NCB5R_NEUCR
ID NCB5R_NEUCR Reviewed; 310 AA.
AC Q7RXL1;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 03-AUG-2022, entry version 99.
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=NCU00216;
OS Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS FGSC 987).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX NCBI_TaxID=367110;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12712197; DOI=10.1038/nature01554;
RA Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT "The genome sequence of the filamentous fungus Neurospora crassa.";
RL Nature 422:859-868(2003).
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; CM002238; EAA27365.1; -; Genomic_DNA.
DR RefSeq; XP_956601.1; XM_951508.3.
DR AlphaFoldDB; Q7RXL1; -.
DR SMR; Q7RXL1; -.
DR STRING; 5141.EFNCRP00000000032; -.
DR EnsemblFungi; EAA27365; EAA27365; NCU00216.
DR GeneID; 3872748; -.
DR KEGG; ncr:NCU00216; -.
DR VEuPathDB; FungiDB:NCU00216; -.
DR HOGENOM; CLU_003827_9_0_1; -.
DR InParanoid; Q7RXL1; -.
DR UniPathway; UPA00559; -.
DR Proteomes; UP000001805; Chromosome 3, Linkage Group III.
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..310
FT /note="NADH-cytochrome b5 reductase 1"
FT /id="PRO_0000330160"
FT TRANSMEM 33..50
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 61..169
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 149..164
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 175..209
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
SQ SEQUENCE 310 AA; 34001 MW; AD00607089CF7B40 CRC64;
MSEESLLERK YFDGIYIPAG LLVFGTVIVK KEWTLYAALA ALILGAIKYF RMLPKKVLKP
AVFQEFELKE KTIISHNVAI YRFKLPTPDS VLGLPIGQHI SIGAAIEQPD GSTKEIVRSY
TPISGDHQPG YFDLLIKSYP TGNISKHMAS LQVGQTIRVK GPKGAFVYTP NMVRHFGMVA
GGTGITPMLQ VIRAIVRGRA AGDRTEVDLI FANVTAQDIL LKEDLDALVA QDKGIRVHYV
LDRPPEGWTG GVGFVTQEMV EKLLPKPASD VKILLCGPPP MISGLKKATE ALGFQKARPV
SKLEDQVFAF
