Q9H9P8 (L2HDH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
L-2-hydroxyglutarate dehydrogenase, mitochondrial
EC=1.1.99.2

Alternative name(s):
Duranin

Gene names

Name:	L2HGDH
Synonyms:	C14orf160

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	463 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Defects in L2HGDH are the cause of L-2-hydroxyglutaric aciduria (L2HGA) [MIM:236792]. L2HGA is 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. 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

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	2-oxoglutarate metabolic process Traceable author statement. Source: Reactome cellular protein metabolic process Inferred from direct assay Ref.5. Source: HGNC
Cellular component	integral to mitochondrial inner membrane Non-traceable author statement Ref.5. Source: HGNC
Molecular function	2-hydroxyglutarate dehydrogenase activity Inferred from direct assay Ref.5. Source: HGNC
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 51	51	Mitochondrion Potential
	Chain	52 – 463	412	L-2-hydroxyglutarate dehydrogenase, mitochondrial		PRO_0000228129
Amino acid modifications
	Modified residue	155	1	N6-acetyllysine Ref.6
Natural variations
	Alternative sequence	400	1	G → QVAVRGPSWLWQQPMKVSDN NIYCFLWRCFALLLTGSTCS FK in isoform 2.		VSP_017662
	Alternative sequence	401 – 463	63	Missing in isoform 2.		VSP_017663
	Natural variant	18	1	L → R. Ref.4 Ref.9 Corresponds to variant rs2275591 [ dbSNP | Ensembl ].		VAR_025681
	Natural variant	33	1	R → S. Corresponds to variant rs35710558 [ dbSNP | Ensembl ].		VAR_057808
	Natural variant	55	1	G → D in L2HGA. Ref.8		VAR_025682
	Natural variant	57	1	G → R in L2HGA. Ref.9		VAR_025683
	Natural variant	81	1	K → E in L2HGA; alters protein processing and abolishes catalytic activity. Ref.1		VAR_025684
	Natural variant	98	1	H → R in L2HGA. Ref.9		VAR_025685
	Natural variant	98	1	H → Y in L2HGA. Ref.8		VAR_025686
	Natural variant	176	1	E → D in L2HGA; alters protein processing and abolishes catalytic activity. Ref.1		VAR_025687
	Natural variant	178	1	Y → F. Ref.9		VAR_025688
	Natural variant	302	1	P → L in L2HGA. Ref.8 Ref.9		VAR_025689
	Natural variant	434	1	H → P in L2HGA. Ref.9		VAR_025690

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 11, 2011. Version 3. Checksum: 1B6BC0C88543B7FF	FASTA	463	50,316
	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
	Isoform 2 [UniParc]. Checksum: 03F7B75151FFF85F	FASTA	441	48,505
	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 EITISDILRQ VAVRGPSWLW QQPMKVSDNN 430 440 IYCFLWRCFA LLLTGSTCSF K

References

	« Hide 'large scale' referencesShow '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: 15548604] [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: 14702039] [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: 12508121] [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: 15489334] [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: 16005139] [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., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-155, MASS SPECTROMETRY.
[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: 21269460] [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: 15385440] [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. , Cabral P., Amorim A., Jakobs C. Hum. Mutat. 26:395-396(2005) [PubMed: 16134148] [Abstract] Cited for: VARIANTS L2HGA ARG-57; ARG-98; LEU-302 AND PRO-434, VARIANTS ARG-18 AND PHE-178.
+	Additional computationally mapped references.

Web resources

GeneReviews

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.
IPI	IPI00016458. IPI00029239.
RefSeq	NP_079160.1. NM_024884.2.
UniGene	Hs.256034.
3D structure databases
ProteinModelPortal	Q9H9P8.
SMR	Q9H9P8. Positions 47-458.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9H9P8.
PTM databases
PhosphoSite	Q9H9P8.
Polymorphism databases
DMDM	90101396.
Proteomic databases
PRIDE	Q9H9P8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000267436; ENSP00000267436; ENSG00000087299.
GeneID	79944.
KEGG	hsa:79944.
UCSC	uc001wxu.1. human.
Organism-specific databases
CTD	79944.
GeneCards	GC14M050704.
H-InvDB	HIX0011640.
HGNC	HGNC:20499. L2HGDH.
MIM	236792. phenotype. 609584. gene.
neXtProt	NX_Q9H9P8.
Orphanet	19. 2-hydroxyglutaricaciduria.
PharmGKB	PA134971279.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11693.
GeneTree	ENSGT00490000043421.
HOGENOM	HBG525746.
HOVERGEN	HBG081883.
InParanoid	Q9H9P8.
OMA	GVHFTRM.
PhylomeDB	Q9H9P8.
Enzyme and pathway databases
BRENDA	1.1.99.2. 2681.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9H9P8.
Bgee	Q9H9P8.
CleanEx	HS_L2HGDH.
Genevestigator	Q9H9P8.
GermOnline	ENSG00000087299. Homo sapiens.
Family and domain databases
InterPro	IPR006076. FAD-dep_OxRdtase. [Graphical view]
KO	K00109.
Pfam	PF01266. DAO. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	69898.
SOURCE	Search...

Entry information

Entry name

L2HDH_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 79 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.