NDUC2_HUMAN
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 03-AUG-2022, entry version 171.
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}.
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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; O95298; -.
DR PeptideAtlas; O95298; -.
DR PRIDE; O95298; -.
DR ProteomicsDB; 22525; -.
DR ProteomicsDB; 23265; -.
DR ProteomicsDB; 50798; -. [O95298-1]
DR TopDownProteomics; O95298-1; -. [O95298-1]
DR Antibodypedia; 31293; 197 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 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 PhylomeDB; O95298; -.
DR TreeFam; TF314723; -.
DR BioCyc; MetaCyc:HS07729-MON; -.
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; 239 hits in 1033 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 181 other tissues.
DR ExpressionAtlas; O95298; baseline and differential.
DR Genevisible; O95298; HS.
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; IC: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:0060547; P:negative regulation of necrotic cell death; IEA:Ensembl.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IEA:Ensembl.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IEA:Ensembl.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; IEA:Ensembl.
DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; IC:ComplexPortal.
DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl.
DR InterPro; IPR009423; NDUC2.
DR PANTHER; PTHR13099; PTHR13099; 1.
DR Pfam; PF06374; NDUF_C2; 1.
DR PIRSF; PIRSF017834; NADH-UbQ_OxRdtase_b14.5b; 1.
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
