NMRA_EMENI
ID NMRA_EMENI Reviewed; 352 AA.
AC Q5AU62; C8V6Y1; O59919;
DT 20-APR-2010, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Nitrogen metabolite repression protein nmrA;
DE AltName: Full=Negative-acting nitrogen regulatory protein nmrA;
DE AltName: Full=Nitrogen metabolite regulation protein;
GN Name=nmrA; ORFNames=AN8168;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DISRUPTION PHENOTYPE.
RX PubMed=9537404; DOI=10.1128/jb.180.7.1973-1977.1998;
RA Andrianopoulos A., Kourambas S., Sharp J.A., Davis M.A., Hynes M.J.;
RT "Characterization of the Aspergillus nidulans nmrA gene involved in
RT nitrogen metabolite repression.";
RL J. Bacteriol. 180:1973-1977(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [4]
RP SUBUNIT.
RX PubMed=11679757; DOI=10.1107/s090744490101410x;
RA Nichols C.E., Cocklin S., Dodds A., Ren J., Lamb H., Hawkins A.R.,
RA Stammers D.K.;
RT "Expression, purification and crystallization of Aspergillus nidulans NmrA,
RT a negative regulatory protein involved in nitrogen-metabolite repression.";
RL Acta Crystallogr. D 57:1722-1725(2001).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY NITROGEN.
RX PubMed=17854403; DOI=10.1111/j.1365-2958.2007.05940.x;
RA Wong K.H., Hynes M.J., Todd R.B., Davis M.A.;
RT "Transcriptional control of nmrA by the bZIP transcription factor MeaB
RT reveals a new level of nitrogen regulation in Aspergillus nidulans.";
RL Mol. Microbiol. 66:534-551(2007).
RN [6] {ECO:0007744|PDB:1K6I, ECO:0007744|PDB:1K6J, ECO:0007744|PDB:1K6X}
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEX WITH NAD.
RX PubMed=11726498; DOI=10.1093/emboj/20.23.6619;
RA Stammers D.K., Ren J., Leslie K., Nichols C.E., Lamb H.K., Cocklin S.,
RA Dodds A., Hawkins A.R.;
RT "The structure of the negative transcriptional regulator NmrA reveals a
RT structural superfamily which includes the short-chain
RT dehydrogenase/reductases.";
RL EMBO J. 20:6619-6626(2001).
RN [7] {ECO:0007744|PDB:1TI7}
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEXES WITH NADP, FUNCTION, AND
RP INTERACTION WITH AREA.
RX PubMed=12764138; DOI=10.1074/jbc.m304104200;
RA Lamb H.K., Leslie K., Dodds A.L., Nutley M., Cooper A., Johnson C.,
RA Thompson P., Stammers D.K., Hawkins A.R.;
RT "The negative transcriptional regulator NmrA discriminates between oxidized
RT and reduced dinucleotides.";
RL J. Biol. Chem. 278:32107-32114(2003).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF MUTANT GLY-12/GLY-18 APOPROTEIN,
RP INTERACTION WITH AREA, FUNCTION, AND MUTAGENESIS OF ASN-12; THR-14; ALA-18;
RP HIS-37; GLU-193; ASP-195; GLN-202; PHE-204; GLU-263 AND GLU-266.
RX PubMed=15537757; DOI=10.1110/ps.04958904;
RA Lamb H.K., Ren J., Park A., Johnson C., Leslie K., Cocklin S., Thompson P.,
RA Mee C., Cooper A., Stammers D.K., Hawkins A.R.;
RT "Modulation of the ligand binding properties of the transcription repressor
RT NmrA by GATA-containing DNA and site-directed mutagenesis.";
RL Protein Sci. 13:3127-3138(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEXES WITH NAD; NADP AND AREA,
RP AND FUNCTION.
RX PubMed=18602114; DOI=10.1016/j.jmb.2008.05.077;
RA Kotaka M., Johnson C., Lamb H.K., Hawkins A.R., Ren J., Stammers D.K.;
RT "Structural analysis of the recognition of the negative regulator NmrA and
RT DNA by the zinc finger from the GATA-type transcription factor AreA.";
RL J. Mol. Biol. 381:373-382(2008).
CC -!- FUNCTION: May be a redox sensor protein. Has much higher affinity for
CC NAD(P) than for NAD(P)H. Has similar affinity for NAD and NADP.
CC Negative transcriptional regulator involved in the post-transcriptional
CC modulation of the GATA-type transcription factor areA, forming part of
CC a system controlling nitrogen metabolite repression (By similarity).
CC Interferes with the interaction between areA and target DNA.
CC Overexpression leads to areA inhibition. {ECO:0000250,
CC ECO:0000269|PubMed:12764138, ECO:0000269|PubMed:15537757,
CC ECO:0000269|PubMed:17854403, ECO:0000269|PubMed:18602114}.
CC -!- SUBUNIT: Monomer. Interacts with areA. {ECO:0000269|PubMed:11679757,
CC ECO:0000269|PubMed:11726498, ECO:0000269|PubMed:12764138,
CC ECO:0000269|PubMed:15537757}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Cytoplasm
CC {ECO:0000269|PubMed:17854403}.
CC -!- INDUCTION: Up-regulated in nitrogen-sufficient conditions and down-
CC regulated in nitrogen-limiting conditions.
CC {ECO:0000269|PubMed:17854403}.
CC -!- DISRUPTION PHENOTYPE: Displays partial derepression of activities
CC subject to nitrogen metabolic repression. {ECO:0000269|PubMed:9537404}.
CC -!- SIMILARITY: Belongs to the NmrA-type oxidoreductase family.
CC {ECO:0000305}.
CC -!- CAUTION: Lacks the conserved Tyr residue in position 127 in the active
CC site triad of Ser-Tyr-Lys that is necessary for dehydrogenase activity,
CC suggesting that it has no oxidoreductase activity. {ECO:0000305}.
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DR EMBL; AF041976; AAC39442.1; -; Genomic_DNA.
DR EMBL; AACD01000141; EAA59190.1; -; Genomic_DNA.
DR EMBL; BN001302; CBF74025.1; -; Genomic_DNA.
DR RefSeq; XP_681437.1; XM_676345.1.
DR PDB; 1K6I; X-ray; 1.80 A; A=1-352.
DR PDB; 1K6J; X-ray; 1.80 A; A/B=1-352.
DR PDB; 1K6X; X-ray; 1.50 A; A=1-352.
DR PDB; 1TI7; X-ray; 1.70 A; A=1-352.
DR PDB; 1XGK; X-ray; 1.40 A; A=1-352.
DR PDB; 2VUS; X-ray; 2.60 A; A/B/C/D/E/F/G/H=1-352.
DR PDB; 2VUT; X-ray; 2.30 A; A/B/C/D/E/F/G/H=1-352.
DR PDB; 2VUU; X-ray; 2.80 A; A/B/C/D/E/F/G/H=1-352.
DR PDBsum; 1K6I; -.
DR PDBsum; 1K6J; -.
DR PDBsum; 1K6X; -.
DR PDBsum; 1TI7; -.
DR PDBsum; 1XGK; -.
DR PDBsum; 2VUS; -.
DR PDBsum; 2VUT; -.
DR PDBsum; 2VUU; -.
DR AlphaFoldDB; Q5AU62; -.
DR SMR; Q5AU62; -.
DR STRING; 162425.CADANIAP00004208; -.
DR EnsemblFungi; CBF74025; CBF74025; ANIA_08168.
DR EnsemblFungi; EAA59190; EAA59190; AN8168.2.
DR GeneID; 2869210; -.
DR KEGG; ani:AN8168.2; -.
DR VEuPathDB; FungiDB:AN8168; -.
DR eggNOG; ENOG502QTW1; Eukaryota.
DR HOGENOM; CLU_027360_0_0_1; -.
DR InParanoid; Q5AU62; -.
DR OMA; PYPLFCM; -.
DR OrthoDB; 885281at2759; -.
DR EvolutionaryTrace; Q5AU62; -.
DR Proteomes; UP000000560; Chromosome II.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:AspGD.
DR GO; GO:0051287; F:NAD binding; IDA:UniProtKB.
DR GO; GO:0070403; F:NAD+ binding; IDA:UniProtKB.
DR GO; GO:0070401; F:NADP+ binding; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0090295; P:nitrogen catabolite repression of transcription; IMP:AspGD.
DR GO; GO:0001081; P:nitrogen catabolite repression of transcription from RNA polymerase II promoter; IMP:AspGD.
DR GO; GO:0006808; P:regulation of nitrogen utilization; IMP:UniProtKB.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR008030; NmrA-like.
DR Pfam; PF05368; NmrA; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; NAD; NADP; Nucleus; Oxidoreductase;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..352
FT /note="Nitrogen metabolite repression protein nmrA"
FT /id="PRO_0000393568"
FT REGION 287..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 12..17
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12764138,
FT ECO:0007744|PDB:1TI7"
FT BINDING 16..17
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11726498,
FT ECO:0007744|PDB:1K6X"
FT BINDING 37
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12764138,
FT ECO:0007744|PDB:1TI7"
FT BINDING 80..82
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11726498,
FT ECO:0007744|PDB:1K6X"
FT BINDING 80
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12764138,
FT ECO:0007744|PDB:1TI7"
FT BINDING 131
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11726498,
FT ECO:0007744|PDB:1K6X"
FT BINDING 131
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12764138,
FT ECO:0007744|PDB:1TI7"
FT BINDING 153..156
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11726498,
FT ECO:0007744|PDB:1K6X"
FT BINDING 153..156
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12764138,
FT ECO:0007744|PDB:1TI7"
FT MUTAGEN 12
FT /note="N->G: 13-fold increase in the Kd for NAD; 2-fold
FT increase in the Kd for NADP and 2-fold increase in the Kd
FT for areA; when associated with G-18."
FT /evidence="ECO:0000269|PubMed:15537757"
FT MUTAGEN 14
FT /note="T->V: 4-fold increase in the Kd for NAD; 7-fold
FT increase in the Kd for NADP and no change in the Kd for
FT areA."
FT /evidence="ECO:0000269|PubMed:15537757"
FT MUTAGEN 18
FT /note="A->G: 13-fold increase in the Kd for NAD; 2-fold
FT increase in the Kd for NADP and 2-fold increase in the Kd
FT for areA; when associated with G-12."
FT /evidence="ECO:0000269|PubMed:15537757"
FT MUTAGEN 37
FT /note="H->W: 4-fold decrease in the Kd for NAD; 24%
FT increase in the Kd for NADP and no change in the Kd for
FT areA."
FT /evidence="ECO:0000269|PubMed:15537757"
FT MUTAGEN 193
FT /note="E->Q: No changes in the Kd for NAD and NADP and
FT almost complete loss of affinity for areA; when associated
FT with N-195."
FT /evidence="ECO:0000269|PubMed:15537757"
FT MUTAGEN 195
FT /note="D->N: No changes in the Kd for NAD and NADP and
FT almost complete loss of affinity for areA; when associated
FT with Q-193."
FT /evidence="ECO:0000269|PubMed:15537757"
FT MUTAGEN 202
FT /note="Q->E: No changes in the Kd for NAD and NADP and 2-
FT fold increase in the Kd for areA; when associated with Y-
FT 204."
FT /evidence="ECO:0000269|PubMed:15537757"
FT MUTAGEN 204
FT /note="F->Y: No changes in the Kd for NAD and NADP and 2-
FT fold increase in the Kd for areA; when associated with E-
FT 202."
FT /evidence="ECO:0000269|PubMed:15537757"
FT MUTAGEN 263
FT /note="E->Q: No changes in the Kd for NAD; NADP and areA;
FT when associated with Q-266."
FT /evidence="ECO:0000269|PubMed:15537757"
FT MUTAGEN 266
FT /note="E->Q: No changes in the Kd for NAD; NADP and areA;
FT when associated with Q-263."
FT /evidence="ECO:0000269|PubMed:15537757"
FT CONFLICT 238
FT /note="R -> L (in Ref. 1; AAC39442)"
FT /evidence="ECO:0000305"
FT STRAND 8..12
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 16..27
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 42..48
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 53..58
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 64..71
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:1TI7"
FT HELIX 88..102
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:1K6I"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 129..139
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 145..150
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 175..181
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:2VUT"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 192..206
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 208..211
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 225..236
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 240..244
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 256..269
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:1XGK"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:1K6J"
FT HELIX 319..324
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 331..337
FT /evidence="ECO:0007829|PDB:1XGK"
FT HELIX 339..345
FT /evidence="ECO:0007829|PDB:1XGK"
SQ SEQUENCE 352 AA; 38796 MW; 4E9982FFAE6F1F89 CRC64;
MAQQKKTIAV VNATGRQAAS LIRVAAAVGH HVRAQVHSLK GLIAEELQAI PNVTLFQGPL
LNNVPLMDTL FEGAHLAFIN TTSQAGDEIA IGKDLADAAK RAGTIQHYIY SSMPDHSLYG
PWPAVPMWAP KFTVENYVRQ LGLPSTFVYA GIYNNNFTSL PYPLFQMELM PDGTFEWHAP
FDPDIPLPWL DAEHDVGPAL LQIFKDGPQK WNGHRIALTF ETLSPVQVCA AFSRALNRRV
TYVQVPKVEI KVNIPVGYRE QLEAIEVVFG EHKAPYFPLP EFSRPAAGSP KGLGPANGKG
AGAGMMQGPG GVISQRVTDE ARKLWSGWRD MEEYAREVFP IEEEANGLDW ML
