VAPB4_MYCTU
ID VAPB4_MYCTU Reviewed; 85 AA.
AC P9WF21; L0T456; O07782; Q7D9K5;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 31.
DE RecName: Full=Antitoxin VapB4;
DE AltName: Full=VapB-mt4;
GN Name=vapB4; OrderedLocusNames=Rv0596c;
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 POSSIBLE FUNCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15718296; DOI=10.1093/nar/gki201;
RA Pandey D.P., Gerdes K.;
RT "Toxin-antitoxin loci are highly abundant in free-living but lost from
RT host-associated prokaryotes.";
RL Nucleic Acids Res. 33:966-976(2005).
RN [3]
RP EXPRESSION IN E.COLI, AND FUNCTION AS AN ANTITOXIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19016878; DOI=10.1111/j.1574-6968.2008.01400.x;
RA Gupta A.;
RT "Killing activity and rescue function of genome-wide toxin-antitoxin loci
RT of Mycobacterium tuberculosis.";
RL FEMS Microbiol. Lett. 290:45-53(2009).
RN [4]
RP FUNCTION AS AN ANTITOXIN, AND INTERACTION WITH VAPC4.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22354968; DOI=10.1074/jbc.m112.340109;
RA Sharp J.D., Cruz J.W., Raman S., Inouye M., Husson R.N., Woychik N.A.;
RT "Growth and translation inhibition through sequence-specific RNA binding by
RT Mycobacterium tuberculosis VapC toxin.";
RL J. Biol. Chem. 287:12835-12847(2012).
RN [5]
RP FUNCTION, INTERACTION WITH VAPC4, DOMAIN, AND MUTAGENESIS OF TRP-48;
RP VAL-54; ASP-64; THR-66; LEU-72; GLN-78 AND THR-80.
RC STRAIN=H37Rv;
RX PubMed=25622615; DOI=10.1128/jb.02508-14;
RA Jin G., Pavelka M.S. Jr., Butler J.S.;
RT "Structure-function analysis of VapB4 antitoxin identifies critical
RT features of a minimal VapC4 toxin-binding module.";
RL J. Bacteriol. 197:1197-1207(2015).
CC -!- FUNCTION: Antitoxin component of a type II toxin-antitoxin (TA) system.
CC Antitoxin that counteracts the effect of its cognate VapC4 toxin. Upon
CC expression in situ, in M.smegmatis or E.coli neutralizes the effect of
CC cognate toxin VapC4. {ECO:0000269|PubMed:19016878,
CC ECO:0000269|PubMed:22354968, ECO:0000269|PubMed:25622615}.
CC -!- SUBUNIT: Interacts with cognate toxin VapC4.
CC {ECO:0000269|PubMed:22354968, ECO:0000269|PubMed:25622615}.
CC -!- DOMAIN: The C-terminal domain (residues 55-85) is sufficient to
CC interact with and neutralize VapC4; exchanging the N-terminus (residues
CC 1-54) with VapB5 allows neutralization, while exchanging the C-terminal
CC domain (residues 55-85) does not. Many single residue mutations in the
CC C-terminal domain construct but not in full-length protein prevent
CC toxin neutralization, they are not all annotated here.
CC {ECO:0000269|PubMed:25622615}.
CC -!- SIMILARITY: Belongs to the phD/YefM antitoxin family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43335.1; -; Genomic_DNA.
DR PIR; G70908; G70908.
DR RefSeq; NP_215110.1; NC_000962.3.
DR RefSeq; WP_003403125.1; NZ_NVQJ01000033.1.
DR AlphaFoldDB; P9WF21; -.
DR SMR; P9WF21; -.
DR STRING; 83332.Rv0596c; -.
DR PaxDb; P9WF21; -.
DR DNASU; 887846; -.
DR GeneID; 45424564; -.
DR GeneID; 887846; -.
DR KEGG; mtu:Rv0596c; -.
DR TubercuList; Rv0596c; -.
DR eggNOG; COG4118; Bacteria.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0097351; F:toxin sequestering activity; IPI:MTBBASE.
DR GO; GO:0098754; P:detoxification; IMP:MTBBASE.
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 Reference proteome; Toxin-antitoxin system.
FT CHAIN 1..85
FT /note="Antitoxin VapB4"
FT /id="PRO_0000408045"
FT REGION 1..54
FT /note="Not required to interact with or neutralize cognate
FT toxin VapC4"
FT /evidence="ECO:0000269|PubMed:25622615"
FT REGION 55..85
FT /note="Sufficient to interact with and neutralize VapC4"
FT /evidence="ECO:0000269|PubMed:25622615"
FT MUTAGEN 48
FT /note="W->G,R: No effect. No longer neutralizes VapC4 in
FT full-length antitoxin, decreased interaction with VapC4
FT (tested for G-48 only); when associated with A-64."
FT /evidence="ECO:0000269|PubMed:25622615"
FT MUTAGEN 54
FT /note="V->E: No effect. No longer neutralizes VapC4 in
FT full-length antitoxin; when associated with A-64."
FT /evidence="ECO:0000269|PubMed:25622615"
FT MUTAGEN 64
FT /note="D->A: No effect. No longer neutralizes VapC4 in
FT full-length VapB4; when associated with G-48; R-48 or E-
FT 54."
FT /evidence="ECO:0000269|PubMed:25622615"
FT MUTAGEN 66
FT /note="T->A: No effect. No longer neutralizes VapC4 in
FT full-length VapB4; when associated with low levels of G-
FT 48."
FT /evidence="ECO:0000269|PubMed:25622615"
FT MUTAGEN 72
FT /note="L->V: No longer neutralizes VapC4 in full-length
FT VapB4; when associated with low levels of G-48."
FT /evidence="ECO:0000269|PubMed:25622615"
FT MUTAGEN 78
FT /note="Q->R: No effect. No longer neutralizes VapC4 in
FT full-length VapB4; when associated with low levels of G-
FT 48."
FT /evidence="ECO:0000269|PubMed:25622615"
FT MUTAGEN 80
FT /note="T->S: No effect. No longer neutralizes VapC4 in
FT full-length VapB4; when associated with low levels of G-
FT 48."
FT /evidence="ECO:0000269|PubMed:25622615"
SQ SEQUENCE 85 AA; 9681 MW; 3410851F93D4EACE CRC64;
MSATIPARDL RNHTAEVLRR VAAGEEIEVL KDNRPVARIV PLKRRRQWLP AAEVIGELVR
LGPDTTNLGE ELRETLTQTT DDVRW
