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Protein

D-2-hydroxyglutarate dehydrogenase, mitochondrial

Gene

D2HGDH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

FAD, Flavoprotein

Enzyme and pathway databases

BioCyciZFISH:ENSG00000180902-MONOMER.
ReactomeiR-HSA-880009. Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.

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

HGNCiHGNC:28358. D2HGDH.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: HGNC
Complete GO annotation...

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 rs121434361dbSNPEnsembl.1
Natural variantiVAR_025891375D → Y in D2HGA1. 1 PublicationCorresponds to variant rs267606759dbSNPEnsembl.1
Natural variantiVAR_025893439N → D in D2HGA1; mild phenotype; altered catalytic activity. 1 PublicationCorresponds to variant rs121434362dbSNPEnsembl.1
Natural variantiVAR_025894444V → A in D2HGA1; severe phenotype; altered catalytic activity. 1 PublicationCorresponds to variant rs121434360dbSNPEnsembl.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. 12 interactors.
IntActiQ8N465. 2 interactors.
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

Contains 1 FAD-binding PCMH-type domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

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

Family and domain databases

Gene3Di1.10.45.10. 1 hit.
3.30.43.10. 1 hit.
3.30.465.10. 1 hit.
InterProiIPR016169. CO_DH_flavot_FAD-bd_sub2.
IPR016166. FAD-bd_2.
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.
[Graphical view]
PfamiPF02913. FAD-oxidase_C. 1 hit.
PF01565. FAD_binding_4. 1 hit.
[Graphical view]
SUPFAMiSSF55103. SSF55103. 1 hit.
SSF56176. SSF56176. 1 hit.
PROSITEiPS51387. FAD_PCMH. 1 hit.
[Graphical view]

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 → G.1 PublicationCorresponds to variant rs4675887dbSNPEnsembl.1
Natural variantiVAR_025890147I → S in D2HGA1; severe phenotype; loss of catalytic activity. 1 PublicationCorresponds to variant rs121434361dbSNPEnsembl.1
Natural variantiVAR_050433338V → I.Corresponds to variant rs1106639dbSNPEnsembl.1
Natural variantiVAR_050434361A → V.Corresponds to variant rs1105273dbSNPEnsembl.1
Natural variantiVAR_025891375D → Y in D2HGA1. 1 PublicationCorresponds to variant rs267606759dbSNPEnsembl.1
Natural variantiVAR_025892436G → V.1 Publication1
Natural variantiVAR_025893439N → D in D2HGA1; mild phenotype; altered catalytic activity. 1 PublicationCorresponds to variant rs121434362dbSNPEnsembl.1
Natural variantiVAR_025894444V → A in D2HGA1; severe phenotype; altered catalytic activity. 1 PublicationCorresponds to variant rs121434360dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8N465.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi608722. 12 interactors.
IntActiQ8N465. 2 interactors.
STRINGi9606.ENSP00000315351.

PTM databases

iPTMnetiQ8N465.
PhosphoSitePlusiQ8N465.

Polymorphism and mutation databases

BioMutaiD2HGDH.
DMDMi91208273.

Proteomic databases

EPDiQ8N465.
MaxQBiQ8N465.
PaxDbiQ8N465.
PeptideAtlasiQ8N465.
PRIDEiQ8N465.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi728294.
DisGeNETi728294.
GeneCardsiD2HGDH.
H-InvDBHIX0023187.
HGNCiHGNC:28358. D2HGDH.
HPAiHPA056216.
MalaCardsiD2HGDH.
MIMi600721. phenotype.
609186. gene.
neXtProtiNX_Q8N465.
OpenTargetsiENSG00000180902.
Orphaneti79315. D-2-hydroxyglutaric aciduria.
PharmGKBiPA143485446.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000180902-MONOMER.
ReactomeiR-HSA-880009. Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.

Miscellaneous databases

ChiTaRSiD2HGDH. human.
GeneWikiiD2HGDH.
GenomeRNAii728294.
PROiQ8N465.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180902.
CleanExiHS_D2HGDH.
ExpressionAtlasiQ8N465. baseline and differential.
GenevisibleiQ8N465. HS.

Family and domain databases

Gene3Di1.10.45.10. 1 hit.
3.30.43.10. 1 hit.
3.30.465.10. 1 hit.
InterProiIPR016169. CO_DH_flavot_FAD-bd_sub2.
IPR016166. FAD-bd_2.
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.
[Graphical view]
PfamiPF02913. FAD-oxidase_C. 1 hit.
PF01565. FAD_binding_4. 1 hit.
[Graphical view]
SUPFAMiSSF55103. SSF55103. 1 hit.
SSF56176. SSF56176. 1 hit.
PROSITEiPS51387. FAD_PCMH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiD2HDH_HUMAN
AccessioniPrimary (citable) accession number: Q8N465
Secondary accession number(s): B4E3L6
, E7ENP2, Q6IQ24, Q8N5Q8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: April 4, 2006
Last modified: November 30, 2016
This is version 132 of the entry and version 3 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.