TNRA_BACSU
ID TNRA_BACSU Reviewed; 110 AA.
AC Q45666;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=HTH-type transcriptional regulator TnrA {ECO:0000303|PubMed:8799114};
DE AltName: Full=Transcriptional nitrogen regulatory protein A {ECO:0000305|PubMed:8799114};
DE Short=TnrA {ECO:0000305|PubMed:8799114};
GN Name=tnrA {ECO:0000303|PubMed:8799114}; Synonyms=scgR;
GN OrderedLocusNames=BSU13310;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=168;
RX PubMed=8799114; DOI=10.1073/pnas.93.17.8841;
RA Wray L.V. Jr., Ferson A.E., Rohrer K., Fisher S.H.;
RT "TnrA, a transcription factor required for global nitrogen regulation in
RT Bacillus subtilis.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:8841-8845(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RA Kontinen V.P., Helander I.M., Tokuda H.;
RT "The secG deletion mutation of Escherichia coli is suppressed by expression
RT of a novel regulatory protein of Bacillus subtilis.";
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RA Devine K.M.;
RT "Sequence of the Bacillus subtilis genome between xlyA and ykoR.";
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=9603886; DOI=10.1128/jb.180.11.2943-2949.1998;
RA Wray L.V. Jr., Zalieckas J.M., Ferson A.E., Fisher S.H.;
RT "Mutational analysis of the TnrA-binding sites in the Bacillus subtilis
RT nrgAB and gabP promoter regions.";
RL J. Bacteriol. 180:2943-2949(1998).
RN [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=10231480; DOI=10.1046/j.1365-2958.1999.01333.x;
RA Fisher S.H.;
RT "Regulation of nitrogen metabolism in Bacillus subtilis: vive la
RT difference!";
RL Mol. Microbiol. 32:223-232(1999).
RN [7]
RP FUNCTION, MUTAGENESIS OF 28-ARG--ARG-31, INDUCTION, AND SUBUNIT.
RC STRAIN=168;
RX PubMed=10864496; DOI=10.1006/jmbi.2000.3846;
RA Wray L.V. Jr., Zalieckas J.M., Fisher S.H.;
RT "Purification and in vitro activities of the Bacillus subtilis TnrA
RT transcription factor.";
RL J. Mol. Biol. 300:29-40(2000).
RN [8]
RP FUNCTION, INTERACTION WITH GLUTAMINE SYNTHETASE, ACTIVITY REGULATION, AND
RP MUTAGENESIS OF GLU-98 AND GLY-99.
RX PubMed=11719184; DOI=10.1016/s0092-8674(01)00572-4;
RA Wray L.V. Jr., Zalieckas J.M., Fisher S.H.;
RT "Bacillus subtilis glutamine synthetase controls gene expression through a
RT protein-protein interaction with transcription factor TnrA.";
RL Cell 107:427-435(2001).
RN [9]
RP FUNCTION.
RX PubMed=12823818; DOI=10.1046/j.1365-2958.2003.03567.x;
RA Yoshida K., Yamaguchi H., Kinehara M., Ohki Y.-H., Nakaura Y., Fujita Y.;
RT "Identification of additional TnrA-regulated genes of Bacillus subtilis
RT associated with a TnrA box.";
RL Mol. Microbiol. 49:157-165(2003).
RN [10]
RP INTERACTION WITH GLNK AND AMTB, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=17001076; DOI=10.1074/jbc.m607582200;
RA Heinrich A., Woyda K., Brauburger K., Meiss G., Detsch C., Stuelke J.,
RA Forchhammer K.;
RT "Interaction of the membrane-bound GlnK-AmtB complex with the master
RT regulator of nitrogen metabolism TnrA in Bacillus subtilis.";
RL J. Biol. Chem. 281:34909-34917(2006).
RN [11]
RP INTERACTION WITH GLNK AND AMTB, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=21435182; DOI=10.1111/j.1742-4658.2011.08102.x;
RA Kayumov A., Heinrich A., Fedorova K., Ilinskaya O., Forchhammer K.;
RT "Interaction of the general transcription factor TnrA with the PII-like
RT protein GlnK and glutamine synthetase in Bacillus subtilis.";
RL FEBS J. 278:1779-1789(2011).
RN [12] {ECO:0007744|PDB:4S0R}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 95-110, ACTIVITY REGULATION,
RP MUTAGENESIS OF LYS-108, AND SUBUNIT.
RX PubMed=25691471; DOI=10.1101/gad.254714.114;
RA Schumacher M.A., Chinnam N.B., Cuthbert B., Tonthat N.K., Whitfill T.;
RT "Structures of regulatory machinery reveal novel molecular mechanisms
RT controlling B. subtilis nitrogen homeostasis.";
RL Genes Dev. 29:451-464(2015).
CC -!- FUNCTION: Transcription regulator that actives the transcription of
CC genes required for nitrogen assimilation such as nrgAB (ammonium
CC transport), nasABCDEF (nitrate/nitrite assimilation), ureABC (urea
CC degradation) and gabP (GABA transport), during nitrogen limitation
CC (PubMed:8799114, PubMed:9603886, PubMed:10231480, PubMed:10864496,
CC PubMed:11719184, PubMed:12823818). Also represses glnRA and gltAB in
CC the absence of ammonium (PubMed:8799114, PubMed:9603886,
CC PubMed:10231480, PubMed:10864496, PubMed:11719184, PubMed:12823818). On
CC the contrary of the MerR members, which require longer DNA sites for
CC high-affinity binding, TnrA requires a DNA sequence of 17 nucleotides
CC as minimal binding site (PubMed:10231480, PubMed:25691471).
CC {ECO:0000269|PubMed:10231480, ECO:0000269|PubMed:10864496,
CC ECO:0000269|PubMed:11719184, ECO:0000269|PubMed:12823818,
CC ECO:0000269|PubMed:25691471, ECO:0000269|PubMed:8799114,
CC ECO:0000269|PubMed:9603886}.
CC -!- ACTIVITY REGULATION: Under conditions of nitrogen excess, the DNA-
CC binding activity is inhibited by the formation of a stable complex with
CC feedback-inhibited GlnA (PubMed:11719184, PubMed:25691471). The
CC presence of glutamine and AMP increases the inhibitory activity of
CC glutamine synthetase by more than 1000-fold (PubMed:11719184).
CC {ECO:0000269|PubMed:11719184, ECO:0000269|PubMed:25691471}.
CC -!- SUBUNIT: Homodimer (PubMed:10864496, PubMed:25691471). Under conditions
CC of nitrogen excess, TnrA forms a stable complex with feedback-inhibited
CC GlnA. Interacts with GlnK-AmtB complex. {ECO:0000269|PubMed:10864496,
CC ECO:0000269|PubMed:17001076, ECO:0000269|PubMed:21435182,
CC ECO:0000269|PubMed:25691471}.
CC -!- INTERACTION:
CC Q45666; P12425: glnA; NbExp=8; IntAct=EBI-8507041, EBI-6402863;
CC Q45666; P40758: glnK; NbExp=6; IntAct=EBI-8507041, EBI-8507093;
CC -!- SUBCELLULAR LOCATION: Cell membrane. Note=Under poor nitrogen source
CC such as nitrate, TnrA is associated with the cell membrane via the
CC ammonium uptake proteins AmtB and its cognate regulator GlnK
CC (PubMed:21435182). Without usable nitrogen source, TnrA is released
CC from the membrane to the cytoplasm where it is degraded by proteolysis
CC (PubMed:21435182). The presence of 4 mM ATP leads to concomitant
CC solubilization of GlnK and TnrA (PubMed:17001076). GlnK and Amtb are
CC required for the membrane association of TnrA (PubMed:17001076).
CC {ECO:0000269|PubMed:17001076, ECO:0000269|PubMed:21435182}.
CC -!- INDUCTION: Under conditions of nitrogen excess, repressed by GlnR.
CC Under conditions of nitrogen-limited growth, it positively regulates
CC its own expression. {ECO:0000269|PubMed:10231480,
CC ECO:0000269|PubMed:10864496, ECO:0000269|PubMed:9603886}.
CC -!- DISRUPTION PHENOTYPE: TnrA mutant is impaired in its ability to utilize
CC allantoin, gamma-aminobutyrate, isoleucine, nitrate, urea and valine as
CC nitrogen sources. During nitrogen-limited growth, transcription of the
CC nrgAB, nasB, gabP, and ure genes is significantly reduced in the tnrA
CC mutant. In contrast, the level of glnRA expression is 4-fold higher in
CC the tnrA mutant than in wild-type cells during nitrogen restriction.
CC {ECO:0000269|PubMed:8799114}.
CC -!- MISCELLANEOUS: The amino acid sequences of the N-terminal DNA binding
CC domains of TnrA and GlnR are highly similar, and both proteins bind to
CC DNA sequences with a common consensus sequence. In contrast, the C-
CC terminal signal transduction domains of TnrA and GlnR have no homology.
CC {ECO:0000305}.
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DR EMBL; U55004; AAC44335.1; -; Genomic_DNA.
DR EMBL; X98512; CAA67135.1; -; Genomic_DNA.
DR EMBL; AJ002571; CAA05609.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB13188.1; -; Genomic_DNA.
DR PIR; S70466; S70466.
DR RefSeq; NP_389214.1; NC_000964.3.
DR RefSeq; WP_003232541.1; NZ_JNCM01000035.1.
DR PDB; 4S0R; X-ray; 3.50 A; 1/2/O/P/Q/R/S/T/U/V/W/X/Y/Z=95-110.
DR PDBsum; 4S0R; -.
DR AlphaFoldDB; Q45666; -.
DR SMR; Q45666; -.
DR IntAct; Q45666; 2.
DR MINT; Q45666; -.
DR STRING; 224308.BSU13310; -.
DR PaxDb; Q45666; -.
DR PRIDE; Q45666; -.
DR EnsemblBacteria; CAB13188; CAB13188; BSU_13310.
DR GeneID; 936445; -.
DR KEGG; bsu:BSU13310; -.
DR PATRIC; fig|224308.179.peg.1446; -.
DR eggNOG; COG0789; Bacteria.
DR InParanoid; Q45666; -.
DR OMA; MQTFEIR; -.
DR PhylomeDB; Q45666; -.
DR BioCyc; BSUB:BSU13310-MON; -.
DR SABIO-RK; Q45666; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IMP:CAFA.
DR GO; GO:0043562; P:cellular response to nitrogen levels; IMP:CAFA.
DR GO; GO:0090294; P:nitrogen catabolite activation of transcription; IMP:CAFA.
DR InterPro; IPR009061; DNA-bd_dom_put_sf.
DR InterPro; IPR000551; MerR-type_HTH_dom.
DR Pfam; PF13411; MerR_1; 1.
DR PRINTS; PR00040; HTHMERR.
DR SMART; SM00422; HTH_MERR; 1.
DR SUPFAM; SSF46955; SSF46955; 1.
DR PROSITE; PS50937; HTH_MERR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cell membrane; DNA-binding; Membrane;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..110
FT /note="HTH-type transcriptional regulator TnrA"
FT /id="PRO_0000098158"
FT DOMAIN 13..81
FT /note="HTH merR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00254"
FT DNA_BIND 16..35
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00254"
FT MUTAGEN 28..31
FT /note="RQIR->AQIA: 1000-fold decrease of the affinity for
FT NrgAB compared to the wild-type. Structure more asymmetric
FT than that of the wild-type."
FT /evidence="ECO:0000269|PubMed:10864496"
FT MUTAGEN 98
FT /note="E->G: Causes constitutive expression of TnrA.
FT Feedback-inhibited GlnA has a greatly reduced ability to
FT block the DNA binding."
FT /evidence="ECO:0000269|PubMed:11719184"
FT MUTAGEN 99
FT /note="G->E: Causes constitutive expression of TnrA.
FT Feedback-inhibited GlnA has a greatly reduced ability to
FT block the DNA-binding."
FT /evidence="ECO:0000269|PubMed:11719184"
FT MUTAGEN 99
FT /note="G->R: Causes constitutive expression of TnrA.
FT Feedback-inhibited GlnA has a greatly reduced ability to
FT block the DNA binding."
FT /evidence="ECO:0000269|PubMed:11719184"
FT MUTAGEN 108
FT /note="K->E: No interaction with glutamine synthetase."
FT /evidence="ECO:0000269|PubMed:25691471"
FT HELIX 97..100
FT /evidence="ECO:0007829|PDB:4S0R"
FT HELIX 102..108
FT /evidence="ECO:0007829|PDB:4S0R"
SQ SEQUENCE 110 AA; 13126 MW; 201AA41E76E0E631 CRC64;
MTTEDHSYKD KKVISIGIVS ELTGLSVRQI RYYEERKLIY PQRSSRGTRK YSFADVERLM
DIANKREDGV QTAEILKDMR KKEQMLKNDP QVRKKMLEGQ LNAHFRYKNR
