DOC_BPP1
ID DOC_BPP1 Reviewed; 126 AA.
AC Q06259;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Protein kinase doc;
DE EC=2.7.11.1 {ECO:0000269|PubMed:24141193};
DE AltName: Full=Death on curing protein;
DE AltName: Full=Toxin doc;
GN Name=doc;
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 FUNCTION AS A TRANSCRIPTION REGULATOR, SUBUNIT, AND MUTAGENESIS OF LEU-12;
RP HIS-66; ASP-70; ALA-76; LEU-82; LEU-84 AND LEU-118.
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 [4]
RP FUNCTION AS A TOXIN, SUBUNIT, AND BINDING TO RIBOSOMES AND THE SMALL
RP RIBOSOMAL 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 [5]
RP FUNCTION AS A KINASE, FUNCTION AS A TRANSLATION INHIBITOR, AND MUTAGENESIS
RP OF ARG-64; HIS-66 AND ASN-78.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-125 IN COMPLEX WITH A PHD
RP FRAGMENT, AND EFFECT ON RELE.
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 [7]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), AND MODE OF TRANSCRIPTION
RP REGULATION.
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 [8]
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: Toxic component of a type II toxin-antitoxin (TA) system
CC (PubMed:18398006, PubMed:24141193). Phosphorylates EF-Tu on 'Thr-383'
CC in vitro; can use ATP or GTP (PubMed:24141193). Also dephosphorylates
CC in the presence of ADP or GDP. Can only phosphorylate before the
CC ternary aminoacyl-tRNA EF-Tu-GTP complex is formed; interaction with
CC cognate antitoxin phd prevents phosphorylation and dephosphorylation of
CC EF-Tu. Overexpression results in inhibition of growth in liquid
CC cultures and a decrease in colony formation by inhibiting translation,
CC stabilizing mRNA and polysomes; these effects are overcome by
CC concomitant expression of antitoxin phd. Binds 70S ribosomes and the
CC 30S ribosomal subunits, the binding site is the same as for the
CC antibiotic hygromycin B (PubMed:18398006). Bacteriophage P1 lysogenizes
CC bacteria as a low-copy number plasmid; doc and phd proteins function in
CC unison to stabilize plasmid number by inducing a lethal response to P1
CC plasmid prophage loss (PubMed:8411153). Overexpression of doc can
CC induce the mRNA interferase activity of host RelE in vivo
CC (PubMed:18757857). {ECO:0000269|PubMed:18398006,
CC ECO:0000269|PubMed:18757857, ECO:0000269|PubMed:24141193,
CC ECO:0000269|PubMed:8411153}.
CC -!- FUNCTION: Antitoxin phd binds to its own promoter repressing its
CC expression; toxin doc acts as a corepressor or derepressor depending on
CC the ratio, repressing or inducing expression.
CC {ECO:0000269|PubMed:20603017, ECO:0000269|PubMed:9829946}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: Interacts with cognate antitoxin phd, the exact ratio of
CC doc:phd varies from 1:1 to 1:3. Interaction with phd prevents kinase or
CC phosphorylase activity on EF-Tu. Interacts with the 30S ribosomal
CC subunit. {ECO:0000269|PubMed:18398006, ECO:0000269|PubMed:18757857,
CC ECO:0000269|PubMed:20696400, ECO:0000269|PubMed:9829946}.
CC -!- INTERACTION:
CC Q06259; Q06253: phd; NbExp=4; IntAct=EBI-2908816, EBI-2908787;
CC Q06259; P0CE47: tufA; Xeno; NbExp=5; IntAct=EBI-2908816, EBI-301077;
CC -!- MISCELLANEOUS: The concentration of antitoxin phd in P1 lysogens is far
CC greater than that of the toxin it antagonizes. Such an excess may
CC assure the well-being of carriers of the addicting plasmid.
CC {ECO:0000305|PubMed:8411153}.
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DR EMBL; M95666; AAA16931.1; -; Unassigned_DNA.
DR EMBL; AF234172; AAQ14075.1; -; Genomic_DNA.
DR PIR; S40016; S40016.
DR RefSeq; YP_006571.1; NC_005856.1.
DR PDB; 3DD7; X-ray; 1.70 A; A/C=1-126.
DR PDB; 3DD9; X-ray; 2.45 A; A/B/C/D/E/F/G/H=1-126.
DR PDB; 3K33; X-ray; 2.40 A; A=1-126.
DR PDB; 3KH2; X-ray; 2.71 A; A/B/C/D=1-126.
DR PDBsum; 3DD7; -.
DR PDBsum; 3DD9; -.
DR PDBsum; 3K33; -.
DR PDBsum; 3KH2; -.
DR BMRB; Q06259; -.
DR SMR; Q06259; -.
DR DIP; DIP-61743N; -.
DR IntAct; Q06259; 2.
DR GeneID; 2777474; -.
DR KEGG; vg:2777474; -.
DR EvolutionaryTrace; Q06259; -.
DR Proteomes; UP000008091; Genome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:CACAO.
DR GO; GO:0044696; P:killing by virus of host cell by post-segregational killing; IMP:CACAO.
DR GO; GO:0044074; P:negative regulation by symbiont of host translation; IMP:CACAO.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0039604; P:suppression by virus of host translation; IDA:CACAO.
DR InterPro; IPR006440; Doc.
DR InterPro; IPR003812; Fido.
DR PANTHER; PTHR39426; PTHR39426; 1.
DR Pfam; PF02661; Fic; 1.
DR PIRSF; PIRSF018297; Doc; 1.
DR TIGRFAMs; TIGR01550; DOC_P1; 1.
DR PROSITE; PS51459; FIDO; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; DNA-binding; Kinase; Nucleotide-binding;
KW Reference proteome; Repressor; Toxin-antitoxin system; Transcription;
KW Transcription regulation; Transferase; Translation regulation.
FT CHAIN 1..126
FT /note="Protein kinase doc"
FT /id="PRO_0000165273"
FT DOMAIN 4..120
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT MUTAGEN 12
FT /note="L->P: Loss of toxin and transcriptional regulatory
FT activity."
FT /evidence="ECO:0000269|PubMed:9829946"
FT MUTAGEN 64
FT /note="R->G: No binding to EF-Tu-GDP."
FT /evidence="ECO:0000269|PubMed:24141193"
FT MUTAGEN 66
FT /note="H->R,Y: Loss of toxin but not transcriptional
FT regulatory activity."
FT /evidence="ECO:0000269|PubMed:24141193,
FT ECO:0000269|PubMed:9829946"
FT MUTAGEN 70
FT /note="D->N: Loss of toxin but not transcriptional
FT regulatory activity."
FT /evidence="ECO:0000269|PubMed:9829946"
FT MUTAGEN 76
FT /note="A->E: Loss of toxin but not transcriptional
FT regulatory activity."
FT /evidence="ECO:0000269|PubMed:9829946"
FT MUTAGEN 78
FT /note="N->W: No change in binding to EF-Tu, 100-fold
FT decrease of affinity of doc-EF-Tu-GTP complex for AMP-PNP
FT (probably also ATP)."
FT /evidence="ECO:0000269|PubMed:24141193"
FT MUTAGEN 82
FT /note="L->P: Loss of toxin and transcriptional regulatory
FT activity."
FT /evidence="ECO:0000269|PubMed:9829946"
FT MUTAGEN 84
FT /note="L->P: Loss of toxin and transcriptional regulatory
FT activity."
FT /evidence="ECO:0000269|PubMed:9829946"
FT MUTAGEN 118
FT /note="L->P: Loss of toxin and transcriptional regulatory
FT activity."
FT /evidence="ECO:0000269|PubMed:9829946"
FT HELIX 6..20
FT /evidence="ECO:0007829|PDB:3DD7"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:3DD7"
FT HELIX 31..45
FT /evidence="ECO:0007829|PDB:3DD7"
FT HELIX 51..65
FT /evidence="ECO:0007829|PDB:3DD7"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:3DD7"
FT HELIX 72..86
FT /evidence="ECO:0007829|PDB:3DD7"
FT HELIX 97..105
FT /evidence="ECO:0007829|PDB:3DD7"
FT HELIX 111..122
FT /evidence="ECO:0007829|PDB:3DD7"
SQ SEQUENCE 126 AA; 13588 MW; E04A397538A595CD CRC64;
MRHISPEELI ALHDANISRY GGLPGMSDPG RAEAIIGRVQ ARVAYEEITD LFEVSATYLV
ATARGHIFND ANKRTALNSA LLFLRRNGVQ VFDSPELADL TVGAATGEIS VSSVADTLRR
LYGSAE
