NDUA2_HUMAN
ID NDUA2_HUMAN Reviewed; 99 AA.
AC O43678; D6RJD6; Q6IAY8;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2;
DE AltName: Full=Complex I-B8;
DE Short=CI-B8;
DE AltName: Full=NADH-ubiquinone oxidoreductase B8 subunit;
GN Name=NDUFA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=9425316; DOI=10.1006/bbrc.1997.7707;
RA Ton C., Hwang D.M., Dempsey A.A., Liew C.-C.;
RT "Identification and primary structure of five human NADH-ubiquinone
RT oxidoreductase subunits.";
RL Biochem. Biophys. Res. Commun. 241:589-594(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Thymus;
RA Iida A., Kondo K., Kitamoto T., Kitamura Y., Mishima C., Osawa K.,
RA Nakamura Y.;
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Adrenal gland;
RA Peng Y., Song H., Huang Q., Huang C., Gu Y., Yang Y., Gao G., Xiao H.,
RA Xu X., Li N., Qian B., Liu F., Qu J., Gao X., Cheng Z., Xu Z., Zeng L.,
RA Xu S., Gu W., Tu Y., Jia J., Fu G., Ren S., Zhong M., Lu G., Hu R.,
RA Chen J., Chen Z., Han Z.;
RT "ADBCGF02_ADB Homo sapiens cDNA clone ADBCGF02 5',mRNA sequence.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12611891; DOI=10.1074/jbc.c300064200;
RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F.,
RA Ghosh S.S., Capaldi R.A.;
RT "The subunit composition of the human NADH dehydrogenase obtained by rapid
RT one-step immunopurification.";
RL J. Biol. Chem. 278:13619-13622(2003).
RN [9]
RP INVOLVEMENT IN MC1DN13.
RX PubMed=18513682; DOI=10.1016/j.ajhg.2008.05.007;
RA Hoefs S.J., Dieteren C.E., Distelmaier F., Janssen R.J., Epplen A.,
RA Swarts H.G., Forkink M., Rodenburg R.J., Nijtmans L.G., Willems P.H.,
RA Smeitink J.A., van den Heuvel L.P.;
RT "NDUFA2 complex I mutation leads to Leigh disease.";
RL Am. J. Hum. Genet. 82:1306-1315(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX.
RX PubMed=27626371; DOI=10.1038/nature19754;
RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E.,
RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R.,
RA Salim A., Ryan M.T.;
RT "Accessory subunits are integral for assembly and function of human
RT mitochondrial complex I.";
RL Nature 538:123-126(2016).
RN [14]
RP STRUCTURE BY NMR, AND DISULFIDE BOND.
RX PubMed=15341729; DOI=10.1016/j.str.2004.06.021;
RA Brockmann C., Diehl A., Rehbein K., Strauss H., Schmieder P., Korn B.,
RA Kuhne R., Oschkinat H.;
RT "The oxidized subunit B8 from human complex I adopts a thioredoxin fold.";
RL Structure 12:1645-1654(2004).
RN [15]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-50.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory
CC chain NADH dehydrogenase (Complex I), that is believed not to be
CC involved in catalysis. Complex I functions in the transfer of electrons
CC from NADH to the respiratory chain. The immediate electron acceptor for
CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}.
CC -!- SUBUNIT: Complex I is composed of 45 different subunits.
CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:12611891}; Peripheral membrane protein
CC {ECO:0000305}; Matrix side {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43678-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43678-2; Sequence=VSP_045479;
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 13 (MC1DN13)
CC [MIM:618235]: A form of mitochondrial complex I deficiency, the most
CC common biochemical signature of mitochondrial disorders, a group of
CC highly heterogeneous conditions characterized by defective oxidative
CC phosphorylation, which collectively affects 1 in 5-10000 live births.
CC Clinical disorders have variable severity, ranging from lethal neonatal
CC disease to adult-onset neurodegenerative disorders. Phenotypes include
CC macrocephaly with progressive leukodystrophy, non-specific
CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh
CC syndrome, Leber hereditary optic neuropathy, and some forms of
CC Parkinson disease. MC1DN13 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:18513682}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the complex I NDUFA2 subunit family.
CC {ECO:0000305}.
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DR EMBL; AF047185; AAC04270.1; -; mRNA.
DR EMBL; AB054976; BAB21453.1; -; Genomic_DNA.
DR EMBL; AF077029; AAD27762.1; -; mRNA.
DR EMBL; AV705564; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CR457016; CAG33297.1; -; mRNA.
DR EMBL; AC116353; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003674; AAH03674.1; -; mRNA.
DR CCDS; CCDS4234.1; -. [O43678-1]
DR CCDS; CCDS54911.1; -. [O43678-2]
DR PIR; JC5824; JC5824.
DR RefSeq; NP_001171941.1; NM_001185012.1. [O43678-2]
DR RefSeq; NP_002479.1; NM_002488.4. [O43678-1]
DR PDB; 1S3A; NMR; -; A=1-99.
DR PDB; 5XTB; EM; 3.40 A; F=14-96.
DR PDB; 5XTD; EM; 3.70 A; F=14-96.
DR PDB; 5XTH; EM; 3.90 A; F=14-96.
DR PDB; 5XTI; EM; 17.40 A; BF/F=14-96.
DR PDBsum; 1S3A; -.
DR PDBsum; 5XTB; -.
DR PDBsum; 5XTD; -.
DR PDBsum; 5XTH; -.
DR PDBsum; 5XTI; -.
DR AlphaFoldDB; O43678; -.
DR SMR; O43678; -.
DR BioGRID; 110775; 215.
DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I.
DR CORUM; O43678; -.
DR IntAct; O43678; 58.
DR MINT; O43678; -.
DR STRING; 9606.ENSP00000252102; -.
DR BindingDB; O43678; -.
DR ChEMBL; CHEMBL2363065; -.
DR DrugBank; DB00157; NADH.
DR DrugCentral; O43678; -.
DR iPTMnet; O43678; -.
DR PhosphoSitePlus; O43678; -.
DR SwissPalm; O43678; -.
DR BioMuta; NDUFA2; -.
DR EPD; O43678; -.
DR jPOST; O43678; -.
DR MassIVE; O43678; -.
DR MaxQB; O43678; -.
DR PaxDb; O43678; -.
DR PeptideAtlas; O43678; -.
DR PRIDE; O43678; -.
DR ProteomicsDB; 15115; -.
DR ProteomicsDB; 49106; -. [O43678-1]
DR TopDownProteomics; O43678-1; -. [O43678-1]
DR Antibodypedia; 15357; 134 antibodies from 25 providers.
DR DNASU; 4695; -.
DR Ensembl; ENST00000252102.9; ENSP00000252102.5; ENSG00000131495.9. [O43678-1]
DR Ensembl; ENST00000512088.1; ENSP00000427220.1; ENSG00000131495.9. [O43678-2]
DR GeneID; 4695; -.
DR KEGG; hsa:4695; -.
DR MANE-Select; ENST00000252102.9; ENSP00000252102.5; NM_002488.5; NP_002479.1.
DR UCSC; uc003lgp.4; human. [O43678-1]
DR CTD; 4695; -.
DR DisGeNET; 4695; -.
DR GeneCards; NDUFA2; -.
DR HGNC; HGNC:7685; NDUFA2.
DR HPA; ENSG00000131495; Low tissue specificity.
DR MalaCards; NDUFA2; -.
DR MIM; 602137; gene.
DR MIM; 618235; phenotype.
DR neXtProt; NX_O43678; -.
DR OpenTargets; ENSG00000131495; -.
DR Orphanet; 85136; Cystic leukoencephalopathy without megalencephaly.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA31491; -.
DR VEuPathDB; HostDB:ENSG00000131495; -.
DR eggNOG; KOG3446; Eukaryota.
DR GeneTree; ENSGT00390000006178; -.
DR HOGENOM; CLU_110897_0_0_1; -.
DR InParanoid; O43678; -.
DR OMA; FIEQQYV; -.
DR OrthoDB; 1633416at2759; -.
DR PhylomeDB; O43678; -.
DR TreeFam; TF300229; -.
DR BioCyc; MetaCyc:HS05539-MON; -.
DR PathwayCommons; O43678; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; O43678; -.
DR SIGNOR; O43678; -.
DR BioGRID-ORCS; 4695; 264 hits in 1076 CRISPR screens.
DR ChiTaRS; NDUFA2; human.
DR EvolutionaryTrace; O43678; -.
DR GeneWiki; NDUFA2; -.
DR GenomeRNAi; 4695; -.
DR Pharos; O43678; Tclin.
DR PRO; PR:O43678; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O43678; protein.
DR Bgee; ENSG00000131495; Expressed in biceps brachii and 211 other tissues.
DR Genevisible; O43678; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IDA:UniProtKB.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB.
DR GO; GO:0009060; P:aerobic respiration; IC:ComplexPortal.
DR GO; GO:0001835; P:blastocyst hatching; IEA:Ensembl.
DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB.
DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; IC:ComplexPortal.
DR InterPro; IPR016464; NADH_Ub_cplx-1_asu_su-2.
DR InterPro; IPR007741; Ribosome/NADH_DH.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR12878; PTHR12878; 1.
DR Pfam; PF05047; L51_S25_CI-B8; 1.
DR PIRSF; PIRSF005822; NDUA2; 1.
DR SMART; SM00916; L51_S25_CI-B8; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Disulfide bond;
KW Electron transport; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Primary mitochondrial disease; Reference proteome; Respiratory chain;
KW Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..99
FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex
FT subunit 2"
FT /id="PRO_0000118789"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 64
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CQ75"
FT MOD_RES 64
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CQ75"
FT DISULFID 24..58
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:15341729"
FT VAR_SEQ 71..99
FT /note="FGQETNVPLNNFSADQVTRALENVLSGKA -> SRVQNS (in isoform
FT 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_045479"
FT VARIANT 50
FT /note="D -> N (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036174"
FT STRAND 19..22
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:1S3A"
FT HELIX 28..38
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 41..47
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:1S3A"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 84..93
FT /evidence="ECO:0007829|PDB:5XTB"
SQ SEQUENCE 99 AA; 10922 MW; EF026F193CAF1DF7 CRC64;
MAAAAASRGV GAKLGLREIR IHLCQRSPGS QGVRDFIEKR YVELKKANPD LPILIRECSD
VQPKLWARYA FGQETNVPLN NFSADQVTRA LENVLSGKA
