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Protein

L-2-hydroxyglutarate dehydrogenase, mitochondrial

Gene

L2HGDH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

(S)-2-hydroxyglutarate + acceptor = 2-oxoglutarate + reduced acceptor.1 Publication

Cofactori

FAD1 Publication

Kineticsi

  1. KM=800 µM for L-2-hydroxyglutarate1 Publication

    GO - Molecular functioni

    • 2-hydroxyglutarate dehydrogenase activity Source: HGNC

    GO - Biological processi

    • 2-oxoglutarate metabolic process Source: Reactome
    • cellular protein metabolic process Source: HGNC
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    FAD, Flavoprotein

    Enzyme and pathway databases

    BioCyciZFISH:HS12294-MONOMER.
    BRENDAi1.1.99.2. 2681.
    ReactomeiR-HSA-880009. Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    L-2-hydroxyglutarate dehydrogenase, mitochondrial (EC:1.1.99.2)
    Alternative name(s):
    Duranin
    Gene namesi
    Name:L2HGDH
    Synonyms:C14orf160
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:20499. L2HGDH.

    Subcellular locationi

    GO - Cellular componenti

    • integral component of membrane Source: HGNC
    • integral component of mitochondrial inner membrane Source: HGNC
    • mitochondrial inner membrane Source: Reactome
    • mitochondrion Source: HGNC
    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    L-2-hydroxyglutaric aciduria (L2HGA)3 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA rare autosomal recessive disorder clinically characterized by mild psychomotor delay in the first years of life, followed by progressive cerebellar ataxia, dysarthria and moderate to severe mental retardation. Diagnosis is based on the presence of an excess of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid.
    See also OMIM:236792
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_02568255G → D in L2HGA. 1 PublicationCorresponds to variant rs118204021dbSNPEnsembl.1
    Natural variantiVAR_02568357G → R in L2HGA. 1 PublicationCorresponds to variant rs199690954dbSNPEnsembl.1
    Natural variantiVAR_02568481K → E in L2HGA; alters protein processing and abolishes catalytic activity. 1 Publication1
    Natural variantiVAR_02568598H → R in L2HGA. 1 PublicationCorresponds to variant rs267607206dbSNPEnsembl.1
    Natural variantiVAR_02568698H → Y in L2HGA. 1 Publication1
    Natural variantiVAR_025687176E → D in L2HGA; alters protein processing and abolishes catalytic activity. 1 Publication1
    Natural variantiVAR_025689302P → L in L2HGA. 2 PublicationsCorresponds to variant rs118204020dbSNPEnsembl.1
    Natural variantiVAR_025690434H → P in L2HGA. 1 PublicationCorresponds to variant rs750044734dbSNPEnsembl.1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi79944.
    MalaCardsiL2HGDH.
    MIMi236792. phenotype.
    OpenTargetsiENSG00000087299.
    Orphaneti79314. L-2-hydroxyglutaric aciduria.
    PharmGKBiPA134971279.

    Polymorphism and mutation databases

    BioMutaiL2HGDH.
    DMDMi317373422.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transit peptidei1 – 51MitochondrionSequence analysisAdd BLAST51
    ChainiPRO_000022812952 – 463L-2-hydroxyglutarate dehydrogenase, mitochondrialAdd BLAST412

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei104N6-acetyllysineBy similarity1
    Modified residuei155N6-acetyllysineCombined sources1
    Modified residuei173N6-acetyllysineBy similarity1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ9H9P8.
    MaxQBiQ9H9P8.
    PaxDbiQ9H9P8.
    PeptideAtlasiQ9H9P8.
    PRIDEiQ9H9P8.

    PTM databases

    iPTMnetiQ9H9P8.
    PhosphoSitePlusiQ9H9P8.

    Expressioni

    Tissue specificityi

    Widely expressed. Highly expressed in brain, testis and muscle. Expressed to a lower extent in lymphocytes, fibroblasts, keratinocytes, placenta, bladder, small intestine, liver and bone marrow.1 Publication

    Gene expression databases

    BgeeiENSG00000087299.
    CleanExiHS_L2HGDH.
    ExpressionAtlasiQ9H9P8. baseline and differential.
    GenevisibleiQ9H9P8. HS.

    Organism-specific databases

    HPAiHPA065409.
    HPA069708.

    Interactioni

    Protein-protein interaction databases

    BioGridi123016. 14 interactors.
    IntActiQ9H9P8. 1 interactor.
    STRINGi9606.ENSP00000267436.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9H9P8.
    SMRiQ9H9P8.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the L2HGDH family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiKOG2665. Eukaryota.
    COG0579. LUCA.
    GeneTreeiENSGT00490000043421.
    HOGENOMiHOG000245180.
    HOVERGENiHBG081883.
    InParanoidiQ9H9P8.
    KOiK00109.
    OMAiGVHFTRM.
    OrthoDBiEOG091G06OM.
    PhylomeDBiQ9H9P8.
    TreeFamiTF105922.

    Family and domain databases

    Gene3Di3.50.50.60. 2 hits.
    InterProiIPR006076. FAD-dep_OxRdtase.
    IPR023753. FAD/NAD-binding_dom.
    [Graphical view]
    PfamiPF01266. DAO. 1 hit.
    [Graphical view]
    SUPFAMiSSF51905. SSF51905. 2 hits.

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9H9P8-1) [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
    MVPALRYLVG ACGRARGLFA GGSPGACGFA SGRPRPLCGG SRSASTSSFD
    60 70 80 90 100
    IVIVGGGIVG LASARALILR HPSLSIGVLE KEKDLAVHQT GHNSGVIHSG
    110 120 130 140 150
    IYYKPESLKA KLCVQGAALL YEYCQQKGIS YKQCGKLIVA VEQEEIPRLQ
    160 170 180 190 200
    ALYEKGLQNG VPGLRLIQQE DIKKKEPYCR GLMAIDCPHT GIVDYRQVAL
    210 220 230 240 250
    SFAQDFQEAG GSVLTNFEVK GIEMAKESPS RSIDGMQYPI VIKNTKGEEI
    260 270 280 290 300
    RCQYVVTCAG LYSDRISELS GCTPDPRIVP FRGDYLLLKP EKCYLVKGNI
    310 320 330 340 350
    YPVPDSRFPF LGVHFTPRMD GSIWLGPNAV LAFKREGYRP FDFSATDVMD
    360 370 380 390 400
    IIINSGLIKL ASQNFSYGVT EMYKACFLGA TVKYLQKFIP EITISDILRG
    410 420 430 440 450
    PAGVRAQALD RDGNLVEDFV FDAGVGDIGN RILHVRNAPS PAATSSIAIS
    460
    GMIADEVQQR FEL
    Length:463
    Mass (Da):50,316
    Last modified:January 11, 2011 - v3
    Checksum:i1B6BC0C88543B7FF
    GO
    Isoform 2 (identifier: Q9H9P8-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         400-400: G → QVAVRGPSWLWQQPMKVSDNNIYCFLWRCFALLLTGSTCSFK
         401-463: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:441
    Mass (Da):48,505
    Checksum:i03F7B75151FFF85F
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_02568118L → R.2 PublicationsCorresponds to variant rs2275591dbSNPEnsembl.1
    Natural variantiVAR_05780833R → S.Corresponds to variant rs35710558dbSNPEnsembl.1
    Natural variantiVAR_02568255G → D in L2HGA. 1 PublicationCorresponds to variant rs118204021dbSNPEnsembl.1
    Natural variantiVAR_02568357G → R in L2HGA. 1 PublicationCorresponds to variant rs199690954dbSNPEnsembl.1
    Natural variantiVAR_02568481K → E in L2HGA; alters protein processing and abolishes catalytic activity. 1 Publication1
    Natural variantiVAR_02568598H → R in L2HGA. 1 PublicationCorresponds to variant rs267607206dbSNPEnsembl.1
    Natural variantiVAR_02568698H → Y in L2HGA. 1 Publication1
    Natural variantiVAR_025687176E → D in L2HGA; alters protein processing and abolishes catalytic activity. 1 Publication1
    Natural variantiVAR_025688178Y → F.1 PublicationCorresponds to variant rs770542189dbSNPEnsembl.1
    Natural variantiVAR_025689302P → L in L2HGA. 2 PublicationsCorresponds to variant rs118204020dbSNPEnsembl.1
    Natural variantiVAR_025690434H → P in L2HGA. 1 PublicationCorresponds to variant rs750044734dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_017662400G → QVAVRGPSWLWQQPMKVSDN NIYCFLWRCFALLLTGSTCS FK in isoform 2. 1 Publication1
    Alternative sequenceiVSP_017663401 – 463Missing in isoform 2. 1 PublicationAdd BLAST63

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY757363 mRNA. Translation: AAV52330.1.
    AK022680 mRNA. Translation: BAB14174.1.
    AL109758 Genomic DNA. No translation available.
    AL359397 Genomic DNA. No translation available.
    BC006117 mRNA. Translation: AAH06117.1.
    CCDSiCCDS9698.1. [Q9H9P8-1]
    RefSeqiNP_079160.1. NM_024884.2. [Q9H9P8-1]
    XP_005268132.1. XM_005268075.4. [Q9H9P8-1]
    UniGeneiHs.256034.

    Genome annotation databases

    EnsembliENST00000267436; ENSP00000267436; ENSG00000087299. [Q9H9P8-1]
    ENST00000421284; ENSP00000405559; ENSG00000087299. [Q9H9P8-1]
    GeneIDi79944.
    KEGGihsa:79944.
    UCSCiuc001wxu.4. human. [Q9H9P8-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY757363 mRNA. Translation: AAV52330.1.
    AK022680 mRNA. Translation: BAB14174.1.
    AL109758 Genomic DNA. No translation available.
    AL359397 Genomic DNA. No translation available.
    BC006117 mRNA. Translation: AAH06117.1.
    CCDSiCCDS9698.1. [Q9H9P8-1]
    RefSeqiNP_079160.1. NM_024884.2. [Q9H9P8-1]
    XP_005268132.1. XM_005268075.4. [Q9H9P8-1]
    UniGeneiHs.256034.

    3D structure databases

    ProteinModelPortaliQ9H9P8.
    SMRiQ9H9P8.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi123016. 14 interactors.
    IntActiQ9H9P8. 1 interactor.
    STRINGi9606.ENSP00000267436.

    PTM databases

    iPTMnetiQ9H9P8.
    PhosphoSitePlusiQ9H9P8.

    Polymorphism and mutation databases

    BioMutaiL2HGDH.
    DMDMi317373422.

    Proteomic databases

    EPDiQ9H9P8.
    MaxQBiQ9H9P8.
    PaxDbiQ9H9P8.
    PeptideAtlasiQ9H9P8.
    PRIDEiQ9H9P8.

    Protocols and materials databases

    DNASUi79944.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000267436; ENSP00000267436; ENSG00000087299. [Q9H9P8-1]
    ENST00000421284; ENSP00000405559; ENSG00000087299. [Q9H9P8-1]
    GeneIDi79944.
    KEGGihsa:79944.
    UCSCiuc001wxu.4. human. [Q9H9P8-1]

    Organism-specific databases

    CTDi79944.
    DisGeNETi79944.
    GeneCardsiL2HGDH.
    H-InvDBHIX0011640.
    HGNCiHGNC:20499. L2HGDH.
    HPAiHPA065409.
    HPA069708.
    MalaCardsiL2HGDH.
    MIMi236792. phenotype.
    609584. gene.
    neXtProtiNX_Q9H9P8.
    OpenTargetsiENSG00000087299.
    Orphaneti79314. L-2-hydroxyglutaric aciduria.
    PharmGKBiPA134971279.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2665. Eukaryota.
    COG0579. LUCA.
    GeneTreeiENSGT00490000043421.
    HOGENOMiHOG000245180.
    HOVERGENiHBG081883.
    InParanoidiQ9H9P8.
    KOiK00109.
    OMAiGVHFTRM.
    OrthoDBiEOG091G06OM.
    PhylomeDBiQ9H9P8.
    TreeFamiTF105922.

    Enzyme and pathway databases

    BioCyciZFISH:HS12294-MONOMER.
    BRENDAi1.1.99.2. 2681.
    ReactomeiR-HSA-880009. Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.

    Miscellaneous databases

    ChiTaRSiL2HGDH. human.
    GeneWikiiL2HGDH.
    GenomeRNAii79944.
    PROiQ9H9P8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000087299.
    CleanExiHS_L2HGDH.
    ExpressionAtlasiQ9H9P8. baseline and differential.
    GenevisibleiQ9H9P8. HS.

    Family and domain databases

    Gene3Di3.50.50.60. 2 hits.
    InterProiIPR006076. FAD-dep_OxRdtase.
    IPR023753. FAD/NAD-binding_dom.
    [Graphical view]
    PfamiPF01266. DAO. 1 hit.
    [Graphical view]
    SUPFAMiSSF51905. SSF51905. 2 hits.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiL2HDH_HUMAN
    AccessioniPrimary (citable) accession number: Q9H9P8
    Secondary accession number(s): Q9BRR1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 21, 2006
    Last sequence update: January 11, 2011
    Last modified: November 2, 2016
    This is version 123 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

    Miscellaneous

    Was named 'duranin' in honor of Marinus Duran, who first described L-2-hydroxyglutaric aciduria.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: 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.