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Protein

D-2-hydroxyglutarate dehydrogenase, mitochondrial

Gene

D2HGDH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the oxidation of D-2-hydroxyglutarate to alpha-ketoglutarate.1 Publication

Catalytic activityi

(R)-2-hydroxyglutarate + acceptor = 2-oxoglutarate + reduced acceptor.

Cofactori

FADCurated

Enzyme regulationi

Activated by zinc and cobalt.1 Publication

GO - Molecular functioni

GO - Biological processi

  • 2-oxoglutarate metabolic process Source: Reactome
  • cellular protein metabolic process Source: HGNC
  • lactate oxidation Source: GO_Central
  • respiratory electron transport chain Source: GO_Central
  • response to cobalt ion Source: HGNC
  • response to manganese ion Source: HGNC
  • response to zinc ion Source: HGNC

Keywordsi

Molecular functionOxidoreductase
LigandFAD, Flavoprotein

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000180902-MONOMER
ReactomeiR-HSA-880009 Interconversion of 2-oxoglutarate and 2-hydroxyglutarate
SIGNORiQ8N465

Names & Taxonomyi

Protein namesi
Recommended name:
D-2-hydroxyglutarate dehydrogenase, mitochondrial (EC:1.1.99.-)
Gene namesi
Name:D2HGDH
Synonyms:D2HGD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000180902.16
HGNCiHGNC:28358 D2HGDH
MIMi609186 gene
neXtProtiNX_Q8N465

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

D-2-hydroxyglutaric aciduria 1 (D2HGA1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare recessive neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine.
See also OMIM:600721
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025890147I → S in D2HGA1; severe phenotype; loss of catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs121434361EnsemblClinVar.1
Natural variantiVAR_025891375D → Y in D2HGA1. 1 PublicationCorresponds to variant dbSNP:rs267606759EnsemblClinVar.1
Natural variantiVAR_025893439N → D in D2HGA1; mild phenotype; altered catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs121434362EnsemblClinVar.1
Natural variantiVAR_025894444V → A in D2HGA1; severe phenotype; altered catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs121434360EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi728294
MalaCardsiD2HGDH
MIMi600721 phenotype
OpenTargetsiENSG00000180902
Orphaneti79315 D-2-hydroxyglutaric aciduria
PharmGKBiPA143485446

Polymorphism and mutation databases

BioMutaiD2HGDH
DMDMi91208273

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 13MitochondrionSequence analysisAdd BLAST13
ChainiPRO_000023167414 – 521D-2-hydroxyglutarate dehydrogenase, mitochondrialAdd BLAST508

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei101N6-succinyllysineBy similarity1

Proteomic databases

EPDiQ8N465
MaxQBiQ8N465
PaxDbiQ8N465
PeptideAtlasiQ8N465
PRIDEiQ8N465

PTM databases

iPTMnetiQ8N465
PhosphoSitePlusiQ8N465

Expressioni

Gene expression databases

BgeeiENSG00000180902
CleanExiHS_D2HGDH
ExpressionAtlasiQ8N465 baseline and differential
GenevisibleiQ8N465 HS

Organism-specific databases

HPAiHPA056216

Interactioni

Protein-protein interaction databases

BioGridi608722, 14 interactors
IntActiQ8N465, 2 interactors
MINTiQ8N465
STRINGi9606.ENSP00000315351

Structurei

3D structure databases

ProteinModelPortaliQ8N465
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini96 – 275FAD-binding PCMH-typePROSITE-ProRule annotationAdd BLAST180

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1232 Eukaryota
COG0277 LUCA
GeneTreeiENSGT00550000075086
HOGENOMiHOG000230997
HOVERGENiHBG079809
InParanoidiQ8N465
KOiK18204
OMAiNEDWMRK
OrthoDBiEOG091G0AXU
PhylomeDBiQ8N465
TreeFamiTF323342

Family and domain databases

Gene3Di1.10.45.10, 1 hit
3.30.43.10, 1 hit
InterProiView protein in InterPro
IPR016166 FAD-bd_2
IPR036318 FAD-bd_2-like_sf
IPR016167 FAD-bd_2_sub1
IPR016164 FAD-linked_Oxase-like_C
IPR004113 FAD-linked_oxidase_C
IPR006094 Oxid_FAD_bind_N
IPR016171 Vanillyl_alc_oxidase_C-sub2
PfamiView protein in Pfam
PF02913 FAD-oxidase_C, 1 hit
PF01565 FAD_binding_4, 1 hit
SUPFAMiSSF55103 SSF55103, 1 hit
SSF56176 SSF56176, 1 hit
PROSITEiView protein in PROSITE
PS51387 FAD_PCMH, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N465-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLPRRPLAWP AWLLRGAPGA AGSWGRPVGP LARRGCCSAP GTPEVPLTRE
60 70 80 90 100
RYPVRRLPFS TVSKQDLAAF ERIVPGGVVT DPEALQAPNV DWLRTLRGCS
110 120 130 140 150
KVLLRPRTSE EVSHILRHCH ERNLAVNPQG GNTGMVGGSV PVFDEIILST
160 170 180 190 200
ARMNRVLSFH SVSGILVCQA GCVLEELSRY VEERDFIMPL DLGAKGSCHI
210 220 230 240 250
GGNVATNAGG LRFLRYGSLH GTVLGLEVVL ADGTVLDCLT SLRKDNTGYD
260 270 280 290 300
LKQLFIGSEG TLGIITTVSI LCPPKPRAVN VAFLGCPGFA EVLQTFSTCK
310 320 330 340 350
GMLGEILSAF EFMDAVCMQL VGRHLHLASP VQESPFYVLI ETSGSNAGHD
360 370 380 390 400
AEKLGHFLEH ALGSGLVTDG TMATDQRKVK MLWALRERIT EALSRDGYVY
410 420 430 440 450
KYDLSLPVER LYDIVTDLRA RLGPHAKHVV GYGHLGDGNL HLNVTAEAFS
460 470 480 490 500
PSLLAALEPH VYEWTAGQQG SVSAEHGVGF RKRDVLGYSK PPGALQLMQQ
510 520
LKALLDPKGI LNPYKTLPSQ A
Length:521
Mass (Da):56,416
Last modified:April 4, 2006 - v3
Checksum:i65D88C4315FA45CE
GO
Isoform 2 (identifier: Q8N465-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     165-172: ILVCQAGC → GL
     285-313: GCPGFAEVLQTFSTCKGMLGEILSAFEFM → VTCVLPACGPGSPRPARLPHPALRTPGLR
     314-521: Missing.

Note: No experimental confirmation available.
Show »
Length:307
Mass (Da):32,933
Checksum:i2EA2EA997C5E4968
GO
Isoform 3 (identifier: Q8N465-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     285-319: GCPGFAEVLQTFSTCKGMLGEILSAFEFMDAVCMQ → VTCVPPACGPGSPRPARLPHPALRTPGVCPQPLRL
     320-521: Missing.

Note: No experimental confirmation available.
Show »
Length:319
Mass (Da):34,173
Checksum:i6C7BDA672635D743
GO

Sequence cautioni

The sequence AAX82020 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55R → Q in AAH36604 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02588915R → G1 PublicationCorresponds to variant dbSNP:rs4675887EnsemblClinVar.1
Natural variantiVAR_025890147I → S in D2HGA1; severe phenotype; loss of catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs121434361EnsemblClinVar.1
Natural variantiVAR_050433338V → I. Corresponds to variant dbSNP:rs1106639EnsemblClinVar.1
Natural variantiVAR_050434361A → V. Corresponds to variant dbSNP:rs1105273EnsemblClinVar.1
Natural variantiVAR_025891375D → Y in D2HGA1. 1 PublicationCorresponds to variant dbSNP:rs267606759EnsemblClinVar.1
Natural variantiVAR_025892436G → V1 Publication1
Natural variantiVAR_025893439N → D in D2HGA1; mild phenotype; altered catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs121434362EnsemblClinVar.1
Natural variantiVAR_025894444V → A in D2HGA1; severe phenotype; altered catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs121434360EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017876165 – 172ILVCQAGC → GL in isoform 2. 1 Publication8
Alternative sequenceiVSP_054389285 – 319GCPGF…AVCMQ → VTCVPPACGPGSPRPARLPH PALRTPGVCPQPLRL in isoform 3. 1 PublicationAdd BLAST35
Alternative sequenceiVSP_017877285 – 313GCPGF…AFEFM → VTCVLPACGPGSPRPARLPH PALRTPGLR in isoform 2. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_017878314 – 521Missing in isoform 2. 1 PublicationAdd BLAST208
Alternative sequenceiVSP_054390320 – 521Missing in isoform 3. 1 PublicationAdd BLAST202

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK304773 mRNA Translation: BAG65528.1
AC114730 Genomic DNA Translation: AAX82020.1 Sequence problems.
BC036604 mRNA Translation: AAH36604.2
BC071598 mRNA Translation: AAH71598.1
CCDSiCCDS33426.1 [Q8N465-1]
RefSeqiNP_001274178.1, NM_001287249.1
NP_689996.4, NM_152783.4 [Q8N465-1]
XP_011510062.1, XM_011511760.2 [Q8N465-3]
UniGeneiHs.516813

Genome annotation databases

EnsembliENST00000321264; ENSP00000315351; ENSG00000180902 [Q8N465-1]
GeneIDi728294
KEGGihsa:728294
UCSCiuc002wce.3 human [Q8N465-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiD2HDH_HUMAN
AccessioniPrimary (citable) accession number: Q8N465
Secondary accession number(s): B4E3L6
, E7ENP2, Q6IQ24, Q8N5Q8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: April 4, 2006
Last modified: May 23, 2018
This is version 143 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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