MCR1_YEAST
ID MCR1_YEAST Reviewed; 302 AA.
AC P36060; A2TBM9; D6VX47;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=NADH-cytochrome b5 reductase 2 {ECO:0000303|PubMed:8001120};
DE EC=1.6.2.2 {ECO:0000305|PubMed:8001120};
DE AltName: Full=Mitochondrial cytochrome b reductase {ECO:0000303|PubMed:8001120};
DE AltName: Full=p34/p32 {ECO:0000303|PubMed:8001120};
DE Contains:
DE RecName: Full=NADH-cytochrome b5 reductase p34 form {ECO:0000303|PubMed:8001120};
DE Contains:
DE RecName: Full=NADH-cytochrome b5 reductase p32 form {ECO:0000303|PubMed:8001120};
DE Flags: Precursor;
GN Name=MCR1 {ECO:0000303|PubMed:8001120}; OrderedLocusNames=YKL150W;
GN ORFNames=YKL605;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 42-52; 70-89 AND
RP 99-113, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8001120; DOI=10.1016/0092-8674(94)90072-8;
RA Hahne K., Haucke V., Ramage L., Schatz G.;
RT "Incomplete arrest in the outer membrane sorts NADH-cytochrome b5 reductase
RT to two different submitochondrial compartments.";
RL Cell 79:829-839(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8091859; DOI=10.1002/yea.320100005;
RA Vandenbol M., Bolle P.-A., Dion C., Portetelle D., Hilger F.;
RT "DNA sequencing of a 36.2 kb fragment located between the FAS1 and LAP loci
RT of chromosome XI of Saccharomyces cerevisiae.";
RL Yeast 10:S35-S40(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-41.
RC STRAIN=ATCC 201390 / BY4743;
RX PubMed=17244705; DOI=10.1073/pnas.0610354104;
RA Juneau K., Palm C., Miranda M., Davis R.W.;
RT "High-density yeast-tiling array reveals previously undiscovered introns
RT and extensive regulation of meiotic splicing.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1522-1527(2007).
RN [6]
RP PROTEIN SEQUENCE OF 1-20, MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 24657 / D273-10B;
RX PubMed=16689936; DOI=10.1111/j.1742-4658.2006.05171.x;
RA Burri L., Vascotto K., Gentle I.E., Chan N.C., Beilharz T., Stapleton D.I.,
RA Ramage L., Lithgow T.;
RT "Integral membrane proteins in the mitochondrial outer membrane of
RT Saccharomyces cerevisiae.";
RL FEBS J. 273:1507-1515(2006).
RN [7]
RP PROTEIN SEQUENCE OF 42-58.
RX PubMed=9866716; DOI=10.1006/abio.1998.2863;
RA Martin H., Eckerskorn C., Gaertner F., Rassow J., Lottspeich F.,
RA Pfanner N.;
RT "The yeast mitochondrial intermembrane space: purification and analysis of
RT two distinct fractions.";
RL Anal. Biochem. 265:123-128(1998).
RN [8]
RP MUTAGENESIS OF 23-ALA-ALA-24.
RX PubMed=9199337; DOI=10.1128/mcb.17.7.4024;
RA Haucke V., Ocana C.S., Hoenlinger A., Tokatlidis K., Pfanner N., Schatz G.;
RT "Analysis of the sorting signals directing NADH-cytochrome b5 reductase to
RT two locations within yeast mitochondria.";
RL Mol. Cell. Biol. 17:4024-4032(1997).
RN [9]
RP FUNCTION.
RX PubMed=11420140; DOI=10.1016/s0304-4165(01)00134-9;
RA Lee J.-S., Huh W.-K., Lee B.-H., Baek Y.-U., Hwang C.-S., Kim S.-T.,
RA Kim Y.-R., Kang S.-O.;
RT "Mitochondrial NADH-cytochrome b(5) reductase plays a crucial role in the
RT reduction of D-erythroascorbyl free radical in Saccharomyces cerevisiae.";
RL Biochim. Biophys. Acta 1527:31-38(2001).
RN [10]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [11]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [12]
RP INDUCTION.
RX PubMed=15590813; DOI=10.1128/ec.3.6.1381-1390.2004;
RA Krantz M., Nordlander B., Valadi H., Johansson M., Gustafsson L.,
RA Hohmann S.;
RT "Anaerobicity prepares Saccharomyces cerevisiae cells for faster adaptation
RT to osmotic shock.";
RL Eukaryot. Cell 3:1381-1390(2004).
RN [13]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16407407; DOI=10.1091/mbc.e05-08-0740;
RA Zahedi R.P., Sickmann A., Boehm A.M., Winkler C., Zufall N.,
RA Schoenfisch B., Guiard B., Pfanner N., Meisinger C.;
RT "Proteomic analysis of the yeast mitochondrial outer membrane reveals
RT accumulation of a subclass of preproteins.";
RL Mol. Biol. Cell 17:1436-1450(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE
RP ANALYSIS].
RX PubMed=22984289; DOI=10.1074/mcp.m112.021105;
RA Voegtle F.N., Burkhart J.M., Rao S., Gerbeth C., Hinrichs J.,
RA Martinou J.C., Chacinska A., Sickmann A., Zahedi R.P., Meisinger C.;
RT "Intermembrane space proteome of yeast mitochondria.";
RL Mol. Cell. Proteomics 11:1840-1852(2012).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27694803; DOI=10.1038/nchembio.2190;
RA Lin Z., Dong M., Zhang Y., Lee E.A., Lin H.;
RT "Cbr1 is a Dph3 reductase required for the tRNA wobble uridine
RT modification.";
RL Nat. Chem. Biol. 12:995-997(2016).
CC -!- FUNCTION: The outer membrane form may mediate the reduction of outer
CC membrane cytochrome b5 (PubMed:8001120). The soluble inter-membrane
CC space form may transfer electrons from external NADH to cytochrome c,
CC thereby mediating an antimycin-insensitive, energy-coupled oxidation of
CC external NADH by yeast mitochondria (PubMed:8001120). Involved in the
CC reduction of D-erythroascorbyl free radicals (PubMed:11420140). May
CC play a minor role in complementing the function of CBR1 as a DPH3
CC reductase in the first step of diphthamide biosynthesis and tRNA Wobble
CC base mcm5s 2U (5-methoxycarbonylmethyl-2-thiouridine) formation
CC (PubMed:27694803). {ECO:0000269|PubMed:11420140,
CC ECO:0000269|PubMed:27694803, ECO:0000269|PubMed:8001120}.
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:0000305|PubMed:8001120};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P38038};
CC -!- INTERACTION:
CC P36060; P39940: RSP5; NbExp=2; IntAct=EBI-10565, EBI-16219;
CC -!- SUBCELLULAR LOCATION: [NADH-cytochrome b5 reductase p32 form]:
CC Mitochondrion intermembrane space {ECO:0000269|PubMed:8001120}.
CC -!- SUBCELLULAR LOCATION: [NADH-cytochrome b5 reductase p34 form]:
CC Mitochondrion outer membrane; Single-pass membrane protein.
CC Mitochondrion intermembrane space {ECO:0000269|PubMed:22984289,
CC ECO:0000269|PubMed:8001120}.
CC -!- INDUCTION: By osmotic stress. {ECO:0000269|PubMed:15590813}.
CC -!- PTM: There are two isoforms of NADH-cytochrome b5 reductase, a 34 kDa
CC form (p34) and a 32 kDa form (p32). The p34 form becomes firmly
CC anchored to the outer mitochondrial membrane after an incomplete
CC translocation arrest. The p32 form is formed after translocation of the
CC p34 precursor to the inner mitochondrial membrane, where it is
CC processed by mitochondrial inner membrane peptidase (IMP) complex and
CC released to the intermembrane space. {ECO:0000269|PubMed:8001120}.
CC -!- MASS SPECTROMETRY: [NADH-cytochrome b5 reductase p34 form]: Mass=34137;
CC Method=Unknown; Evidence={ECO:0000269|PubMed:16689936};
CC -!- DISRUPTION PHENOTYPE: Simultaneous disruption of CBR1 results in
CC resistance to diphtheria toxin and K.lactis killer toxin.
CC {ECO:0000269|PubMed:27694803}.
CC -!- MISCELLANEOUS: Present with 1920 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
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DR EMBL; X81474; CAA57227.1; -; Genomic_DNA.
DR EMBL; Z26877; CAA81503.1; -; Genomic_DNA.
DR EMBL; Z28150; CAA81991.1; -; Genomic_DNA.
DR EMBL; EF123132; ABM97476.1; -; mRNA.
DR EMBL; BK006944; DAA09013.1; -; Genomic_DNA.
DR PIR; S37800; S37800.
DR RefSeq; NP_012772.1; NM_001179716.1.
DR AlphaFoldDB; P36060; -.
DR SMR; P36060; -.
DR BioGRID; 33987; 137.
DR DIP; DIP-5475N; -.
DR IntAct; P36060; 17.
DR MINT; P36060; -.
DR STRING; 4932.YKL150W; -.
DR iPTMnet; P36060; -.
DR UCD-2DPAGE; P36060; -.
DR MaxQB; P36060; -.
DR PaxDb; P36060; -.
DR PRIDE; P36060; -.
DR EnsemblFungi; YKL150W_mRNA; YKL150W; YKL150W.
DR GeneID; 853707; -.
DR KEGG; sce:YKL150W; -.
DR SGD; S000001633; MCR1.
DR VEuPathDB; FungiDB:YKL150W; -.
DR eggNOG; KOG0534; Eukaryota.
DR HOGENOM; CLU_003827_9_1_1; -.
DR InParanoid; P36060; -.
DR OMA; NKHDHIA; -.
DR BioCyc; YEAST:YKL150W-MON; -.
DR PRO; PR:P36060; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P36060; protein.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; IDA:SGD.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:SGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; IDA:SGD.
DR GO; GO:0003954; F:NADH dehydrogenase activity; IDA:CACAO.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:SGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IDA:SGD.
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 Direct protein sequencing; FAD; Flavoprotein; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..302
FT /note="NADH-cytochrome b5 reductase p34 form"
FT /id="PRO_0000019404"
FT PROPEP 1..41
FT /note="Removed in p32 form"
FT /evidence="ECO:0000269|PubMed:8001120,
FT ECO:0000269|PubMed:9866716"
FT /id="PRO_0000019405"
FT CHAIN 42..302
FT /note="NADH-cytochrome b5 reductase p32 form"
FT /id="PRO_0000019406"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 51..155
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 158..193
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P38038"
FT SITE 41..42
FT /note="Cleavage; by IMP1"
FT MOD_RES 278
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950"
FT MUTAGEN 23..24
FT /note="AA->QQ: Prevents insertion into the outer membrane
FT and increases the efficiency of import into the
FT intermembrane space."
FT /evidence="ECO:0000269|PubMed:9199337"
FT CONFLICT 2
FT /note="Missing (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="N -> L (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 302 AA; 34138 MW; D3CB56356E8C572F CRC64;
MFSRLSRSHS KALPIALGTV AIAAATAFYF ANRNQHSFVF NESNKVFKGD DKWIDLPISK
IEEESHDTRR FTFKLPTEDS EMGLVLASAL FAKFVTPKGS NVVRPYTPVS DLSQKGHFQL
VVKHYEGGKM TSHLFGLKPN DTVSFKGPIM KWKWQPNQFK SITLLGAGTG INPLYQLAHH
IVENPNDKTK VNLLYGNKTP QDILLRKELD ALKEKYPDKF NVTYFVDDKQ DDQDFDGEIS
FISKDFIQEH VPGPKESTHL FVCGPPPFMN AYSGEKKSPK DQGELIGILN NLGYSKDQVF
KF
