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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

    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)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti55 – 551G → D in L2HGA. 1 Publication
    Corresponds to variant rs118204021 [ dbSNP | Ensembl ].
    VAR_025682
    Natural varianti57 – 571G → R in L2HGA. 1 Publication
    Corresponds to variant rs199690954 [ dbSNP | Ensembl ].
    VAR_025683
    Natural varianti81 – 811K → E in L2HGA; alters protein processing and abolishes catalytic activity. 1 Publication
    VAR_025684
    Natural varianti98 – 981H → R in L2HGA. 1 Publication
    Corresponds to variant rs267607206 [ dbSNP | Ensembl ].
    VAR_025685
    Natural varianti98 – 981H → Y in L2HGA. 1 Publication
    VAR_025686
    Natural varianti176 – 1761E → D in L2HGA; alters protein processing and abolishes catalytic activity. 1 Publication
    VAR_025687
    Natural varianti302 – 3021P → L in L2HGA. 2 Publications
    Corresponds to variant rs118204020 [ dbSNP | Ensembl ].
    VAR_025689
    Natural varianti434 – 4341H → P in L2HGA. 1 Publication
    Corresponds to variant rs750044734 [ dbSNP | Ensembl ].
    VAR_025690

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

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

    Polymorphism and mutation databases

    BioMutaiL2HGDH.
    DMDMi317373422.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 5151MitochondrionSequence analysisAdd
    BLAST
    Chaini52 – 463412L-2-hydroxyglutarate dehydrogenase, mitochondrialPRO_0000228129Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei104 – 1041N6-acetyllysineBy similarity
    Modified residuei155 – 1551N6-acetyllysineCombined sources
    Modified residuei173 – 1731N6-acetyllysineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ9H9P8.
    MaxQBiQ9H9P8.
    PaxDbiQ9H9P8.
    PeptideAtlasiQ9H9P8.
    PRIDEiQ9H9P8.

    PTM databases

    iPTMnetiQ9H9P8.
    PhosphoSiteiQ9H9P8.

    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. 11 interactions.
    IntActiQ9H9P8. 1 interaction.
    STRINGi9606.ENSP00000267436.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9H9P8.
    SMRiQ9H9P8. Positions 47-328.
    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)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti18 – 181L → R.2 Publications
    Corresponds to variant rs2275591 [ dbSNP | Ensembl ].
    VAR_025681
    Natural varianti33 – 331R → S.
    Corresponds to variant rs35710558 [ dbSNP | Ensembl ].
    VAR_057808
    Natural varianti55 – 551G → D in L2HGA. 1 Publication
    Corresponds to variant rs118204021 [ dbSNP | Ensembl ].
    VAR_025682
    Natural varianti57 – 571G → R in L2HGA. 1 Publication
    Corresponds to variant rs199690954 [ dbSNP | Ensembl ].
    VAR_025683
    Natural varianti81 – 811K → E in L2HGA; alters protein processing and abolishes catalytic activity. 1 Publication
    VAR_025684
    Natural varianti98 – 981H → R in L2HGA. 1 Publication
    Corresponds to variant rs267607206 [ dbSNP | Ensembl ].
    VAR_025685
    Natural varianti98 – 981H → Y in L2HGA. 1 Publication
    VAR_025686
    Natural varianti176 – 1761E → D in L2HGA; alters protein processing and abolishes catalytic activity. 1 Publication
    VAR_025687
    Natural varianti178 – 1781Y → F.1 Publication
    Corresponds to variant rs770542189 [ dbSNP | Ensembl ].
    VAR_025688
    Natural varianti302 – 3021P → L in L2HGA. 2 Publications
    Corresponds to variant rs118204020 [ dbSNP | Ensembl ].
    VAR_025689
    Natural varianti434 – 4341H → P in L2HGA. 1 Publication
    Corresponds to variant rs750044734 [ dbSNP | Ensembl ].
    VAR_025690

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei400 – 4001G → QVAVRGPSWLWQQPMKVSDN NIYCFLWRCFALLLTGSTCS FK in isoform 2. 1 PublicationVSP_017662
    Alternative sequencei401 – 46363Missing in isoform 2. 1 PublicationVSP_017663Add
    BLAST

    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. Positions 47-328.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi123016. 11 interactions.
    IntActiQ9H9P8. 1 interaction.
    STRINGi9606.ENSP00000267436.

    PTM databases

    iPTMnetiQ9H9P8.
    PhosphoSiteiQ9H9P8.

    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.
    GeneCardsiL2HGDH.
    H-InvDBHIX0011640.
    HGNCiHGNC:20499. L2HGDH.
    HPAiHPA065409.
    HPA069708.
    MalaCardsiL2HGDH.
    MIMi236792. phenotype.
    609584. gene.
    neXtProtiNX_Q9H9P8.
    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

    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: September 7, 2016
    This is version 121 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.