ID   LDHD_DANRE              Reviewed;         497 AA.
AC   F1QXM5; Q803V9;
DT   16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT   03-MAY-2011, sequence version 1.
DT   03-AUG-2022, entry version 61.
DE   RecName: Full=Probable D-lactate dehydrogenase, mitochondrial;
DE            Short=DLD;
DE            Short=Lactate dehydrogenase D;
DE            EC=1.1.2.4 {ECO:0000305|PubMed:30931947};
GN   Name=ldhd;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=AB;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=30931947; DOI=10.1038/s41467-019-09458-6;
RA   Monroe G.R., van Eerde A.M., Tessadori F., Duran K.J., Savelberg S.M.C.,
RA   van Alfen J.C., Terhal P.A., van der Crabben S.N., Lichtenbelt K.D.,
RA   Fuchs S.A., Gerrits J., van Roosmalen M.J., van Gassen K.L.,
RA   van Aalderen M., Koot B.G., Oostendorp M., Duran M., Visser G.,
RA   de Koning T.J., Cali F., Bosco P., Geleijns K.,
RA   de Sain-van der Velden M.G.M., Knoers N.V., Bakkers J.,
RA   Verhoeven-Duif N.M., van Haaften G., Jans J.J.;
RT   "Identification of human D lactate dehydrogenase deficiency.";
RL   Nat. Commun. 10:1477-1477(2019).
CC   -!- FUNCTION: Involved in D-lactate, but not L-lactate catabolic process.
CC       {ECO:0000269|PubMed:30931947}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(R)-lactate + 2 Fe(III)-[cytochrome c] = 2 Fe(II)-[cytochrome
CC         c] + 2 H(+) + pyruvate; Xref=Rhea:RHEA:13521, Rhea:RHEA-COMP:10350,
CC         Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16004, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.1.2.4;
CC         Evidence={ECO:0000305|PubMed:30931947};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:P39976};
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q7TNG8}.
CC   -!- DISRUPTION PHENOTYPE: At 3 dpf, mutant embryos show no visible
CC       abnormalities compared to wild-type embryos. They do not display any
CC       ocular abnormalities at 5 dpf. They nevertheless exhibit elevated
CC       levels of D-lactate, but not L-lactate compared to wild-type larvae.
CC       {ECO:0000269|PubMed:30931947}.
CC   -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC       4 family.
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DR   EMBL; CR388073; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC044171; AAH44171.1; -; mRNA.
DR   RefSeq; NP_956167.1; NM_199873.1.
DR   AlphaFoldDB; F1QXM5; -.
DR   STRING; 7955.ENSDARP00000056720; -.
DR   PaxDb; F1QXM5; -.
DR   Ensembl; ENSDART00000056721; ENSDARP00000056720; ENSDARG00000038845.
DR   GeneID; 334208; -.
DR   KEGG; dre:334208; -.
DR   CTD; 197257; -.
DR   ZFIN; ZDB-GENE-030131-6140; ldhd.
DR   eggNOG; KOG1231; Eukaryota.
DR   GeneTree; ENSGT00940000158705; -.
DR   HOGENOM; CLU_017779_3_0_1; -.
DR   InParanoid; F1QXM5; -.
DR   OMA; TPRTCGE; -.
DR   OrthoDB; 824020at2759; -.
DR   PhylomeDB; F1QXM5; -.
DR   TreeFam; TF314122; -.
DR   Reactome; R-DRE-1268020; Mitochondrial protein import.
DR   PRO; PR:F1QXM5; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 25.
DR   Bgee; ENSDARG00000038845; Expressed in heart and 24 other tissues.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0004458; F:D-lactate dehydrogenase (cytochrome) activity; IBA:GO_Central.
DR   GO; GO:0008720; F:D-lactate dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR   GO; GO:1903457; P:lactate catabolic process; IMP:UniProtKB.
DR   Gene3D; 1.10.45.10; -; 1.
DR   Gene3D; 3.30.465.10; -; 1.
DR   InterPro; IPR016166; FAD-bd_PCMH.
DR   InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR   InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR   InterPro; IPR016164; FAD-linked_Oxase-like_C.
DR   InterPro; IPR004113; FAD-linked_oxidase_C.
DR   InterPro; IPR006094; Oxid_FAD_bind_N.
DR   InterPro; IPR016171; Vanillyl_alc_oxidase_C-sub2.
DR   Pfam; PF02913; FAD-oxidase_C; 1.
DR   Pfam; PF01565; FAD_binding_4; 1.
DR   SUPFAM; SSF55103; SSF55103; 1.
DR   SUPFAM; SSF56176; SSF56176; 1.
DR   PROSITE; PS51387; FAD_PCMH; 1.
PE   2: Evidence at transcript level;
KW   FAD; Flavoprotein; Mitochondrion; Oxidoreductase; Reference proteome;
KW   Transit peptide.
FT   CHAIN           1..497
FT                   /note="Probable D-lactate dehydrogenase, mitochondrial"
FT                   /id="PRO_0000448096"
FT   DOMAIN          65..246
FT                   /note="FAD-binding PCMH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT   CONFLICT        110
FT                   /note="G -> S (in Ref. 2; AAH44171)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        419
FT                   /note="T -> P (in Ref. 2; AAH44171)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        461
FT                   /note="V -> L (in Ref. 2; AAH44171)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        487
FT                   /note="V -> L (in Ref. 2; AAH44171)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   497 AA;  53954 MW;  31A0600139B46279 CRC64;
     MTLFRHLVRI TSPRLPFICG SSRRFSAKTA AVERVVSSFR SVTGDEGVSV GSAVREQHGR
     DESVHRCRPP DVVVFPRSVE EVSALAKICH HYRLPIIPFG TGTGLEGGVG ALQGGVCFSL
     RKMEQVVDLH QEDFDVTVEP GVTRKSLNSY LRDTGLWFPV DPGADASLCG MAATSASGTN
     AVRYGTMREN VLNLEVVLAD GTILHTAGKG RRPRKTAAGY NLTNLFVGSE GTLGIITKAT
     LRLYGVPESM VSAVCSFPSV QSAVDSTVQI LQAGVPIARI EFLDDVMINA CNRFNNLSYA
     VTPTLFLEFH GSSKSMEEQV SVTEEITRDN GGSDFAWAED EETRSRLWKA RHDAWYAAMA
     LRPGCKAYST DVCVPISRLP QIIVETKADL ISNNITGPIA GHVGDGNFHC LIVLDPNDTD
     EVQRVHSFTE RLARRALAMD GTCTGEHGIG LGKRALLREE VGPLAIEVMK GLKASLDPRN
     LMNPGKVLEL TQTNTEQ