NDUAA_HUMAN
ID NDUAA_HUMAN Reviewed; 355 AA.
AC O95299; Q8WXC9;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial;
DE AltName: Full=Complex I-42kD;
DE Short=CI-42kD;
DE AltName: Full=NADH-ubiquinone oxidoreductase 42 kDa subunit;
DE Flags: Precursor;
GN Name=NDUFA10;
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).
RX PubMed=9878551; DOI=10.1006/bbrc.1998.9786;
RA Loeffen J.L.C.M., Triepels R.H., van den Heuvel L.P., Schuelke M.,
RA Buskens C.A.F., Smeets R.J.P., Trijbels J.M.F., Smeitink J.A.M.;
RT "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase:
RT human complex I cDNA characterization completed.";
RL Biochem. Biophys. Res. Commun. 253:415-422(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Hu W., Tang L.-J., Shi Y.-W., Tian J.-Y., Jian Y.-S.;
RT "Homo sapiens, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
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 [6]
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 [7]
RP INVOLVEMENT IN MC1DN22, AND VARIANT MC1DN22 ARG-142.
RX PubMed=21150889; DOI=10.1038/ejhg.2010.204;
RA Hoefs S.J., van Spronsen F.J., Lenssen E.W., Nijtmans L.G., Rodenburg R.J.,
RA Smeitink J.A., van den Heuvel L.P.;
RT "NDUFA10 mutations cause complex I deficiency in a patient with Leigh
RT disease.";
RL Eur. J. Hum. Genet. 19:270-274(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
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 [10]
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 [11]
RP INVOLVEMENT IN MC1DN22, AND VARIANT MC1DN22 PRO-294.
RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679;
RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y.,
RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H.,
RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y.,
RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K.,
RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M.,
RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K.,
RA Ohtake A., Okazaki Y.;
RT "A comprehensive genomic analysis reveals the genetic landscape of
RT mitochondrial respiratory chain complex deficiencies.";
RL PLoS Genet. 12:E1005679-E1005679(2016).
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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Note=Binds 1 FAD per subunit.;
CC -!- SUBUNIT: Complex I is composed of 45 different subunits. This a
CC component of the hydrophobic protein fraction.
CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000305|PubMed:12611891}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95299-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95299-2; Sequence=VSP_056417, VSP_056418, VSP_056419;
CC -!- PTM: Phosphorylation at Ser-250 by PINK1 is required for the binding
CC and/or reduction of the complex I substrate ubiquinone.
CC {ECO:0000250|UniProtKB:Q99LC3}.
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 22 (MC1DN22)
CC [MIM:618243]: 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. MC1DN22 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:21150889,
CC ECO:0000269|PubMed:26741492}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complex I NDUFA10 subunit family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF087661; AAD09755.1; -; mRNA.
DR EMBL; AF453834; AAL50984.1; -; mRNA.
DR EMBL; AC013469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC114750; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC233275; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003417; AAH03417.1; -; mRNA.
DR CCDS; CCDS2531.1; -. [O95299-1]
DR PIR; JE0385; JE0385.
DR RefSeq; NP_004535.1; NM_004544.3. [O95299-1]
DR PDB; 5XTC; EM; 3.70 A; w=36-355.
DR PDB; 5XTD; EM; 3.70 A; w=36-355.
DR PDB; 5XTH; EM; 3.90 A; w=36-355.
DR PDB; 5XTI; EM; 17.40 A; Bw/w=36-355.
DR PDBsum; 5XTC; -.
DR PDBsum; 5XTD; -.
DR PDBsum; 5XTH; -.
DR PDBsum; 5XTI; -.
DR AlphaFoldDB; O95299; -.
DR SMR; O95299; -.
DR BioGRID; 110785; 135.
DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I.
DR CORUM; O95299; -.
DR IntAct; O95299; 52.
DR MINT; O95299; -.
DR STRING; 9606.ENSP00000252711; -.
DR BindingDB; O95299; -.
DR ChEMBL; CHEMBL2363065; -.
DR DrugBank; DB00157; NADH.
DR DrugCentral; O95299; -.
DR iPTMnet; O95299; -.
DR PhosphoSitePlus; O95299; -.
DR SwissPalm; O95299; -.
DR BioMuta; NDUFA10; -.
DR EPD; O95299; -.
DR jPOST; O95299; -.
DR MassIVE; O95299; -.
DR MaxQB; O95299; -.
DR PaxDb; O95299; -.
DR PeptideAtlas; O95299; -.
DR PRIDE; O95299; -.
DR ProteomicsDB; 50799; -. [O95299-1]
DR ProteomicsDB; 75009; -.
DR Antibodypedia; 34509; 196 antibodies from 29 providers.
DR DNASU; 4705; -.
DR Ensembl; ENST00000252711.7; ENSP00000252711.2; ENSG00000130414.13. [O95299-1]
DR Ensembl; ENST00000307300.8; ENSP00000302321.4; ENSG00000130414.13. [O95299-2]
DR Ensembl; ENST00000676929.1; ENSP00000503956.1; ENSG00000130414.13. [O95299-1]
DR Ensembl; ENST00000678158.1; ENSP00000504765.1; ENSG00000130414.13. [O95299-1]
DR GeneID; 4705; -.
DR KEGG; hsa:4705; -.
DR MANE-Select; ENST00000252711.7; ENSP00000252711.2; NM_004544.4; NP_004535.1.
DR UCSC; uc002vyn.3; human. [O95299-1]
DR CTD; 4705; -.
DR DisGeNET; 4705; -.
DR GeneCards; NDUFA10; -.
DR GeneReviews; NDUFA10; -.
DR HGNC; HGNC:7684; NDUFA10.
DR HPA; ENSG00000130414; Tissue enhanced (tongue).
DR MalaCards; NDUFA10; -.
DR MIM; 603835; gene.
DR MIM; 618243; phenotype.
DR neXtProt; NX_O95299; -.
DR OpenTargets; ENSG00000130414; -.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA31490; -.
DR VEuPathDB; HostDB:ENSG00000130414; -.
DR eggNOG; KOG3877; Eukaryota.
DR GeneTree; ENSGT00390000016151; -.
DR HOGENOM; CLU_050591_0_0_1; -.
DR InParanoid; O95299; -.
DR OMA; MFRQGYI; -.
DR PhylomeDB; O95299; -.
DR TreeFam; TF314616; -.
DR BioCyc; MetaCyc:HS05385-MON; -.
DR PathwayCommons; O95299; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; O95299; -.
DR SIGNOR; O95299; -.
DR BioGRID-ORCS; 4705; 171 hits in 1085 CRISPR screens.
DR ChiTaRS; NDUFA10; human.
DR GeneWiki; NDUFA10; -.
DR GenomeRNAi; 4705; -.
DR Pharos; O95299; Tclin.
DR PRO; PR:O95299; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O95299; protein.
DR Bgee; ENSG00000130414; Expressed in apex of heart and 202 other tissues.
DR ExpressionAtlas; O95299; baseline and differential.
DR Genevisible; O95299; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB.
DR GO; GO:0009060; P:aerobic respiration; IC:ComplexPortal.
DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IBA:GO_Central.
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 CDD; cd02030; NDUO42; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR031314; DNK_dom.
DR InterPro; IPR015828; NDUFA10.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF01712; dNK; 1.
DR PIRSF; PIRSF000543; NADH_UQ_42KD; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disease variant; Electron transport;
KW FAD; Flavoprotein; Mitochondrion; Phosphoprotein;
KW Primary mitochondrial disease; Reference proteome; Respiratory chain;
KW Transit peptide; Transport.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P34942"
FT CHAIN 36..355
FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex
FT subunit 10, mitochondrial"
FT /id="PRO_0000019988"
FT MOD_RES 250
FT /note="Phosphoserine; by PINK1"
FT /evidence="ECO:0000250|UniProtKB:Q99LC3"
FT MOD_RES 285
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LC3"
FT VAR_SEQ 183
FT /note="C -> CESALQTHFWTGVAGASGKLESGSSEEVLLINERGGRSKPG (in
FT isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_056417"
FT VAR_SEQ 214..223
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_056418"
FT VAR_SEQ 334..355
FT /note="LPGRKYSPGYNTEVGDKWIWLK -> RLDWTVCFGEESTEVKHQGHLLSVQP
FT GTVALTVGSWLRSCLLGLHWKLLFLFPESPMHTTAFMFLC (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_056419"
FT VARIANT 2
FT /note="A -> G (in dbSNP:rs11541494)"
FT /id="VAR_034149"
FT VARIANT 142
FT /note="Q -> R (in MC1DN22; dbSNP:rs387906873)"
FT /evidence="ECO:0000269|PubMed:21150889"
FT /id="VAR_078937"
FT VARIANT 294
FT /note="L -> P (in MC1DN22; unknown pathological
FT significance; dbSNP:rs1057519414)"
FT /evidence="ECO:0000269|PubMed:26741492"
FT /id="VAR_081458"
SQ SEQUENCE 355 AA; 40751 MW; B5C27BC150A3E691 CRC64;
MALRLLKLAA TSASARVVAA GAQRVRGIHS SVQCKLRYGM WHFLLGDKAS KRLTERSRVI
TVDGNICTGK GKLAKEIAEK LGFKHFPEAG IHYPDSTTGD GKPLATDYNG NCSLEKFYDD
PRSNDGNSYR LQSWLYSSRL LQYSDALEHL LTTGQGVVLE RSIFSDFVFL EAMYNQGFIR
KQCVDHYNEV KSVTICDYLP PHLVIYIDVP VPEVQRRIQK KGDPHEMKIT SAYLQDIENA
YKKTFLPEMS EKCEVLQYSA REAQDSKKVV EDIEYLKFDK GPWLKQDNRT LYHLRLLVQD
KFEVLNYTSI PIFLPEVTIG AHQTDRVLHQ FRELPGRKYS PGYNTEVGDK WIWLK
