NDUF2_HUMAN
ID NDUF2_HUMAN Reviewed; 169 AA.
AC Q8N183; A8K5I1;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 2;
DE AltName: Full=B17.2-like;
DE Short=B17.2L;
DE AltName: Full=Mimitin {ECO:0000303|PubMed:15774466};
DE AltName: Full=Myc-induced mitochondrial protein {ECO:0000303|PubMed:15774466};
DE Short=MMTN {ECO:0000303|PubMed:15774466};
DE AltName: Full=NDUFA12-like protein;
DE Flags: Precursor;
GN Name=NDUFAF2; Synonyms=NDUFA12L;
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], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INDUCTION.
RX PubMed=15774466; DOI=10.1074/jbc.m501231200;
RA Tsuneoka M., Teye K., Arima N., Soejima M., Otera H., Ohashi K., Koga Y.,
RA Fujita H., Shirouzu K., Kimura H., Koda Y.;
RT "A novel Myc-target gene, mimitin, that is involved in cell proliferation
RT of esophageal squamous cell carcinoma.";
RL J. Biol. Chem. 280:19977-19985(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and Hypothalamus;
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 FUNCTION AS A CHAPERONE, TISSUE SPECIFICITY, INVOLVEMENT IN MC1DN10, AND
RP VARIANT MC1DN10 47-ARG--GLN-169 DEL.
RX PubMed=16200211; DOI=10.1172/jci26020;
RA Ogilvie I., Kennaway N.G., Shoubridge E.A.;
RT "A molecular chaperone for mitochondrial complex I assembly is mutated in a
RT progressive encephalopathy.";
RL J. Clin. Invest. 115:2784-2792(2005).
RN [6]
RP INVOLVEMENT IN MC1DN10.
RX PubMed=18180188; DOI=10.1016/j.ymgme.2007.11.013;
RA Barghuti F., Elian K., Gomori J.M., Shaag A., Edvardson S., Saada A.,
RA Elpeleg O.;
RT "The unique neuroradiology of complex I deficiency due to NDUFA12L
RT defect.";
RL Mol. Genet. Metab. 94:78-82(2008).
RN [7]
RP FUNCTION, INVOLVEMENT IN MC1DN10, VARIANT MC1DN10 38-TYR--GLN-169 DEL, AND
RP CHARACTERIZATION OF VARIANT MC1DN10 38-TYR--GLN-169 DEL.
RX PubMed=19384974; DOI=10.1002/humu.21037;
RA Hoefs S.J., Dieteren C.E., Rodenburg R.J., Naess K., Bruhn H., Wibom R.,
RA Wagena E., Willems P.H., Smeitink J.A., Nijtmans L.G., van den Heuvel L.P.;
RT "Baculovirus complementation restores a novel NDUFAF2 mutation causing
RT complex I deficiency.";
RL Hum. Mutat. 30:E728-E736(2009).
RN [8]
RP INVOLVEMENT IN MC1DN10, AND VARIANT MC1DN10 3-TRP--GLN-169 DEL.
RX PubMed=20571988; DOI=10.1055/s-0030-1255062;
RA Herzer M., Koch J., Prokisch H., Rodenburg R., Rauscher C., Radauer W.,
RA Forstner R., Pilz P., Rolinski B., Freisinger P., Mayr J.A., Sperl W.;
RT "Leigh disease with brainstem involvement in complex I deficiency due to
RT assembly factor NDUFAF2 defect.";
RL Neuropediatrics 41:30-34(2010).
RN [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
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 [12]
RP FUNCTION.
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).
CC -!- FUNCTION: Acts as a molecular chaperone for mitochondrial complex I
CC assembly (PubMed:16200211, PubMed:19384974). Complex I functions in the
CC transfer of electrons from NADH to the respiratory chain. The immediate
CC electron acceptor for the enzyme is believed to be ubiquinone
CC (PubMed:16200211, PubMed:27626371). {ECO:0000269|PubMed:16200211,
CC ECO:0000269|PubMed:19384974, ECO:0000269|PubMed:27626371}.
CC -!- INTERACTION:
CC Q8N183; O43169: CYB5B; NbExp=3; IntAct=EBI-2682365, EBI-1058710;
CC Q8N183; O43561-2: LAT; NbExp=3; IntAct=EBI-2682365, EBI-8070286;
CC Q8N183; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-2682365, EBI-12033434;
CC Q8N183; O75396: SEC22B; NbExp=3; IntAct=EBI-2682365, EBI-1058865;
CC Q8N183; B2RUZ4: SMIM1; NbExp=3; IntAct=EBI-2682365, EBI-12188413;
CC Q8N183; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-2682365, EBI-742688;
CC Q8N183; Q9UNK0: STX8; NbExp=3; IntAct=EBI-2682365, EBI-727240;
CC Q8N183; Q5SNT2-2: TMEM201; NbExp=3; IntAct=EBI-2682365, EBI-11994282;
CC Q8N183; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-2682365, EBI-12111910;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:15774466}.
CC -!- TISSUE SPECIFICITY: Highly expressed in ESCC cells. Also expressed in
CC heart, skeletal muscle, liver, and in fibroblasts.
CC {ECO:0000269|PubMed:15774466, ECO:0000269|PubMed:16200211}.
CC -!- INDUCTION: By MYC. Direct transcriptional target of MYC.
CC {ECO:0000269|PubMed:15774466}.
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 10 (MC1DN10)
CC [MIM:618233]: 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. MC1DN10 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:16200211,
CC ECO:0000269|PubMed:18180188, ECO:0000269|PubMed:19384974,
CC ECO:0000269|PubMed:20571988}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complex I NDUFA12 subunit family.
CC {ECO:0000305}.
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DR EMBL; AB183433; BAD91205.1; -; mRNA.
DR EMBL; AK291296; BAF83985.1; -; mRNA.
DR EMBL; CH471123; EAW55008.1; -; Genomic_DNA.
DR EMBL; BC001753; AAH01753.2; -; mRNA.
DR EMBL; BC033965; AAH33965.1; -; mRNA.
DR CCDS; CCDS3979.1; -.
DR RefSeq; NP_777549.1; NM_174889.4.
DR AlphaFoldDB; Q8N183; -.
DR SMR; Q8N183; -.
DR BioGRID; 124893; 123.
DR IntAct; Q8N183; 34.
DR MINT; Q8N183; -.
DR STRING; 9606.ENSP00000296597; -.
DR BindingDB; Q8N183; -.
DR ChEMBL; CHEMBL2363065; -.
DR DrugCentral; Q8N183; -.
DR GlyGen; Q8N183; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8N183; -.
DR MetOSite; Q8N183; -.
DR PhosphoSitePlus; Q8N183; -.
DR BioMuta; NDUFAF2; -.
DR DMDM; 67461055; -.
DR EPD; Q8N183; -.
DR jPOST; Q8N183; -.
DR MassIVE; Q8N183; -.
DR MaxQB; Q8N183; -.
DR PaxDb; Q8N183; -.
DR PeptideAtlas; Q8N183; -.
DR PRIDE; Q8N183; -.
DR ProteomicsDB; 71569; -.
DR TopDownProteomics; Q8N183; -.
DR Antibodypedia; 23660; 208 antibodies from 30 providers.
DR DNASU; 91942; -.
DR Ensembl; ENST00000296597.10; ENSP00000296597.5; ENSG00000164182.12.
DR GeneID; 91942; -.
DR KEGG; hsa:91942; -.
DR MANE-Select; ENST00000296597.10; ENSP00000296597.5; NM_174889.5; NP_777549.1.
DR UCSC; uc003jsp.4; human.
DR CTD; 91942; -.
DR DisGeNET; 91942; -.
DR GeneCards; NDUFAF2; -.
DR GeneReviews; NDUFAF2; -.
DR HGNC; HGNC:28086; NDUFAF2.
DR HPA; ENSG00000164182; Low tissue specificity.
DR MalaCards; NDUFAF2; -.
DR MIM; 609653; gene.
DR MIM; 618233; phenotype.
DR neXtProt; NX_Q8N183; -.
DR OpenTargets; ENSG00000164182; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA162397398; -.
DR VEuPathDB; HostDB:ENSG00000164182; -.
DR eggNOG; ENOG502S21I; Eukaryota.
DR GeneTree; ENSGT00390000002743; -.
DR HOGENOM; CLU_138027_0_0_1; -.
DR InParanoid; Q8N183; -.
DR OMA; VPEYKNW; -.
DR OrthoDB; 1394421at2759; -.
DR PhylomeDB; Q8N183; -.
DR TreeFam; TF314761; -.
DR PathwayCommons; Q8N183; -.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; Q8N183; -.
DR BioGRID-ORCS; 91942; 58 hits in 1053 CRISPR screens.
DR ChiTaRS; NDUFAF2; human.
DR GenomeRNAi; 91942; -.
DR Pharos; Q8N183; Tclin.
DR PRO; PR:Q8N183; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q8N183; protein.
DR Bgee; ENSG00000164182; Expressed in calcaneal tendon and 96 other tissues.
DR ExpressionAtlas; Q8N183; baseline and differential.
DR Genevisible; Q8N183; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:FlyBase.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:FlyBase.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
DR InterPro; IPR007763; NDUFA12.
DR Pfam; PF05071; NDUFA12; 1.
PE 1: Evidence at protein level;
KW Chaperone; Disease variant; Mitochondrion; Phosphoprotein;
KW Primary mitochondrial disease; Reference proteome; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..169
FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex
FT assembly factor 2"
FT /id="PRO_0000020054"
FT REGION 116..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 146..169
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 3..169
FT /note="Missing (in MC1DN10)"
FT /evidence="ECO:0000269|PubMed:20571988"
FT /id="VAR_081422"
FT VARIANT 38..169
FT /note="Missing (in MC1DN10; patient cells homozygous for
FT the variant do not express detectable amounts of protein;
FT complex I assembly is altered and activity is severely
FT reduced in patient cells compared to control)"
FT /evidence="ECO:0000269|PubMed:19384974"
FT /id="VAR_081423"
FT VARIANT 47..169
FT /note="Missing (in MC1DN10)"
FT /evidence="ECO:0000269|PubMed:16200211"
FT /id="VAR_081424"
SQ SEQUENCE 169 AA; 19856 MW; 3D72AE8B5942E0FA CRC64;
MGWSQDLFRA LWRSLSREVK EHVGTDQFGN KYYYIPQYKN WRGQTIREKR IVEAANKKEV
DYEAGDIPTE WEAWIRRTRK TPPTMEEILK NEKHREEIKI KSQDFYEKEK LLSKETSEEL
LPPPVQTQIK GHASAPYFGK EEPSVAPSST GKTFQPGSWM PRDGKSHNQ
