NUOG_MYCTU
ID NUOG_MYCTU Reviewed; 806 AA.
AC P9WIV9; L0TBP2; P95175;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=NADH-quinone oxidoreductase subunit G;
DE EC=7.1.1.-;
DE AltName: Full=NADH dehydrogenase I subunit G;
DE AltName: Full=NDH-1 subunit G;
GN Name=nuoG; OrderedLocusNames=Rv3151; ORFNames=MTCY03A2.07c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17658950; DOI=10.1371/journal.ppat.0030110;
RA Velmurugan K., Chen B., Miller J.L., Azogue S., Gurses S., Hsu T.,
RA Glickman M., Jacobs W.R. Jr., Porcelli S.A., Briken V.;
RT "Mycobacterium tuberculosis nuoG is a virulence gene that inhibits
RT apoptosis of infected host cells.";
RL PLoS Pathog. 3:E110-E110(2007).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20421951; DOI=10.1371/journal.ppat.1000864;
RA Miller J.L., Velmurugan K., Cowan M.J., Briken V.;
RT "The type I NADH dehydrogenase of Mycobacterium tuberculosis counters
RT phagosomal NOX2 activity to inhibit TNF-alpha-mediated host cell
RT apoptosis.";
RL PLoS Pathog. 6:E1000864-E1000864(2010).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=22264515; DOI=10.1016/j.chom.2011.11.012;
RA Blomgran R., Desvignes L., Briken V., Ernst J.D.;
RT "Mycobacterium tuberculosis inhibits neutrophil apoptosis, leading to
RT delayed activation of naive CD4 T cells.";
RL Cell Host Microbe 11:81-90(2012).
CC -!- FUNCTION: NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur
CC (Fe-S) centers, to quinones in the respiratory chain. The immediate
CC electron acceptor for the enzyme in this species is believed to be
CC menaquinone. Couples the redox reaction to proton translocation (for
CC every two electrons transferred, four hydrogen ions are translocated
CC across the cytoplasmic membrane), and thus conserves the redox energy
CC in a proton gradient (By similarity). {ECO:0000250}.
CC -!- FUNCTION: Plays a critical role in M.tuberculosis ability to inhibit
CC apoptosis of infected macrophages; thus helps the bacterium in its
CC struggle to resist the host immune response (PubMed:17658950). In fact,
CC via a NuoG-dependent mechanism, M.tuberculosis can neutralize NOX2-
CC derived reactive oxygen species (ROS) in order to inhibit TNF-alpha-
CC mediated host cell apoptosis (PubMed:20421951). Also mediates
CC inhibition of neutrophil apoptosis, leading to delayed activation of
CC naive CD4 T cells (PubMed:22264515). {ECO:0000269|PubMed:17658950,
CC ECO:0000269|PubMed:20421951, ECO:0000269|PubMed:22264515}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + 5 H(+)(in) + NADH = a quinol + 4 H(+)(out) +
CC NAD(+); Xref=Rhea:RHEA:57888, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:132124;
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135; Evidence={ECO:0000250};
CC Note=Binds 1 [2Fe-2S] cluster per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250};
CC Note=Binds 3 [4Fe-4S] clusters per subunit. {ECO:0000250};
CC -!- SUBUNIT: The type I NADH dehydrogenase consists of 14 different
CC subunits. {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Deletion of nuoG in M.tuberculosis reduces its
CC ability to inhibit apoptosis of infected human or mouse macrophages and
CC significantly decreases its virulence in mice (PubMed:17658950). The
CC apoptogenic phenotype of the mutant strain is significantly reduced in
CC human macrophages treated with caspase-3 and -8 inhibitors, TNF-alpha-
CC neutralizing antibodies, and also after infection of murine TNF(-/-)
CC macrophages. Moreover, incubation of macrophages with inhibitors of
CC reactive oxygen species (ROS) reduces not only the apoptosis induced by
CC the nuoG deletion mutant, but also its capacity to increase macrophage
CC TNF-alpha secretion. The phagosomes infected with the mutant show
CC increased ROS levels compared to M.tuberculosis phagosomes in primary
CC murine and human alveolar macrophages. The increase in nuoG deletion
CC mutant induced ROS and apoptosis is abolished in NOX-2 deficient
CC (gp91(-/-)) macrophages (PubMed:20421951). Compared to wild-type, the
CC nuoG deletion mutant spreads to a larger number of lung phagocytic
CC cells. Consistent with the shorter lifespan of infected neutrophils,
CC infection with the nuoG mutant results in fewer bacteria per infected
CC neutrophil, accelerated bacterial acquisition by dendritic cells,
CC earlier trafficking of these dendritic cells to lymph nodes, and faster
CC CD4 T cell priming. Neutrophil depletion abrogates accelerated CD4 T
CC cell priming by the nuoG mutant, suggesting that inhibiting neutrophil
CC apoptosis delays adaptive immunity in tuberculosis (PubMed:22264515).
CC {ECO:0000269|PubMed:17658950, ECO:0000269|PubMed:20421951,
CC ECO:0000269|PubMed:22264515}.
CC -!- SIMILARITY: Belongs to the complex I 75 kDa subunit family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP45962.1; -; Genomic_DNA.
DR PIR; H70647; H70647.
DR RefSeq; NP_217667.1; NC_000962.3.
DR RefSeq; WP_003916519.1; NZ_NVQJ01000019.1.
DR AlphaFoldDB; P9WIV9; -.
DR SMR; P9WIV9; -.
DR STRING; 83332.Rv3151; -.
DR iPTMnet; P9WIV9; -.
DR PaxDb; P9WIV9; -.
DR GeneID; 887540; -.
DR KEGG; mtu:Rv3151; -.
DR TubercuList; Rv3151; -.
DR eggNOG; COG1034; Bacteria.
DR OMA; NVYFGRV; -.
DR PhylomeDB; P9WIV9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0045272; C:plasma membrane respiratory chain complex I; IBA:GO_Central.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043546; F:molybdopterin cofactor binding; IEA:InterPro.
DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IEA:InterPro.
DR GO; GO:0048038; F:quinone binding; IEA:UniProtKB-KW.
DR GO; GO:0042773; P:ATP synthesis coupled electron transport; IEA:InterPro.
DR GO; GO:0045333; P:cellular respiration; IBA:GO_Central.
DR GO; GO:0033668; P:negative regulation by symbiont of host apoptotic process; IMP:MTBBASE.
DR CDD; cd00207; fer2; 1.
DR InterPro; IPR036010; 2Fe-2S_ferredoxin-like_sf.
DR InterPro; IPR001041; 2Fe-2S_ferredoxin-type.
DR InterPro; IPR009010; Asp_de-COase-like_dom_sf.
DR InterPro; IPR006657; MoPterin_dinucl-bd_dom.
DR InterPro; IPR006656; Mopterin_OxRdtase.
DR InterPro; IPR006963; Mopterin_OxRdtase_4Fe-4S_dom.
DR InterPro; IPR000283; NADH_UbQ_OxRdtase_75kDa_su_CS.
DR InterPro; IPR010228; NADH_UbQ_OxRdtase_Gsu.
DR InterPro; IPR019574; NADH_UbQ_OxRdtase_Gsu_4Fe4S-bd.
DR Pfam; PF00384; Molybdopterin; 1.
DR Pfam; PF01568; Molydop_binding; 1.
DR Pfam; PF10588; NADH-G_4Fe-4S_3; 1.
DR SMART; SM00926; Molybdop_Fe4S4; 1.
DR SMART; SM00929; NADH-G_4Fe-4S_3; 1.
DR SUPFAM; SSF50692; SSF50692; 1.
DR SUPFAM; SSF54292; SSF54292; 1.
DR TIGRFAMs; TIGR01973; NuoG; 1.
DR PROSITE; PS51085; 2FE2S_FER_2; 1.
DR PROSITE; PS51839; 4FE4S_HC3; 1.
DR PROSITE; PS51669; 4FE4S_MOW_BIS_MGD; 1.
DR PROSITE; PS00641; COMPLEX1_75K_1; 1.
DR PROSITE; PS00642; COMPLEX1_75K_2; 1.
DR PROSITE; PS00643; COMPLEX1_75K_3; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; 4Fe-4S; Acetylation; Iron; Iron-sulfur; Metal-binding; NAD;
KW Quinone; Reference proteome; Translocase; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..806
FT /note="NADH-quinone oxidoreductase subunit G"
FT /id="PRO_0000118559"
FT DOMAIN 15..93
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 95..134
FT /note="4Fe-4S His(Cys)3-ligated-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184"
FT DOMAIN 233..289
FT /note="4Fe-4S Mo/W bis-MGD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01004"
FT BINDING 49
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 60
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 63
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 77
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250"
FT BINDING 111
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184"
FT BINDING 115
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184"
FT BINDING 118
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184"
FT BINDING 124
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184"
FT BINDING 164
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 170
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 214
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 240
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000255"
FT BINDING 243
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000255"
FT BINDING 247
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000255"
FT BINDING 275
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
SQ SEQUENCE 806 AA; 85424 MW; 519A1EA833181064 CRC64;
MTQAADTDIR VGQPEMVTLT IDGVEISVPK GTLVIRAAEL MGIQIPRFCD HPLLEPVGAC
RQCLVEVEGQ RKPLASCTTV ATDDMVVRTQ LTSEIADKAQ HGVMELLLIN HPLDCPMCDK
GGECPLQNQA MSNGRTDSRF TEAKRTFAKP INISAQVLLD RERCILCARC TRFSDQIAGD
PFIDMQERGA LQQVGIYADE PFESYFSGNT VQICPVGALT GTAYRFRARP FDLVSSPSVC
EHCASGCAQR TDHRRGKVLR RLAGDDPEVN EEWNCDKGRW AFTYATQPDV ITTPLIRDGG
DPKGALVPTS WSHAMAVAAQ GLAAARGRTG VLVGGRVTWE DAYAYAKFAR ITLGTNDIDF
RARPHSAEEA DFLAARIAGR HMAVSYADLE SAPVVLLVGF EPEDESPIVF LRLRKAARRH
RVPVYTIAPF ATGGLHKMSG RLIKTVPGGE PAALDDLATG AVGDLLATPG AVIIVGERLA
TVPGGLSAAA RLADTTGARL AWVPRRAGER GALEAGALPT LLPGGRPLAD EVARAQVCAA
WHIAELPAAA GRDADGILAA AADETLAALL VGGIEPADFA DPDAVLAALD ATGFVVSLEL
RHSTVTERAD VVFPVAPTTQ KAGAFVNWEG RYRTFEPALR GSTLQAGQSD HRVLDALADD
MGVHLGVPTV EAAREELAAL GIWDGKHAAG PHIAATGPTQ PEAGEAILTG WRMLLDEGRL
QDGEPYLAGT ARTPVVRLSP DTAAEIGAAD GEAVTVSTSR GSITLPCSVT DMPDRVVWLP
LNSAGSTVHR QLRVTIGSIV KIGAGS
