D2HDH_RAT
ID D2HDH_RAT Reviewed; 535 AA.
AC P84850;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=D-2-hydroxyglutarate dehydrogenase, mitochondrial;
DE EC=1.1.99.39 {ECO:0000269|PubMed:15070399};
DE Flags: Precursor;
GN Name=D2hgdh {ECO:0000250|UniProtKB:Q8N465};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000269|PubMed:15057822};
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15070399; DOI=10.1042/bj20031933;
RA Achouri Y., Noel G., Vertommen D., Rider M.H., Veiga-Da-Cunha M.,
RA van Schaftingen E.;
RT "Identification of a dehydrogenase acting on D-2-hydroxyglutarate.";
RL Biochem. J. 381:35-42(2004).
CC -!- FUNCTION: Catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) to
CC alpha-ketoglutarate (PubMed:15070399). Also catalyzes the oxidation of
CC other D-2-hydroxyacids, such as D-malate (D-MAL) and D-lactate (D-LAC)
CC (PubMed:15070399). Exhibits high activities towards D-2-HG and D-MAL
CC but a very weak activity towards D-LAC (By similarity).
CC {ECO:0000250|UniProtKB:Q8N465, ECO:0000269|PubMed:15070399}.
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:15070399};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-malate + A = AH2 + oxaloacetate; Xref=Rhea:RHEA:67460,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15588, ChEBI:CHEBI:16452,
CC ChEBI:CHEBI:17499; Evidence={ECO:0000250|UniProtKB:Q8N465};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67461;
CC Evidence={ECO:0000250|UniProtKB:Q8N465};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- ACTIVITY REGULATION: Activated by zinc, cobalt and manganese ions
CC (PubMed:15070399). Inhibited by EDTA (PubMed:15070399).
CC {ECO:0000269|PubMed:15070399}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:15070399}.
CC -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC 4 family. {ECO:0000255}.
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DR EMBL; AABR03068074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03072218; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03072243; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_006245583.1; XM_006245521.3.
DR RefSeq; XP_006245584.1; XM_006245522.3.
DR AlphaFoldDB; P84850; -.
DR SMR; P84850; -.
DR STRING; 10116.ENSRNOP00000025711; -.
DR iPTMnet; P84850; -.
DR PhosphoSitePlus; P84850; -.
DR PaxDb; P84850; -.
DR PRIDE; P84850; -.
DR GeneID; 301624; -.
DR UCSC; RGD:1307976; rat.
DR CTD; 728294; -.
DR RGD; 1307976; D2hgdh.
DR VEuPathDB; HostDB:ENSRNOG00000019012; -.
DR eggNOG; KOG1232; Eukaryota.
DR HOGENOM; CLU_017779_4_1_1; -.
DR InParanoid; P84850; -.
DR OMA; CNDNMLA; -.
DR OrthoDB; 515900at2759; -.
DR PhylomeDB; P84850; -.
DR TreeFam; TF323342; -.
DR Reactome; R-RNO-880009; Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.
DR PRO; PR:P84850; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000019012; Expressed in liver and 18 other tissues.
DR ExpressionAtlas; P84850; baseline and differential.
DR Genevisible; P84850; RN.
DR GO; GO:0005739; C:mitochondrion; IDA:HGNC-UCL.
DR GO; GO:0051990; F:(R)-2-hydroxyglutarate dehydrogenase activity; IDA:HGNC-UCL.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0006108; P:malate metabolic process; ISS:UniProtKB.
DR GO; GO:0019538; P:protein metabolic process; IDA:HGNC-UCL.
DR GO; GO:0032025; P:response to cobalt ion; IDA:HGNC-UCL.
DR GO; GO:0010042; P:response to manganese ion; IDA:HGNC-UCL.
DR GO; GO:0010043; P:response to zinc ion; IDA:HGNC-UCL.
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; Metal-binding; Mitochondrion; Oxidoreductase;
KW Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1..50
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 51..535
FT /note="D-2-hydroxyglutarate dehydrogenase, mitochondrial"
FT /id="PRO_0000234528"
FT DOMAIN 110..289
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT BINDING 400
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 400
FT /ligand="(R)-lactate"
FT /ligand_id="ChEBI:CHEBI:16004"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 400
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 404
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 404
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 415
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 415
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 448
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 455
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 457
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 489
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 490
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 490
FT /ligand="(R)-lactate"
FT /ligand_id="ChEBI:CHEBI:16004"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 490
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT MOD_RES 115
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CIM3"
SQ SEQUENCE 535 AA; 58805 MW; B326B0083868216C CRC64;
MVLHLVPRWS ASLFRASPRW KKTYSQRASA QLKWLGCPRS VYSPLACRAY SKVSGSPEVM
LTPERYPVQR LPFSTVSEED LAAFECIIPG RVITDPEQLQ TCNVDWLRTV RGCSKVLLRP
QTSEEVSQIL RHCYKRNLAV NPQGGNTGMV GGSVPVFDEV ILSTALMNQV ISFHDVSGIL
VCQAGCVLEE LSRYVQERDF IMPLDLGAKG SCHIGGNVAT NAGGLRFLRY GSLRGTVLGL
EVVLADGTIL NCLTSLRKDN TGYDLKQMFI GSEGTLGVIT AVSIVCPPRP KAVNVAFLGC
PGFTEVLQTF RTCKGQLGEI LSAFEFMDAE CMQLVGQHLH LTNPVQESPF YVLVETSGSS
AGHDAEKLTN VLEQVLNSGL VIDGTMATDQ RKVQMLWALR ERITEALSRD GYVFKYDLSL
PVERLYDLVI DLRTRLGPRA KHVVGYGHLG DGNLHLNVTA EAFSQELLGA LEPYVYAWTA
EQRGSVSAEH GLGFKKKNVL GYSKPPVAVK LMQQLKAMLD PKGILNPYKT LPARA
