PRRA_MYCTU
ID PRRA_MYCTU Reviewed; 233 AA.
AC P9WGM1; L0T590; P0A5Z6; Q10531;
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=Transcriptional regulatory protein PrrA;
GN Name=prrA; OrderedLocusNames=Rv0903c; ORFNames=MTCY31.31c;
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.
RC STRAIN=Mt103;
RX PubMed=11953357; DOI=10.1128/iai.70.5.2256-2263.2002;
RA Ewann F., Jackson M., Pethe K., Cooper A., Mielcarek N., Ensergueix D.,
RA Gicquel B., Locht C., Supply P.;
RT "Transient requirement of the PrrA-PrrB two-component system for early
RT intracellular multiplication of Mycobacterium tuberculosis.";
RL Infect. Immun. 70:2256-2263(2002).
RN [3]
RP FUNCTION, AND PHOSPHORYLATION.
RC STRAIN=Mt103;
RX PubMed=14702417; DOI=10.1099/mic.0.26516-0;
RA Ewann F., Locht C., Supply P.;
RT "Intracellular autoregulation of the Mycobacterium tuberculosis PrrA
RT response regulator.";
RL Microbiology 150:241-246(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 INDUCTION BY NITROGEN-LIMITING CONDITIONS.
RX PubMed=22081401; DOI=10.1128/jb.06258-11;
RA Haydel S.E., Malhotra V., Cornelison G.L., Clark-Curtiss J.E.;
RT "The prrAB two-component system is essential for Mycobacterium tuberculosis
RT viability and is induced under nitrogen-limiting conditions.";
RL J. Bacteriol. 194:354-361(2012).
RN [6] {ECO:0007744|PDB:1YS7}
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) IN COMPLEX WITH MAGNESIUM.
RX PubMed=16434396; DOI=10.1074/jbc.m512004200;
RA Nowak E., Panjikar S., Konarev P., Svergun D.I., Tucker P.A.;
RT "The structural basis of signal transduction for the response regulator
RT PrrA from Mycobacterium tuberculosis.";
RL J. Biol. Chem. 281:9659-9666(2006).
RN [7]
RP FUNCTION, PHOSPHORYLATION AT THR-6 AND ASP-58, AND MUTAGENESIS OF THR-6 AND
RP ASP-58.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=29101285; DOI=10.1042/bcj20170596;
RA Mishra A.K., Yabaji S.M., Dubey R.K., Dhamija E., Srivastava K.K.;
RT "Dual phosphorylation in response regulator protein PrrA is crucial for
RT intracellular survival of mycobacteria consequent upon transcriptional
RT activation.";
RL Biochem. J. 474:4119-4136(2017).
CC -!- FUNCTION: Member of the two-component regulatory system PrrB/PrrA that
CC is involved specifically in early intracellular multiplication of
CC Mycobacterium and is essential for its viability (PubMed:11953357,
CC PubMed:22081401). Upon phosphorylation by PrrB, functions as a
CC transcription regulator by direct binding to promoter regions of target
CC genes to positively regulate their expression. Autoregulates its own
CC expression (PubMed:14702417, PubMed:29101285).
CC {ECO:0000269|PubMed:11953357, ECO:0000269|PubMed:14702417,
CC ECO:0000269|PubMed:22081401, ECO:0000269|PubMed:29101285}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- INDUCTION: By nitrogen-limiting conditions.
CC {ECO:0000269|PubMed:22081401}.
CC -!- PTM: Phosphorylated by PrrB at Asp-58. Also phosphorylated on Thr-6 by
CC PknG/PknK/PknJ. The two phosphorylations act synergistically to
CC activate the DNA-binding activity of PrrA.
CC {ECO:0000269|PubMed:29101285}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP43651.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL123456; CCP43651.1; ALT_INIT; Genomic_DNA.
DR PIR; D70783; D70783.
DR RefSeq; NP_215418.1; NC_000962.3.
DR PDB; 1YS6; X-ray; 1.77 A; A/B=1-233.
DR PDB; 1YS7; X-ray; 1.58 A; A/B=1-233.
DR PDBsum; 1YS6; -.
DR PDBsum; 1YS7; -.
DR AlphaFoldDB; P9WGM1; -.
DR SMR; P9WGM1; -.
DR DIP; DIP-29035N; -.
DR IntAct; P9WGM1; 1.
DR STRING; 83332.Rv0903c; -.
DR PaxDb; P9WGM1; -.
DR DNASU; 885209; -.
DR GeneID; 885209; -.
DR KEGG; mtu:Rv0903c; -.
DR PATRIC; fig|83332.12.peg.1006; -.
DR TubercuList; Rv0903c; -.
DR eggNOG; COG0745; Bacteria.
DR OMA; KYLMSHP; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0032993; C:protein-DNA complex; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IDA:MTBBASE.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0000156; F:phosphorelay response regulator activity; IBA:GO_Central.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR CDD; cd00383; trans_reg_C; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR011006; CheY-like_superfamily.
DR InterPro; IPR001867; OmpR/PhoB-type_DNA-bd.
DR InterPro; IPR001789; Sig_transdc_resp-reg_receiver.
DR InterPro; IPR039420; WalR-like.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR48111; PTHR48111; 1.
DR Pfam; PF00072; Response_reg; 1.
DR Pfam; PF00486; Trans_reg_C; 1.
DR SMART; SM00448; REC; 1.
DR SMART; SM00862; Trans_reg_C; 1.
DR SUPFAM; SSF52172; SSF52172; 1.
DR PROSITE; PS51755; OMPR_PHOB; 1.
DR PROSITE; PS50110; RESPONSE_REGULATORY; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; DNA-binding; Magnesium; Metal-binding;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Two-component regulatory system.
FT CHAIN 1..233
FT /note="Transcriptional regulatory protein PrrA"
FT /id="PRO_0000081327"
FT DOMAIN 9..123
FT /note="Response regulatory"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT DNA_BIND 134..232
FT /note="OmpR/PhoB-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01091"
FT BINDING 15
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:16434396,
FT ECO:0007744|PDB:1YS7"
FT BINDING 58
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:16434396,
FT ECO:0007744|PDB:1YS7"
FT BINDING 60
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:16434396,
FT ECO:0007744|PDB:1YS7"
FT MOD_RES 6
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:29101285"
FT MOD_RES 58
FT /note="4-aspartylphosphate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169,
FT ECO:0000269|PubMed:29101285"
FT MUTAGEN 6
FT /note="T->A: Loss of phosphorylation by PknG/PknK/PknJ."
FT /evidence="ECO:0000269|PubMed:29101285"
FT MUTAGEN 58
FT /note="D->A: Loss of phosphorylation by PrrB."
FT /evidence="ECO:0000269|PubMed:29101285"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:1YS7"
FT HELIX 17..29
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:1YS7"
FT HELIX 40..49
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 53..60
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:1YS7"
FT HELIX 66..75
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 82..86
FT /evidence="ECO:0007829|PDB:1YS7"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:1YS7"
FT TURN 96..101
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 103..109
FT /evidence="ECO:0007829|PDB:1YS7"
FT HELIX 112..127
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:1YS7"
FT TURN 146..149
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 150..153
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:1YS6"
FT HELIX 162..173
FT /evidence="ECO:0007829|PDB:1YS7"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:1YS7"
FT HELIX 181..189
FT /evidence="ECO:0007829|PDB:1YS7"
FT HELIX 199..212
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:1YS7"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:1YS7"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:1YS7"
SQ SEQUENCE 233 AA; 25009 MW; B8B38C20BF917082 CRC64;
MDTGVTSPRV LVVDDDSDVL ASLERGLRLS GFEVATAVDG AEALRSATEN RPDAIVLDIN
MPVLDGVSVV TALRAMDNDV PVCVLSARSS VDDRVAGLEA GADDYLVKPF VLAELVARVK
ALLRRRGSTA TSSSETITVG PLEVDIPGRR ARVNGVDVDL TKREFDLLAV LAEHKTAVLS
RAQLLELVWG YDFAADTNVV DVFIGYLRRK LEAGGGPRLL HTVRGVGFVL RMQ
