NDUS6_HUMAN
ID NDUS6_HUMAN Reviewed; 124 AA.
AC O75380;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial;
DE AltName: Full=Complex I-13kD-A;
DE Short=CI-13kD-A;
DE AltName: Full=NADH-ubiquinone oxidoreductase 13 kDa-A subunit;
DE Flags: Precursor;
GN Name=NDUFS6;
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=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 human
RT nuclear encoded iron sulphur protein (IP) subunits of complex I: the human
RT IP fraction is completed.";
RL Biochem. Biophys. Res. Commun. 247:751-758(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Skin;
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 [3]
RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
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 [4]
RP INVOLVEMENT IN MC1DN9.
RX PubMed=15372108; DOI=10.1172/jci200420683;
RA Kirby D.M., Salemi R., Sugiana C., Ohtake A., Parry L., Bell K.M.,
RA Kirk E.P., Boneh A., Taylor R.W., Dahl H.H., Ryan M.T., Thorburn D.R.;
RT "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial
RT complex I deficiency.";
RL J. Clin. Invest. 114:837-845(2004).
RN [5]
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 [6]
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 [7]
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 [8]
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 [9]
RP VARIANT MC1DN9 TYR-115.
RX PubMed=19259137; DOI=10.1038/ejhg.2009.24;
RA Spiegel R., Shaag A., Mandel H., Reich D., Penyakov M., Hujeirat Y.,
RA Saada A., Elpeleg O., Shalev S.A.;
RT "Mutated NDUFS6 is the cause of fatal neonatal lactic acidemia in Caucasus
RT Jews.";
RL Eur. J. Hum. Genet. 17:1200-1203(2009).
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: Mammalian complex I is composed of 45 different subunits
CC (PubMed:12611891, PubMed:27626371). This is a component of the iron-
CC sulfur (IP) fragment of the enzyme (PubMed:12611891).
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 -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 9 (MC1DN9)
CC [MIM:618232]: 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. MC1DN9 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:15372108,
CC ECO:0000269|PubMed:19259137}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complex I NDUFS6 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; AF044959; AAC27799.1; -; mRNA.
DR EMBL; BC038664; AAH38664.1; -; mRNA.
DR EMBL; BC046155; AAH46155.1; -; mRNA.
DR CCDS; CCDS3866.1; -.
DR PIR; JE0194; JE0194.
DR RefSeq; NP_004544.1; NM_004553.4.
DR PDB; 5XTB; EM; 3.40 A; T=29-123.
DR PDB; 5XTD; EM; 3.70 A; T=29-123.
DR PDB; 5XTH; EM; 3.90 A; T=29-123.
DR PDB; 5XTI; EM; 17.40 A; BT/T=29-123.
DR PDBsum; 5XTB; -.
DR PDBsum; 5XTD; -.
DR PDBsum; 5XTH; -.
DR PDBsum; 5XTI; -.
DR AlphaFoldDB; O75380; -.
DR SMR; O75380; -.
DR BioGRID; 110805; 238.
DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I.
DR CORUM; O75380; -.
DR IntAct; O75380; 96.
DR MINT; O75380; -.
DR STRING; 9606.ENSP00000274137; -.
DR BindingDB; O75380; -.
DR ChEMBL; CHEMBL2363065; -.
DR DrugBank; DB00157; NADH.
DR DrugCentral; O75380; -.
DR iPTMnet; O75380; -.
DR PhosphoSitePlus; O75380; -.
DR SwissPalm; O75380; -.
DR BioMuta; NDUFS6; -.
DR UCD-2DPAGE; O75380; -.
DR EPD; O75380; -.
DR jPOST; O75380; -.
DR MassIVE; O75380; -.
DR PaxDb; O75380; -.
DR PeptideAtlas; O75380; -.
DR PRIDE; O75380; -.
DR ProteomicsDB; 49952; -.
DR TopDownProteomics; O75380; -.
DR Antibodypedia; 22354; 220 antibodies from 32 providers.
DR DNASU; 4726; -.
DR Ensembl; ENST00000274137.10; ENSP00000274137.6; ENSG00000145494.12.
DR GeneID; 4726; -.
DR KEGG; hsa:4726; -.
DR MANE-Select; ENST00000274137.10; ENSP00000274137.6; NM_004553.6; NP_004544.1.
DR CTD; 4726; -.
DR DisGeNET; 4726; -.
DR GeneCards; NDUFS6; -.
DR HGNC; HGNC:7713; NDUFS6.
DR HPA; ENSG00000145494; Tissue enhanced (skeletal).
DR MalaCards; NDUFS6; -.
DR MIM; 603848; gene.
DR MIM; 618232; phenotype.
DR neXtProt; NX_O75380; -.
DR OpenTargets; ENSG00000145494; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR PharmGKB; PA31523; -.
DR VEuPathDB; HostDB:ENSG00000145494; -.
DR eggNOG; KOG3456; Eukaryota.
DR GeneTree; ENSGT00390000015775; -.
DR HOGENOM; CLU_083053_3_2_1; -.
DR InParanoid; O75380; -.
DR OMA; VRFVNAK; -.
DR OrthoDB; 1641902at2759; -.
DR PhylomeDB; O75380; -.
DR TreeFam; TF315128; -.
DR BioCyc; MetaCyc:ENSG00000145494-MON; -.
DR PathwayCommons; O75380; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; O75380; -.
DR SIGNOR; O75380; -.
DR BioGRID-ORCS; 4726; 14 hits in 1079 CRISPR screens.
DR ChiTaRS; NDUFS6; human.
DR GeneWiki; NDUFS6; -.
DR GenomeRNAi; 4726; -.
DR Pharos; O75380; Tclin.
DR PRO; PR:O75380; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O75380; protein.
DR Bgee; ENSG00000145494; Expressed in tendon of biceps brachii and 201 other tissues.
DR ExpressionAtlas; O75380; baseline and differential.
DR Genevisible; O75380; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IDA:UniProtKB.
DR GO; GO:0009055; F:electron transfer activity; NAS:UniProtKB.
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:0042776; P:proton motive force-driven mitochondrial ATP synthesis; IC:ComplexPortal.
DR InterPro; IPR016668; NDUFS6.
DR InterPro; IPR019401; Znf_CHCC.
DR Pfam; PF10276; zf-CHCC; 1.
DR PIRSF; PIRSF016564; CI-13KD-A; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Disease variant; Electron transport; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Respiratory chain; Transit peptide; Transport.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 29..124
FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein
FT 6, mitochondrial"
FT /id="PRO_0000020020"
FT MOD_RES 98
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P52503"
FT VARIANT 115
FT /note="C -> Y (in MC1DN9; dbSNP:rs267606913)"
FT /evidence="ECO:0000269|PubMed:19259137"
FT /id="VAR_078947"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 51..56
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 68..74
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:5XTB"
SQ SEQUENCE 124 AA; 13712 MW; 0A1465160BCA772D CRC64;
MAAAMTFCRL LNRCGEAARS LPLGARCFGV RVSPTGEKVT HTGQVYDDKD YRRIRFVGRQ
KEVNENFAID LIAEQPVSEV ETRVIACDGG GGALGHPKVY INLDKETKTG TCGYCGLQFR
QHHH
