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Q9H9P8 (L2HDH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
L-2-hydroxyglutarate dehydrogenase, mitochondrial

EC=1.1.99.2
Alternative name(s):
Duranin
Gene names
Name:L2HGDH
Synonyms:C14orf160
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length463 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

(S)-2-hydroxyglutarate + acceptor = 2-oxoglutarate + reduced acceptor. Ref.5

Cofactor

FAD. Ref.5

Subcellular location

Mitochondrion Ref.5.

Tissue specificity

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. Ref.8

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.8 Ref.9

Miscellaneous

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

Sequence similarities

Belongs to the L2HGDH family.

Biophysicochemical properties

Kinetic parameters:

KM=800 µM for L-2-hydroxyglutarate Ref.5

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9H9P8-1)

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.
Isoform 2 (identifier: Q9H9P8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     400-400: G → QVAVRGPSWLWQQPMKVSDNNIYCFLWRCFALLLTGSTCSFK
     401-463: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5151Mitochondrion Potential
Chain52 – 463412L-2-hydroxyglutarate dehydrogenase, mitochondrial
PRO_0000228129

Amino acid modifications

Modified residue1041N6-acetyllysine Ref.6
Modified residue1551N6-acetyllysine Ref.6
Modified residue1731N6-acetyllysine By similarity

Natural variations

Alternative sequence4001G → QVAVRGPSWLWQQPMKVSDN NIYCFLWRCFALLLTGSTCS FK in isoform 2.
VSP_017662
Alternative sequence401 – 46363Missing in isoform 2.
VSP_017663
Natural variant181L → R. Ref.4 Ref.9
Corresponds to variant rs2275591 [ dbSNP | Ensembl ].
VAR_025681
Natural variant331R → S.
Corresponds to variant rs35710558 [ dbSNP | Ensembl ].
VAR_057808
Natural variant551G → D in L2HGA. Ref.8
VAR_025682
Natural variant571G → R in L2HGA. Ref.9
VAR_025683
Natural variant811K → E in L2HGA; alters protein processing and abolishes catalytic activity. Ref.1
VAR_025684
Natural variant981H → R in L2HGA. Ref.9
VAR_025685
Natural variant981H → Y in L2HGA. Ref.8
VAR_025686
Natural variant1761E → D in L2HGA; alters protein processing and abolishes catalytic activity. Ref.1
VAR_025687
Natural variant1781Y → F. Ref.9
VAR_025688
Natural variant3021P → L in L2HGA. Ref.8 Ref.9
VAR_025689
Natural variant4341H → P in L2HGA. Ref.9
VAR_025690

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 11, 2011. Version 3.
Checksum: 1B6BC0C88543B7FF

FASTA46350,316
        10         20         30         40         50         60 
MVPALRYLVG ACGRARGLFA GGSPGACGFA SGRPRPLCGG SRSASTSSFD IVIVGGGIVG 

        70         80         90        100        110        120 
LASARALILR HPSLSIGVLE KEKDLAVHQT GHNSGVIHSG IYYKPESLKA KLCVQGAALL 

       130        140        150        160        170        180 
YEYCQQKGIS YKQCGKLIVA VEQEEIPRLQ ALYEKGLQNG VPGLRLIQQE DIKKKEPYCR 

       190        200        210        220        230        240 
GLMAIDCPHT GIVDYRQVAL SFAQDFQEAG GSVLTNFEVK GIEMAKESPS RSIDGMQYPI 

       250        260        270        280        290        300 
VIKNTKGEEI RCQYVVTCAG LYSDRISELS GCTPDPRIVP FRGDYLLLKP EKCYLVKGNI 

       310        320        330        340        350        360 
YPVPDSRFPF LGVHFTPRMD GSIWLGPNAV LAFKREGYRP FDFSATDVMD IIINSGLIKL 

       370        380        390        400        410        420 
ASQNFSYGVT EMYKACFLGA TVKYLQKFIP EITISDILRG PAGVRAQALD RDGNLVEDFV 

       430        440        450        460 
FDAGVGDIGN RILHVRNAPS PAATSSIAIS GMIADEVQQR FEL 

« Hide

Isoform 2 [UniParc].

Checksum: 03F7B75151FFF85F
Show »

FASTA44148,505

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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]"Novel L2HGDH mutations in 21 patients with L-2-hydroxyglutaric aciduria of Portuguese origin."
Vilarinho L., Cardoso M.L., Gaspar P., Barbot C., Azevedo L., Diogo L., Santos M., Carrilho I., Fineza I., Kok F., Chorao R., Alegria P., Martins E., Teixeira J., Cabral-Fernandes H., Verhoeven N.M., Salomons G.S., Santorelli F.M. expand/collapse author list , Cabral P., Amorim A., Jakobs C.
Hum. Mutat. 26:395-396(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS L2HGA ARG-57; ARG-98; LEU-302 AND PRO-434, VARIANTS ARG-18 AND PHE-178.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS9698.1. [Q9H9P8-1]
RefSeqNP_079160.1. NM_024884.2. [Q9H9P8-1]
XP_005268132.1. XM_005268075.2. [Q9H9P8-1]
UniGeneHs.256034.

3D structure databases

ProteinModelPortalQ9H9P8.
SMRQ9H9P8. Positions 45-328.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123016. 1 interaction.
STRING9606.ENSP00000267436.

PTM databases

PhosphoSiteQ9H9P8.

Polymorphism databases

DMDM317373422.

Proteomic databases

MaxQBQ9H9P8.
PaxDbQ9H9P8.
PRIDEQ9H9P8.

Protocols and materials databases

DNASU79944.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000267436; ENSP00000267436; ENSG00000087299. [Q9H9P8-1]
ENST00000421284; ENSP00000405559; ENSG00000087299. [Q9H9P8-1]
GeneID79944.
KEGGhsa:79944.
UCSCuc001wxu.3. human. [Q9H9P8-1]

Organism-specific databases

CTD79944.
GeneCardsGC14M050704.
H-InvDBHIX0011640.
HGNCHGNC:20499. L2HGDH.
MIM236792. phenotype.
609584. gene.
neXtProtNX_Q9H9P8.
Orphanet79314. L-2-hydroxyglutaric aciduria.
PharmGKBPA134971279.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0579.
HOGENOMHOG000245180.
HOVERGENHBG081883.
InParanoidQ9H9P8.
KOK00109.
OMASEMSGCN.
PhylomeDBQ9H9P8.
TreeFamTF105922.

Enzyme and pathway databases

BRENDA1.1.99.2. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ9H9P8.
BgeeQ9H9P8.
CleanExHS_L2HGDH.
GenevestigatorQ9H9P8.

Family and domain databases

InterProIPR006076. FAD-dep_OxRdtase.
[Graphical view]
PfamPF01266. DAO. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSL2HGDH. human.
GeneWikiL2HGDH.
GenomeRNAi79944.
NextBio69898.
PROQ9H9P8.
SOURCESearch...

Entry information

Entry nameL2HDH_HUMAN
AccessionPrimary (citable) accession number: Q9H9P8
Secondary accession number(s): Q9BRR1
Entry history
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 102 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM