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Q9H9P8

- L2HDH_HUMAN

UniProt

Q9H9P8 - L2HDH_HUMAN

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Protein

L-2-hydroxyglutarate dehydrogenase, mitochondrial

Gene

L2HGDH

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. 2-hydroxyglutarate dehydrogenase activity Source: HGNC

GO - Biological processi

  1. 2-oxoglutarate metabolic process Source: Reactome
  2. cellular metabolic process Source: Reactome
  3. cellular protein metabolic process Source: HGNC
  4. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

FAD, Flavoprotein

Enzyme and pathway databases

BRENDAi1.1.99.2. 2681.
ReactomeiREACT_25367. 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
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:20499. L2HGDH.

Subcellular locationi

Mitochondrion 1 Publication

GO - Cellular componenti

  1. integral component of membrane Source: HGNC
  2. integral component of mitochondrial inner membrane Source: HGNC
  3. mitochondrial inner membrane Source: Reactome
  4. mitochondrion Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

L-2-hydroxyglutaric aciduria (L2HGA) [MIM:236792]: A 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.3 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti55 – 551G → D in L2HGA. 1 Publication
VAR_025682
Natural varianti57 – 571G → R in L2HGA. 1 Publication
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
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
VAR_025689
Natural varianti434 – 4341H → P in L2HGA. 1 Publication
VAR_025690

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

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-acetyllysine1 Publication
Modified residuei155 – 1551N6-acetyllysine1 Publication
Modified residuei173 – 1731N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ9H9P8.
PaxDbiQ9H9P8.
PRIDEiQ9H9P8.

PTM databases

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

BgeeiQ9H9P8.
CleanExiHS_L2HGDH.
ExpressionAtlasiQ9H9P8. baseline and differential.
GenevestigatoriQ9H9P8.

Interactioni

Protein-protein interaction databases

BioGridi123016. 9 interactions.
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

eggNOGiCOG0579.
GeneTreeiENSGT00490000043421.
HOGENOMiHOG000245180.
HOVERGENiHBG081883.
InParanoidiQ9H9P8.
KOiK00109.
OMAiSEMSGCN.
PhylomeDBiQ9H9P8.
TreeFamiTF105922.

Family and domain databases

InterProiIPR006076. FAD-dep_OxRdtase.
[Graphical view]
PfamiPF01266. DAO. 1 hit.
[Graphical view]

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. Align

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
VAR_025682
Natural varianti57 – 571G → R in L2HGA. 1 Publication
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
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
VAR_025688
Natural varianti302 – 3021P → L in L2HGA. 2 Publications
VAR_025689
Natural varianti434 – 4341H → P in L2HGA. 1 Publication
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_005268075.2. [Q9H9P8-1]
UniGeneiHs.256034.

Genome annotation databases

EnsembliENST00000267436; ENSP00000267436; ENSG00000087299. [Q9H9P8-1]
ENST00000421284; ENSP00000405559; ENSG00000087299. [Q9H9P8-1]
GeneIDi79944.
KEGGihsa:79944.
UCSCiuc001wxu.3. human. [Q9H9P8-1]

Polymorphism databases

DMDMi317373422.

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 .
CCDSi CCDS9698.1. [Q9H9P8-1 ]
RefSeqi NP_079160.1. NM_024884.2. [Q9H9P8-1 ]
XP_005268132.1. XM_005268075.2. [Q9H9P8-1 ]
UniGenei Hs.256034.

3D structure databases

ProteinModelPortali Q9H9P8.
SMRi Q9H9P8. Positions 47-328.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 123016. 9 interactions.
STRINGi 9606.ENSP00000267436.

PTM databases

PhosphoSitei Q9H9P8.

Polymorphism databases

DMDMi 317373422.

Proteomic databases

MaxQBi Q9H9P8.
PaxDbi Q9H9P8.
PRIDEi Q9H9P8.

Protocols and materials databases

DNASUi 79944.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000267436 ; ENSP00000267436 ; ENSG00000087299 . [Q9H9P8-1 ]
ENST00000421284 ; ENSP00000405559 ; ENSG00000087299 . [Q9H9P8-1 ]
GeneIDi 79944.
KEGGi hsa:79944.
UCSCi uc001wxu.3. human. [Q9H9P8-1 ]

Organism-specific databases

CTDi 79944.
GeneCardsi GC14M050704.
H-InvDB HIX0011640.
HGNCi HGNC:20499. L2HGDH.
MIMi 236792. phenotype.
609584. gene.
neXtProti NX_Q9H9P8.
Orphaneti 79314. L-2-hydroxyglutaric aciduria.
PharmGKBi PA134971279.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0579.
GeneTreei ENSGT00490000043421.
HOGENOMi HOG000245180.
HOVERGENi HBG081883.
InParanoidi Q9H9P8.
KOi K00109.
OMAi SEMSGCN.
PhylomeDBi Q9H9P8.
TreeFami TF105922.

Enzyme and pathway databases

BRENDAi 1.1.99.2. 2681.
Reactomei REACT_25367. Interconversion of 2-oxoglutarate and 2-hydroxyglutarate.

Miscellaneous databases

ChiTaRSi L2HGDH. human.
GeneWikii L2HGDH.
GenomeRNAii 79944.
NextBioi 69898.
PROi Q9H9P8.
SOURCEi Search...

Gene expression databases

Bgeei Q9H9P8.
CleanExi HS_L2HGDH.
ExpressionAtlasi Q9H9P8. baseline and differential.
Genevestigatori Q9H9P8.

Family and domain databases

InterProi IPR006076. FAD-dep_OxRdtase.
[Graphical view ]
Pfami PF01266. DAO. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria."
    Rzem R., Veiga-da-Cunha M., Noel G., Goffette S., Nassogne M.-C., Tabarki B., Schoeller C., Marquardt T., Vikkula M., van Schaftingen E.
    Proc. Natl. Acad. Sci. U.S.A. 101:16849-16854(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS L2HGA GLU-81 AND ASP-176, CHARACTERIZATION OF VARIANTS L2HGA GLU-81 AND ASP-176.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  3. "The DNA sequence and analysis of human chromosome 14."
    Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
    , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
    Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ARG-18.
    Tissue: Placenta.
  5. "The gene mutated in L-2-hydroxyglutaric aciduria encodes L-2-hydroxyglutarate dehydrogenase."
    Rzem R., Van Schaftingen E., Veiga-da-Cunha M.
    Biochimie 88:113-116(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, COFACTOR.
  6. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-104 AND LYS-155, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. "L-2-hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1."
    Topcu M., Jobard F., Halliez S., Coskun T., Yalcinkayal C., Gerceker F.O., Wanders R.J.A., Prud'homme J.-F., Lathrop M., Ozguc M., Fischer J.
    Hum. Mol. Genet. 13:2803-2811(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS L2HGA ASP-55; TYR-98 AND LEU-302, TISSUE SPECIFICITY.
  9. Cited for: VARIANTS L2HGA ARG-57; ARG-98; LEU-302 AND PRO-434, VARIANTS ARG-18 AND PHE-178.

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 26, 2014
This is version 106 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

External Data

Dasty 3