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   27-MAR-2024, entry version 179.
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/jci20683;
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; 243.
DR   ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I.
DR   CORUM; O75380; -.
DR   IntAct; O75380; 97.
DR   MINT; O75380; -.
DR   STRING; 9606.ENSP00000274137; -.
DR   BindingDB; O75380; -.
DR   ChEMBL; CHEMBL2363065; -.
DR   DrugBank; DB00157; NADH.
DR   DrugCentral; O75380; -.
DR   GlyGen; O75380; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O75380; -.
DR   PhosphoSitePlus; O75380; -.
DR   SwissPalm; O75380; -.
DR   BioMuta; NDUFS6; -.
DR   EPD; O75380; -.
DR   jPOST; O75380; -.
DR   MassIVE; O75380; -.
DR   PaxDb; 9606-ENSP00000274137; -.
DR   PeptideAtlas; O75380; -.
DR   ProteomicsDB; 49952; -.
DR   Pumba; O75380; -.
DR   TopDownProteomics; O75380; -.
DR   Antibodypedia; 22354; 247 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   AGR; HGNC:7713; -.
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; PRGVRCF; -.
DR   OrthoDB; 6826at2759; -.
DR   PhylomeDB; O75380; -.
DR   TreeFam; TF315128; -.
DR   BioCyc; MetaCyc:ENSG00000145494-MONOMER; -.
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; 15 hits in 1160 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 203 other cell types or tissues.
DR   ExpressionAtlas; O75380; baseline and differential.
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; NAS: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; NAS:ComplexPortal.
DR   Gene3D; 2.60.260.40; q5lls5 like domains; 1.
DR   InterPro; IPR016668; NDUFS6.
DR   InterPro; IPR019401; Znf_CHCC.
DR   PANTHER; PTHR13156:SF0; NADH DEHYDROGENASE [UBIQUINONE] IRON-SULFUR PROTEIN 6, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR13156; NADH-UBIQUINONE OXIDOREDUCTASE 13 KD-A SUBUNIT; 1.
DR   Pfam; PF10276; zf-CHCC; 1.
DR   PIRSF; PIRSF016564; CI-13KD-A; 1.
DR   UCD-2DPAGE; O75380; -.
DR   Genevisible; O75380; HS.
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
//