VAPC4_MYCTU
ID VAPC4_MYCTU Reviewed; 130 AA.
AC O07783; L0T5U5;
DT 03-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 3.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Ribonuclease VapC4 {ECO:0000255|HAMAP-Rule:MF_00265};
DE Short=RNase VapC4 {ECO:0000255|HAMAP-Rule:MF_00265};
DE EC=3.1.-.-;
DE AltName: Full=Toxin VapC4 {ECO:0000255|HAMAP-Rule:MF_00265};
DE AltName: Full=VapC-mt4;
GN Name=vapC4 {ECO:0000255|HAMAP-Rule:MF_00265}; OrderedLocusNames=Rv0595c;
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 A TOXIN.
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 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 AS A TOXIN, FUNCTION AS A RIBONUCLEASE, RNA-BINDING, INTERACTION
RP WITH VAPB4, AND MUTAGENESIS OF ASP-9; GLU-40; ASP-98; THR-114 AND ASP-116.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=23345537; DOI=10.1074/mcp.m112.018846;
RA Albrethsen J., Agner J., Piersma S.R., Hoejrup P., Pham T.V., Weldingh K.,
RA Jimenez C.R., Andersen P., Rosenkrands I.;
RT "Proteomic profiling of Mycobacterium tuberculosis identifies nutrient-
RT starvation-responsive toxin-antitoxin systems.";
RL Mol. Cell. Proteomics 12:1180-1191(2013).
RN [7]
RP FUNCTION, AND INTERACTION WITH VAPB4.
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: Toxic component of a type II toxin-antitoxin (TA) system.
CC Probably exerts its toxic effect by binding to mRNA, inhibiting
CC translation. Binds to, recognizes and cleaves ssRNA at ACGC and
CC AC(A/U)GC sequences, usually between the G and C; cleavage is not very
CC efficient, nor is cleavage required to inhibit protein synthesis. Upon
CC expression in situ, in M.smegmatis or E.coli inhibits cell growth and
CC colony formation; in at least E.coli also causes increased levels of
CC cellular RNA. Its toxic effect is neutralized by coexpression with
CC cognate antitoxin VapB4. {ECO:0000269|PubMed:19016878,
CC ECO:0000269|PubMed:22354968, ECO:0000269|PubMed:25622615}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00265};
CC -!- SUBUNIT: Interacts with cognate antitoxin VapB4.
CC {ECO:0000269|PubMed:22354968}.
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Following 6 weeks of nutrient
CC starvation. {ECO:0000269|PubMed:23345537}.
CC -!- SIMILARITY: Belongs to the PINc/VapC protein family.
CC {ECO:0000255|HAMAP-Rule:MF_00265}.
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DR EMBL; AL123456; CCP43334.1; -; Genomic_DNA.
DR PIR; F70908; F70908.
DR RefSeq; NP_215109.1; NC_000962.3.
DR RefSeq; WP_003403122.1; NZ_NVQJ01000033.1.
DR AlphaFoldDB; O07783; -.
DR SMR; O07783; -.
DR STRING; 83332.Rv0595c; -.
DR PaxDb; O07783; -.
DR DNASU; 887835; -.
DR GeneID; 887835; -.
DR KEGG; mtu:Rv0595c; -.
DR TubercuList; Rv0595c; -.
DR eggNOG; COG1487; Bacteria.
DR InParanoid; O07783; -.
DR OMA; CFAGIAD; -.
DR PhylomeDB; O07783; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004540; F:ribonuclease activity; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0097351; F:toxin sequestering activity; IPI:MTBBASE.
DR GO; GO:0044003; P:modulation by symbiont of host process; IMP:MTBBASE.
DR HAMAP; MF_00265; VapC_Nob1; 1.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR002716; PIN_dom.
DR InterPro; IPR022907; VapC_family.
DR Pfam; PF01850; PIN; 1.
DR SUPFAM; SSF88723; SSF88723; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Magnesium; Metal-binding; Nuclease; Reference proteome;
KW RNA-binding; Secreted; Toxin-antitoxin system.
FT CHAIN 1..130
FT /note="Ribonuclease VapC4"
FT /id="PRO_0000407867"
FT DOMAIN 7..130
FT /note="PINc"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00265"
FT BINDING 9
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00265"
FT BINDING 98
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00265"
FT MUTAGEN 9
FT /note="D->A: Does not inhibit growth, forms complex with
FT VapB4."
FT /evidence="ECO:0000269|PubMed:22354968"
FT MUTAGEN 40
FT /note="E->A: Does not inhibit growth, forms complex with
FT VapB4."
FT /evidence="ECO:0000269|PubMed:22354968"
FT MUTAGEN 98
FT /note="D->A: Does not inhibit growth, forms complex with
FT VapB4."
FT /evidence="ECO:0000269|PubMed:22354968"
FT MUTAGEN 114
FT /note="T->A: Does not inhibit growth, forms complex with
FT VapB4."
FT /evidence="ECO:0000269|PubMed:22354968"
FT MUTAGEN 116
FT /note="D->A: Does not inhibit growth, forms complex with
FT VapB4."
FT /evidence="ECO:0000269|PubMed:22354968"
SQ SEQUENCE 130 AA; 14112 MW; 7B38EAE492156816 CRC64;
MNVRRALADT SVFIGIEATR FDPDRFAGYE WGVSVVTLGE LRLGVLQASG PEAAARRLST
YQLAQRFEPL GIDEAVSEAW ALLVSKLRAA KLRVPINDSW IAATAVAHGI AILTQDNDYA
AMPDVEVITI
