NDUA1_HUMAN
ID NDUA1_HUMAN Reviewed; 70 AA.
AC O15239;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1;
DE AltName: Full=Complex I-MWFE;
DE Short=CI-MWFE;
DE AltName: Full=NADH-ubiquinone oxidoreductase MWFE subunit;
GN Name=NDUFA1;
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].
RX PubMed=8938439; DOI=10.1006/geno.1996.0561;
RA Zhuchenko O., Wehnert M., Bailey J., Sun Z.S., Lee C.C.;
RT "Isolation, mapping, and genomic structure of an X-linked gene for a
RT subunit of human mitochondrial complex I.";
RL Genomics 37:281-288(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=9224902; DOI=10.1016/s0378-1119(97)00108-x;
RA Frattini A., Faranda S., Bagnasco L., Patrosso C., Nulli P., Zucchi I.,
RA Vezzoni P.;
RT "Identification of a new member (ZNF183) of the Ring finger gene family in
RT Xq24-25.";
RL Gene 192:291-298(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhuchenko O.P., Wehnert M., Bailey J., Sun Z.S., Lee C.C.;
RT "hMWFE gene -- component of human mitochondrial complex I.";
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 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 [7]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-53.
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).
RN [8]
RP VARIANTS MC1DN12 ARG-8 AND SER-37.
RX PubMed=17262856; DOI=10.1002/ana.21036;
RA Fernandez-Moreira D., Ugalde C., Smeets R., Rodenburg R.J.T.,
RA Lopez-Laso E., Ruiz-Falco M.L., Briones P., Martin M.A., Smeitink J.A.M.,
RA Arenas J.;
RT "X-linked NDUFA1 gene mutations associated with mitochondrial
RT encephalomyopathy.";
RL Ann. Neurol. 61:73-83(2007).
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}; Single-pass membrane protein
CC {ECO:0000255}; Matrix side {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Primarily expressed in heart and skeletal muscle.
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 12 (MC1DN12)
CC [MIM:301020]: 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. {ECO:0000269|PubMed:17262856}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complex I NDUFA1 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; X81900; CAA57489.1; -; mRNA.
DR EMBL; U54993; AAD00084.1; -; mRNA.
DR EMBL; BC000266; AAH00266.1; -; mRNA.
DR CCDS; CCDS14590.1; -.
DR RefSeq; NP_004532.1; NM_004541.3.
DR PDB; 5XTC; EM; 3.70 A; S=1-70.
DR PDB; 5XTD; EM; 3.70 A; S=1-70.
DR PDB; 5XTH; EM; 3.90 A; S=1-70.
DR PDB; 5XTI; EM; 17.40 A; BS/S=1-70.
DR PDBsum; 5XTC; -.
DR PDBsum; 5XTD; -.
DR PDBsum; 5XTH; -.
DR PDBsum; 5XTI; -.
DR AlphaFoldDB; O15239; -.
DR SMR; O15239; -.
DR BioGRID; 110774; 43.
DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I.
DR CORUM; O15239; -.
DR IntAct; O15239; 7.
DR MINT; O15239; -.
DR STRING; 9606.ENSP00000360492; -.
DR BindingDB; O15239; -.
DR ChEMBL; CHEMBL2363065; -.
DR DrugBank; DB00157; NADH.
DR DrugCentral; O15239; -.
DR GlyGen; O15239; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O15239; -.
DR PhosphoSitePlus; O15239; -.
DR BioMuta; NDUFA1; -.
DR EPD; O15239; -.
DR jPOST; O15239; -.
DR MassIVE; O15239; -.
DR PaxDb; O15239; -.
DR PeptideAtlas; O15239; -.
DR PRIDE; O15239; -.
DR ProteomicsDB; 48530; -.
DR TopDownProteomics; O15239; -.
DR Antibodypedia; 29846; 231 antibodies from 27 providers.
DR DNASU; 4694; -.
DR Ensembl; ENST00000371437.5; ENSP00000360492.4; ENSG00000125356.7.
DR GeneID; 4694; -.
DR KEGG; hsa:4694; -.
DR MANE-Select; ENST00000371437.5; ENSP00000360492.4; NM_004541.4; NP_004532.1.
DR CTD; 4694; -.
DR DisGeNET; 4694; -.
DR GeneCards; NDUFA1; -.
DR GeneReviews; NDUFA1; -.
DR HGNC; HGNC:7683; NDUFA1.
DR HPA; ENSG00000125356; Low tissue specificity.
DR MalaCards; NDUFA1; -.
DR MIM; 300078; gene.
DR MIM; 301020; phenotype.
DR neXtProt; NX_O15239; -.
DR OpenTargets; ENSG00000125356; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR PharmGKB; PA31489; -.
DR VEuPathDB; HostDB:ENSG00000125356; -.
DR eggNOG; ENOG502S3S5; Eukaryota.
DR GeneTree; ENSGT00390000007560; -.
DR HOGENOM; CLU_185502_2_0_1; -.
DR InParanoid; O15239; -.
DR OMA; AYIHKFT; -.
DR OrthoDB; 1608843at2759; -.
DR PhylomeDB; O15239; -.
DR TreeFam; TF333394; -.
DR BioCyc; MetaCyc:HS04875-MON; -.
DR PathwayCommons; O15239; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; O15239; -.
DR SIGNOR; O15239; -.
DR BioGRID-ORCS; 4694; 108 hits in 707 CRISPR screens.
DR ChiTaRS; NDUFA1; human.
DR GeneWiki; NADH_dehydrogenase_(ubiquinone),_alpha_1; -.
DR GenomeRNAi; 4694; -.
DR Pharos; O15239; Tclin.
DR PRO; PR:O15239; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O15239; protein.
DR Bgee; ENSG00000125356; Expressed in left ventricle myocardium and 204 other tissues.
DR ExpressionAtlas; O15239; baseline and differential.
DR Genevisible; O15239; 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:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; TAS:ProtInc.
DR GO; GO:0009060; P:aerobic respiration; IC:ComplexPortal.
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; IPR017384; NADH_Ub_cplx-1_asu_su-1.
DR PANTHER; PTHR17098; PTHR17098; 1.
DR Pfam; PF15879; MWFE; 1.
DR PIRSF; PIRSF038095; NDUA1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Electron transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Respiratory chain; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..70
FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex
FT subunit 1"
FT /id="PRO_0000118817"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 8
FT /note="G -> R (in MC1DN12; dbSNP:rs104894884)"
FT /evidence="ECO:0000269|PubMed:17262856"
FT /id="VAR_035099"
FT VARIANT 32
FT /note="G -> R (in dbSNP:rs1801316)"
FT /id="VAR_014485"
FT VARIANT 37
FT /note="R -> S (in MC1DN12; dbSNP:rs104894885)"
FT /evidence="ECO:0000269|PubMed:17262856"
FT /id="VAR_035100"
FT VARIANT 53
FT /note="R -> C (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1257734702)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036173"
SQ SEQUENCE 70 AA; 8072 MW; E4004A62117BF253 CRC64;
MWFEILPGLS VMGVCLLIPG LATAYIHRFT NGGKEKRVAH FGYHWSLMER DRRISGVDRY
YVSKGLENID
