NCB5R_YEAS7
ID NCB5R_YEAS7 Reviewed; 284 AA.
AC A6ZVM6;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=NADH-cytochrome b5 reductase 1;
DE EC=1.6.2.2 {ECO:0000250|UniProtKB:P38626};
DE AltName: Full=Microsomal cytochrome b reductase;
DE AltName: Full=P35;
GN Name=CBR1; ORFNames=SCY_2742;
OS Saccharomyces cerevisiae (strain YJM789) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=307796;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=YJM789;
RX PubMed=17652520; DOI=10.1073/pnas.0701291104;
RA Wei W., McCusker J.H., Hyman R.W., Jones T., Ning Y., Cao Z., Gu Z.,
RA Bruno D., Miranda M., Nguyen M., Wilhelmy J., Komp C., Tamse R., Wang X.,
RA Jia P., Luedi P., Oefner P.J., David L., Dietrich F.S., Li Y., Davis R.W.,
RA Steinmetz L.M.;
RT "Genome sequencing and comparative analysis of Saccharomyces cerevisiae
RT strain YJM789.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:12825-12830(2007).
CC -!- FUNCTION: NADH-dependent reductase for KTI11/DPH3 and cytochrome b5.
CC Required for the first step of diphthamide biosynthesis, a post-
CC translational modification of histidine which occurs in elongation
CC factor 2. DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group
CC from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction
CC is assisted by a reduction system comprising KTI11/DPH3 and a NADH-
CC dependent reductase, predominantly CBR1. By reducing KTI11/DPH3, also
CC involved in the formation of the tRNA wobble base modification mcm5s 2U
CC (5-methoxycarbonylmethyl-2-thiouridine), mediated by the elongator
CC complex. The cytochrome b5/NADH cytochrome b5 reductase electron
CC transfer system supports the catalytic activity of several sterol
CC biosynthetic enzymes. Plays a role in bud morphology.
CC {ECO:0000250|UniProtKB:P38626}.
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:P38626};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(3+)-[Dph3] + NADH = 2 Fe(2+)-[Dph3] + H(+) + NAD(+);
CC Xref=Rhea:RHEA:71231, Rhea:RHEA-COMP:18002, Rhea:RHEA-COMP:18003,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:83228;
CC Evidence={ECO:0000250|UniProtKB:P38626};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71232;
CC Evidence={ECO:0000250|UniProtKB:P38626};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000255};
CC -!- ACTIVITY REGULATION: Competitively inhibited by NAD(+). Inhibited by
CC mercurials such as p-chloromercuribenzoate (PCMB) and HgCl(2).
CC Enzymatic activity increases under anaerobic conditions (By
CC similarity). {ECO:0000250|UniProtKB:P38626}.
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC {ECO:0000250|UniProtKB:P38626}.
CC -!- SUBUNIT: Monomer. Component of the 2-(3-amino-3-carboxypropyl)histidine
CC synthase complex composed of DPH1, DPH2, KTI11/DPH3 and a NADH-
CC dependent reductase, predominantly CBR1 (By similarity). Interacts with
CC KTI11/DPH3 (By similarity). Interacts with STE20 (By similarity).
CC {ECO:0000250|UniProtKB:P38626}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P38626}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Protein levels are highest during exponential growth phase
CC and lowest in stationary phase. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EDN61451.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AAFW02000124; EDN61451.1; ALT_INIT; Genomic_DNA.
DR AlphaFoldDB; A6ZVM6; -.
DR SMR; A6ZVM6; -.
DR TopDownProteomics; A6ZVM6; -.
DR EnsemblFungi; EDN61451; EDN61451; SCY_2742.
DR HOGENOM; CLU_003827_9_0_1; -.
DR UniPathway; UPA00559; -.
DR Proteomes; UP000007060; Unassembled WGS sequence.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0003954; F:NADH dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; ISS:UniProtKB.
DR GO; GO:0002926; P:tRNA wobble base 5-methoxycarbonylmethyl-2-thiouridinylation; ISS:UniProtKB.
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 3: Inferred from homology;
KW FAD; Flavoprotein; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW NAD; Oxidoreductase; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..284
FT /note="NADH-cytochrome b5 reductase 1"
FT /id="PRO_0000330167"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 38..142
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 148..180
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
SQ SEQUENCE 284 AA; 31422 MW; CF24B16DD34A7A12 CRC64;
MAIDAQKLVV VIVIVVVPLL FKFIIGPKTK PVLDPKRNDF QSFPLVEKTI LTHNTSMYKF
GLPHADDVLG LPIGQHIVIK ANINGKDITR SYTPTSLDGD TKGNFELLVK SYPTGNVSKM
IGELKIGDSI QIKGPRGNYH YERNCRSHLG MIAGGTGIAP MYQIMKAIAM DSHDTTKVSL
VFGNVHEEDI LLKKELEALV AMKPSQFKIV YYLDSPDRED WAGGVGYITK DVIKEHLPAA
TVDNVQILIC GPPAMVASVR RSTVDLGFRR SKPLSKMEDQ VFVF
