DLD3_YEAST
ID DLD3_YEAST Reviewed; 496 AA.
AC P39976; D3DLI0;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=D-2-hydroxyglutarate--pyruvate transhydrogenase DLD3 {ECO:0000305};
DE Short=D-2HG--pyruvate transhydrogenase DLD3 {ECO:0000303|PubMed:26774271};
DE EC=1.1.99.40 {ECO:0000269|PubMed:26774271};
DE AltName: Full=(R)-2-hydroxyglutarate--pyruvate transhydrogenase {ECO:0000305};
DE AltName: Full=D-lactate dehydrogenase [cytochrome] 3;
DE EC=1.1.2.4;
DE AltName: Full=D-lactate ferricytochrome C oxidoreductase;
DE Short=D-LCR;
GN Name=DLD3; OrderedLocusNames=YEL071W;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169868;
RA Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA Botstein D., Davis R.W.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL Nature 387:78-81(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=10509019;
RX DOI=10.1002/(sici)1097-0061(19990930)15:13<1377::aid-yea473>3.0.co;2-0;
RA Chelstowska A., Liu Z., Jia Y., Amberg D., Butow R.A.;
RT "Signalling between mitochondria and the nucleus regulates the expression
RT of a new D-lactate dehydrogenase activity in yeast.";
RL Yeast 15:1377-1391(1999).
RN [4]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [5]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-17.
RC STRAIN=SUB592;
RX PubMed=12872131; DOI=10.1038/nbt849;
RA Peng J., Schwartz D., Elias J.E., Thoreen C.C., Cheng D., Marsischky G.,
RA Roelofs J., Finley D., Gygi S.P.;
RT "A proteomics approach to understanding protein ubiquitination.";
RL Nat. Biotechnol. 21:921-926(2003).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 201388 / BY4741;
RX PubMed=26774271; DOI=10.1074/jbc.m115.704494;
RA Becker-Kettern J., Paczia N., Conrotte J.F., Kay D.P., Guignard C.,
RA Jung P.P., Linster C.L.;
RT "Saccharomyces cerevisiae forms D-2-hydroxyglutarate and couples its
RT degradation to D-lactate formation via a cytosolic transhydrogenase.";
RL J. Biol. Chem. 291:6036-6058(2016).
CC -!- FUNCTION: Catalyzes the reversible oxidation of (R)-2-hydroxyglutarate
CC to 2-oxoglutarate coupled to reduction of pyruvate to (R)-lactate. Can
CC also use oxaloacetate as electron acceptor instead of pyruvate
CC producing (R)-malate. {ECO:0000269|PubMed:26774271}.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-2-hydroxyglutarate + pyruvate = (R)-lactate + 2-
CC oxoglutarate; Xref=Rhea:RHEA:51608, ChEBI:CHEBI:15361,
CC ChEBI:CHEBI:15801, ChEBI:CHEBI:16004, ChEBI:CHEBI:16810;
CC EC=1.1.99.40; Evidence={ECO:0000269|PubMed:26774271};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=111 uM for (R)-2-hydroxyglutarate {ECO:0000269|PubMed:26774271};
CC KM=450 uM for pyruvate {ECO:0000269|PubMed:26774271};
CC KM=533 uM for (R)-lactate {ECO:0000269|PubMed:26774271};
CC Note=kcat is 4.0 sec(-1) for (R)-2-hydroxyglutarate oxidation with
CC pyruvate as electron acceptor. kcat is 6.6 sec(-1) for (R)-2-
CC hydroxyglutarate oxidation with DCIP as electron acceptor. kcat is
CC 4.9 sec(-1) for pyruvate reduction with (R)-2-hydroxyglutarate as
CC electron donor. kcat is 16.5 sec(-1) for (R)-lactate reduction with
CC DCIP as electron donor. {ECO:0000269|PubMed:26774271};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10509019}.
CC -!- MISCELLANEOUS: Present with 13000 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC 4 family. {ECO:0000305}.
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DR EMBL; U18795; AAB65016.1; -; Genomic_DNA.
DR EMBL; BK006939; DAA07584.1; -; Genomic_DNA.
DR PIR; S50518; S50518.
DR RefSeq; NP_010843.1; NM_001178886.1.
DR AlphaFoldDB; P39976; -.
DR SMR; P39976; -.
DR BioGRID; 36660; 65.
DR DIP; DIP-6418N; -.
DR IntAct; P39976; 6.
DR MINT; P39976; -.
DR STRING; 4932.YEL071W; -.
DR iPTMnet; P39976; -.
DR MaxQB; P39976; -.
DR PaxDb; P39976; -.
DR PRIDE; P39976; -.
DR EnsemblFungi; YEL071W_mRNA; YEL071W; YEL071W.
DR GeneID; 856638; -.
DR KEGG; sce:YEL071W; -.
DR SGD; S000000797; DLD3.
DR VEuPathDB; FungiDB:YEL071W; -.
DR eggNOG; KOG1232; Eukaryota.
DR GeneTree; ENSGT00550000075086; -.
DR HOGENOM; CLU_017779_4_1_1; -.
DR InParanoid; P39976; -.
DR OMA; YLHYSKD; -.
DR BioCyc; YEAST:YEL071W-MON; -.
DR BRENDA; 1.1.99.40; 984.
DR PRO; PR:P39976; -.
DR Proteomes; UP000002311; Chromosome V.
DR RNAct; P39976; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0099615; F:(D)-2-hydroxyglutarate-pyruvate transhydrogenase activity; IDA:SGD.
DR GO; GO:0004458; F:D-lactate dehydrogenase (cytochrome) activity; IDA:SGD.
DR GO; GO:0071949; F:FAD binding; IDA:SGD.
DR GO; GO:0030447; P:filamentous growth; IMP:SGD.
DR GO; GO:0019249; P:lactate biosynthetic process; IMP:SGD.
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 Cytoplasm; FAD; Flavoprotein; Isopeptide bond; Oxidoreductase;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..496
FT /note="D-2-hydroxyglutarate--pyruvate transhydrogenase
FT DLD3"
FT /id="PRO_0000128176"
FT DOMAIN 64..243
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT CROSSLNK 17
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:12872131"
SQ SEQUENCE 496 AA; 55225 MW; 4809F74EDF07F520 CRC64;
MTAAHPVAQL TAEAYPKVKR NPNFKVLDSE DLAYFRSILS NDEILNSQAP EELASFNQDW
MKKYRGQSNL ILLPNSTDKV SKIMKYCNDK KLAVVPQGGN TDLVGASVPV FDEIVLSLRN
MNKVRDFDPV SGTFKCDAGV VMRDAHQFLH DHDHIFPLDL PSRNNCQVGG VVSTNAGGLN
FLRYGSLHGN VLGLEVVLPN GEIISNINAL RKDNTGYDLK QLFIGAEGTI GVVTGVSIVA
AAKPKALNAV FFGIENFDTV QKLFVKAKSE LSEILSAFEF MDRGSIECTI EYLKDLPFPL
ENQHNFYVLI ETSGSNKRHD DEKLTAFLKD TTDSKLISEG MMAKDKADFD RLWTWRKSVP
TACNSYGGMY KYDMSLQLKD LYSVSAAVTE RLNAAGLIGD APKPVVKSCG YGHVGDGNIH
LNIAVREFTK QIEDLLEPFV YEYIASKKGS ISAEHGIGFH KKGKLHYTRS DIEIRFMKDI
KNHYDPNGIL NPYKYI
