D2HDH_DANRE
ID D2HDH_DANRE Reviewed; 533 AA.
AC A1L258;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=D-2-hydroxyglutarate dehydrogenase, mitochondrial;
DE EC=1.1.99.39 {ECO:0000250|UniProtKB:Q8N465};
DE Flags: Precursor;
GN Name=d2hgdh; ORFNames=zgc:158661;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
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 -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC 4 family. {ECO:0000305}.
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DR EMBL; BC129361; AAI29362.1; -; mRNA.
DR RefSeq; NP_001074066.1; NM_001080597.1.
DR AlphaFoldDB; A1L258; -.
DR SMR; A1L258; -.
DR STRING; 7955.ENSDARP00000079032; -.
DR PaxDb; A1L258; -.
DR PeptideAtlas; A1L258; -.
DR GeneID; 565889; -.
DR KEGG; dre:565889; -.
DR CTD; 728294; -.
DR ZFIN; ZDB-GENE-070112-482; d2hgdh.
DR eggNOG; KOG1232; Eukaryota.
DR InParanoid; A1L258; -.
DR OrthoDB; 515900at2759; -.
DR PhylomeDB; A1L258; -.
DR Reactome; R-DRE-880009; Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.
DR PRO; PR:A1L258; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
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 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 2: Evidence at transcript level;
KW FAD; Flavoprotein; Metal-binding; Mitochondrion; Oxidoreductase;
KW Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1..55
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 56..533
FT /note="D-2-hydroxyglutarate dehydrogenase, mitochondrial"
FT /id="PRO_0000347235"
FT DOMAIN 107..286
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT BINDING 397
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 397
FT /ligand="(R)-lactate"
FT /ligand_id="ChEBI:CHEBI:16004"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 397
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 401
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 401
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 412
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 412
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 445
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 452
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 454
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 486
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 487
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 487
FT /ligand="(R)-lactate"
FT /ligand_id="ChEBI:CHEBI:16004"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 487
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
SQ SEQUENCE 533 AA; 58714 MW; A6636E8DB7B1485A CRC64;
MGLFQKCSRL SLRSSYMWSV CPQYSIAVTA RETPDRALIV HWTQHRDVHN SRRLGANPAN
PSAAPPRLPF SRVTQEDLSF FRALLPGRTI TDPDLLKSSN VDWLKTVQGS SDVLLRPKTT
EGVSQILRYC NERNLAVCPQ GGNTGLVGGS VPVFDEIILS TSLMNQVFAF DNISGILTCQ
AGCVLENLSH YLEERDFIMP LDLGAKGSCH IGGNVSTNAG GLRLLRYGSL RGTVLGLEVV
LADGHVLNCL ATLRKDNTGY DLKQLFIGSE GTLGVITAVS ILCPRKPKAV NVAFLGCSSF
QQLLETFQCC RGMLGEILSA FEFLDASCMN LLEKHLKLTN PITECPFYIV IETAGSNATH
DEEKLHQFLE EVMTSSLVTD GTVATEATKI KALWSLRERV TEALTHEGYT YKYDISLPVE
KIYDLVQDMR RHLGGMAKNV VGYGHVGDGN LHLNITSPSK DFDLLAAIEP YVYEWTSQWK
GSISAEHGLG LKKRNYIYYS KPSEAVALMG SIKAMLDPKG ILNPYKTLPD NIN
