NCB5R_CRYNJ
ID NCB5R_CRYNJ Reviewed; 294 AA.
AC P0CP14; Q55IJ8; Q5K838;
DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 03-AUG-2022, entry version 48.
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; OrderedLocusNames=CNM00240;
OS Cryptococcus neoformans var. neoformans serotype D (strain JEC21 / ATCC
OS MYA-565) (Filobasidiella neoformans).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=214684;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=JEC21 / ATCC MYA-565;
RX PubMed=15653466; DOI=10.1126/science.1103773;
RA Loftus B.J., Fung E., Roncaglia P., Rowley D., Amedeo P., Bruno D.,
RA Vamathevan J., Miranda M., Anderson I.J., Fraser J.A., Allen J.E.,
RA Bosdet I.E., Brent M.R., Chiu R., Doering T.L., Donlin M.J., D'Souza C.A.,
RA Fox D.S., Grinberg V., Fu J., Fukushima M., Haas B.J., Huang J.C.,
RA Janbon G., Jones S.J.M., Koo H.L., Krzywinski M.I., Kwon-Chung K.J.,
RA Lengeler K.B., Maiti R., Marra M.A., Marra R.E., Mathewson C.A.,
RA Mitchell T.G., Pertea M., Riggs F.R., Salzberg S.L., Schein J.E.,
RA Shvartsbeyn A., Shin H., Shumway M., Specht C.A., Suh B.B., Tenney A.,
RA Utterback T.R., Wickes B.L., Wortman J.R., Wye N.H., Kronstad J.W.,
RA Lodge J.K., Heitman J., Davis R.W., Fraser C.M., Hyman R.W.;
RT "The genome of the basidiomycetous yeast and human pathogen Cryptococcus
RT neoformans.";
RL Science 307:1321-1324(2005).
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; AE017353; AAW46852.1; -; Genomic_DNA.
DR RefSeq; XP_568369.1; XM_568369.1.
DR AlphaFoldDB; P0CP14; -.
DR SMR; P0CP14; -.
DR STRING; 5207.AAW46852; -.
DR PaxDb; P0CP14; -.
DR EnsemblFungi; AAW46852; AAW46852; CNM00240.
DR GeneID; 3255044; -.
DR KEGG; cne:CNM00240; -.
DR VEuPathDB; FungiDB:CNM00240; -.
DR eggNOG; KOG0534; Eukaryota.
DR HOGENOM; CLU_003827_9_0_1; -.
DR InParanoid; P0CP14; -.
DR OMA; KDMRFSF; -.
DR OrthoDB; 1311668at2759; -.
DR UniPathway; UPA00559; -.
DR Proteomes; UP000002149; Chromosome 13.
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..294
FT /note="NADH-cytochrome b5 reductase 1"
FT /id="PRO_0000330151"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 44..147
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 127..142
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 153..185
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
SQ SEQUENCE 294 AA; 32306 MW; 1A2180C468812C0D CRC64;
MFTIEVLAQK LAPHASFLGG LVVAAILGLF IFFQEKDRKV LDPVEWRSFK LVDKDHLSHN
TALYRFALPR ASDSLGLPIG QHISVAAEIN GKQVVRSYTP TTLDDDKGHF DLVVKTYEKG
NISRYLSLLT IGQEIKVKGP KGKFVYTPNM APHLVMIAGG TGITPMYQII KSSIKTPGDK
TRLSLIYANI QEDDILLKKE IDELQAKSNG RFDVKYVLNN PPEGWTGGVG FVTKEMIEEA
MPSSGVGSAN HGEGHKVLMC GPPPMITAMK GHLAQIGYPA PRSVSKLEDQ VFLF
