDK EVISHDTRRF
RFALPSPEHI LGLPVGQHIY LSARIDGNLV IRPYTPVSSD DDKGFVDLVI KVYFKDTHPK
FPAGGKMSQY LESMKIGDTI EFRGPNGLLV YQGKGKFAIR PDKKSDPVIK TVKSVGMIAG
GTGITPMLQV IRAIMKDPDD HTVCHLLFAN QTEKDILLRP ELEELRNEHS ARFKLWYTVD
KAPEAWDYSQ GFVNEEMIRD HLPPPEEEPL VLMCGPPPMI QYACLPNLDR VGHPKERCFA
F
