DLD2_YEAST
ID DLD2_YEAST Reviewed; 530 AA.
AC P46681; D6VRH4; Q66RH8;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=D-2-hydroxyglutarate--pyruvate transhydrogenase DLD2 {ECO:0000305};
DE Short=D-2HG--pyruvate transhydrogenase DLD2 {ECO:0000303|PubMed:26774271};
DE EC=1.1.99.40 {ECO:0000269|PubMed:26774271};
DE AltName: Full=Actin-interacting protein 2;
DE AltName: Full=D-lactate dehydrogenase [cytochrome] 2, mitochondrial;
DE EC=1.1.2.4;
DE AltName: Full=D-lactate ferricytochrome C oxidoreductase;
DE Short=D-LCR;
DE Flags: Precursor;
GN Name=DLD2; Synonyms=AIP2; OrderedLocusNames=YDL178W;
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 [GENOMIC DNA].
RA Amberg D.C., Botstein D.;
RT "AIP1, AIP2 and AIP3 encode novel components of the yeast actin
RT cytoskeleton.";
RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP FUNCTION, AND 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 [6]
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 [7]
RP INTERACTION WITH ACTIN.
RX PubMed=15158445; DOI=10.1016/j.bbrc.2004.04.146;
RA Hachiya N.S., Sakasegawa Y., Jozuka A., Tsukita S., Kaneko K.;
RT "Interaction of D-lactate dehydrogenase protein 2 (Dld2p) with F-actin:
RT implication for an alternative function of Dld2p.";
RL Biochem. Biophys. Res. Commun. 319:78-82(2004).
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 (PubMed:26774271). In addition to its enzymatic
CC role it could play an important role in the yeast cell morphology
CC (PubMed:10509019). {ECO:0000269|PubMed:10509019,
CC 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=74 uM for (R)-2-hydroxyglutarate {ECO:0000269|PubMed:26774271};
CC KM=5.2 mM for (R)-lactate {ECO:0000269|PubMed:26774271};
CC Note=kcat is 0.11 sec(-1) for (R)-2-hydroxyglutarate oxidation with
CC pyruvate as electron acceptor. kcat is 0.18 sec(-1) for (R)-2-
CC hydroxyglutarate oxidation with DCIP as electron acceptor. kcat is
CC 1.31 sec(-1) for (R)-lactate reduction with DCIP as electron donor.
CC {ECO:0000269|PubMed:26774271};
CC -!- SUBUNIT: Interacts with F-actin. {ECO:0000269|PubMed:15158445}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:10509019}.
CC -!- MISCELLANEOUS: Present with 11400 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; U35667; AAA79142.1; -; Genomic_DNA.
DR EMBL; Z67750; CAA91567.1; -; Genomic_DNA.
DR EMBL; Z74226; CAA98752.1; -; Genomic_DNA.
DR EMBL; AY723765; AAU09682.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11684.1; -; Genomic_DNA.
DR PIR; S61034; S61034.
DR RefSeq; NP_010103.1; NM_001180238.1.
DR AlphaFoldDB; P46681; -.
DR SMR; P46681; -.
DR BioGRID; 31888; 42.
DR DIP; DIP-956N; -.
DR IntAct; P46681; 1.
DR STRING; 4932.YDL178W; -.
DR MaxQB; P46681; -.
DR PaxDb; P46681; -.
DR PRIDE; P46681; -.
DR EnsemblFungi; YDL178W_mRNA; YDL178W; YDL178W.
DR GeneID; 851376; -.
DR KEGG; sce:YDL178W; -.
DR SGD; S000002337; DLD2.
DR VEuPathDB; FungiDB:YDL178W; -.
DR eggNOG; KOG1232; Eukaryota.
DR GeneTree; ENSGT00550000075086; -.
DR HOGENOM; CLU_017779_4_1_1; -.
DR InParanoid; P46681; -.
DR OMA; CNDNMLA; -.
DR BioCyc; YEAST:YDL178W-MON; -.
DR Reactome; R-SCE-880009; Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.
DR PRO; PR:P46681; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P46681; protein.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0051990; F:(R)-2-hydroxyglutarate dehydrogenase activity; IDA:SGD.
DR GO; GO:0003779; F:actin binding; IMP: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:1903457; P:lactate catabolic 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 FAD; Flavoprotein; Mitochondrion; Oxidoreductase; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..530
FT /note="D-2-hydroxyglutarate--pyruvate transhydrogenase
FT DLD2"
FT /id="PRO_0000020429"
FT DOMAIN 98..277
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT CONFLICT 239
FT /note="N -> S (in Ref. 4; AAU09682)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 530 AA; 59268 MW; 42FDFBE5CA7E11B7 CRC64;
MLRNILVRST GSNFKFAGRY MKSSALLGYY RRVNYYSTKI QTRLTSENYP DVHRDPRFKK
LTSDDLNYFK SILSEQEILR ASESEDLSFY NEDWMRKYKG QSKLVLRPKS VEKVSLILNY
CNDEKIAVVP QGGNTGLVGG SVPIFDELIL SLANLNKIRD FDPVSGILKC DAGVILENAN
NYVMEQNYMF PLDLGAKGSC HVGGVVATNA GGLRLLRYGS LHGSVLGLEV VMPNGQIVNS
MHSMRKDNTG YDLKQLFIGS EGTIGIITGV SILTVPKPKA FNVSYLSVES FEDVQKVFVR
ARQELSEILS AFEFMDAKSQ VLAKSQLKDA AFPLEDEHPF YILIETSGSN KDHDDSKLET
FLENVMEEGI VTDGVVAQDE TELQNLWKWR EMIPEASQAN GGVYKYDVSL PLKDLYSLVE
ATNARLSEAE LVGDSPKPVV GAIGYGHVGD GNLHLNVAVR EYNKNIEKTL EPFVYEFVSS
KHGSVSAEHG LGFQKKNYIG YSKSPEEVKM MKDLKVHYDP NGILNPYKYI
