CYB2_WICAO
ID CYB2_WICAO Reviewed; 573 AA.
AC P09437;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=L-lactate dehydrogenase (cytochrome);
DE EC=1.1.2.3 {ECO:0000250|UniProtKB:P00175};
DE AltName: Full=Cytochrome b2;
DE AltName: Full=Flavocytochrome b2 {ECO:0000303|PubMed:2688640, ECO:0000303|PubMed:2813072, ECO:0000303|PubMed:3319613};
DE Short=FCB2;
DE AltName: Full=L-lactate ferricytochrome c oxidoreductase;
DE Short=L-LCR;
DE Flags: Precursor;
GN Name=CYB2;
OS Wickerhamomyces anomalus (Yeast) (Hansenula anomala).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Phaffomycetaceae; Wickerhamomyces.
OX NCBI_TaxID=4927;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2813072; DOI=10.1093/nar/17.20.8381;
RA Risler Y., Tegoni M., Gervais M.;
RT "Nucleotide sequence of the Hansenula anomala gene encoding flavocytochrome
RT b2 (L-lactate:cytochrome c oxidoreductase).";
RL Nucleic Acids Res. 17:8381-8381(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2688640; DOI=10.1042/bj2630973;
RA Black M.T., Gunn F.J., Chapman S.K., Reid G.A.;
RT "Structural basis for the kinetic differences between flavocytochromes b2
RT from the yeasts Hansenula anomala and Saccharomyces cerevisiae.";
RL Biochem. J. 263:973-976(1989).
RN [3]
RP PROTEIN SEQUENCE OF 80-163.
RX PubMed=3319613; DOI=10.1111/j.1432-1033.1987.tb13642.x;
RA Haumont P.-Y., Thomas M.-A., Labeyrie F., Lederer F.;
RT "Amino-acid sequence of the cytochrome-b5-like heme-binding domain from
RT Hansenula anomala flavocytochrome b2.";
RL Eur. J. Biochem. 169:539-546(1987).
CC -!- FUNCTION: Catalyzes the oxidation of (S)-lactate (L-lactate) to
CC pyruvate with subsequent transfer of electrons to cytochrome c. Is
CC involved in the utilization of (S)-lactate as a sole source of carbon
CC for growth. {ECO:0000250|UniProtKB:P00175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate + 2 Fe(III)-[cytochrome c] = 2 Fe(II)-[cytochrome
CC c] + 2 H(+) + pyruvate; Xref=Rhea:RHEA:19909, Rhea:RHEA-COMP:10350,
CC Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16651, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.1.2.3;
CC Evidence={ECO:0000250|UniProtKB:P00175};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19910;
CC Evidence={ECO:0000250|UniProtKB:P00175};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:P00175};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000250|UniProtKB:P00175};
CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group non-covalently
CC per subunit. {ECO:0000250|UniProtKB:P00175};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P00175}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:P00175}.
CC -!- DOMAIN: Consists of two discrete domains, an N-terminal cytochrome b
CC domain and a C-terminal flavin-binding domain. In addition there is an
CC extended C-terminal tail. The cytochrome b domain is required for
CC efficient cytochrome c reduction. {ECO:0000250|UniProtKB:P00175}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the cytochrome b5
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the FMN-dependent
CC alpha-hydroxy acid dehydrogenase family. {ECO:0000305}.
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DR EMBL; X16051; CAA34183.1; -; Genomic_DNA.
DR PIR; S06600; S06600.
DR AlphaFoldDB; P09437; -.
DR SMR; P09437; -.
DR PRIDE; P09437; -.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell.
DR GO; GO:0070469; C:respirasome; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0004460; F:L-lactate dehydrogenase (cytochrome) activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR CDD; cd02922; FCB2_FMN; 1.
DR Gene3D; 3.10.120.10; -; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
DR InterPro; IPR018506; Cyt_B5_heme-BS.
DR InterPro; IPR000262; FMN-dep_DH.
DR InterPro; IPR037396; FMN_HAD.
DR InterPro; IPR008259; FMN_hydac_DH_AS.
DR InterPro; IPR037458; L-MDH/L-LDH_FMN-bd.
DR Pfam; PF00173; Cyt-b5; 1.
DR Pfam; PF01070; FMN_dh; 1.
DR SMART; SM01117; Cyt-b5; 1.
DR SUPFAM; SSF55856; SSF55856; 1.
DR PROSITE; PS00191; CYTOCHROME_B5_1; 1.
DR PROSITE; PS50255; CYTOCHROME_B5_2; 1.
DR PROSITE; PS00557; FMN_HYDROXY_ACID_DH_1; 1.
DR PROSITE; PS51349; FMN_HYDROXY_ACID_DH_2; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Electron transport; Flavoprotein; FMN; Heme;
KW Iron; Metal-binding; Mitochondrion; Oxidoreductase; Respiratory chain;
KW Transit peptide; Transport.
FT TRANSIT 1..73
FT /note="Mitochondrion"
FT CHAIN 74..573
FT /note="L-lactate dehydrogenase (cytochrome)"
FT /id="PRO_0000006479"
FT DOMAIN 80..157
FT /note="Cytochrome b5 heme-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT DOMAIN 182..542
FT /note="FMN hydroxy acid dehydrogenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 115
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 138
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 208
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 208
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 260..263
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 290
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 313
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 315
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 341
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 357
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 408
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 432
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 435
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 468..472
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 491..492
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
SQ SEQUENCE 573 AA; 64202 MW; 83EEF645C580BC8E CRC64;
MFKSQLRTAT ARSSFRSLAS KLNPQRFNSS KTPLLNATRG SNRSKNSLIA LAISLSAVSS
SYYLYQKDKF ISADVPHWKD IELTPEIVSQ HNKKDDLWVV LNGQVYDLTD FLPNHPGGQK
IIIRYAGKDA TKIFVPIHPP DTIEKFIPPE KHLGPLVGEF EQEEEELSDE EIDRLERIER
KPPLSQMINL HDFETIARQI LPPPALAYYC SAADDEVTLR ENHNAYHRIF FNPKILIDVK
DVDISTEFFG EKTSAPFYIS ATALAKLGHP EGEVAIAKGA GREDVVQMIS TLASCSFDEI
ADARIPGQQQ WYQLYVNADR SITEKAVRHA EERGMKGLFI TVDAPSLGRR EKDMKMKFEA
DSDVQGDDED IDRSQGASRA LSSFIDPSLS WKDIAFIKSI TKMPIVIKGV QRKEDVLLAA
EHGLQGVVLS NHGGRQLDYT RAPVEVLAEV MPILKERGLD QKIDIFVDGG VRRGTDVLKA
LCLGAKGVGL GRPFLYAMSS YGDKGVTKAI QLLKDEIEMN MRLLGVNKIE ELTPELLDTR
SIHNRAVPVA KDYLYEQNYQ RMSGAEFRPG IED
