LDHD_MOUSE
ID LDHD_MOUSE Reviewed; 484 AA.
AC Q7TNG8; Q8BYU7; Q8CIV4;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Probable D-lactate dehydrogenase, mitochondrial;
DE Short=DLD;
DE Short=Lactate dehydrogenase D;
DE EC=1.1.2.4 {ECO:0000250|UniProtKB:Q86WU2};
DE Flags: Precursor;
GN Name=Ldhd {ECO:0000312|MGI:MGI:106428};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAM50323.1}
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CSRP3, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC STRAIN=129/Sv {ECO:0000312|EMBL:AAM50323.1};
RX PubMed=12127981; DOI=10.1016/s0006-291x(02)00768-4;
RA Flick M.J., Konieczny S.F.;
RT "Identification of putative mammalian D-lactate dehydrogenase enzymes.";
RL Biochem. Biophys. Res. Commun. 295:910-916(2002).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAH39155.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH39155.1};
RC TISSUE=Kidney {ECO:0000312|EMBL:AAH39155.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAC29917.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 286-430.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC29917.1};
RC TISSUE=Thymus {ECO:0000312|EMBL:BAC29917.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-335, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-36; LYS-292; LYS-335; LYS-422 AND
RP LYS-449, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Involved in D-lactate, but not L-lactate catabolic process.
CC {ECO:0000250|UniProtKB:Q86WU2}.
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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13522;
CC Evidence={ECO:0000250|UniProtKB:Q86WU2};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P39976};
CC -!- SUBUNIT: Interacts with CSRP3. {ECO:0000269|PubMed:12127981}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:12127981}.
CC -!- TISSUE SPECIFICITY: Readily detected in liver and kidney, with a weaker
CC signal observed in heart, skeletal muscle, stomach, brain, and lung.
CC {ECO:0000269|PubMed:12127981}.
CC -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC 4 family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM50323.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC29917.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY092768; AAM50323.1; ALT_FRAME; mRNA.
DR EMBL; BC039155; AAH39155.1; -; mRNA.
DR EMBL; BC055443; AAH55443.1; -; mRNA.
DR EMBL; AK037996; BAC29917.1; ALT_FRAME; mRNA.
DR CCDS; CCDS22677.1; -.
DR RefSeq; NP_081846.3; NM_027570.3.
DR AlphaFoldDB; Q7TNG8; -.
DR IntAct; Q7TNG8; 1.
DR MINT; Q7TNG8; -.
DR STRING; 10090.ENSMUSP00000068086; -.
DR iPTMnet; Q7TNG8; -.
DR PhosphoSitePlus; Q7TNG8; -.
DR SwissPalm; Q7TNG8; -.
DR jPOST; Q7TNG8; -.
DR MaxQB; Q7TNG8; -.
DR PaxDb; Q7TNG8; -.
DR PeptideAtlas; Q7TNG8; -.
DR PRIDE; Q7TNG8; -.
DR ProteomicsDB; 252462; -.
DR Antibodypedia; 30293; 238 antibodies from 27 providers.
DR DNASU; 52815; -.
DR Ensembl; ENSMUST00000070004; ENSMUSP00000068086; ENSMUSG00000031958.
DR GeneID; 52815; -.
DR KEGG; mmu:52815; -.
DR UCSC; uc009nmn.1; mouse.
DR CTD; 197257; -.
DR MGI; MGI:106428; Ldhd.
DR VEuPathDB; HostDB:ENSMUSG00000031958; -.
DR eggNOG; KOG1231; Eukaryota.
DR GeneTree; ENSGT00940000158705; -.
DR HOGENOM; CLU_017779_3_0_1; -.
DR InParanoid; Q7TNG8; -.
DR OMA; TPRTCGE; -.
DR OrthoDB; 824020at2759; -.
DR PhylomeDB; Q7TNG8; -.
DR TreeFam; TF314122; -.
DR Reactome; R-MMU-1268020; Mitochondrial protein import.
DR BioGRID-ORCS; 52815; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Ldhd; mouse.
DR PRO; PR:Q7TNG8; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q7TNG8; protein.
DR Bgee; ENSMUSG00000031958; Expressed in right kidney and 123 other tissues.
DR Genevisible; Q7TNG8; MM.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
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:0006754; P:ATP biosynthetic process; NAS:UniProtKB.
DR GO; GO:1903457; P:lactate catabolic process; ISS:UniProtKB.
DR Gene3D; 1.10.45.10; -; 1.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
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 1: Evidence at protein level;
KW Acetylation; FAD; Flavoprotein; Mitochondrion; Oxidoreductase;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..52
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 53..484
FT /note="Probable D-lactate dehydrogenase, mitochondrial"
FT /id="PRO_0000262953"
FT DOMAIN 62..242
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT MOD_RES 36
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 292
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 335
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 335
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 422
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 449
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CONFLICT 413
FT /note="D -> H (in Ref. 2; BAC29917)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 484 AA; 51848 MW; 78BDF31A861B9A82 CRC64;
MAMLLRVATQ RLSPWRSFCS RGSQGGLSQD FVEALKAVVG SPHVSTASAV REQHGHDESM
HRCQPPDAVV WPQNVDQVSR VASLCYNQGV PIIPFGTGTG VEGGVCAVQG GVCINLTHMD
QITELNTEDF SVVVEPGVTR KALNTHLRDS GLWFPVDPGA DASLCGMAAT GASGTNAVRY
GTMRDNVINL EVVLPDGRLL HTAGRGRHYR KSAAGYNLTG LFVGSEGTLG IITSTTLRLH
PAPEATVAAT CAFPSVQAAV DSTVQILQAA VPVARIEFLD DVMMDACNRH SKLNCPVAPT
LFLEFHGSQQ TLAEQLQRTE AITQDNGGSH FSWAKEAEKR NELWAARHNA WYAALALSPG
SKAYSTDVCV PISRLPEILV ETKEEIKASK LTGAIVGHVG DGNFHCILLV DPDDAEEQRR
VKAFAENLGR RALALGGTCT GEHGIGLGKR QLLQEEVGPV GVETMRQLKN TLDPRGLMNP
GKVL
