ID   MCR1_AJECN              Reviewed;         324 AA.
AC   A6R1T7;
DT   29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   21-AUG-2007, sequence version 1.
DT   03-AUG-2022, entry version 69.
DE   RecName: Full=NADH-cytochrome b5 reductase 2;
DE            EC=1.6.2.2;
DE   AltName: Full=Mitochondrial cytochrome b reductase;
GN   Name=MCR1; ORFNames=HCAG_03595;
OS   Ajellomyces capsulatus (strain NAm1 / WU24) (Darling's disease fungus)
OS   (Histoplasma capsulatum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Onygenales; Ajellomycetaceae; Histoplasma;
OC   unclassified Histoplasma.
OX   NCBI_TaxID=2059318;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=NAm1 / WU24;
RX   PubMed=19717792; DOI=10.1101/gr.087551.108;
RA   Sharpton T.J., Stajich J.E., Rounsley S.D., Gardner M.J., Wortman J.R.,
RA   Jordar V.S., Maiti R., Kodira C.D., Neafsey D.E., Zeng Q., Hung C.-Y.,
RA   McMahan C., Muszewska A., Grynberg M., Mandel M.A., Kellner E.M.,
RA   Barker B.M., Galgiani J.N., Orbach M.J., Kirkland T.N., Cole G.T.,
RA   Henn M.R., Birren B.W., Taylor J.W.;
RT   "Comparative genomic analyses of the human fungal pathogens Coccidioides
RT   and their relatives.";
RL   Genome Res. 19:1722-1731(2009).
CC   -!- FUNCTION: May mediate the reduction of outer membrane cytochrome b5.
CC       {ECO:0000250}.
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   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000250};
CC       Single-pass membrane protein {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC       reductase family. {ECO:0000305}.
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DR   EMBL; CH476657; EDN07064.1; -; Genomic_DNA.
DR   RefSeq; XP_001541497.1; XM_001541447.1.
DR   AlphaFoldDB; A6R1T7; -.
DR   SMR; A6R1T7; -.
DR   STRING; 339724.A6R1T7; -.
DR   EnsemblFungi; EDN07064; EDN07064; HCAG_03595.
DR   GeneID; 5447518; -.
DR   KEGG; aje:HCAG_03595; -.
DR   VEuPathDB; FungiDB:HCAG_03595; -.
DR   HOGENOM; CLU_003827_9_1_1; -.
DR   OMA; NKHDHIA; -.
DR   OrthoDB; 1311668at2759; -.
DR   Proteomes; UP000009297; Unassembled WGS sequence.
DR   GO; GO:0031307; C:integral component of mitochondrial outer membrane; IEA:EnsemblFungi.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; IEA:EnsemblFungi.
DR   GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; IEA:UniProtKB-EC.
DR   GO; GO:0003954; F:NADH dehydrogenase activity; IEA:EnsemblFungi.
DR   GO; GO:0034599; P:cellular response to oxidative stress; IEA:EnsemblFungi.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IEA:EnsemblFungi.
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; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..324
FT                   /note="NADH-cytochrome b5 reductase 2"
FT                   /id="PRO_0000330168"
FT   TRANSMEM        31..47
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          70..178
FT                   /note="FAD-binding FR-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT   BINDING         181..216
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   324 AA;  36615 MW;  54489BF296707A0F CRC64;
     MFARYTFRCS QPLAQSVRKY SSEAPAKSSR IPLIGGITLA AGAGYYYYWQ TTSAKSEPKE
     RSTVFKGGDQ GWIGLKLAHI DNVNHNVKKL RFEFEDPESV SGLHIASALL TKYKGLTDEK
     PTIRPYTPVS DEGMWASLGY LDLLVKRYPN GPMSNHLHNM AVGQRLDFKG PLPKYPWEPS
     KHDHICLIAG GTGITPMYQL VRKIFSNPED KTKVTLVFAN VTEEDILLRK EFEHLENTYP
     RRFRAFYTLD KPPKNWAQGT GFITKDLLKT VLPEPKTENI KIFVCGPPAM YKAISGQKVS
     PKDQGELSGI LKELGYSKEQ VYKF