Reviewed, UniProtKB/Swiss-Prot O75306 (NDUS2_HUMAN)

Names and origin

Protein names

Recommended name:
    NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
    EC=1.6.5.3
    EC=1.6.99.3
Alternative name(s):
    NADH-ubiquinone oxidoreductase 49 kDa subunit
    Complex I-49kD
      Short name=CI-49kD

Gene names

Name:

NDUFS2

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)

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.
Catalytic activity	NADH + ubiquinone = NAD(+) + ubiquinol. NADH + acceptor = NAD(+) + reduced acceptor.
Cofactor	Binds 1 4Fe-4S cluster.
Subunit structure	Complex I is composed of 45 different subunits. Component of the iron-sulfur (IP) fragment of the enzyme.
Subcellular location	Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.
Involvement in disease	Defects in NDUFS2 are a cause of complex I mitochondrial respiratory chain deficiency [MIM:252010]. Complex I (NADH-ubiquinone oxidoreductase), the largest complex of the mitochondrial respiratory chain, contains more than 40 subunits. It is embedded in the inner mitochondrial membrane and is partly protruding in the matrix. Complex I deficiency is the most common cause of mitochondrial disorders. It represents largely one-third of all cases of respiratory chain deficiency and is responsible for a variety of clinical symptoms, ranging from neurological disorders to cardiomyopathy, liver failure, and myopathy.
Sequence similarities	Belongs to the complex I 49 kDa subunit family.

Ontologies

Keywords
Biological process	Electron transport Respiratory chain Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	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.1 Non-traceable author statement. 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 direct assay. Source: UniProtKB
Molecular function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW NAD binding Inferred from electronic annotation. Source: InterPro NADH dehydrogenase (ubiquinone) activity Ref.1 Non-traceable author statement. Source: UniProtKB electron carrier activity Ref.1 Non-traceable author statement. Source: UniProtKB 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 – 33	33	Mitochondrion By similarity
	Chain	34 – 463	430	NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial		PRO_0000019981
Sites
	Metal binding	326	1	Iron-sulfur (4Fe-4S) Potential
	Metal binding	332	1	Iron-sulfur (4Fe-4S) Potential
	Metal binding	347	1	Iron-sulfur (4Fe-4S) Potential
Natural variations
	Natural variant	20	1	P → T: dbSNP rs11538340.		VAR_034150
	Natural variant	228	1	R → Q in complex I deficiency.		VAR_019535
	Natural variant	229	1	P → A: dbSNP rs16827493.		VAR_034151
	Natural variant	229	1	P → Q in complex I deficiency.		VAR_019536
	Natural variant	352	1	P → A: dbSNP rs11576415.		VAR_034152
	Natural variant	413	1	S → P in complex I deficiency.		VAR_019537
Experimental info
	Sequence conflict	24	1	V → G in AAC34362. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O75306-1 [UniParc]. Last modified April 16, 2002. Version 2. Checksum: A2BF56F008B6312C	FASTA	463	52,546
	10 20 30 40 50 60 MAALRALCGF RGVAAQVLRP GAGVRLPIQP SRGVRQWQPD VEWAQQFGGA VMYPSKETAH 70 80 90 100 110 120 WKPPPWNDVD PPKDTIVKNI TLNFGPQHPA AHGVLRLVME LSGEMVRKCD PHIGLLHRGT 130 140 150 160 170 180 EKLIEYKTYL QALPYFDRLD YVSMMCNEQA YSLAVEKLLN IRPPPRAQWI RVLFGEITRL 190 200 210 220 230 240 LNHIMAVTTH ALDLGAMTPF FWLFEEREKM FEFYERVSGA RMHAAYIRPG GVHQDLPLGL 250 260 270 280 290 300 MDDIYQFSKN FSLRLDELEE LLTNNRIWRN RTIDIGVVTA EEALNYGFSG VMLRGSGIQW 310 320 330 340 350 360 DLRKTQPYDV YDQVEFDVPV GSRGDCYDRY LCRVEEMRQS LRIIAQCLNK MPPGEIKVDD 370 380 390 400 410 420 AKVSPPKRAE MKTSMESLIH HFKLYTEGYQ VPPGATYTAI EAPKGEFGVY LVSDGSSRPY 430 440 450 460 RCKIKAPGFA HLAGLDKMSK GHMLADVVAI IGTQDIVFGE VDR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA sequence and chromosomal localization of the remaining three human nuclear encoded iron sulphur protein (IP) subunits of complex I: the human IP fraction is completed." Loeffen J., van den Heuvel L., Smeets R., Triepels R., Sengers R., Trijbels F., Smeitink J. Biochem. Biophys. Res. Commun. 247:751-758(1998) [PubMed: 9647766] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Mapping to 1q23 of the human gene (NDUFS2) encoding the 49-kDa subunit of the mitochondrial respiratory complex I and immunodetection of the mature protein in mitochondria." Procaccio V., de Sury R., Martinez P., Depetris D., Rabilloud T., Soularue P., Lunardi J., Issartel J.-P. Mamm. Genome 9:482-484(1998) [PubMed: 9585441] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Muscle and Placenta.
[6]	"Mutations in the complex I NDUFS2 gene of patients with cardiomyopathy and encephalomyopathy." Loeffen J., Elpeleg O., Smeitink J., Smeets R., Stoeckler-Ipsiroglu S., Mandel H., Sengers R., Trijbels F., van den Heuvel L. Ann. Neurol. 49:195-201(2001) [PubMed: 11220739] [Abstract] Cited for: VARIANTS COMPLEX I DEFICIENCY GLN-228; GLN-229 AND PRO-413.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF050640 mRNA. Translation: AAC27453.1. AF013160 mRNA. Translation: AAC34362.1. AL590714 Genomic DNA. Translation: CAH72148.1. CH471121 Genomic DNA. Translation: EAW52625.1. BC000170 mRNA. Translation: AAH00170.1. BC001456 mRNA. Translation: AAH01456.1. BC008868 mRNA. Translation: AAH08868.1.
PIR	JE0193.
RefSeq	NP_004541.1.
UniGene	Hs.173611
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	O75306.
Proteomic databases
PeptideAtlas	O75306.
Genome annotation databases
Ensembl	ENSG00000158864. Homo sapiens. [Contig view]
GeneID	4720.
KEGG	hsa:4720.
Organism-specific databases
HGNC	HGNC:7708. NDUFS2.
MIM	252010. phenotype. 602985. gene.
Orphanet	2609. NADH-CoQ reductase deficiency.
PharmGKB	PA31519.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	O75306.
Enzyme and pathway databases
Reactome	REACT_6305. Electron Transport Chain.
Gene expression databases
ArrayExpress	O75306.
CleanEx	HS_NDUFS2.
GermOnline	ENSG00000158864. Homo sapiens.
Family and domain databases
InterPro	IPR014029. NADH-UbQ_OxRdtase_49kDa_CS. IPR010219. NADH_DH_1_dsu. IPR001135. NADH_UbQ_OxRdtase_49kDa. [Graphical view]
Pfam	PF00346. Complex1_49kDa. 1 hit. [Graphical view]
TIGRFAMs	TIGR01962. NuoD. 1 hit.
PROSITE	PS00535. COMPLEX1_49K. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00157. NADH.
NextBio	18206.
SOURCE	Search...

Entry information

Entry name

NDUS2_HUMAN

Accession

Primary (citable) accession number: O75306
Secondary accession number(s): Q5VTW0, Q969P3, Q9UEV3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	April 16, 2002
Last modified:	November 25, 2008
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)