NDUA9_HUMAN
ID NDUA9_HUMAN Reviewed; 377 AA.
AC Q16795; Q14076; Q2NKX0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial;
DE AltName: Full=Complex I-39kD;
DE Short=CI-39kD;
DE AltName: Full=NADH-ubiquinone oxidoreductase 39 kDa subunit;
DE Flags: Precursor;
GN Name=NDUFA9; Synonyms=NDUFS2L;
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].
RA Loeffen J.L.C.M., Smeets R.J.P., Triepels R., Ruitenbeek W.,
RA Smeitink J.A.M., van den Heuvel L.;
RT "39 kDa subunit of NADH-ubiquinone oxidoreductase.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, Muscle, and Skeletal muscle;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
RC TISSUE=Blood;
RX PubMed=8012384; DOI=10.1038/ng0394-236;
RA Cross S.H., Charlton J.A., Nan X., Bird A.P.;
RT "Purification of CpG islands using a methylated DNA binding column.";
RL Nat. Genet. 6:236-244(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-377.
RC TISSUE=Liver;
RX PubMed=8486360; DOI=10.1006/geno.1993.1161;
RA Baens M., Chaffanet M., Cassiman J.-J., van den Berghe H., Marynen P.;
RT "Construction and evaluation of a hncDNA library of human 12p transcribed
RT sequences derived from a somatic cell hybrid.";
RL Genomics 16:214-218(1993).
RN [5]
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 [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 INTERACTION WITH BLOC1S1, AND ACETYLATION.
RX PubMed=22309213; DOI=10.1042/bj20120118;
RA Scott I., Webster B.R., Li J.H., Sack M.N.;
RT "Identification of a molecular component of the mitochondrial acetyl
RT transferase program; a novel role for GCN5L1.";
RL Biochem. J. 443:655-661(2012).
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 MC1DN26, VARIANT MC1DN26 PRO-321, AND FUNCTION.
RX PubMed=22114105; DOI=10.1136/jmedgenet-2011-100466;
RA van den Bosch B.J., Gerards M., Sluiter W., Stegmann A.P., Jongen E.L.,
RA Hellebrekers D.M., Oegema R., Lambrichs E.H., Prokisch H., Danhauser K.,
RA Schoonderwoerd K., de Coo I.F., Smeets H.J.;
RT "Defective NDUFA9 as a novel cause of neonatally fatal complex I disease.";
RL J. Med. Genet. 49:10-15(2012).
RN [12]
RP ACETYLATION, AND INTERACTION WITH CLOCK.
RX PubMed=28985504; DOI=10.1016/j.molcel.2017.09.008;
RA Lin R., Mo Y., Zha H., Qu Z., Xie P., Zhu Z.J., Xu Y., Xiong Y., Guan K.L.;
RT "CLOCK acetylates ASS1 to drive circadian rhythm of ureagenesis.";
RL Mol. Cell 68:198-209(2017).
RN [13]
RP FUNCTION, INVOLVEMENT IN MC1DN26, VARIANTS MC1DN26 PRO-321 AND CYS-360, AND
RP CHARACTERIZATION OF VARIANTS MC1DN26 PRO-321 AND CYS-360.
RX PubMed=28671271; DOI=10.1111/cge.13089;
RA Baertling F., Sanchez-Caballero L., van den Brand M.A.M., Fung C.W.,
RA Chan S.H., Wong V.C., Hellebrekers D.M.E., de Coo I.F.M., Smeitink J.A.M.,
RA Rodenburg R.J.T., Nijtmans L.G.J.;
RT "NDUFA9 point mutations cause a variable mitochondrial complex I assembly
RT defect.";
RL Clin. Genet. 93:111-118(2018).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RAB5IF.
RX PubMed=31536960; DOI=10.1016/j.isci.2019.08.057;
RA Moutaoufik M.T., Malty R., Amin S., Zhang Q., Phanse S., Gagarinova A.,
RA Zilocchi M., Hoell L., Minic Z., Gagarinova M., Aoki H., Stockwell J.,
RA Jessulat M., Goebels F., Broderick K., Scott N.E., Vlasblom J., Musso G.,
RA Prasad B., Lamantea E., Garavaglia B., Rajput A., Murayama K., Okazaki Y.,
RA Foster L.J., Bader G.D., Cayabyab F.S., Babu M.;
RT "Rewiring of the Human Mitochondrial Interactome during Neuronal
RT Reprogramming Reveals Regulators of the Respirasome and Neurogenesis.";
RL IScience 19:1114-1132(2019).
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. Required for proper complex I assembly
CC (PubMed:28671271). 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:22114105,
CC ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:28671271}.
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 (PubMed:12611891,
CC PubMed:27626371). Interacts with BLOC1S1 (PubMed:22309213). Interacts
CC with SLC2A4 (By similarity). Interacts with CLOCK (PubMed:28985504).
CC Interacts with RAB5IF (PubMed:31536960). {ECO:0000250|UniProtKB:Q5BK63,
CC ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:22309213,
CC ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:28985504,
CC ECO:0000269|PubMed:31536960}.
CC -!- INTERACTION:
CC Q16795; P78537: BLOC1S1; NbExp=3; IntAct=EBI-1045087, EBI-348630;
CC Q16795; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1045087, EBI-3867333;
CC Q16795; P42858: HTT; NbExp=7; IntAct=EBI-1045087, EBI-466029;
CC Q16795; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-1045087, EBI-11962084;
CC Q16795; Q8NC60: NOA1; NbExp=2; IntAct=EBI-1045087, EBI-717871;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000305|PubMed:12611891}.
CC -!- PTM: Acetylated on lysine residues. BLOC1S1 is required for acetylation
CC (PubMed:22309213). Acetylated by CLOCK in a circadian manner
CC (PubMed:28985504). {ECO:0000269|PubMed:22309213,
CC ECO:0000269|PubMed:28985504}.
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 26 (MC1DN26)
CC [MIM:618247]: 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. MC1DN26 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:22114105,
CC ECO:0000269|PubMed:28671271}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complex I NDUFA9 subunit family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA54099.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF050641; AAD42055.1; -; mRNA.
DR EMBL; BC009311; AAH09311.1; -; mRNA.
DR EMBL; BC015837; AAH15837.1; -; mRNA.
DR EMBL; BC111546; AAI11547.1; -; mRNA.
DR EMBL; X76665; CAA54099.1; ALT_FRAME; Genomic_DNA.
DR EMBL; L04490; AAA36350.1; -; mRNA.
DR CCDS; CCDS8532.1; -.
DR PIR; I37258; I37258.
DR RefSeq; NP_004993.1; NM_005002.4.
DR PDB; 5XTB; EM; 3.40 A; J=40-376.
DR PDB; 5XTD; EM; 3.70 A; J=40-376.
DR PDB; 5XTH; EM; 3.90 A; J=40-376.
DR PDB; 5XTI; EM; 17.40 A; BJ/J=40-376.
DR PDBsum; 5XTB; -.
DR PDBsum; 5XTD; -.
DR PDBsum; 5XTH; -.
DR PDBsum; 5XTI; -.
DR AlphaFoldDB; Q16795; -.
DR SMR; Q16795; -.
DR BioGRID; 110784; 316.
DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I.
DR CORUM; Q16795; -.
DR DIP; DIP-38526N; -.
DR IntAct; Q16795; 90.
DR MINT; Q16795; -.
DR STRING; 9606.ENSP00000266544; -.
DR BindingDB; Q16795; -.
DR ChEMBL; CHEMBL2363065; -.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB00157; NADH.
DR DrugCentral; Q16795; -.
DR CarbonylDB; Q16795; -.
DR GlyGen; Q16795; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q16795; -.
DR PhosphoSitePlus; Q16795; -.
DR SwissPalm; Q16795; -.
DR BioMuta; NDUFA9; -.
DR DMDM; 2833280; -.
DR EPD; Q16795; -.
DR jPOST; Q16795; -.
DR MassIVE; Q16795; -.
DR MaxQB; Q16795; -.
DR PaxDb; Q16795; -.
DR PeptideAtlas; Q16795; -.
DR PRIDE; Q16795; -.
DR ProteomicsDB; 61072; -.
DR TopDownProteomics; Q16795; -.
DR Antibodypedia; 22301; 261 antibodies from 29 providers.
DR DNASU; 4704; -.
DR Ensembl; ENST00000266544.10; ENSP00000266544.5; ENSG00000139180.11.
DR GeneID; 4704; -.
DR KEGG; hsa:4704; -.
DR MANE-Select; ENST00000266544.10; ENSP00000266544.5; NM_005002.5; NP_004993.1.
DR UCSC; uc001qnc.4; human.
DR CTD; 4704; -.
DR DisGeNET; 4704; -.
DR GeneCards; NDUFA9; -.
DR HGNC; HGNC:7693; NDUFA9.
DR HPA; ENSG00000139180; Low tissue specificity.
DR MalaCards; NDUFA9; -.
DR MIM; 603834; gene.
DR MIM; 618247; phenotype.
DR neXtProt; NX_Q16795; -.
DR OpenTargets; ENSG00000139180; -.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA31499; -.
DR VEuPathDB; HostDB:ENSG00000139180; -.
DR eggNOG; KOG2865; Eukaryota.
DR GeneTree; ENSGT00390000006865; -.
DR HOGENOM; CLU_007383_6_4_1; -.
DR InParanoid; Q16795; -.
DR OMA; FFNRFAA; -.
DR OrthoDB; 721605at2759; -.
DR PhylomeDB; Q16795; -.
DR TreeFam; TF105961; -.
DR BioCyc; MetaCyc:HS06589-MON; -.
DR PathwayCommons; Q16795; -.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; Q16795; -.
DR SIGNOR; Q16795; -.
DR BioGRID-ORCS; 4704; 181 hits in 1091 CRISPR screens.
DR ChiTaRS; NDUFA9; human.
DR GeneWiki; NDUFA9; -.
DR GenomeRNAi; 4704; -.
DR Pharos; Q16795; Tclin.
DR PRO; PR:Q16795; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q16795; protein.
DR Bgee; ENSG00000139180; Expressed in apex of heart and 203 other tissues.
DR ExpressionAtlas; Q16795; baseline and differential.
DR Genevisible; Q16795; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB.
DR GO; GO:0003954; F:NADH dehydrogenase activity; IMP:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:MGI.
DR GO; GO:0009060; P:aerobic respiration; IC:ComplexPortal.
DR GO; GO:0007623; P:circadian rhythm; IDA:UniProtKB.
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 GO; GO:0006814; P:sodium ion transport; NAS:UniProtKB.
DR GO; GO:1901006; P:ubiquinone-6 biosynthetic process; IBA:GO_Central.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01370; Epimerase; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Disease variant; Electron transport; FAD;
KW Flavoprotein; Mitochondrion; Primary mitochondrial disease;
KW Reference proteome; Respiratory chain; Transit peptide; Transport.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 36..377
FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex
FT subunit 9, mitochondrial"
FT /id="PRO_0000019992"
FT MOD_RES 175
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DC69"
FT MOD_RES 189
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DC69"
FT MOD_RES 370
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DC69"
FT VARIANT 321
FT /note="R -> P (in MC1DN26; loss of function in complex I
FT assembly; accumulation of several low and high molecular
FT weight assembly intermediates is observed in patient
FT fibroblasts; dbSNP:rs199592341)"
FT /evidence="ECO:0000269|PubMed:22114105,
FT ECO:0000269|PubMed:28671271"
FT /id="VAR_078936"
FT VARIANT 360
FT /note="R -> C (in MC1DN26; loss of function in complex I
FT assembly; accumulation of several low and high molecular
FT weight assembly intermediates is observed in patient
FT fibroblasts; dbSNP:rs3210083)"
FT /evidence="ECO:0000269|PubMed:28671271"
FT /id="VAR_081457"
FT STRAND 43..51
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 64..75
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 89..97
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 114..119
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 120..122
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 147..159
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 162..167
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 179..194
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 212..223
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 230..233
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 242..254
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 273..284
FT /evidence="ECO:0007829|PDB:5XTB"
FT STRAND 290..293
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 295..305
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 316..323
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 335..337
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 349..353
FT /evidence="ECO:0007829|PDB:5XTB"
FT TURN 354..356
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 359..362
FT /evidence="ECO:0007829|PDB:5XTB"
FT HELIX 367..369
FT /evidence="ECO:0007829|PDB:5XTB"
SQ SEQUENCE 377 AA; 42510 MW; 66A1CC7FCE86DD0E CRC64;
MAAAAQSRVV RVLSMSRSAI TAIATSVCHG PPCRQLHHAL MPHGKGGRSS VSGIVATVFG
ATGFLGRYVV NHLGRMGSQV IIPYRCDKYD IMHLRPMGDL GQLLFLEWDA RDKDSIRRVV
QHSNVVINLI GRDWETKNFD FEDVFVKIPQ AIAQLSKEAG VEKFIHVSHL NANIKSSSRY
LRNKAVGEKV VRDAFPEAII VKPSDIFGRE DRFLNSFASM HRFGPIPLGS LGWKTVKQPV
YVVDVSKGIV NAVKDPDANG KSFAFVGPSR YLLFHLVKYI FAVAHRLFLP FPLPLFAYRW
VARVFEISPF EPWITRDKVE RMHITDMKLP HLPGLEDLGI QATPLELKAI EVLRRHRTYR
WLSAEIEDVK PAKTVNI
