ID   Q4GEA1_HUMAN            Unreviewed;       347 AA.
AC   Q4GEA1;
DT   30-AUG-2005, integrated into UniProtKB/TrEMBL.
DT   30-AUG-2005, sequence version 1.
DT   08-NOV-2023, entry version 99.
DE   RecName: Full=NADH-ubiquinone oxidoreductase chain 2 {ECO:0000256|ARBA:ARBA00021008, ECO:0000256|RuleBase:RU003403};
DE            EC=7.1.1.2 {ECO:0000256|ARBA:ARBA00012944, ECO:0000256|RuleBase:RU003403};
GN   Name=NADH2 {ECO:0000313|EMBL:BAE13242.1};
GN   Synonyms=ND2 {ECO:0000313|EMBL:AEG63015.1}, ndh2
GN   {ECO:0000313|EMBL:BAN79759.1};
OS   Homo sapiens (Human).
OG   Mitochondrion {ECO:0000313|EMBL:BAE13242.1}.
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606 {ECO:0000313|EMBL:BAE13242.1};
RN   [1] {ECO:0000313|EMBL:BAE13242.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=HNsq0238 {ECO:0000313|EMBL:BAE13242.1};
RX   PubMed=15466285; DOI=10.1101/gr.2286304;
RA   Tanaka M., Cabrera V.M., Gonzalez A.M., Larruga J.M., Takeyasu T., Fuku N.,
RA   Guo L., Hirose R., Fujita Y., Kurata M., Shinoda K., Umetsu K., Yamada Y.,
RA   Oshida Y., Sato Y., Hattori N., Mizuno Y., Arai Y., Hirose N., Ohta S.,
RA   Ogawa O., Tanaka Y., Kawamori R., Shamoto-Nagai M., Maruyama W.,
RA   Shimokata H., Suzuki R., Shimodaira H.;
RT   "Mitochondrial genome variation in eastern Asia and the peopling of
RT   Japan.";
RL   Genome Res. 14:1832-1850(2004).
RN   [2] {ECO:0000313|EMBL:BAG39189.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=Mdmd38 {ECO:0000313|EMBL:BAG39189.1}, and Mdmd39
RC   {ECO:0000313|EMBL:BAG39202.1};
RX   PubMed=16048457; DOI=10.1111/j.1440-1819.2005.01404.x;
RA   Kazuno A., Munakata K., Mori K., Tanaka M., Nanko S., Kunugi H.,
RA   Umekage T., Tochigi M., Kohda K., Sasaki T., Akiyama T., Washizuka S.,
RA   Kato N., Kato T.;
RT   "Mitochondrial DNA sequence analysis of patients with 'atypical
RT   psychosis'.";
RL   Psychiatry Clin. Neurosci. 59:497-503(2005).
RN   [3] {ECO:0000313|EMBL:BAE13242.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=HNsq0238 {ECO:0000313|EMBL:BAE13242.1};
RA   Tanaka M.;
RT   "Human mitochondrial genome polymorphism database (mtSNP).";
RL   Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4] {ECO:0000313|EMBL:BAG39189.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=Mdmd38 {ECO:0000313|EMBL:BAG39189.1}, and Mdmd39
RC   {ECO:0000313|EMBL:BAG39202.1};
RX   PubMed=16895436; DOI=10.1371/journal.pgen.0020128;
RA   Kazuno A., Munakata K., Nagai T., Shimozono S., Tanaka M., Yoneda M.,
RA   Kato N., Miyawaki A., Kato T.;
RT   "Identification of mitochondrial DNA polymorphisms that alter mitochondrial
RT   matrix pH and intracellular calcium dynamics.";
RL   PLoS Genet. 2:e128-e128(2006).
RN   [5] {ECO:0000313|EMBL:BAG39189.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=Mdmd38 {ECO:0000313|EMBL:BAG39189.1}, and Mdmd39
RC   {ECO:0000313|EMBL:BAG39202.1};
RA   Kazuno A., Munakata K., Mori K., Nanko S., Kunugi H., Nakamura K., Mori N.,
RA   Yamada K., Yoshikawa T., Kato N., Kato T.;
RT   "Mitochondrial DNA haplogroup analysis in patients with Bipolar Disorder.";
RL   Am. J. Med. Genet. B Neuropsychiatr. Genet. 0:0-0(2008).
RN   [6] {ECO:0000313|EMBL:BAG39189.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=Mdmd38 {ECO:0000313|EMBL:BAG39189.1}, and Mdmd39
RC   {ECO:0000313|EMBL:BAG39202.1};
RX   PubMed=17288645;
RA   Kazuno A., Munakata K., Kato N., Kato T.;
RT   "Mitochondrial DNA-dependent effects of valproate on mitochondrial calcium
RT   levels in transmitochondrial cybrids.";
RL   Int. J. Neuropsychopharmacol. 11:71-78(2008).
RN   [7] {ECO:0000313|EMBL:BAG39189.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=Mdmd38 {ECO:0000313|EMBL:BAG39189.1}, and Mdmd39
RC   {ECO:0000313|EMBL:BAG39202.1};
RX   PubMed=18226984; DOI=10.1016/j.mito.2007.12.002;
RA   Kazuno A., Munakata K., Tanaka M., Kato N., Kato T.;
RT   "Relationships between mitochondrial DNA subhaplogroups and intracellular
RT   calcium dynamics.";
RL   Mitochondrion 8:164-169(2008).
RN   [8] {ECO:0000313|EMBL:BAH11055.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=19066930; DOI=10.1007/s00414-008-0308-5;
RA   Nohira C., Maruyama S., Minaguchi K.;
RT   "Phylogenetic classification of Japanese mtDNA assisted by complete
RT   mitochondrial DNA sequences.";
RL   Int. J. Legal Med. 124:7-12(2010).
RN   [9] {ECO:0000313|EMBL:AEG63015.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Esophageal cancerous tissue {ECO:0000313|EMBL:AEG63015.1}, and
RC   Paracancerous normal esophageal tissue {ECO:0000313|EMBL:AEG64224.1};
RX   PubMed=22130971; DOI=10.1093/molbev/msr290;
RA   Liu J., Wang L.D., Sun Y.B., Li E.M., Xu L.Y., Zhang Y.P., Yao Y.G.,
RA   Kong Q.P.;
RT   "Deciphering the signature of selective constraints on cancerous
RT   mitochondrial genome.";
RL   Mol. Biol. Evol. 29:1255-1261(2012).
RN   [10] {ECO:0000313|EMBL:BAN79759.1}
RP   NUCLEOTIDE SEQUENCE.
RA   Mikami E., Fuku N., Kong Q.P., Takahashi H., Ohiwa N., Murakami H.,
RA   Miyachi M., Pitsiladis Y.P., Higuchi M., Kawahara T., Tanaka M.;
RT   "Comprehensive analysis of common and rare mitochondrial DNA variants in
RT   elite Japanese athletes: Case-control study.";
RL   Submitted (AUG-2013) to the EMBL/GenBank/DDBJ databases.
RN   [11] {ECO:0000313|EMBL:AFO26853.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=24341918; DOI=10.1111/acel.12186;
RA   Raule N., Sevini F., Li S., Barbieri A., Tallaro F., Lomartire L.,
RA   Vianello D., Montesanto A., Moilanen J.S., Bezrukov V., Blanche H.,
RA   Hervonen A., Christensen K., Deiana L., Gonos E.S., Kirkwood T.B.,
RA   Kristensen P., Leon A., Pelicci P.G., Poulain M., Rea I.M., Remacle J.,
RA   Robine J.M., Schreiber S., Sikora E., Eline Slagboom P., Spazzafumo L.,
RA   Antonietta Stazi M., Toussaint O., Vaupel J.W., Rose G., Majamaa K.,
RA   Perola M., Johnson T.E., Bolund L., Yang H., Passarino G., Franceschi C.;
RT   "The co-occurrence of mtDNA mutations on different oxidative
RT   phosphorylation subunits, not detected by haplogroup analysis, affects
RT   human longevity and is population specific.";
RL   Aging Cell 13:401-407(2014).
RN   [12] {ECO:0000313|EMBL:ALD87808.1}
RP   NUCLEOTIDE SEQUENCE.
RA   Zheng H.-X., Qin Z.-D., Jin L.;
RT   "The mitochondrial DNA diversity of World populations.";
RL   Submitted (DEC-2014) to the EMBL/GenBank/DDBJ databases.
RN   [13] {ECO:0000313|EMBL:AQX91655.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Blood {ECO:0000313|EMBL:AQX91655.1};
RX   PubMed=28187756; DOI=10.1186/s12881-017-0377-8;
RA   Soini H.K., Vaisanen A., Karppa M., Hinttala R., Kytovuori L.,
RA   Moilanen J.S., Uusimaa J., Majamaa K.;
RT   "A novel MTTT mutation m.15933G?>?A revealed in analysis of mitochondrial
RT   DNA in patients with suspected mitochondrial disease.";
RL   BMC Med. Genet. 18:14-14(2017).
CC   -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain
CC       NADH dehydrogenase (Complex I) which catalyzes electron transfer from
CC       NADH through the respiratory chain, using ubiquinone as an electron
CC       acceptor. Essential for the catalytic activity and assembly of complex
CC       I. {ECO:0000256|RuleBase:RU003403}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ubiquinone + 5 H(+)(in) + NADH = a ubiquinol + 4 H(+)(out) +
CC         NAD(+); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA-
CC         COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2;
CC         Evidence={ECO:0000256|ARBA:ARBA00000766,
CC         ECO:0000256|RuleBase:RU003403};
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004141}; Multi-
CC       pass membrane protein {ECO:0000256|ARBA:ARBA00004141}. Mitochondrion
CC       inner membrane {ECO:0000256|ARBA:ARBA00004448,
CC       ECO:0000256|RuleBase:RU003403}; Multi-pass membrane protein
CC       {ECO:0000256|ARBA:ARBA00004448, ECO:0000256|RuleBase:RU003403}.
CC   -!- SIMILARITY: Belongs to the complex I subunit 2 family.
CC       {ECO:0000256|ARBA:ARBA00007012, ECO:0000256|RuleBase:RU003403}.
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DR   EMBL; JF824882; AEG63015.1; -; Genomic_DNA.
DR   EMBL; JF824975; AEG64224.1; -; Genomic_DNA.
DR   EMBL; JX153283; AFO26853.1; -; Genomic_DNA.
DR   EMBL; KP240884; ALD87808.1; -; Genomic_DNA.
DR   EMBL; KY496893; AQX91655.1; -; Genomic_DNA.
DR   EMBL; AP008712; BAE13242.1; -; Genomic_DNA.
DR   EMBL; AP009456; BAG39189.1; -; Genomic_DNA.
DR   EMBL; AP009457; BAG39202.1; -; Genomic_DNA.
DR   EMBL; AP010836; BAH11055.1; -; Genomic_DNA.
DR   EMBL; AP013142; BAN79759.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q4GEA1; -.
DR   PeptideAtlas; Q4GEA1; -.
DR   ChiTaRS; ND2; human.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0070469; C:respirasome; IEA:UniProtKB-KW.
DR   GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IEA:UniProtKB-EC.
DR   GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IEA:InterPro.
DR   InterPro; IPR010933; NADH_DH_su2_C.
DR   InterPro; IPR003917; NADH_UbQ_OxRdtase_chain2.
DR   InterPro; IPR001750; ND/Mrp_mem.
DR   PANTHER; PTHR46552; NADH-UBIQUINONE OXIDOREDUCTASE CHAIN 2; 1.
DR   PANTHER; PTHR46552:SF1; NADH-UBIQUINONE OXIDOREDUCTASE CHAIN 2; 1.
DR   Pfam; PF06444; NADH_dehy_S2_C; 1.
DR   Pfam; PF00361; Proton_antipo_M; 1.
DR   PRINTS; PR01436; NADHDHGNASE2.
PE   3: Inferred from homology;
KW   Electron transport {ECO:0000256|RuleBase:RU003403};
KW   Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU003403};
KW   Mitochondrion {ECO:0000256|ARBA:ARBA00023128,
KW   ECO:0000256|RuleBase:RU003403};
KW   Mitochondrion inner membrane {ECO:0000256|ARBA:ARBA00022792,
KW   ECO:0000256|RuleBase:RU003403}; NAD {ECO:0000256|RuleBase:RU003403};
KW   Respiratory chain {ECO:0000256|RuleBase:RU003403};
KW   Translocase {ECO:0000256|RuleBase:RU003403};
KW   Transmembrane {ECO:0000256|ARBA:ARBA00022692,
KW   ECO:0000256|RuleBase:RU003403};
KW   Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW   ECO:0000256|RuleBase:RU003403}; Transport {ECO:0000256|ARBA:ARBA00022448};
KW   Ubiquinone {ECO:0000256|RuleBase:RU003403}.
FT   TRANSMEM        56..76
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU003403"
FT   TRANSMEM        96..115
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU003403"
FT   TRANSMEM        151..171
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU003403"
FT   TRANSMEM        178..196
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU003403"
FT   TRANSMEM        202..219
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU003403"
FT   TRANSMEM        239..257
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU003403"
FT   TRANSMEM        277..305
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU003403"
FT   TRANSMEM        325..346
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU003403"
FT   DOMAIN          23..284
FT                   /note="NADH:quinone oxidoreductase/Mrp antiporter membrane
FT                   subunit"
FT                   /evidence="ECO:0000259|Pfam:PF00361"
FT   DOMAIN          290..344
FT                   /note="NADH dehydrogenase subunit 2 C-terminal"
FT                   /evidence="ECO:0000259|Pfam:PF06444"
SQ   SEQUENCE   347 AA;  38927 MW;  208FD982317C358D CRC64;
     MNPLAQPVIY STIFAGTLIT ALSSHWFFTW VGLEMNMLAF IPVLTKKMNP RSTEAAIKYF
     LTQATASMIL LMAILFNNML SGQWTMTNTT NQYSSLMIMM AMAMKLGMAP FHFWVPEVTQ
     GTPLTSGLLL LTWQKLAPIS IMYQISPSLN VSLLLTLSIL SIMAGSWGGL NQTQLRKILA
     YSSITHMGWM MAVLPYNPNM TILNLTIYII LTTTAFLLLN LNSSTTTLLL SRTWNKLTWL
     TPLIPSTLLS LGGLPPLTGF LPKWAIIEEF TKNNSLIIPT IMATITLLNL YFYLRLIYST
     SITLLPMSNN VKMKWQLEHT KPTPFLPTLI ALTTLLLPIS PFMLMIL
//