NCB5R_PICST
ID NCB5R_PICST Reviewed; 284 AA.
AC A3GF86;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JAN-2010, sequence version 2.
DT 03-AUG-2022, entry version 86.
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;
GN Name=CBR1; ORFNames=PICST_68997;
OS Scheffersomyces stipitis (strain ATCC 58785 / CBS 6054 / NBRC 10063 / NRRL
OS Y-11545) (Yeast) (Pichia stipitis).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Scheffersomyces.
OX NCBI_TaxID=322104;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 58785 / CBS 6054 / NBRC 10063 / NRRL Y-11545;
RX PubMed=17334359; DOI=10.1038/nbt1290;
RA Jeffries T.W., Grigoriev I.V., Grimwood J., Laplaza J.M., Aerts A.,
RA Salamov A., Schmutz J., Lindquist E., Dehal P., Shapiro H., Jin Y.-S.,
RA Passoth V., Richardson P.M.;
RT "Genome sequence of the lignocellulose-bioconverting and xylose-fermenting
RT yeast Pichia stipitis.";
RL Nat. Biotechnol. 25:319-326(2007).
CC -!- FUNCTION: NADH-dependent reductase for DPH3 and cytochrome b5. Required
CC for the first step of diphthamide biosynthesis, a post-translational
CC modification of histidine which occurs in elongation factor 2. DPH1 and
CC DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-
CC methionine (SAM) to a histidine residue, the reaction is assisted by a
CC reduction system comprising DPH3 and a NADH-dependent reductase,
CC predominantly CBR1. By reducing DPH3, also involved in the formation of
CC the tRNA wobble base modification mcm5s 2U (5-methoxycarbonylmethyl-2-
CC thiouridine), mediated by the elongator complex. The cytochrome b5/NADH
CC cytochrome b5 reductase electron transfer system supports the catalytic
CC activity of several sterol biosynthetic enzymes.
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 -!- 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, DPH3 and a NADH-dependent
CC reductase, predominantly CBR1. {ECO:0000250|UniProtKB:P38626}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P38626}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
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DR EMBL; AAVQ01000001; EAZ63709.2; -; Genomic_DNA.
DR RefSeq; XP_001387732.2; XM_001387695.1.
DR AlphaFoldDB; A3GF86; -.
DR SMR; A3GF86; -.
DR STRING; 4924.XP_001387732.2; -.
DR EnsemblFungi; EAZ63709; EAZ63709; PICST_68997.
DR GeneID; 4850935; -.
DR KEGG; pic:PICST_68997; -.
DR eggNOG; KOG0534; Eukaryota.
DR HOGENOM; CLU_003827_9_0_1; -.
DR InParanoid; A3GF86; -.
DR OMA; KDMRFSF; -.
DR OrthoDB; 1311668at2759; -.
DR UniPathway; UPA00559; -.
DR Proteomes; UP000002258; Chromosome 1.
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; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..284
FT /note="NADH-cytochrome b5 reductase 1"
FT /id="PRO_0000330163"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 41..144
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 124..139
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 150..182
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
SQ SEQUENCE 284 AA; 31274 MW; 0B825044D2C04489 CRC64;
MADTEPSPLF VFSTIAIIIS TFVIFYFVQQ SKKNTPVLKP DTFQKFPLIE KTRVSHNSSV
YRFGLPKSTD RLGLPIGQHI SIGATIGGKE VVRSYTPIST DDELGYFDLL IKTYENGNIS
KHVDSKKVGE YVEIRGPKGF FTYTPNMVKS FGMIAGGTGI APMYQIITAI LRNPADKTKI
SLIYANVTES DILLKSELDK WAEEHPDNFS VHYVLNEAPE NWKGSVGFVT PEIIDSKLPK
ASDDSNLLLC GPPPMISAMK KAAVGLGFAK AKPVSKLGDQ VFVF
