O75306 (NDUS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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):
Complex I-49kD
Short name=CI-49kD
NADH-ubiquinone oxidoreductase 49 kDa subunit

Gene names

Name:

NDUFS2

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	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. HAMAP-Rule MF_01358
Catalytic activity	NADH + ubiquinone = NAD+ + ubiquinol. HAMAP-Rule MF_01358 NADH + acceptor = NAD+ + reduced acceptor. HAMAP-Rule MF_01358
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. Interacts with NDUFAF3 and NDUFAF7. Ref.7 Ref.8 Ref.9
Subcellular location	Mitochondrion inner membrane; Peripheral membrane protein; Matrix side HAMAP-Rule MF_01358.
Involvement in disease	Mitochondrial complex I deficiency (MT-C1D) [MIM:252010]: A disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11
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	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	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.1PubMed 9878551. 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.7PubMed 17209039. 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 Non-traceable author statement Ref.1PubMed 9878551. Source: UniProtKB electron carrier activity Non-traceable author statement Ref.1. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW quinone binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NDUFS3	O75489	5	EBI-1224806,EBI-1224896

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75306-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O75306-2)

The sequence of this isoform differs from the canonical sequence as follows:
     454-463: QDIVFGEVDR → RPIV

Note: No experimental confirmation available.

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 HAMAP-Rule MF_01358		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
	Alternative sequence	454 – 463	10	QDIVFGEVDR → RPIV in isoform 2.		VSP_046466
	Natural variant	20	1	P → T. Corresponds to variant rs11538340 [ dbSNP | Ensembl ].		VAR_034150
	Natural variant	228	1	R → Q in MT-C1D. Ref.11		VAR_019535
	Natural variant	229	1	P → A. Corresponds to variant rs16827493 [ dbSNP | Ensembl ].		VAR_034151
	Natural variant	229	1	P → Q in MT-C1D. Ref.11		VAR_019536
	Natural variant	352	1	P → A. Corresponds to variant rs11576415 [ dbSNP | Ensembl ].		VAR_034152
	Natural variant	413	1	S → P in MT-C1D. Ref.11		VAR_019537
Experimental info
	Sequence conflict	24	1	V → G in AAC34362. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 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
	Isoform 2 [UniParc]. Checksum: 312C97A91028FF66	FASTA	457	51,852
	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 RCKIKAPGFA HLAGLDKMSK GHMLADVVAI IGTRPIV

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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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].
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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].
[6]	"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]. Tissue: Muscle and Placenta.
[7]	"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.
[8]	"Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease." Saada A., Vogel R.O., Hoefs S.J., van den Brand M.A., Wessels H.J., Willems P.H., Venselaar H., Shaag A., Barghuti F., Reish O., Shohat M., Huynen M.A., Smeitink J.A.M., van den Heuvel L.P., Nijtmans L.G. Am. J. Hum. Genet. 84:718-727(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NDUFAF3.
[9]	"MidA is a putative methyltransferase that is required for mitochondrial complex I function." Carilla-Latorre S., Gallardo M.E., Annesley S.J., Calvo-Garrido J., Grana O., Accari S.L., Smith P.K., Valencia A., Garesse R., Fisher P.R., Escalante R. J. Cell Sci. 123:1674-1683(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NDUFAF7.
[10]	"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].
[11]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS MT-C1D GLN-228; GLN-229 AND PRO-413.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF050640 mRNA. Translation: AAC27453.1. AF013160 mRNA. Translation: AAC34362.1. AK314807 mRNA. No translation available. AL590714 Genomic DNA. Translation: CAH72148.1. CH471121 Genomic DNA. Translation: EAW52625.1. CH471121 Genomic DNA. Translation: EAW52626.1. BC000170 mRNA. Translation: AAH00170.1. BC001456 mRNA. Translation: AAH01456.1. BC008868 mRNA. Translation: AAH08868.1.
IPI	IPI00025239.
PIR	JE0193.
RefSeq	NP_001159631.1. NM_001166159.1. NP_004541.1. NM_004550.4.
UniGene	Hs.173611.
3D structure databases
ProteinModelPortal	O75306.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75306. 11 interactions.
STRING	9606.ENSP00000356972.
PTM databases
PhosphoSite	O75306.
Proteomic databases
PaxDb	O75306.
PeptideAtlas	O75306.
PRIDE	O75306.
Protocols and materials databases
DNASU	4720.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000367993; ENSP00000356972; ENSG00000158864. ENST00000392179; ENSP00000376018; ENSG00000158864.
GeneID	4720.
KEGG	hsa:4720.
UCSC	uc001fyv.3. human.
Organism-specific databases
CTD	4720.
GeneCards	GC01P161166.
HGNC	HGNC:7708. NDUFS2.
HPA	HPA055140.
MIM	252010. phenotype. 602985. gene.
neXtProt	NX_O75306.
Orphanet	2609. Isolated NADH-CoQ reductase deficiency.
PharmGKB	PA31519.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0649.
HOGENOM	HOG000228264.
HOVERGEN	HBG000760.
InParanoid	O75306.
KO	K03935.
OMA	QSNRIIK.
OrthoDB	EOG4D7Z5H.
PhylomeDB	O75306.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	O75306.
Bgee	O75306.
CleanEx	HS_NDUFS2.
Genevestigator	O75306.
GermOnline	ENSG00000158864. Homo sapiens.
Family and domain databases
HAMAP	MF_01358. NDH1_NuoD.
InterPro	IPR001135. NADH_Q_OxRdtase_suD. IPR014029. NADH_UbQ_OxRdtase_49kDa_CS. IPR022885. NDH1_su_D/H. [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
BindingDB	O75306.
ChEMBL	CHEMBL3039.
ChiTaRS	NDUFS2. human.
DrugBank	DB00157. NADH.
GenomeRNAi	4720.
NextBio	18206.
SOURCE	Search...

Entry information

Entry name

NDUS2_HUMAN

Accession

Primary (citable) accession number: O75306
Secondary accession number(s): D3DVG7 , J3KPM7, Q5VTW0, Q969P3, Q9UEV3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	April 16, 2002
Last modified:	May 1, 2013
This is version 135 of the entry and version 2 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.