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O00217 (NDUS8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. 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·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial

EC=1.6.5.3
EC=1.6.99.3
Alternative name(s):
Complex I-23kD
Short name=CI-23kD
NADH-ubiquinone oxidoreductase 23 kDa subunit
TYKY subunit
Gene names
Name:NDUFS8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length210 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone By similarity. May donate electrons to ubiquinone. HAMAP-Rule MF_01351

Catalytic activity

NADH + ubiquinone + 5 H+(In) = NAD+ + ubiquinol + 4 H+(Out). HAMAP-Rule MF_01351

NADH + acceptor = NAD+ + reduced acceptor. HAMAP-Rule MF_01351

Cofactor

Binds 2 4Fe-4S clusters per subunit By similarity. HAMAP-Rule MF_01351

Subunit structure

Mammalian complex I is composed of 45 different subunits. Ref.5

Subcellular location

Mitochondrion Probable HAMAP-Rule MF_01351.

Involvement in disease

Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the complex I 23 kDa subunit family.

Contains 2 4Fe-4S ferredoxin-type domains.

Ontologies

Keywords
   Biological processElectron transport
Respiratory chain
Transport
   Cellular componentMitochondrion
   DiseaseDisease mutation
Leigh syndrome
   DomainRepeat
Transit peptide
   Ligand4Fe-4S
Iron
Iron-sulfur
Metal-binding
NAD
Ubiquinone
   Molecular functionOxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular metabolic process

Traceable author statement. Source: Reactome

mitochondrial electron transport, NADH to ubiquinone

Non-traceable author statement Ref.2PubMed 9878551. Source: UniProtKB

mitochondrial respiratory chain complex I assembly

Inferred from mutant phenotype PubMed 11112787PubMed 15159508. Source: UniProtKB

respiratory electron transport chain

Traceable author statement. Source: Reactome

response to oxidative stress

Inferred from direct assay PubMed 12857734. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentmitochondrial inner membrane

Traceable author statement. Source: Reactome

mitochondrial respiratory chain complex I

Inferred from direct assay Ref.5. Source: UniProtKB

mitochondrion

Inferred from direct assay Ref.2. Source: UniProtKB

   Molecular_function4 iron, 4 sulfur cluster binding

Inferred from electronic annotation. Source: UniProtKB-KW

NADH dehydrogenase (ubiquinone) activity

Non-traceable author statement PubMed 9878551. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3434Mitochondrion By similarity
Chain35 – 210176NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial HAMAP-Rule MF_01351
PRO_0000020012

Regions

Domain102 – 131304Fe-4S ferredoxin-type 1
Domain141 – 170304Fe-4S ferredoxin-type 2

Sites

Metal binding1111Iron-sulfur 1 (4Fe-4S) By similarity
Metal binding1141Iron-sulfur 1 (4Fe-4S) By similarity
Metal binding1171Iron-sulfur 1 (4Fe-4S) By similarity
Metal binding1211Iron-sulfur 2 (4Fe-4S) By similarity
Metal binding1501Iron-sulfur 2 (4Fe-4S) By similarity
Metal binding1531Iron-sulfur 2 (4Fe-4S) By similarity
Metal binding1561Iron-sulfur 2 (4Fe-4S) By similarity
Metal binding1601Iron-sulfur 1 (4Fe-4S) By similarity

Natural variations

Natural variant791P → L in LS. Ref.7
Corresponds to variant rs28939679 [ dbSNP | Ensembl ].
VAR_019538
Natural variant1021R → H in LS. Ref.7
VAR_019539

Sequences

Sequence LengthMass (Da)Tools
O00217 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 8C3EBD205BFA0112

FASTA21023,705
        10         20         30         40         50         60 
MRCLTTPMLL RALAQAARAG PPGGRSLHSS AVAATYKYVN MQDPEMDMKS VTDRAARTLL 

        70         80         90        100        110        120 
WTELFRGLGM TLSYLFREPA TINYPFEKGP LSPRFRGEHA LRRYPSGEER CIACKLCEAI 

       130        140        150        160        170        180 
CPAQAITIEA EPRADGSRRT TRYDIDMTKC IYCGFCQEAC PVDAIVEGPN FEFSTETHEE 

       190        200        210 
LLYNKEKLLN NGDKWEAEIA ANIQADYLYR 

« Hide

References

« Hide 'large scale' references
[1]"cDNA sequence and chromosomal localization of the NDUFS8 human gene coding for the 23 kDa subunit of the mitochondrial complex I."
Procaccio V., Depetris D., Soularue P., Mattei M.-G., Lunardi J., Issartel J.-P.
Biochim. Biophys. Acta 1351:37-41(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"Genomic structure of the human NDUFS8 gene coding for the iron-sulfur TYKY subunit of the mitochondrial NADH:ubiquinone oxidoreductase."
de Sury R., Martinez P., Procaccio V., Lunardi J., Issartel J.-P.
Gene 215:1-10(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"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].
Tissue: Uterus.
[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].
[5]"The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification."
Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., Ghosh S.S., Capaldi R.A.
J. Biol. Chem. 278:13619-13622(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY.
[6]"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].
[7]"The first nuclear-encoded complex I mutation in a patient with Leigh syndrome."
Loeffen J., Smeitink J., Triepels R., Smeets R., Schuelke M., Sengers R., Trijbels F., Hamel B.C.J., Mullaart R., van den Heuvel L.
Am. J. Hum. Genet. 63:1598-1608(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LS LEU-79 AND HIS-102.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U65579 mRNA. Translation: AAB51776.1.
AF038406 Genomic DNA. Translation: AAC34273.1.
AK314546 mRNA. Translation: BAG37133.1.
BC119754 mRNA. Translation: AAI19755.1.
RefSeqNP_002487.1. NM_002496.3.
XP_005274070.1. XM_005274013.1.
XP_005274071.1. XM_005274014.1.
UniGeneHs.90443.

3D structure databases

ProteinModelPortalO00217.
SMRO00217. Positions 84-189.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110806. 27 interactions.
IntActO00217. 5 interactions.
MINTMINT-2997478.
STRING9606.ENSP00000315774.

Chemistry

BindingDBO00217.
ChEMBLCHEMBL2363065.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteO00217.

2D gel databases

OGPO00217.

Proteomic databases

PaxDbO00217.
PeptideAtlasO00217.
PRIDEO00217.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000313468; ENSP00000315774; ENSG00000110717.
GeneID4728.
KEGGhsa:4728.
UCSCuc001onc.3. human.

Organism-specific databases

CTD4728.
GeneCardsGC11P067798.
HGNCHGNC:7715. NDUFS8.
HPAHPA018524.
MIM256000. phenotype.
602141. gene.
neXtProtNX_O00217.
Orphanet2609. Isolated NADH-CoQ reductase deficiency.
255241. Leigh syndrome with leukodystrophy.
PharmGKBPA31525.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1143.
HOGENOMHOG000228289.
HOVERGENHBG006547.
InParanoidO00217.
KOK03941.
OMATYKYVNL.
OrthoDBEOG7J9VQT.
PhylomeDBO00217.
TreeFamTF105610.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressO00217.
BgeeO00217.
CleanExHS_NDUFS8.
GenevestigatorO00217.

Family and domain databases

HAMAPMF_01351. NDH1_NuoI.
InterProIPR001450. 4Fe4S-bd_dom.
IPR017896. 4Fe4S_Fe-S-bd.
IPR017900. 4Fe4S_Fe_S_CS.
IPR010226. NADH_quinone_OxRdtase_chainI.
[Graphical view]
PfamPF12838. Fer4_7. 1 hit.
[Graphical view]
TIGRFAMsTIGR01971. NuoI. 1 hit.
PROSITEPS00198. 4FE4S_FER_1. 2 hits.
PS51379. 4FE4S_FER_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNDUFS8.
GenomeRNAi4728.
NextBio18230.
PROO00217.
SOURCESearch...

Entry information

Entry nameNDUS8_HUMAN
AccessionPrimary (citable) accession number: O00217
Secondary accession number(s): B2RB86, Q0VDA8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 139 of the entry and version 1 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 11

Human chromosome 11: entries, gene names and cross-references to MIM