Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q96HY7 (DHTK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 93. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Probable 2-oxoglutarate dehydrogenase E1 component DHKTD1, mitochondrial

EC=1.2.4.2
Alternative name(s):
Dehydrogenase E1 and transketolase domain-containing protein 1
Gene names
Name:DHTKD1
Synonyms:KIAA1630
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length919 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO2. It contains multiple copies of three enzymatic components: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) By similarity.

Catalytic activity

2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2.

Cofactor

Thiamine pyrophosphate By similarity.

Subcellular location

Mitochondrion Ref.5.

Involvement in disease

Charcot-Marie-Tooth disease 2Q (CMT2Q) [MIM:615025]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

2-aminoadipic 2-oxoadipic aciduria (AMOXAD) [MIM:204750]: A metabolic disorder characterized by increased levels of 2-oxoadipate and 2-hydroxyadipate in the urine, and elevated 2-aminoadipate in the plasma. Patients can have mild to severe intellectual disability, muscular hypotonia, developmental delay, ataxia, and epilepsy. Most cases are asymptomatic.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the alpha-ketoglutarate dehydrogenase family.

Sequence caution

The sequence BAB13456.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence BAB13456.1 differs from that shown. Reason: Chimeric cDNA. C-terminal exons are derived from the neighboring gene.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion Potential
Chain? – 919Probable 2-oxoglutarate dehydrogenase E1 component DHKTD1, mitochondrialPRO_0000307936

Amino acid modifications

Modified residue1831N6-succinyllysine By similarity
Modified residue1881N6-succinyllysine By similarity
Modified residue8001N6-succinyllysine By similarity
Modified residue8181N6-succinyllysine By similarity

Natural variations

Natural variant201F → L. Ref.2 Ref.3
Corresponds to variant rs1279138 [ dbSNP | Ensembl ].
VAR_036715
Natural variant2721Y → D. Ref.2 Ref.3
Corresponds to variant rs3740015 [ dbSNP | Ensembl ].
VAR_036716
Natural variant3081R → L. Ref.2
Corresponds to variant rs17849603 [ dbSNP | Ensembl ].
VAR_036717
Natural variant3501N → D.
Corresponds to variant rs34716552 [ dbSNP | Ensembl ].
VAR_036718
Natural variant6071I → M. Ref.2 Ref.3 Ref.4
Corresponds to variant rs2062988 [ dbSNP | Ensembl ].
VAR_036719
Natural variant7291G → R in AMOXAD. Ref.6
VAR_069585

Sequences

Sequence LengthMass (Da)Tools
Q96HY7 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: CD1E437F919324B6

FASTA919103,077
        10         20         30         40         50         60 
MASATAAAAR RGLGRALPLF WRGYQTERGV YGYRPRKPES REPQGALERP PVDHGLARLV 

        70         80         90        100        110        120 
TVYCEHGHKA AKINPLFTGQ ALLENVPEIQ ALVQTLQGPF HTAGLLNMGK EEASLEEVLV 

       130        140        150        160        170        180 
YLNQIYCGQI SIETSQLQSQ DEKDWFAKRF EELQKETFTT EERKHLSKLM LESQEFDHFL 

       190        200        210        220        230        240 
ATKFSTVKRY GGEGAESMMG FFHELLKMSA YSGITDVIIG MPHRGRLNLL TGLLQFPPEL 

       250        260        270        280        290        300 
MFRKMRGLSE FPENFSATGD VLSHLTSSVD LYFGAHHPLH VTMLPNPSHL EAVNPVAVGK 

       310        320        330        340        350        360 
TRGRQQSRQD GDYSPDNSAQ PGDRVICLQV HGDASFCGQG IVPETFTLSN LPHFRIGGSV 

       370        380        390        400        410        420 
HLIVNNQLGY TTPAERGRSS LYCSDIGKLV GCAIIHVNGD SPEEVVRATR LAFEYQRQFR 

       430        440        450        460        470        480 
KDVIIDLLCY RQWGHNELDE PFYTNPIMYK IIRARKSIPD TYAEHLIAGG LMTQEEVSEI 

       490        500        510        520        530        540 
KSSYYAKLND HLNNMAHYRP PALNLQAHWQ GLAQPEAQIT TWSTGVPLDL LRFVGMKSVE 

       550        560        570        580        590        600 
VPRELQMHSH LLKTHVQSRM EKMMDGIKLD WATAEALALG SLLAQGFNVR LSGQDVGRGT 

       610        620        630        640        650        660 
FSQRHAIVVC QETDDTYIPL NHMDPNQKGF LEVSNSPLSE EAVLGFEYGM SIESPKLLPL 

       670        680        690        700        710        720 
WEAQFGDFFN GAQIIFDTFI SGGEAKWLLQ SGIVILLPHG YDGAGPDHSS CRIERFLQMC 

       730        740        750        760        770        780 
DSAEEGVDGD TVNMFVVHPT TPAQYFHLLR RQMVRNFRKP LIVASPKMLL RLPAAVSTLQ 

       790        800        810        820        830        840 
EMAPGTTFNP VIGDSSVDPK KVKTLVFCSG KHFYSLVKQR ESLGAKKHDF AIIRVEELCP 

       850        860        870        880        890        900 
FPLDSLQQEM SKYKHVKDHI WSQEEPQNMG PWSFVSPRFE KQLACKLRLV GRPPLPVPAV 

       910 
GIGTVHLHQH EDILAKTFA 

« Hide

References

« Hide 'large scale' references
[1]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"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], VARIANTS LEU-20; ASP-272; LEU-308 AND MET-607.
Tissue: Kidney and Uterus.
[3]"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.
DNA Res. 7:273-281(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-886, VARIANTS LEU-20; ASP-272 AND MET-607.
Tissue: Brain.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 380-919, VARIANT MET-607.
Tissue: Melanoma.
[5]"A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in a large Chinese pedigree."
Xu W.Y., Gu M.M., Sun L.H., Guo W.T., Zhu H.B., Ma J.F., Yuan W.T., Kuang Y., Ji B.J., Wu X.L., Chen Y., Zhang H.X., Sun F.T., Huang W., Huang L., Chen S.D., Wang Z.G.
Am. J. Hum. Genet. 91:1088-1094(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CMT2Q, SUBCELLULAR LOCATION.
[6]"DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria."
Danhauser K., Sauer S.W., Haack T.B., Wieland T., Staufner C., Graf E., Zschocke J., Strom T.M., Traub T., Okun J.G., Meitinger T., Hoffmann G.F., Prokisch H., Koelker S.
Am. J. Hum. Genet. 91:1082-1087(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AMOXAD ARG-729.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC073160 Genomic DNA. No translation available.
BC002477 mRNA. Translation: AAH02477.1.
BC007955 mRNA. Translation: AAH07955.1.
AB046850 mRNA. Translation: BAB13456.1. Sequence problems.
CR749726 mRNA. Translation: CAH18489.1.
CCDSCCDS7087.1.
PIRT50617.
RefSeqNP_061176.3. NM_018706.6.
UniGeneHs.104980.
Hs.568075.

3D structure databases

ProteinModelPortalQ96HY7.
SMRQ96HY7. Positions 58-919.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000263035.

PTM databases

PhosphoSiteQ96HY7.

Polymorphism databases

DMDM296434477.

Proteomic databases

MaxQBQ96HY7.
PaxDbQ96HY7.
PRIDEQ96HY7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263035; ENSP00000263035; ENSG00000181192.
GeneID55526.
KEGGhsa:55526.
UCSCuc001ild.5. human.

Organism-specific databases

CTD55526.
GeneCardsGC10P012028.
HGNCHGNC:23537. DHTKD1.
HPAHPA037950.
MIM204750. phenotype.
614984. gene.
615025. phenotype.
neXtProtNX_Q96HY7.
Orphanet79154. 2-aminoadipic 2-oxoadipic aciduria.
329258. Autosomal dominant Charcot-Marie-Tooth disease type 2Q.
PharmGKBPA134962952.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0567.
HOGENOMHOG000259586.
HOVERGENHBG001892.
InParanoidQ96HY7.
KOK15791.
OMALCSGKHY.
OrthoDBEOG7CZK4Z.
PhylomeDBQ96HY7.
TreeFamTF314198.

Enzyme and pathway databases

BioCycMetaCyc:HS11585-MONOMER.

Gene expression databases

ArrayExpressQ96HY7.
BgeeQ96HY7.
CleanExHS_DHTKD1.
GenevestigatorQ96HY7.

Family and domain databases

Gene3D3.40.50.970. 2 hits.
InterProIPR011603. 2oxoglutarate_DH_E1.
IPR001017. DH_E1.
IPR029061. THDP-binding.
IPR005475. Transketolase-like_Pyr-bd.
[Graphical view]
PANTHERPTHR23152. PTHR23152. 1 hit.
PfamPF00676. E1_dh. 1 hit.
PF02779. Transket_pyr. 1 hit.
[Graphical view]
PIRSFPIRSF000157. Oxoglu_dh_E1. 1 hit.
SMARTSM00861. Transket_pyr. 1 hit.
[Graphical view]
SUPFAMSSF52518. SSF52518. 2 hits.
TIGRFAMsTIGR00239. 2oxo_dh_E1. 1 hit.
ProtoNetSearch...

Other

ChiTaRSDHTKD1. human.
GenomeRNAi55526.
NextBio59950.
PROQ96HY7.
SOURCESearch...

Entry information

Entry nameDHTK1_HUMAN
AccessionPrimary (citable) accession number: Q96HY7
Secondary accession number(s): Q68CU5, Q9BUM8, Q9HCE2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 93 of the entry and version 2 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 10

Human chromosome 10: entries, gene names and cross-references to MIM