NB5R3_MOUSE
ID NB5R3_MOUSE Reviewed; 301 AA.
AC Q9DCN2;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 167.
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|MGI:MGI:94893}; Synonyms=Dia1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ILS, and ISS;
RX PubMed=11471062; DOI=10.1007/s00335-001-1001-x;
RA Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J.,
RA Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.;
RT "High-throughput sequence identification of gene coding variants within
RT alcohol-related QTLs.";
RL Mamm. Genome 12:657-663(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129, C57BL/6J, and FVB/N; TISSUE=Brain, Kidney, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 127-135, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-120, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=16916647; DOI=10.1016/j.molcel.2006.06.026;
RA Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y.,
RA Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.;
RT "Substrate and functional diversity of lysine acetylation revealed by a
RT proteomics survey.";
RL Mol. Cell 23:607-618(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-42 AND LYS-50, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-42, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [9]
RP INTERACTION WITH MTLN, AND MUTAGENESIS OF GLY-2.
RX PubMed=31296841; DOI=10.1038/s41419-019-1767-y;
RA Lin Y.F., Xiao M.H., Chen H.X., Meng Y., Zhao N., Yang L., Tang H.,
RA Wang J.L., Liu X., Zhu Y., Zhuang S.M.;
RT "A novel mitochondrial micropeptide MPM enhances mitochondrial respiratory
RT activity and promotes myogenic differentiation.";
RL Cell Death Dis. 10:528-528(2019).
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 (PubMed:31296841). {ECO:0000250|UniProtKB:P83686,
CC ECO:0000269|PubMed:31296841}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P00387}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P00387}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P00387}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P00387}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P00387}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P00387}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Note=Produces the soluble
CC form found in erythrocytes. {ECO:0000250|UniProtKB:P00387}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1; Synonyms=M;
CC IsoId=Q9DCN2-1; Sequence=Displayed;
CC Name=2; Synonyms=S;
CC IsoId=Q9DCN2-2; Sequence=VSP_012952;
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
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DR EMBL; AF332059; AAK56088.1; -; mRNA.
DR EMBL; AF332060; AAK56089.1; -; mRNA.
DR EMBL; AK002640; BAB22252.1; -; mRNA.
DR EMBL; BC004760; AAH04760.1; -; mRNA.
DR EMBL; BC032013; AAH32013.1; -; mRNA.
DR EMBL; BC043074; AAH43074.1; -; mRNA.
DR CCDS; CCDS27698.1; -. [Q9DCN2-1]
DR RefSeq; NP_084063.1; NM_029787.2. [Q9DCN2-1]
DR RefSeq; XP_006520346.1; XM_006520283.3. [Q9DCN2-2]
DR AlphaFoldDB; Q9DCN2; -.
DR SMR; Q9DCN2; -.
DR BioGRID; 225010; 6.
DR DIP; DIP-57517N; -.
DR IntAct; Q9DCN2; 4.
DR MINT; Q9DCN2; -.
DR STRING; 10090.ENSMUSP00000018186; -.
DR iPTMnet; Q9DCN2; -.
DR PhosphoSitePlus; Q9DCN2; -.
DR SwissPalm; Q9DCN2; -.
DR EPD; Q9DCN2; -.
DR jPOST; Q9DCN2; -.
DR MaxQB; Q9DCN2; -.
DR PaxDb; Q9DCN2; -.
DR PeptideAtlas; Q9DCN2; -.
DR PRIDE; Q9DCN2; -.
DR ProteomicsDB; 286151; -. [Q9DCN2-1]
DR ProteomicsDB; 286152; -. [Q9DCN2-2]
DR TopDownProteomics; Q9DCN2-1; -. [Q9DCN2-1]
DR TopDownProteomics; Q9DCN2-2; -. [Q9DCN2-2]
DR Antibodypedia; 219; 442 antibodies from 36 providers.
DR DNASU; 109754; -.
DR Ensembl; ENSMUST00000018186; ENSMUSP00000018186; ENSMUSG00000018042. [Q9DCN2-1]
DR Ensembl; ENSMUST00000162834; ENSMUSP00000124062; ENSMUSG00000018042. [Q9DCN2-2]
DR GeneID; 109754; -.
DR KEGG; mmu:109754; -.
DR UCSC; uc007xac.2; mouse. [Q9DCN2-1]
DR CTD; 1727; -.
DR MGI; MGI:94893; Cyb5r3.
DR VEuPathDB; HostDB:ENSMUSG00000018042; -.
DR eggNOG; KOG0534; Eukaryota.
DR GeneTree; ENSGT00940000153962; -.
DR HOGENOM; CLU_003827_9_2_1; -.
DR InParanoid; Q9DCN2; -.
DR OMA; HAKERCF; -.
DR OrthoDB; 1311668at2759; -.
DR PhylomeDB; Q9DCN2; -.
DR TreeFam; TF314333; -.
DR BioCyc; MetaCyc:MON-14527; -.
DR Reactome; R-MMU-196836; Vitamin C (ascorbate) metabolism.
DR Reactome; R-MMU-211945; Phase I - Functionalization of compounds.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 109754; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Cyb5r3; mouse.
DR PRO; PR:Q9DCN2; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q9DCN2; protein.
DR Bgee; ENSMUSG00000018042; Expressed in placenta labyrinth and 258 other tissues.
DR ExpressionAtlas; Q9DCN2; baseline and differential.
DR Genevisible; Q9DCN2; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005811; C:lipid droplet; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1903958; C:nitric-oxide synthase complex; ISO:MGI.
DR GO; GO:0043531; F:ADP binding; ISO:MGI.
DR GO; GO:0016208; F:AMP binding; ISO:MGI.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; ISO:MGI.
DR GO; GO:0071949; F:FAD binding; ISO:MGI.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISO:MGI.
DR GO; GO:0051287; F:NAD binding; ISO:MGI.
DR GO; GO:0050421; F:nitrite reductase (NO-forming) activity; ISO:MGI.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; ISO:MGI.
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; 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:0000250|UniProtKB:P07514"
FT CHAIN 2..301
FT /note="NADH-cytochrome b5 reductase 3 membrane-bound form"
FT /id="PRO_0000019398"
FT CHAIN 27..301
FT /note="NADH-cytochrome b5 reductase 3 soluble form"
FT /id="PRO_0000019400"
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:0007744|PubMed:23576753,
FT ECO:0007744|PubMed:23806337"
FT MOD_RES 43
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P00387"
FT MOD_RES 50
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 120
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:16916647"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P00387"
FT VAR_SEQ 1..23
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_012952"
FT MUTAGEN 2
FT /note="G->A: Decreased levels in mitochondrion and reduced
FT activity of mitochondrial respiratory complex I."
FT /evidence="ECO:0000269|PubMed:31296841"
SQ SEQUENCE 301 AA; 34128 MW; 984D5B73430F725D CRC64;
MGAQLSTLSH VVLSPVWFIY SLFMKLFQRS TPAITLENPD IKYPLRLIDK EVISPDTRRF
RFALPSPQHI LGLPIGQHIY LSTRIDGNLV IRPYTPVSSD DDKGFVDLVV KVYFKDTHPK
FPAGGKMSQY LENMKIGDTI EFRGPNGLLV YQGKGKFAIR ADKKSNPVVR TVKSVGMIAG
GTGITPMLQV IRAVLKDPND HTVCYLLFAN QSEKDILLRP ELEELRNEHS ARFKLWYTVD
KAPDAWDYSQ GFVNEEMIRD HLPTPGEEPL ILMCGPPPMI QFACLPNLER VGHPKERCFT
F
