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Protein

L-2-hydroxyglutarate dehydrogenase, mitochondrial

Gene

L2HGDH

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

Functioni

Miscellaneous

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

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

    Keywordsi

    Molecular functionOxidoreductase
    LigandFAD, Flavoprotein

    Enzyme and pathway databases

    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

    EuPathDBiHostDB:ENSG00000087299.11
    HGNCiHGNC:20499 L2HGDH
    MIMi609584 gene
    neXtProtiNX_Q9H9P8

    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

    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 dbSNP:rs118204021EnsemblClinVar.1
    Natural variantiVAR_02568357G → R in L2HGA. 1 PublicationCorresponds to variant dbSNP:rs199690954Ensembl.1
    Natural variantiVAR_02568481K → E in L2HGA; alters protein processing and abolishes catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs970541687Ensembl.1
    Natural variantiVAR_02568598H → R in L2HGA. 1 PublicationCorresponds to variant dbSNP:rs267607206EnsemblClinVar.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 dbSNP:rs118204020EnsemblClinVar.1
    Natural variantiVAR_025690434H → P in L2HGA. 1 PublicationCorresponds to variant dbSNP:rs750044734Ensembl.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
    ProteomicsDBi81345
    81346 [Q9H9P8-2]

    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, 15 interactors
    IntActiQ9H9P8, 2 interactors
    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, 3 hits
    InterProiView protein in InterPro
    IPR006076 FAD-dep_OxRdtase
    IPR036188 FAD/NAD-bd_sf
    PfamiView protein in Pfam
    PF01266 DAO, 1 hit
    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 → R2 PublicationsCorresponds to variant dbSNP:rs2275591EnsemblClinVar.1
    Natural variantiVAR_05780833R → S. Corresponds to variant dbSNP:rs35710558EnsemblClinVar.1
    Natural variantiVAR_02568255G → D in L2HGA. 1 PublicationCorresponds to variant dbSNP:rs118204021EnsemblClinVar.1
    Natural variantiVAR_02568357G → R in L2HGA. 1 PublicationCorresponds to variant dbSNP:rs199690954Ensembl.1
    Natural variantiVAR_02568481K → E in L2HGA; alters protein processing and abolishes catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs970541687Ensembl.1
    Natural variantiVAR_02568598H → R in L2HGA. 1 PublicationCorresponds to variant dbSNP:rs267607206EnsemblClinVar.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 → F1 PublicationCorresponds to variant dbSNP:rs770542189Ensembl.1
    Natural variantiVAR_025689302P → L in L2HGA. 2 PublicationsCorresponds to variant dbSNP:rs118204020EnsemblClinVar.1
    Natural variantiVAR_025690434H → P in L2HGA. 1 PublicationCorresponds to variant dbSNP:rs750044734Ensembl.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

    Similar proteinsi

    Entry informationi

    Entry nameiL2HDH_HUMAN
    AccessioniPrimary (citable) accession number: Q9H9P8
    Secondary accession number(s): Q9BRR1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 21, 2006
    Last sequence update: January 11, 2011
    Last modified: June 20, 2018
    This is version 134 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

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