Reviewed, UniProtKB/Swiss-Prot O00217 (NDUS8_HUMAN)

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):
    NADH-ubiquinone oxidoreductase 23 kDa subunit
    Complex I-23kD
      Short name=CI-23kD
    TYKY subunit

Gene names

Name:

NDUFS8

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	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.
Subcellular location	Mitochondrion Probable.
Involvement in disease	Defects in NDUFS8 are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions. Ref.6
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
Gene Ontology (GO)
Biological process	mitochondrial electron transport, NADH to ubiquinone Ref.2 Non-traceable author statement. Source: UniProtKB mitochondrial respiratory chain complex I assembly Inferred from mutant phenotype. Source: UniProtKB response to oxidative stress Inferred from direct assay. Source: UniProtKB transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial respiratory chain complex I Inferred from mutant phenotype. Source: UniProtKB
Molecular function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW NADH dehydrogenase (ubiquinone) activity Ref.6 Non-traceable author statement. Source: UniProtKB electron carrier activity Inferred from electronic annotation. Source: InterPro iron 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.6		VAR_019538
	Natural variant	102	1	R → H in LS. Ref.6		VAR_019539

Sequences

	Sequence		Length	Mass (Da)
	O00217-1 [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: 9116042] [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: 9666055] [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: 14702039] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]	"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: 9837812] [Abstract] Cited for: VARIANTS LS LEU-79 AND HIS-102.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
UniGene	Hs.495985 Hs.90443
3D structure databases
HSSP	HSSP built from PDB template 2FDN based on UniProtKB P00198.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00217. 1 interaction.
PTM databases
PhosphoSite	O00217.
2-D gel databases
OGP	O00217.
Proteomic databases
PeptideAtlas	O00217.
PRIDE	O00217.
Genome annotation databases
Ensembl	ENSG00000110717. Homo sapiens. [Contig view]
GeneID	4728.
KEGG	hsa:4728.
NMPDR	fig|9606.3.peg.6162.
Organism-specific databases
GeneCards	GC11P067554.
H-InvDB	HIX0023060.
HGNC	HGNC:7715. NDUFS8.
HPA	HPA018524.
MIM	256000. phenotype. 602141. gene.
Orphanet	506. Leigh syndrome. 2609. NADH-CoQ reductase deficiency.
PharmGKB	PA31525.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O00217.
OMA	O00217. QADFLYR.
Enzyme and pathway databases
BRENDA	1.6.5.3. 247. 1.6.99.3. 247.
Reactome	REACT_6305. Electron Transport Chain.
Gene expression databases
ArrayExpress	O00217.
Bgee	O00217.
CleanEx	HS_NDUFS8.
GermOnline	ENSG00000110717. Homo sapiens.
Family and domain databases
InterPro	IPR017896. 4Fe4S_Fe-S-bd. IPR001450. 4Fe4S_Fe_S_bd_subgr. IPR017900. 4Fe4S_Fe_S_CS. IPR010226. NADH_quinone_OxRdtase_chainI. [Graphical view]
Pfam	PF00037. Fer4. 2 hits. [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 Resources
DrugBank	DB00157. NADH.
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:	June 16, 2009
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)