NDUF3_HUMAN
ID NDUF3_HUMAN Reviewed; 184 AA.
AC Q9BU61;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3;
GN Name=NDUFAF3; Synonyms=C3orf60;
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 [LARGE SCALE MRNA] (ISOFORMS A AND B).
RC TISSUE=Lung, and Testis;
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 [2]
RP FUNCTION, INTERACTION WITH NDUFAF4; NDUFS2 AND NDUFS3, SUBCELLULAR
RP LOCATION, INVOLVEMENT IN MC1DN18, AND VARIANTS MC1DN18 ARG-77 AND PRO-122.
RX PubMed=19463981; DOI=10.1016/j.ajhg.2009.04.020;
RA Saada A., Vogel R.O., Hoefs S.J., van den Brand M.A., Wessels H.J.,
RA Willems P.H., Venselaar H., Shaag A., Barghuti F., Reish O., Shohat M.,
RA Huynen M.A., Smeitink J.A.M., van den Heuvel L.P., Nijtmans L.G.;
RT "Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting
RT complex I assembly protein, cause fatal neonatal mitochondrial disease.";
RL Am. J. Hum. Genet. 84:718-727(2009).
RN [3]
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 [4]
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 [5]
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 [6]
RP INVOLVEMENT IN MC1DN18, AND VARIANT MC1DN18 VAL-165.
RX PubMed=27986404; DOI=10.1016/j.ymgme.2016.12.005;
RA Baertling F., Sanchez-Caballero L., Timal S., van den Brand M.A., Ngu L.H.,
RA Distelmaier F., Rodenburg R.J., Nijtmans L.G.;
RT "Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh
RT syndrome.";
RL Mol. Genet. Metab. 120:243-246(2017).
CC -!- FUNCTION: Essential factor for the assembly of mitochondrial
CC NADH:ubiquinone oxidoreductase complex (complex I).
CC {ECO:0000269|PubMed:19463981}.
CC -!- SUBUNIT: Interacts with NDUFAF4, NDUFS2 and NDUFS3.
CC {ECO:0000269|PubMed:19463981}.
CC -!- INTERACTION:
CC Q9BU61; Q6RW13-2: AGTRAP; NbExp=3; IntAct=EBI-2114801, EBI-11522760;
CC Q9BU61; Q9NPB3: CABP2; NbExp=3; IntAct=EBI-2114801, EBI-12011224;
CC Q9BU61; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2114801, EBI-3867333;
CC Q9BU61; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-2114801, EBI-5916454;
CC Q9BU61; Q0VD86: INCA1; NbExp=3; IntAct=EBI-2114801, EBI-6509505;
CC Q9BU61; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-2114801, EBI-3044087;
CC Q9BU61; Q8WWY6: MBD3L1; NbExp=3; IntAct=EBI-2114801, EBI-12516603;
CC Q9BU61; Q9P032: NDUFAF4; NbExp=10; IntAct=EBI-2114801, EBI-2606839;
CC Q9BU61; Q16633: POU2AF1; NbExp=3; IntAct=EBI-2114801, EBI-943588;
CC Q9BU61; Q9BYM8: RBCK1; NbExp=3; IntAct=EBI-2114801, EBI-2340624;
CC Q9BU61; Q9NTX7-2: RNF146; NbExp=3; IntAct=EBI-2114801, EBI-11750630;
CC Q9BU61; P09012: SNRPA; NbExp=6; IntAct=EBI-2114801, EBI-607085;
CC Q9BU61; Q8TAS1-2: UHMK1; NbExp=3; IntAct=EBI-2114801, EBI-12157345;
CC Q9BU61-2; Q9P032: NDUFAF4; NbExp=8; IntAct=EBI-10298649, EBI-2606839;
CC Q9BU61-2; Q9BYM8: RBCK1; NbExp=3; IntAct=EBI-10298649, EBI-2340624;
CC Q9BU61-2; Q04864: REL; NbExp=3; IntAct=EBI-10298649, EBI-307352;
CC Q9BU61-2; P09012: SNRPA; NbExp=3; IntAct=EBI-10298649, EBI-607085;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Mitochondrion inner
CC membrane {ECO:0000269|PubMed:19463981}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=Q9BU61-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q9BU61-2; Sequence=VSP_041086;
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 18 (MC1DN18)
CC [MIM:618240]: 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. MC1DN18 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:19463981,
CC ECO:0000269|PubMed:27986404}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; BC002873; AAH02873.1; -; mRNA.
DR EMBL; BQ652614; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS2784.1; -. [Q9BU61-1]
DR CCDS; CCDS2785.1; -. [Q9BU61-2]
DR RefSeq; NP_951032.1; NM_199069.1. [Q9BU61-1]
DR AlphaFoldDB; Q9BU61; -.
DR SMR; Q9BU61; -.
DR BioGRID; 117419; 118.
DR IntAct; Q9BU61; 46.
DR MINT; Q9BU61; -.
DR STRING; 9606.ENSP00000323076; -.
DR BindingDB; Q9BU61; -.
DR ChEMBL; CHEMBL2363065; -.
DR DrugCentral; Q9BU61; -.
DR iPTMnet; Q9BU61; -.
DR PhosphoSitePlus; Q9BU61; -.
DR SwissPalm; Q9BU61; -.
DR BioMuta; NDUFAF3; -.
DR DMDM; 74733183; -.
DR EPD; Q9BU61; -.
DR jPOST; Q9BU61; -.
DR MassIVE; Q9BU61; -.
DR MaxQB; Q9BU61; -.
DR PaxDb; Q9BU61; -.
DR PeptideAtlas; Q9BU61; -.
DR PRIDE; Q9BU61; -.
DR ProteomicsDB; 79053; -. [Q9BU61-1]
DR ProteomicsDB; 79054; -. [Q9BU61-2]
DR Antibodypedia; 48697; 80 antibodies from 16 providers.
DR DNASU; 25915; -.
DR Ensembl; ENST00000326912.8; ENSP00000323003.4; ENSG00000178057.15. [Q9BU61-2]
DR Ensembl; ENST00000326925.11; ENSP00000323076.5; ENSG00000178057.15. [Q9BU61-1]
DR Ensembl; ENST00000395458.6; ENSP00000378843.2; ENSG00000178057.15. [Q9BU61-2]
DR Ensembl; ENST00000451378.2; ENSP00000402465.2; ENSG00000178057.15. [Q9BU61-2]
DR GeneID; 25915; -.
DR KEGG; hsa:25915; -.
DR MANE-Select; ENST00000326925.11; ENSP00000323076.5; NM_199069.2; NP_951032.1.
DR UCSC; uc003cvn.4; human. [Q9BU61-1]
DR CTD; 25915; -.
DR DisGeNET; 25915; -.
DR GeneCards; NDUFAF3; -.
DR HGNC; HGNC:29918; NDUFAF3.
DR HPA; ENSG00000178057; Tissue enhanced (testis).
DR MalaCards; NDUFAF3; -.
DR MIM; 612911; gene.
DR MIM; 618240; phenotype.
DR neXtProt; NX_Q9BU61; -.
DR OpenTargets; ENSG00000178057; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR Orphanet; 70474; Leigh syndrome with cardiomyopathy.
DR PharmGKB; PA164723795; -.
DR VEuPathDB; HostDB:ENSG00000178057; -.
DR eggNOG; KOG3363; Eukaryota.
DR GeneTree; ENSGT00390000018312; -.
DR HOGENOM; CLU_074390_3_4_1; -.
DR InParanoid; Q9BU61; -.
DR OMA; FSKAYDH; -.
DR PhylomeDB; Q9BU61; -.
DR TreeFam; TF321072; -.
DR PathwayCommons; Q9BU61; -.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; Q9BU61; -.
DR BioGRID-ORCS; 25915; 295 hits in 1077 CRISPR screens.
DR ChiTaRS; NDUFAF3; human.
DR GeneWiki; C3orf60; -.
DR GenomeRNAi; 25915; -.
DR Pharos; Q9BU61; Tclin.
DR PRO; PR:Q9BU61; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9BU61; protein.
DR Bgee; ENSG00000178057; Expressed in left testis and 196 other tissues.
DR ExpressionAtlas; Q9BU61; baseline and differential.
DR Genevisible; Q9BU61; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:LIFEdb.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB.
DR CDD; cd05125; Mth938_2P1-like; 1.
DR Gene3D; 3.40.1230.10; -; 1.
DR InterPro; IPR036748; MTH938-like_sf.
DR InterPro; IPR034095; NDUF3.
DR InterPro; IPR007523; NDUFAF3/AAMDC.
DR PANTHER; PTHR21192; PTHR21192; 1.
DR Pfam; PF04430; DUF498; 1.
DR SUPFAM; SSF64076; SSF64076; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Primary mitochondrial disease;
KW Reference proteome.
FT CHAIN 1..184
FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex
FT assembly factor 3"
FT /id="PRO_0000281154"
FT VAR_SEQ 1..57
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041086"
FT VARIANT 77
FT /note="G -> R (in MC1DN18; dbSNP:rs121918134)"
FT /evidence="ECO:0000269|PubMed:19463981"
FT /id="VAR_058491"
FT VARIANT 122
FT /note="R -> P (in MC1DN18; dbSNP:rs121918135)"
FT /evidence="ECO:0000269|PubMed:19463981"
FT /id="VAR_058492"
FT VARIANT 165
FT /note="A -> V (in MC1DN18; dbSNP:rs138275059)"
FT /evidence="ECO:0000269|PubMed:27986404"
FT /id="VAR_081425"
SQ SEQUENCE 184 AA; 20350 MW; FCFF7B0CB6ADBCD8 CRC64;
MATALALRSL YRARPSLRCP PVELPWAPRR GHRLSPADDE LYQRTRISLL QREAAQAMYI
DSYNSRGFMI NGNRVLGPCA LLPHSVVQWN VGSHQDITED SFSLFWLLEP RIEIVVVGTG
DRTERLQSQV LQAMRQRGIA VEVQDTPNAC ATFNFLCHEG RVTGAALIPP PGGTSLTSLG
QAAQ
