ID NDUC2_HUMAN Reviewed; 119 AA. AC O95298; E9PNU8; E9PRB2; Q549M5; Q6FIH8; Q9UBJ9; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 24-JAN-2024, entry version 178. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 subunit C2 {ECO:0000305}; DE AltName: Full=Complex I-B14.5b; DE Short=CI-B14.5b; DE AltName: Full=Human lung cancer oncogene 1 protein; DE Short=HLC-1; DE AltName: Full=NADH-ubiquinone oxidoreductase subunit B14.5b; GN Name=NDUFC2 {ECO:0000312|HGNC:HGNC:7706}; ORFNames=HLC1; 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=9878551; DOI=10.1006/bbrc.1998.9786; RA Loeffen J.L.C.M., Triepels R.H., van den Heuvel L.P., Schuelke M., RA Buskens C.A.F., Smeets R.J.P., Trijbels J.M.F., Smeitink J.A.M.; RT "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: RT human complex I cDNA characterization completed."; RL Biochem. Biophys. Res. Commun. 253:415-422(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Dai F.Y., Yu L., Yang J., Huang H.B., Wang X.K., Zhao S.Y.; RT "Cloning and expression of a new human cDNA homology to B.taurus NADH RT dehydrogenase (ubiquinone) mRNA."; RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-46. RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-46. RC TISSUE=Kidney; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-46. RA Kim J.W.; RT "Identification of a new oncogene in human cancer."; RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-46. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; 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 [10] 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 [11] 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 [12] 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 [13] 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 [14] RP INTERACTION WITH TMEM242. RX PubMed=33753518; DOI=10.1073/pnas.2100558118; RA Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.; RT "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase RT and interact with assembly factors for complex I."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). RN [15] RP VARIANT MC1DN36 TYR-58, CHARACTERIZATION OF VARIANT MC1DN36 TYR-58, AND RP FUNCTION. RX PubMed=32969598; DOI=10.15252/emmm.202012619; RA Alahmad A., Nasca A., Heidler J., Thompson K., Olahova M., Legati A., RA Lamantea E., Meisterknecht J., Spagnolo M., He L., Alameer S., Hakami F., RA Almehdar A., Ardissone A., Alston C.L., McFarland R., Wittig I., Ghezzi D., RA Taylor R.W.; RT "Bi-allelic pathogenic variants in NDUFC2 cause early-onset Leigh syndrome RT and stalled biogenesis of complex I."; RL EMBO Mol. Med. 12:e12619-e12619(2020). 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 but required for the complex assembly. Complex I CC functions in the transfer of electrons from NADH to the respiratory CC chain. The immediate electron acceptor for the enzyme is believed to be CC ubiquinone. {ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:32969598}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits. Interacts with CC TMEM242 (PubMed:33753518). {ECO:0000269|PubMed:12611891, CC ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:33753518}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Single-pass membrane protein CC {ECO:0000255}; Matrix side {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=3; CC IsoId=O95298-1; Sequence=Displayed; CC Name=4; CC IsoId=O95298-2; Sequence=VSP_047317; CC Name=5; CC IsoId=O95298-3; Sequence=VSP_047318; CC Name=2; Synonyms=NDUFC2-KCTD14; CC IsoId=E9PQ53-1; Sequence=External; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 36 (MC1DN36) CC [MIM:619170]: 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. MC1DN36 is characterized by global developmental CC delay, hypotonia, and failure to thrive apparent from infancy or early CC childhood. Affected individuals usually do not acquire ambulation, show CC progressive spasticity, and have impaired intellectual development with CC absent speech. MC1DN36 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:32969598}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFC2 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; AF087659; AAD09754.1; -; mRNA. DR EMBL; AF087899; AAP97198.1; -; mRNA. DR EMBL; AF070652; AAD20958.1; -; mRNA. DR EMBL; AL050278; CAB43379.1; -; mRNA. DR EMBL; AF369951; AAM21294.1; -; mRNA. DR EMBL; CR533448; CAG38479.1; -; mRNA. DR EMBL; AP003032; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW75046.1; -; Genomic_DNA. DR EMBL; BC007323; AAH07323.1; -; mRNA. DR CCDS; CCDS55779.1; -. [O95298-2] DR CCDS; CCDS55781.1; -. [O95298-3] DR CCDS; CCDS8257.1; -. [O95298-1] DR PIR; T08728; T08728. DR RefSeq; NP_001190983.1; NM_001204054.1. [O95298-3] DR RefSeq; NP_001190984.1; NM_001204055.1. [O95298-2] DR RefSeq; NP_004540.1; NM_004549.5. [O95298-1] DR PDB; 5XTC; EM; 3.70 A; g=1-119. DR PDB; 5XTD; EM; 3.70 A; g=1-119. DR PDB; 5XTH; EM; 3.90 A; g=1-119. DR PDB; 5XTI; EM; 17.40 A; Bg/g=1-119. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR AlphaFoldDB; O95298; -. DR SMR; O95298; -. DR BioGRID; 110798; 78. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O95298; -. DR IntAct; O95298; 30. DR MINT; O95298; -. DR STRING; 9606.ENSP00000281031; -. DR BindingDB; O95298; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB00157; NADH. DR DrugCentral; O95298; -. DR iPTMnet; O95298; -. DR PhosphoSitePlus; O95298; -. DR BioMuta; NDUFC2; -. DR EPD; O95298; -. DR jPOST; O95298; -. DR MassIVE; O95298; -. DR MaxQB; O95298; -. DR PaxDb; 9606-ENSP00000281031; -. DR PeptideAtlas; O95298; -. DR ProteomicsDB; 22525; -. DR ProteomicsDB; 23265; -. DR ProteomicsDB; 50798; -. [O95298-1] DR Pumba; O95298; -. DR TopDownProteomics; O95298-1; -. [O95298-1] DR Antibodypedia; 31293; 219 antibodies from 30 providers. DR DNASU; 4718; -. DR Ensembl; ENST00000281031.5; ENSP00000281031.4; ENSG00000151366.13. [O95298-1] DR Ensembl; ENST00000525085.1; ENSP00000434262.1; ENSG00000151366.13. [O95298-2] DR Ensembl; ENST00000527806.1; ENSP00000432739.1; ENSG00000151366.13. [O95298-3] DR GeneID; 4718; -. DR KEGG; hsa:4718; -. DR MANE-Select; ENST00000281031.5; ENSP00000281031.4; NM_004549.6; NP_004540.1. DR UCSC; uc009yuw.4; human. [O95298-1] DR AGR; HGNC:7706; -. DR CTD; 4718; -. DR DisGeNET; 4718; -. DR GeneCards; NDUFC2; -. DR HGNC; HGNC:7706; NDUFC2. DR HPA; ENSG00000151366; Low tissue specificity. DR MalaCards; NDUFC2; -. DR MIM; 603845; gene. DR MIM; 619170; phenotype. DR neXtProt; NX_O95298; -. DR OpenTargets; ENSG00000151366; -. DR PharmGKB; PA31517; -. DR VEuPathDB; HostDB:ENSG00000151366; -. DR eggNOG; KOG4516; Eukaryota. DR GeneTree; ENSGT00390000010352; -. DR HOGENOM; CLU_156652_0_0_1; -. DR InParanoid; O95298; -. DR OMA; WFIGYHL; -. DR OrthoDB; 5292807at2759; -. DR PhylomeDB; O95298; -. DR TreeFam; TF314723; -. DR BioCyc; MetaCyc:HS07729-MONOMER; -. DR PathwayCommons; O95298; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O95298; -. DR SIGNOR; O95298; -. DR BioGRID-ORCS; 4718; 243 hits in 1108 CRISPR screens. DR GeneWiki; NDUFC2; -. DR GenomeRNAi; 4718; -. DR Pharos; O95298; Tclin. DR PRO; PR:O95298; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; O95298; Protein. DR Bgee; ENSG00000151366; Expressed in right adrenal gland and 183 other cell types or tissues. DR ExpressionAtlas; O95298; baseline and differential. DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome. DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb. 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:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. 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; 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; NAS:ComplexPortal. DR InterPro; IPR009423; NDUC2. DR PANTHER; PTHR13099:SF0; NADH DEHYDROGENASE [UBIQUINONE] 1 SUBUNIT C2-RELATED; 1. DR PANTHER; PTHR13099; NADH-UBIQUINONE OXIDOREDUCTASE SUBUNIT B14.5B; 1. DR Pfam; PF06374; NDUF_C2; 1. DR PIRSF; PIRSF017834; NADH-UbQ_OxRdtase_b14.5b; 1. DR Genevisible; O95298; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disease variant; Electron transport; KW Membrane; Mitochondrion; Mitochondrion inner membrane; KW Primary mitochondrial disease; Reference proteome; Respiratory chain; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..119 FT /note="NADH dehydrogenase [ubiquinone] 1 subunit C2" FT /id="PRO_0000118837" FT TRANSMEM 56..75 FT /note="Helical" FT /evidence="ECO:0000255" FT VAR_SEQ 56..78 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_047317" FT VAR_SEQ 77..119 FT /note="REDYLYAVRDREMFGYMKLHPEDFPEEDKKTYGEIFEKFHPIR -> LEAYA FT NLYVDTL (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_047318" FT VARIANT 46 FT /note="L -> V (in dbSNP:rs8875)" FT /evidence="ECO:0000269|PubMed:11042152, FT ECO:0000269|PubMed:11230166, ECO:0000269|Ref.5, FT ECO:0000269|Ref.6" FT /id="VAR_014486" FT VARIANT 58 FT /note="H -> Y (in MC1DN36; highly decreased mitochondrial FT membrane respiratory chain NADH dehydrogenase complex I FT activity; decreased complex I assembly and protein levels; FT dbSNP:rs1306743145)" FT /evidence="ECO:0000269|PubMed:32969598" FT /id="VAR_085236" SQ SEQUENCE 119 AA; 14188 MW; 9A47DEE33DC9244D CRC64; MIARRNPEPL RFLPDEARSL PPPKLTDPRL LYIGFLGYCS GLIDNLIRRR PIATAGLHRQ LLYITAFFFA GYYLVKREDY LYAVRDREMF GYMKLHPEDF PEEDKKTYGE IFEKFHPIR //