D2HDH_ARATH
ID D2HDH_ARATH Reviewed; 559 AA.
AC O23240; Q93Z78;
DT 20-APR-2010, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 3.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=D-2-hydroxyglutarate dehydrogenase, mitochondrial;
DE Short=AtD-2HGDH;
DE EC=1.1.99.39;
DE Flags: Precursor;
GN Name=D2HGDH; OrderedLocusNames=At4g36400; ORFNames=AP22.14, C7A10.960;
OS Arabidopsis thaliana (Mouse-ear cress).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=9461215; DOI=10.1038/35140;
RA Bevan M., Bancroft I., Bent E., Love K., Goodman H.M., Dean C.,
RA Bergkamp R., Dirkse W., van Staveren M., Stiekema W., Drost L., Ridley P.,
RA Hudson S.-A., Patel K., Murphy G., Piffanelli P., Wedler H., Wedler E.,
RA Wambutt R., Weitzenegger T., Pohl T., Terryn N., Gielen J., Villarroel R.,
RA De Clercq R., van Montagu M., Lecharny A., Aubourg S., Gy I., Kreis M.,
RA Lao N., Kavanagh T., Hempel S., Kotter P., Entian K.-D., Rieger M.,
RA Schaefer M., Funk B., Mueller-Auer S., Silvey M., James R., Monfort A.,
RA Pons A., Puigdomenech P., Douka A., Voukelatou E., Milioni D.,
RA Hatzopoulos P., Piravandi E., Obermaier B., Hilbert H., Duesterhoeft A.,
RA Moores T., Jones J.D.G., Eneva T., Palme K., Benes V., Rechmann S.,
RA Ansorge W., Cooke R., Berger C., Delseny M., Voet M., Volckaert G.,
RA Mewes H.-W., Klosterman S., Schueller C., Chalwatzis N.;
RT "Analysis of 1.9 Mb of contiguous sequence from chromosome 4 of Arabidopsis
RT thaliana.";
RL Nature 391:485-488(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=10617198; DOI=10.1038/47134;
RA Mayer K.F.X., Schueller C., Wambutt R., Murphy G., Volckaert G., Pohl T.,
RA Duesterhoeft A., Stiekema W., Entian K.-D., Terryn N., Harris B.,
RA Ansorge W., Brandt P., Grivell L.A., Rieger M., Weichselgartner M.,
RA de Simone V., Obermaier B., Mache R., Mueller M., Kreis M., Delseny M.,
RA Puigdomenech P., Watson M., Schmidtheini T., Reichert B., Portetelle D.,
RA Perez-Alonso M., Boutry M., Bancroft I., Vos P., Hoheisel J.,
RA Zimmermann W., Wedler H., Ridley P., Langham S.-A., McCullagh B.,
RA Bilham L., Robben J., van der Schueren J., Grymonprez B., Chuang Y.-J.,
RA Vandenbussche F., Braeken M., Weltjens I., Voet M., Bastiaens I., Aert R.,
RA Defoor E., Weitzenegger T., Bothe G., Ramsperger U., Hilbert H., Braun M.,
RA Holzer E., Brandt A., Peters S., van Staveren M., Dirkse W., Mooijman P.,
RA Klein Lankhorst R., Rose M., Hauf J., Koetter P., Berneiser S., Hempel S.,
RA Feldpausch M., Lamberth S., Van den Daele H., De Keyser A., Buysshaert C.,
RA Gielen J., Villarroel R., De Clercq R., van Montagu M., Rogers J.,
RA Cronin A., Quail M.A., Bray-Allen S., Clark L., Doggett J., Hall S.,
RA Kay M., Lennard N., McLay K., Mayes R., Pettett A., Rajandream M.A.,
RA Lyne M., Benes V., Rechmann S., Borkova D., Bloecker H., Scharfe M.,
RA Grimm M., Loehnert T.-H., Dose S., de Haan M., Maarse A.C., Schaefer M.,
RA Mueller-Auer S., Gabel C., Fuchs M., Fartmann B., Granderath K., Dauner D.,
RA Herzl A., Neumann S., Argiriou A., Vitale D., Liguori R., Piravandi E.,
RA Massenet O., Quigley F., Clabauld G., Muendlein A., Felber R., Schnabl S.,
RA Hiller R., Schmidt W., Lecharny A., Aubourg S., Chefdor F., Cooke R.,
RA Berger C., Monfort A., Casacuberta E., Gibbons T., Weber N., Vandenbol M.,
RA Bargues M., Terol J., Torres A., Perez-Perez A., Purnelle B., Bent E.,
RA Johnson S., Tacon D., Jesse T., Heijnen L., Schwarz S., Scholler P.,
RA Heber S., Francs P., Bielke C., Frishman D., Haase D., Lemcke K.,
RA Mewes H.-W., Stocker S., Zaccaria P., Bevan M., Wilson R.K.,
RA de la Bastide M., Habermann K., Parnell L., Dedhia N., Gnoj L., Schutz K.,
RA Huang E., Spiegel L., Sekhon M., Murray J., Sheet P., Cordes M.,
RA Abu-Threideh J., Stoneking T., Kalicki J., Graves T., Harmon G.,
RA Edwards J., Latreille P., Courtney L., Cloud J., Abbott A., Scott K.,
RA Johnson D., Minx P., Bentley D., Fulton B., Miller N., Greco T., Kemp K.,
RA Kramer J., Fulton L., Mardis E., Dante M., Pepin K., Hillier L.W.,
RA Nelson J., Spieth J., Ryan E., Andrews S., Geisel C., Layman D., Du H.,
RA Ali J., Berghoff A., Jones K., Drone K., Cotton M., Joshu C., Antonoiu B.,
RA Zidanic M., Strong C., Sun H., Lamar B., Yordan C., Ma P., Zhong J.,
RA Preston R., Vil D., Shekher M., Matero A., Shah R., Swaby I.K.,
RA O'Shaughnessy A., Rodriguez M., Hoffman J., Till S., Granat S., Shohdy N.,
RA Hasegawa A., Hameed A., Lodhi M., Johnson A., Chen E., Marra M.A.,
RA Martienssen R., McCombie W.R.;
RT "Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.";
RL Nature 402:769-777(1999).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=19586914; DOI=10.1074/jbc.m109.021253;
RA Engqvist M., Drincovich M.F., Fluegge U.I., Maurino V.G.;
RT "Two D-2-hydroxy-acid dehydrogenases in Arabidopsis thaliana with catalytic
RT capacities to participate in the last reactions of the methylglyoxal and
RT beta-oxidation pathways.";
RL J. Biol. Chem. 284:25026-25037(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20501910; DOI=10.1105/tpc.110.075630;
RA Araujo W.L., Ishizaki K., Nunes-Nesi A., Larson T.R., Tohge T.,
RA Krahnert I., Witt S., Obata T., Schauer N., Graham I.A., Leaver C.J.,
RA Fernie A.R.;
RT "Identification of the 2-hydroxyglutarate and isovaleryl-CoA dehydrogenases
RT as alternative electron donors linking lysine catabolism to the electron
RT transport chain of Arabidopsis mitochondria.";
RL Plant Cell 22:1549-1563(2010).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=21296880; DOI=10.1074/jbc.m110.194175;
RA Engqvist M.K., Kuhn A., Wienstroer J., Weber K., Jansen E.E., Jakobs C.,
RA Weber A.P., Maurino V.G.;
RT "Plant D-2-hydroxyglutarate dehydrogenase participates in the catabolism of
RT lysine especially during senescence.";
RL J. Biol. Chem. 286:11382-11390(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND CLEAVAGE OF TRANSIT PEPTIDE AFTER
RP PHE-78.
RX PubMed=25732537; DOI=10.1093/jxb/erv064;
RA Carrie C., Venne A.S., Zahedi R.P., Soll J.;
RT "Identification of cleavage sites and substrate proteins for two
RT mitochondrial intermediate peptidases in Arabidopsis thaliana.";
RL J. Exp. Bot. 66:2691-2708(2015).
CC -!- FUNCTION: Catalyzes the oxidation of (R)-2-hydroxyglutarate to 2-
CC oxoglutarate. May be involved in the catabolism of propionyl-CoA
CC derived from beta-oxidation. Involved in degradation of lysine for the
CC supply of carbon and electrons to the ETF/ETFQO complex during dark-
CC induced sugar starvation. {ECO:0000269|PubMed:19586914,
CC ECO:0000269|PubMed:20501910, ECO:0000269|PubMed:21296880}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-2-hydroxyglutarate + A = 2-oxoglutarate + AH2;
CC Xref=Rhea:RHEA:38295, ChEBI:CHEBI:13193, ChEBI:CHEBI:15801,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:17499; EC=1.1.99.39;
CC Evidence={ECO:0000269|PubMed:19586914};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:19586914};
CC Note=Binds 1 FAD per monomer. {ECO:0000269|PubMed:19586914};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=584 uM for (R)-2-hydroxyglutarate (with DCIP as acceptor molecule)
CC {ECO:0000269|PubMed:19586914};
CC Note=Very low activity toward D-lactate, D-2-hydroxybutyrate and
CC meso-tartrate. Does not efficiently use cytochrome c as electron
CC acceptor and is not able to transfer electrons to NAD or NADP.;
CC pH dependence:
CC Optimum pH is 8.5-9.5. {ECO:0000269|PubMed:19586914};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19586914}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:19586914,
CC ECO:0000269|PubMed:21296880, ECO:0000305|PubMed:25732537}.
CC -!- INDUCTION: By dark-induced senescence. {ECO:0000269|PubMed:21296880}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype when grown under standard
CC conditions. {ECO:0000269|PubMed:19586914, ECO:0000269|PubMed:20501910}.
CC -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC 4 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL24169.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=CAB16815.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAB80306.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; Z99708; CAB16815.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL161589; CAB80306.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CP002687; AEE86651.1; -; Genomic_DNA.
DR EMBL; CP002687; AEE86652.1; -; Genomic_DNA.
DR EMBL; AY058061; AAL24169.1; ALT_SEQ; mRNA.
DR EMBL; AY090301; AAL90962.1; -; mRNA.
DR PIR; F85429; F85429.
DR RefSeq; NP_001320151.1; NM_001342409.1.
DR RefSeq; NP_974692.1; NM_202963.2.
DR AlphaFoldDB; O23240; -.
DR SMR; O23240; -.
DR BioGRID; 15074; 1.
DR STRING; 3702.AT4G36400.2; -.
DR PaxDb; O23240; -.
DR PRIDE; O23240; -.
DR ProteomicsDB; 222598; -.
DR EnsemblPlants; AT4G36400.1; AT4G36400.1; AT4G36400.
DR EnsemblPlants; AT4G36400.2; AT4G36400.2; AT4G36400.
DR GeneID; 829792; -.
DR Gramene; AT4G36400.1; AT4G36400.1; AT4G36400.
DR Gramene; AT4G36400.2; AT4G36400.2; AT4G36400.
DR KEGG; ath:AT4G36400; -.
DR Araport; AT4G36400; -.
DR TAIR; locus:2115230; AT4G36400.
DR eggNOG; KOG1232; Eukaryota.
DR HOGENOM; CLU_017779_4_1_1; -.
DR InParanoid; O23240; -.
DR OMA; CNDNMLA; -.
DR OrthoDB; 515900at2759; -.
DR PhylomeDB; O23240; -.
DR BioCyc; ARA:MONQT-4168; -.
DR PRO; PR:O23240; -.
DR Proteomes; UP000006548; Chromosome 4.
DR ExpressionAtlas; O23240; baseline and differential.
DR Genevisible; O23240; AT.
DR GO; GO:0005739; C:mitochondrion; HDA:TAIR.
DR GO; GO:0005886; C:plasma membrane; HDA:TAIR.
DR GO; GO:0051990; F:(R)-2-hydroxyglutarate dehydrogenase activity; IDA:TAIR.
DR GO; GO:0047545; F:2-hydroxyglutarate dehydrogenase activity; IDA:TAIR.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0010230; P:alternative respiration; IMP:TAIR.
DR GO; GO:0006807; P:nitrogen compound metabolic process; IGI:TAIR.
DR GO; GO:0009853; P:photorespiration; IGI:TAIR.
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..78
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:25732537"
FT CHAIN 79..559
FT /note="D-2-hydroxyglutarate dehydrogenase, mitochondrial"
FT /id="PRO_0000393389"
FT DOMAIN 130..309
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
SQ SEQUENCE 559 AA; 61445 MW; 53D72B588A7302A9 CRC64;
MMMQKLRRSG EFIRFGCKSL ISSRPNKDSV SRSVSGFVNH YKSKGKLFEL SDGNYKTELH
HPCISRNVGM LLQQYKCFGS SAASLIQRNP LFSSLDSKDV SYFKEILGEK NVVEDKERLE
TANTDWMHKY KGSSKLMLLP KNTQEVSQIL EYCDSRRLAV VPQGGNTGLV GGSVPVFDEV
IVNVGLMNKI LSFDEVSGVL VCEAGCILEN LATFLDTKGF IMPLDLGAKG SCHIGGNVST
NAGGLRLIRY GSLHGTVLGL EAVTANGNVL DMLGTLRKDN TGYDLKHLFI GSEGSLGIVT
KVSILTQPKL SSVNLAFIAC KDYLSCQKLL VEAKRNLGEI LSAFEFLDNN SMDLVLNHLD
GVRNPVSSSE NFYILIETTG SDETNDREKL EAFLLKSLEK GLVSDGVIAQ DINQASSFWR
IREGITEALQ KAGAVYKYDL SLPVEEIYNI VNDLRGRLGD LANVMGYGHL GDGNLHLNIS
AAEYNDKLLG LIEPYVYEWT SKHRGSISAE HGLGVMKANE IFYSKSPETV ALMASIKKLL
DPKGILNPYK VLPHSLFSN
