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O75306 (NDUS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length463 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. HAMAP-Rule MF_01358

Catalytic activity

NADH + ubiquinone + 5 H+(In) = NAD+ + ubiquinol + 4 H+(Out). 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 processElectron transport
Respiratory chain
Transport
   Cellular componentMembrane
Mitochondrion
Mitochondrion inner membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainTransit peptide
   Ligand4Fe-4S
Iron
Iron-sulfur
Metal-binding
NAD
Ubiquinone
   Molecular functionOxidoreductase
   PTMAcetylation
Methylation
   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.1PubMed 9878551. 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.7PubMed 17209039. Source: UniProtKB

mitochondrion

Inferred from direct assay Ref.2. Source: UniProtKB

nucleus

Inferred from direct assay. Source: HPA

   Molecular_function4 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

protein binding

Inferred from physical interaction Ref.8Ref.9. Source: UniProtKB

quinone binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NDUFS3O754895EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3333Mitochondrion By similarity
Chain34 – 463430NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial HAMAP-Rule MF_01358
PRO_0000019981

Sites

Metal binding3261Iron-sulfur (4Fe-4S) Potential
Metal binding3321Iron-sulfur (4Fe-4S) Potential
Metal binding3471Iron-sulfur (4Fe-4S) Potential

Amino acid modifications

Modified residue621N6-acetyllysine By similarity
Modified residue1181Symmetric dimethylarginine By similarity

Natural variations

Alternative sequence454 – 46310QDIVFGEVDR → RPIV in isoform 2.
VSP_046466
Natural variant201P → T.
Corresponds to variant rs11538340 [ dbSNP | Ensembl ].
VAR_034150
Natural variant2281R → Q in MT-C1D. Ref.11
VAR_019535
Natural variant2291P → A.
Corresponds to variant rs16827493 [ dbSNP | Ensembl ].
VAR_034151
Natural variant2291P → Q in MT-C1D. Ref.11
VAR_019536
Natural variant3521P → A.
Corresponds to variant rs11576415 [ dbSNP | Ensembl ].
VAR_034152
Natural variant4131S → P in MT-C1D. Ref.11
VAR_019537

Experimental info

Sequence conflict241V → G in AAC34362. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 16, 2002. Version 2.
Checksum: A2BF56F008B6312C

FASTA46352,546
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 312C97A91028FF66
Show »

FASTA45751,852

References

« Hide '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. 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].
[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. expand/collapse author list , 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. expand/collapse author list , 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: IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY.
[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.
CCDSCCDS1224.1. [O75306-1]
CCDS53404.1. [O75306-2]
PIRJE0193.
RefSeqNP_001159631.1. NM_001166159.1. [O75306-2]
NP_004541.1. NM_004550.4. [O75306-1]
XP_005245265.1. XM_005245208.1. [O75306-1]
UniGeneHs.173611.

3D structure databases

ProteinModelPortalO75306.
SMRO75306. Positions 80-463.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110800. 26 interactions.
IntActO75306. 16 interactions.
STRING9606.ENSP00000356972.

Chemistry

BindingDBO75306.
ChEMBLCHEMBL2363065.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteO75306.

Proteomic databases

MaxQBO75306.
PaxDbO75306.
PeptideAtlasO75306.
PRIDEO75306.

Protocols and materials databases

DNASU4720.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367993; ENSP00000356972; ENSG00000158864. [O75306-1]
ENST00000392179; ENSP00000376018; ENSG00000158864. [O75306-2]
GeneID4720.
KEGGhsa:4720.
UCSCuc001fyv.3. human. [O75306-1]

Organism-specific databases

CTD4720.
GeneCardsGC01P161166.
HGNCHGNC:7708. NDUFS2.
HPAHPA055140.
MIM252010. phenotype.
602985. gene.
neXtProtNX_O75306.
Orphanet2609. Isolated NADH-CoQ reductase deficiency.
PharmGKBPA31519.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0649.
HOGENOMHOG000228264.
HOVERGENHBG000760.
InParanoidO75306.
KOK03935.
OMAQCFALAV.
OrthoDBEOG7WT411.
PhylomeDBO75306.
TreeFamTF300370.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressO75306.
BgeeO75306.
CleanExHS_NDUFS2.
GenevestigatorO75306.

Family and domain databases

Gene3D1.10.645.10. 1 hit.
HAMAPMF_01358. NDH1_NuoD.
InterProIPR001135. NADH_Q_OxRdtase_suD.
IPR014029. NADH_UbQ_OxRdtase_49kDa_CS.
IPR022885. NDH1_su_D/H.
IPR029014. NiFe_Hase-like.
[Graphical view]
PfamPF00346. Complex1_49kDa. 1 hit.
[Graphical view]
SUPFAMSSF56762. SSF56762. 1 hit.
TIGRFAMsTIGR01962. NuoD. 1 hit.
PROSITEPS00535. COMPLEX1_49K. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNDUFS2. human.
GeneWikiNDUFS2.
GenomeRNAi4720.
NextBio18206.
PROO75306.
SOURCESearch...

Entry information

Entry nameNDUS2_HUMAN
AccessionPrimary (citable) accession number: O75306
Secondary accession number(s): D3DVG7 expand/collapse secondary AC list , J3KPM7, Q5VTW0, Q969P3, Q9UEV3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: April 16, 2002
Last modified: July 9, 2014
This is version 148 of the entry and version 2 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 1

Human chromosome 1: entries, gene names and cross-references to MIM