ID   NDUS2_HUMAN             Reviewed;         463 AA.
AC   O75306; Q5VTW0; Q969P3; Q9UEV3;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2002, sequence version 2.
DT   07-JUL-2009, entry version 92.
DE   RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial;
DE            EC=1.6.5.3;
DE            EC=1.6.99.3;
DE   AltName: Full=NADH-ubiquinone oxidoreductase 49 kDa subunit;
DE   AltName: Full=Complex I-49kD;
DE            Short=CI-49kD;
DE   Flags: Precursor;
GN   Name=NDUFS2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=98321200; PubMed=9647766; DOI=10.1006/bbrc.1998.8882;
RA   Loeffen J., van den Heuvel L., Smeets R., Triepels R., Sengers R.,
RA   Trijbels F., Smeitink J.;
RT   "cDNA sequence and chromosomal localization of the remaining three
RT   human nuclear encoded iron sulphur protein (IP) subunits of complex I:
RT   the human IP fraction is completed.";
RL   Biochem. Biophys. Res. Commun. 247:751-758(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=98252804; PubMed=9585441; DOI=10.1007/s003359900803;
RA   Procaccio V., de Sury R., Martinez P., Depetris D., Rabilloud T.,
RA   Soularue P., Lunardi J., Issartel J.-P.;
RT   "Mapping to 1q23 of the human gene (NDUFS2) encoding the 49-kDa
RT   subunit of the mitochondrial respiratory complex I and immunodetection
RT   of the mature protein in mitochondria.";
RL   Mamm. Genome 9:482-484(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Muscle, and Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RA   Colinge J., Superti-Furga G., Bennett K.L.;
RL   Submitted (OCT-2008) to UniProtKB.
RN   [7]
RP   VARIANTS COMPLEX I DEFICIENCY GLN-228; GLN-229 AND PRO-413.
RX   PubMed=11220739;
RX   DOI=10.1002/1531-8249(20010201)49:2<195::AID-ANA39>3.0.CO;2-M;
RA   Loeffen J., Elpeleg O., Smeitink J., Smeets R.,
RA   Stoeckler-Ipsiroglu S., Mandel H., Sengers R., Trijbels F.,
RA   van den Heuvel L.;
RT   "Mutations in the complex I NDUFS2 gene of patients with
RT   cardiomyopathy and encephalomyopathy.";
RL   Ann. Neurol. 49:195-201(2001).
CC   -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory
CC       chain NADH dehydrogenase (Complex I) that is believed to belong to
CC       the minimal assembly required for catalysis. Complex I functions
CC       in the transfer of electrons from NADH to the respiratory chain.
CC       The immediate electron acceptor for the enzyme is believed to be
CC       ubiquinone (By similarity).
CC   -!- CATALYTIC ACTIVITY: NADH + ubiquinone = NAD(+) + ubiquinol.
CC   -!- CATALYTIC ACTIVITY: NADH + acceptor = NAD(+) + reduced acceptor.
CC   -!- COFACTOR: Binds 1 4Fe-4S cluster.
CC   -!- SUBUNIT: Complex I is composed of 45 different subunits. Component
CC       of the iron-sulfur (IP) fragment of the enzyme.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral
CC       membrane protein; Matrix side.
CC   -!- DISEASE: Defects in NDUFS2 are a cause of complex I mitochondrial
CC       respiratory chain deficiency [MIM:252010]. Complex I (NADH-
CC       ubiquinone oxidoreductase), the largest complex of the
CC       mitochondrial respiratory chain, contains more than 40 subunits.
CC       It is embedded in the inner mitochondrial membrane and is partly
CC       protruding in the matrix. Complex I deficiency is the most common
CC       cause of mitochondrial disorders. It represents largely one-third
CC       of all cases of respiratory chain deficiency and is responsible
CC       for a variety of clinical symptoms, ranging from neurological
CC       disorders to cardiomyopathy, liver failure, and myopathy.
CC   -!- SIMILARITY: Belongs to the complex I 49 kDa subunit family.
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DR   EMBL; AF050640; AAC27453.1; -; mRNA.
DR   EMBL; AF013160; AAC34362.1; -; mRNA.
DR   EMBL; AL590714; CAH72148.1; -; Genomic_DNA.
DR   EMBL; CH471121; EAW52625.1; -; Genomic_DNA.
DR   EMBL; BC000170; AAH00170.1; -; mRNA.
DR   EMBL; BC001456; AAH01456.1; -; mRNA.
DR   EMBL; BC008868; AAH08868.1; -; mRNA.
DR   IPI; IPI00025239; -.
DR   PIR; JE0193; JE0193.
DR   RefSeq; NP_004541.1; -.
DR   UniGene; Hs.173611; -.
DR   PhosphoSite; O75306; -.
DR   PeptideAtlas; O75306; -.
DR   PRIDE; O75306; -.
DR   Ensembl; ENSG00000158864; Homo sapiens.
DR   GeneID; 4720; -.
DR   KEGG; hsa:4720; -.
DR   UCSC; uc001fyv.1; human.
DR   GeneCards; GC01P159435; -.
DR   HGNC; HGNC:7708; NDUFS2.
DR   MIM; 252010; phenotype.
DR   MIM; 602985; gene.
DR   Orphanet; 99739; Cardiomyopathy, familial, hypertrophic.
DR   Orphanet; 2609; NADH-CoQ reductase deficiency.
DR   PharmGKB; PA31519; -.
DR   HOVERGEN; O75306; -.
DR   OMA; O75306; MYEAVSG.
DR   BRENDA; 1.6.5.3; 247.
DR   BRENDA; 1.6.99.3; 247.
DR   Reactome; REACT_1505; Integration of energy metabolism.
DR   Reactome; REACT_15380; Diabetes pathways.
DR   DrugBank; DB00157; NADH.
DR   NextBio; 18206; -.
DR   ArrayExpress; O75306; -.
DR   Bgee; O75306; -.
DR   CleanEx; HS_NDUFS2; -.
DR   GermOnline; ENSG00000158864; Homo sapiens.
DR   GO; GO:0005747; C:mitochondrial respiratory chain complex I; IDA:UniProtKB.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0009055; F:electron carrier activity; NAS:UniProtKB.
DR   GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0051287; F:NAD or NADH binding; IEA:InterPro.
DR   GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB.
DR   GO; GO:0048038; F:quinone binding; IEA:InterPro.
DR   GO; GO:0006120; P:mitochondrial electron transport, NADH to u...; NAS:UniProtKB.
DR   GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR   GO; GO:0006810; P:transport; IEA:UniProtKB-KW.
DR   InterPro; IPR010219; NADH_DH_1_dsu.
DR   InterPro; IPR001135; NADH_Q_OxRdtase_suD.
DR   InterPro; IPR014029; NADH_UbQ_OxRdtase_su-49kDa_CS.
DR   Pfam; PF00346; Complex1_49kDa; 1.
DR   TIGRFAMs; TIGR01962; NuoD; 1.
DR   PROSITE; PS00535; COMPLEX1_49K; 1.
PE   1: Evidence at protein level;
KW   4Fe-4S; Complete proteome; Disease mutation; Electron transport; Iron;
KW   Iron-sulfur; Membrane; Metal-binding; Mitochondrion;
KW   Mitochondrion inner membrane; NAD; Oxidoreductase; Polymorphism;
KW   Respiratory chain; Transit peptide; Transport; Ubiquinone.
FT   TRANSIT       1     33       Mitochondrion (By similarity).
FT   CHAIN        34    463       NADH dehydrogenase [ubiquinone] iron-
FT                                sulfur protein 2, mitochondrial.
FT                                /FTId=PRO_0000019981.
FT   METAL       326    326       Iron-sulfur (4Fe-4S) (Potential).
FT   METAL       332    332       Iron-sulfur (4Fe-4S) (Potential).
FT   METAL       347    347       Iron-sulfur (4Fe-4S) (Potential).
FT   VARIANT      20     20       P -> T (in dbSNP:rs11538340).
FT                                /FTId=VAR_034150.
FT   VARIANT     228    228       R -> Q (in complex I deficiency).
FT                                /FTId=VAR_019535.
FT   VARIANT     229    229       P -> A (in dbSNP:rs16827493).
FT                                /FTId=VAR_034151.
FT   VARIANT     229    229       P -> Q (in complex I deficiency).
FT                                /FTId=VAR_019536.
FT   VARIANT     352    352       P -> A (in dbSNP:rs11576415).
FT                                /FTId=VAR_034152.
FT   VARIANT     413    413       S -> P (in complex I deficiency).
FT                                /FTId=VAR_019537.
FT   CONFLICT     24     24       V -> G (in Ref. 2; AAC34362).
SQ   SEQUENCE   463 AA;  52546 MW;  A2BF56F008B6312C CRC64;
     MAALRALCGF RGVAAQVLRP GAGVRLPIQP SRGVRQWQPD VEWAQQFGGA VMYPSKETAH
     WKPPPWNDVD PPKDTIVKNI TLNFGPQHPA AHGVLRLVME LSGEMVRKCD PHIGLLHRGT
     EKLIEYKTYL QALPYFDRLD YVSMMCNEQA YSLAVEKLLN IRPPPRAQWI RVLFGEITRL
     LNHIMAVTTH ALDLGAMTPF FWLFEEREKM FEFYERVSGA RMHAAYIRPG GVHQDLPLGL
     MDDIYQFSKN FSLRLDELEE LLTNNRIWRN RTIDIGVVTA EEALNYGFSG VMLRGSGIQW
     DLRKTQPYDV YDQVEFDVPV GSRGDCYDRY LCRVEEMRQS LRIIAQCLNK MPPGEIKVDD
     AKVSPPKRAE MKTSMESLIH HFKLYTEGYQ VPPGATYTAI EAPKGEFGVY LVSDGSSRPY
     RCKIKAPGFA HLAGLDKMSK GHMLADVVAI IGTQDIVFGE VDR
//