D2HDH_MOUSE
ID D2HDH_MOUSE Reviewed; 535 AA.
AC Q8CIM3; E9QLL1; Q149H0; Q3TDF5; Q8BU06;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=D-2-hydroxyglutarate dehydrogenase, mitochondrial;
DE EC=1.1.99.39 {ECO:0000250|UniProtKB:Q8N465};
DE Flags: Precursor;
GN Name=D2hgdh;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, and Spleen;
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-115, 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).
CC -!- FUNCTION: Catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) to
CC alpha-ketoglutarate (By similarity). Also catalyzes the oxidation of
CC other D-2-hydroxyacids, such as D-malate (D-MAL) and D-lactate (D-LAC)
CC (By similarity). Exhibits high activities towards D-2-HG and D-MAL but
CC a very weak activity towards D-LAC (By similarity).
CC {ECO:0000250|UniProtKB:Q8N465}.
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:0000250|UniProtKB:Q8N465};
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 and cobalt ions.
CC {ECO:0000250|UniProtKB:Q8N465}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC 4 family. {ECO:0000305}.
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DR EMBL; AK088200; BAC40205.1; -; mRNA.
DR EMBL; AK170226; BAE41647.1; -; mRNA.
DR EMBL; AC167139; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC023277; AAH23277.1; -; mRNA.
DR EMBL; BC117794; AAI17795.1; -; mRNA.
DR CCDS; CCDS15196.1; -.
DR RefSeq; NP_849213.2; NM_178882.4.
DR AlphaFoldDB; Q8CIM3; -.
DR SMR; Q8CIM3; -.
DR BioGRID; 221035; 1.
DR STRING; 10090.ENSMUSP00000095235; -.
DR iPTMnet; Q8CIM3; -.
DR PhosphoSitePlus; Q8CIM3; -.
DR SwissPalm; Q8CIM3; -.
DR MaxQB; Q8CIM3; -.
DR PaxDb; Q8CIM3; -.
DR PeptideAtlas; Q8CIM3; -.
DR PRIDE; Q8CIM3; -.
DR ProteomicsDB; 279872; -.
DR Antibodypedia; 34576; 117 antibodies from 18 providers.
DR Ensembl; ENSMUST00000097633; ENSMUSP00000095235; ENSMUSG00000073609.
DR GeneID; 98314; -.
DR KEGG; mmu:98314; -.
DR UCSC; uc007cep.2; mouse.
DR CTD; 728294; -.
DR MGI; MGI:2138209; D2hgdh.
DR VEuPathDB; HostDB:ENSMUSG00000073609; -.
DR eggNOG; KOG1232; Eukaryota.
DR GeneTree; ENSGT00550000075086; -.
DR HOGENOM; CLU_017779_4_1_1; -.
DR InParanoid; Q8CIM3; -.
DR OMA; CNDNMLA; -.
DR OrthoDB; 515900at2759; -.
DR TreeFam; TF323342; -.
DR Reactome; R-MMU-880009; Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.
DR BioGRID-ORCS; 98314; 2 hits in 71 CRISPR screens.
DR ChiTaRS; D2hgdh; mouse.
DR PRO; PR:Q8CIM3; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8CIM3; protein.
DR Bgee; ENSMUSG00000073609; Expressed in left lobe of liver and 219 other tissues.
DR ExpressionAtlas; Q8CIM3; baseline and differential.
DR Genevisible; Q8CIM3; MM.
DR GO; GO:0005739; C:mitochondrion; ISS:HGNC-UCL.
DR GO; GO:0051990; F:(R)-2-hydroxyglutarate dehydrogenase activity; ISS:UniProtKB.
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; ISS:HGNC-UCL.
DR GO; GO:0032025; P:response to cobalt ion; ISS:HGNC-UCL.
DR GO; GO:0010042; P:response to manganese ion; ISS:HGNC-UCL.
DR GO; GO:0010043; P:response to zinc ion; ISS: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_0000231675"
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:0007744|PubMed:23806337"
FT CONFLICT 56
FT /note="G -> S (in Ref. 3; AAH23277)"
FT /evidence="ECO:0000305"
FT CONFLICT 451
FT /note="D -> G (in Ref. 1; BAE41647)"
FT /evidence="ECO:0000305"
FT CONFLICT 522
FT /note="E -> K (in Ref. 1; BAE41647/BAC40205 and 3;
FT AAH23277/AAI17795)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 535 AA; 58576 MW; 1056007386DE4043 CRC64;
MVLPLVSRWS ARVLWASPGW RRTYTQRACV GLKRLGCPRG VYSPLAHRAY SVVAGGPEVT
LTPERYPVQR LPFSTVSEED LAAFECIIPG RVITDPEQLQ TCNVDWLKTV RGCSKVLLRP
QTSEEVSQIL RHCYKRNLAV NPQGGNTGMV GGSVPVFDEV ILSTALMNQV ISFHDVSGIL
VCQAGCVLEE LSRYVQERDF IMPLDLGAKG SCHIGGNVAT NAGGLRFLRY GSLRGTVLGL
EVVLADGTIL NCLTSLRKDN TGYDLKQMFI GSEGTLGVIT AVSIVCPPRP KAVNVAFLGC
PGFAEVLQTF RTCRGMLGEI LSAFEFMDTE CMQLVGQHLQ LTNPVQESPF YVLVETSGSS
AGHDAEKLTN VLEQVLNSGL VTDGTMATDQ RKVQMLWALR ERITEALSRD GYVFKYDLSL
PVERLYDLVI DLRTRLGPRA KHVVGYGHLG DGNLHLNVTA EAFSRELLGA LEPYVYAWTA
EQRGSVSAEH GLGFKKKDVL GYSKPPVAVT LMQQLKAMLD PEGILNPYKT LPAQA
