PHD_BPP1
ID PHD_BPP1 Reviewed; 73 AA.
AC Q06253;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Antitoxin phd;
DE AltName: Full=Addiction protein pdh;
DE AltName: Full=Prevent host death protein;
GN Name=phd;
OS Escherichia phage P1 (Bacteriophage P1).
OC Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes;
OC Caudovirales; Myoviridae; Punavirus.
OX NCBI_TaxID=2886926;
OH NCBI_TaxID=543; Enterobacteriaceae.
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=8411153; DOI=10.1006/jmbi.1993.1521;
RA Lehnherr H., Maguin E., Jafri S., Yarmolinsky M.B.;
RT "Plasmid addiction genes of bacteriophage P1: doc, which causes cell death
RT on curing of prophage, and phd, which prevents host death when prophage is
RT retained.";
RL J. Mol. Biol. 233:414-428(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15489417; DOI=10.1128/jb.186.21.7032-7068.2004;
RA Lobocka M.B., Rose D.J., Plunkett G. III, Rusin M., Samojedny A.,
RA Lehnherr H., Yarmolinsky M.B., Blattner F.R.;
RT "Genome of bacteriophage P1.";
RL J. Bacteriol. 186:7032-7068(2004).
RN [3]
RP CLEAVAGE BY THE CLPXP PROTEASE.
RX PubMed=7724551; DOI=10.1073/pnas.92.8.3274;
RA Lehnherr H., Yarmolinsky M.B.;
RT "Addiction protein Phd of plasmid prophage P1 is a substrate of the ClpXP
RT serine protease of Escherichia coli.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3274-3277(1995).
RN [4]
RP FUNCTION AS A TRANSCRIPTION REGULATOR, DNA-BINDING, AND SUBUNIT.
RX PubMed=9829946; DOI=10.1128/jb.180.23.6342-6351.1998;
RA Magnuson R., Yarmolinsky M.B.;
RT "Corepression of the P1 addiction operon by Phd and Doc.";
RL J. Bacteriol. 180:6342-6351(1998).
RN [5]
RP FUNCTION AS AN ANTITOXIN, AND SUBUNIT.
RX PubMed=18398006; DOI=10.1073/pnas.0711949105;
RA Liu M., Zhang Y., Inouye M., Woychik N.A.;
RT "Bacterial addiction module toxin Doc inhibits translation elongation
RT through its association with the 30S ribosomal subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:5885-5890(2008).
RN [6]
RP FUNCTION AS ANTITOXIN, AND DOMAIN.
RX PubMed=24141193; DOI=10.1038/nchembio.1364;
RA Castro-Roa D., Garcia-Pino A., De Gieter S., van Nuland N.A., Loris R.,
RA Zenkin N.;
RT "The Fic protein Doc uses an inverted substrate to phosphorylate and
RT inactivate EF-Tu.";
RL Nat. Chem. Biol. 9:811-817(2013).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 51-73 IN COMPLEX WITH TOXIN DOC.
RX PubMed=18757857; DOI=10.1074/jbc.m805654200;
RA Garcia-Pino A., Christensen-Dalsgaard M., Wyns L., Yarmolinsky M.,
RA Magnuson R.D., Gerdes K., Loris R.;
RT "Doc of prophage P1 is inhibited by its antitoxin partner Phd through fold
RT complementation.";
RL J. Biol. Chem. 283:30821-30827(2008).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), MODE OF TRANSCRIPTION REGULATION,
RP AND MUTAGENESIS OF PHE-44; TYR-47 AND LYS-48.
RX PubMed=20603017; DOI=10.1016/j.cell.2010.05.039;
RA Garcia-Pino A., Balasubramanian S., Wyns L., Gazit E., De Greve H.,
RA Magnuson R.D., Charlier D., van Nuland N.A., Loris R.;
RT "Allostery and intrinsic disorder mediate transcription regulation by
RT conditional cooperativity.";
RL Cell 142:101-111(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS), AND SUBUNIT.
RX PubMed=20696400; DOI=10.1016/j.str.2010.04.018;
RA Arbing M.A., Handelman S.K., Kuzin A.P., Verdon G., Wang C., Su M.,
RA Rothenbacher F.P., Abashidze M., Liu M., Hurley J.M., Xiao R., Acton T.,
RA Inouye M., Montelione G.T., Woychik N.A., Hunt J.F.;
RT "Crystal structures of Phd-Doc, HigA, and YeeU establish multiple
RT evolutionary links between microbial growth-regulating toxin-antitoxin
RT systems.";
RL Structure 18:996-1010(2010).
CC -!- FUNCTION: Antitoxin component of a type II toxin-antitoxin (TA) system
CC (PubMed:18398006, PubMed:24141193, PubMed:18757857). A labile antitoxin
CC that binds to cognate doc toxin and neutralizes its ability to
CC phosphorylate host EF-Tu. Does not reverse phosphorylation.
CC Bacteriophage P1 lysogenizes bacteria as a low-copy number plasmid; phd
CC and doc proteins function in unison to stabilize plasmid number by
CC inducing a lethal response to P1 plasmid prophage loss
CC (PubMed:8411153). {ECO:0000269|PubMed:18398006,
CC ECO:0000269|PubMed:18757857, ECO:0000269|PubMed:24141193,
CC ECO:0000269|PubMed:8411153}.
CC -!- FUNCTION: Binds to its own promoter repressing its expression; toxin
CC doc acts as a corepressor or derepressor depending on the ratio,
CC repressing or inducing expression. {ECO:0000269|PubMed:20603017,
CC ECO:0000269|PubMed:9829946}.
CC -!- SUBUNIT: Homodimer. Interacts with cognate toxin doc, the exact ratio
CC of doc:phd varies from 1:1 to 1:3. Interaction with doc prevents both
CC kinase activity and dephosphorylation of EF-Tu.
CC {ECO:0000269|PubMed:18398006, ECO:0000269|PubMed:18757857,
CC ECO:0000269|PubMed:20696400, ECO:0000269|PubMed:9829946}.
CC -!- INTERACTION:
CC Q06253; Q06259: doc; NbExp=4; IntAct=EBI-2908787, EBI-2908816;
CC -!- PTM: Degraded by the ClpXP protease. {ECO:0000269|PubMed:7724551}.
CC -!- MISCELLANEOUS: The concentration of phd in P1 lysogens is far greater
CC than that of the toxin it antagonizes. Such an excess may assure the
CC well-being of carriers of the addicting plasmid.
CC {ECO:0000305|PubMed:8411153}.
CC -!- SIMILARITY: Belongs to the phD/YefM antitoxin family. {ECO:0000305}.
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DR EMBL; M95666; AAA16932.1; -; Unassigned_DNA.
DR EMBL; AF234172; AAQ14074.1; -; Genomic_DNA.
DR PIR; S40015; S40015.
DR RefSeq; YP_006570.1; NC_005856.1.
DR PDB; 3DD7; X-ray; 1.70 A; B/D=51-73.
DR PDB; 3HRY; X-ray; 2.25 A; A/B/C=1-73.
DR PDB; 3HS2; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-58.
DR PDB; 3K33; X-ray; 2.40 A; B/C/D=1-73.
DR PDB; 3KH2; X-ray; 2.71 A; E/F/G/H=1-73.
DR PDB; 4ZLX; X-ray; 2.31 A; A/B=1-45.
DR PDB; 4ZM0; X-ray; 3.17 A; A/B/C/D=1-73.
DR PDB; 4ZM2; X-ray; 3.88 A; A/B/C/D=1-73.
DR PDBsum; 3DD7; -.
DR PDBsum; 3HRY; -.
DR PDBsum; 3HS2; -.
DR PDBsum; 3K33; -.
DR PDBsum; 3KH2; -.
DR PDBsum; 4ZLX; -.
DR PDBsum; 4ZM0; -.
DR PDBsum; 4ZM2; -.
DR SMR; Q06253; -.
DR DIP; DIP-62083N; -.
DR IntAct; Q06253; 1.
DR GeneID; 2777473; -.
DR KEGG; vg:2777473; -.
DR EvolutionaryTrace; Q06253; -.
DR Proteomes; UP000008091; Genome.
DR GO; GO:0032993; C:protein-DNA complex; IDA:CAFA.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:CAFA.
DR DisProt; DP00288; -.
DR InterPro; IPR006442; Antitoxin_Phd/YefM.
DR InterPro; IPR036165; YefM-like_sf.
DR Pfam; PF02604; PhdYeFM_antitox; 1.
DR SUPFAM; SSF143120; SSF143120; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Reference proteome; Repressor; Toxin-antitoxin system;
KW Transcription; Transcription regulation.
FT CHAIN 1..73
FT /note="Antitoxin phd"
FT /id="PRO_0000165279"
FT REGION 50..73
FT /note="Sufficient for antitoxin activity, its presence
FT prevents formation of a doc-EF-Tu complex"
FT MUTAGEN 44
FT /note="F->A: Significantly decreases repressor activity,
FT binds DNA less well, inhibits doc normally."
FT /evidence="ECO:0000269|PubMed:20603017"
FT MUTAGEN 47
FT /note="Y->A: Decreases repressor activity, binds DNA less
FT well, inhibits doc normally."
FT /evidence="ECO:0000269|PubMed:20603017"
FT MUTAGEN 48
FT /note="K->M: Decreases repressor activity, binds DNA less
FT well, inhibits doc normally."
FT /evidence="ECO:0000269|PubMed:20603017"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:3HS2"
FT HELIX 6..11
FT /evidence="ECO:0007829|PDB:3HS2"
FT HELIX 13..21
FT /evidence="ECO:0007829|PDB:3HS2"
FT STRAND 26..29
FT /evidence="ECO:0007829|PDB:3HS2"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:3HRY"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:3HS2"
FT HELIX 41..49
FT /evidence="ECO:0007829|PDB:3HRY"
FT TURN 50..53
FT /evidence="ECO:0007829|PDB:3HRY"
FT HELIX 55..62
FT /evidence="ECO:0007829|PDB:3DD7"
FT HELIX 64..70
FT /evidence="ECO:0007829|PDB:3DD7"
SQ SEQUENCE 73 AA; 8133 MW; 5FDB9D3565440050 CRC64;
MQSINFRTAR GNLSEVLNNV EAGEEVEITR RGREPAVIVS KATFEAYKKA ALDAEFASLF
DTLDSTNKEL VNR
