O00217 (NDUS8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	210 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)

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.
Catalytic activity	NADH + ubiquinone = NAD+ + ubiquinol. NADH + acceptor = NAD+ + reduced acceptor.
Cofactor	Binds 2 4Fe-4S clusters per subunit By similarity.
Subunit structure	Mammalian complex I is composed of 45 different subunits. Ref.5
Subcellular location	Mitochondrion Probable.
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 process	Electron transport Respiratory chain Transport
Cellular component	Mitochondrion
Disease	Disease mutation Leigh syndrome
Domain	Repeat Transit peptide
Ligand	4Fe-4S Iron Iron-sulfur Metal-binding NAD Ubiquinone
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 response to oxidative stress Inferred from direct assay PubMed 12857734. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	mitochondrial respiratory chain complex I Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW NADH dehydrogenase (ubiquinone) activity Non-traceable author statement PubMed 9878551. Source: UniProtKB electron carrier activity Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 34	34	Mitochondrion By similarity
	Chain	35 – 210	176	NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial		PRO_0000020012
Regions
	Domain	102 – 131	30	4Fe-4S ferredoxin-type 1
	Domain	141 – 170	30	4Fe-4S ferredoxin-type 2
Sites
	Metal binding	111	1	Iron-sulfur 1 (4Fe-4S) By similarity
	Metal binding	114	1	Iron-sulfur 1 (4Fe-4S) By similarity
	Metal binding	117	1	Iron-sulfur 1 (4Fe-4S) By similarity
	Metal binding	121	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	150	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	153	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	156	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	160	1	Iron-sulfur 1 (4Fe-4S) By similarity
Natural variations
	Natural variant	79	1	P → L in LS. Ref.7 Corresponds to variant rs28939679 [ dbSNP | Ensembl ].		VAR_019538
	Natural variant	102	1	R → H in LS. Ref.7		VAR_019539

Sequences

	Sequence		Length	Mass (Da)
	O00217 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 8C3EBD205BFA0112	FASTA	210	23,705
	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

References

	« Hide 'large scale' referencesShow '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. , 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: MASS SPECTROMETRY, IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX.
[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

GeneReviews

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.
IPI	IPI00010845.
RefSeq	NP_002487.1. NM_002496.3.
UniGene	Hs.90443.
3D structure databases
ProteinModelPortal	O00217.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00217. 4 interactions.
STRING	9606.ENSP00000315774.
PTM databases
PhosphoSite	O00217.
2D gel databases
OGP	O00217.
Proteomic databases
PaxDb	O00217.
PeptideAtlas	O00217.
PRIDE	O00217.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000313468; ENSP00000315774; ENSG00000110717.
GeneID	4728.
KEGG	hsa:4728.
UCSC	uc001onc.3. human.
Organism-specific databases
CTD	4728.
GeneCards	GC11P067798.
HGNC	HGNC:7715. NDUFS8.
HPA	HPA018524.
MIM	256000. phenotype. 602141. gene.
neXtProt	NX_O00217.
Orphanet	2609. Isolated NADH-CoQ reductase deficiency. 255241. Leigh syndrome with leukodystrophy.
PharmGKB	PA31525.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1143.
HOGENOM	HOG000228289.
HOVERGEN	HBG006547.
InParanoid	O00217.
KO	K03941.
OMA	CPAMAIT.
OrthoDB	EOG43R3NR.
PhylomeDB	O00217.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	O00217.
Bgee	O00217.
CleanEx	HS_NDUFS8.
Genevestigator	O00217.
GermOnline	ENSG00000110717. Homo sapiens.
Family and domain databases
Gene3D	1.10.1060.10. 1 hit.
InterPro	IPR001450. 4Fe4S-bd_dom. IPR017896. 4Fe4S_Fe-S-bd. IPR017900. 4Fe4S_Fe_S_CS. IPR012285. Fum_reductase_C. IPR010226. NADH_quinone_OxRdtase_chainI. [Graphical view]
Pfam	PF12838. Fer4_7. 1 hit. [Graphical view]
TIGRFAMs	TIGR01971. NuoI. 1 hit.
PROSITE	PS00198. 4FE4S_FER_1. 2 hits. PS51379. 4FE4S_FER_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O00217.
ChEMBL	CHEMBL2090.
DrugBank	DB00157. NADH.
GenomeRNAi	4728.
NextBio	18230.
SOURCE	Search...

Entry information

Entry name

NDUS8_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 129 of the entry and version 1 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.