VPC15_MYCTU
ID VPC15_MYCTU Reviewed; 132 AA.
AC P9WF97; L0T8D0; P64925; Q10847;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Ribonuclease VapC15 {ECO:0000255|HAMAP-Rule:MF_00265, ECO:0000303|PubMed:20011113};
DE Short=RNase VapC15 {ECO:0000255|HAMAP-Rule:MF_00265};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_00265};
DE AltName: Full=Toxin VapC15 {ECO:0000255|HAMAP-Rule:MF_00265};
GN Name=vapC15 {ECO:0000255|HAMAP-Rule:MF_00265}; OrderedLocusNames=Rv2010;
GN ORFNames=MTCY39.07c;
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 M.SMEGMATIS, FUNCTION AS A TOXIN, AND INDUCTION BY HYPOXIA.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=20011113; DOI=10.1371/journal.pgen.1000767;
RA Ramage H.R., Connolly L.E., Cox J.S.;
RT "Comprehensive functional analysis of Mycobacterium tuberculosis toxin-
RT antitoxin systems: implications for pathogenesis, stress responses, and
RT evolution.";
RL PLoS Genet. 5:E1000767-E1000767(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 X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH VAPB15; MAGNESIUM AND
RP MANGANESE, FUNCTION, COFACTOR, ACTIVITY REGULATION, AND SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=25450593; DOI=10.1016/j.jsb.2014.10.002;
RA Das U., Pogenberg V., Subhramanyam U.K., Wilmanns M., Gourinath S.,
RA Srinivasan A.;
RT "Crystal structure of the VapBC-15 complex from Mycobacterium tuberculosis
RT reveals a two-metal ion dependent PIN-domain ribonuclease and a variable
RT mode of toxin-antitoxin assembly.";
RL J. Struct. Biol. 188:249-258(2014).
CC -!- FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system.
CC Degrades total E.coli RNA, which is partially inhibited by cognate
CC antitoxin VapB15 (PubMed:25450593). Upon expression in M.smegmatis
CC inhibits colony formation, which is neutralized by coexpression with
CC VapB15 (PubMed:20011113). {ECO:0000255|HAMAP-Rule:MF_00265,
CC ECO:0000269|PubMed:20011113, ECO:0000269|PubMed:25450593}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00265,
CC ECO:0000269|PubMed:25450593};
CC Note=The heterotrimer binds 1 Mg(2+)-Mn(2+) pair while the
CC heterotetramer binds 2 pairs. Both metals are shared by the toxin-
CC antitoxin pair. {ECO:0000269|PubMed:25450593};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:25450593};
CC Note=The heterotrimer binds 1 Mg(2+)-Mn(2+) pair while the
CC heterotetramer binds 2 pairs. Both metals are shared by the toxin-
CC antitoxin pair. {ECO:0000269|PubMed:25450593};
CC -!- ACTIVITY REGULATION: RNase activity inhibited by EDTA.
CC {ECO:0000269|PubMed:25450593}.
CC -!- SUBUNIT: Crystallizes as a VapB15-VapC15(2) heterotrimer and as a
CC VapB15(2)-VapC15(2) heterotetramer; each toxin pair forms a homodimer
CC which creates a channel in which the antitoxin binds.
CC {ECO:0000269|PubMed:25450593}.
CC -!- INDUCTION: Induced by hypoxia. {ECO:0000269|PubMed:20011113}.
CC -!- MISCELLANEOUS: In this enzyme the conserved residue Asp-4 binds Mg(2+)
CC via H(2)O. {ECO:0000269|PubMed:25450593}.
CC -!- SIMILARITY: Belongs to the PINc/VapC protein family.
CC {ECO:0000255|HAMAP-Rule:MF_00265}.
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DR EMBL; AL123456; CCP44782.1; -; Genomic_DNA.
DR PIR; H70759; H70759.
DR RefSeq; NP_216526.1; NC_000962.3.
DR RefSeq; WP_003410075.1; NZ_NVQJ01000043.1.
DR PDB; 4CHG; X-ray; 2.10 A; A/B/C/D/E/F=1-132.
DR PDBsum; 4CHG; -.
DR AlphaFoldDB; P9WF97; -.
DR SMR; P9WF97; -.
DR STRING; 83332.Rv2010; -.
DR PaxDb; P9WF97; -.
DR DNASU; 888933; -.
DR GeneID; 888933; -.
DR KEGG; mtu:Rv2010; -.
DR TubercuList; Rv2010; -.
DR eggNOG; COG1487; Bacteria.
DR PhylomeDB; P9WF97; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004540; F:ribonuclease activity; IBA:GO_Central.
DR GO; GO:0045926; P:negative regulation of growth; IMP:MTBBASE.
DR GO; GO:0001666; P:response to hypoxia; IEP: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 3D-structure; Hydrolase; Magnesium; Manganese; Metal-binding; Nuclease;
KW Reference proteome; Toxin-antitoxin system.
FT CHAIN 1..132
FT /note="Ribonuclease VapC15"
FT /id="PRO_0000103939"
FT DOMAIN 1..121
FT /note="PINc"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00265"
FT BINDING 96
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="ligand shared with antitoxin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00265,
FT ECO:0000269|PubMed:25450593"
FT BINDING 96
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="ligand shared with antitoxin"
FT /evidence="ECO:0000269|PubMed:25450593"
FT BINDING 114
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="ligand shared with antitoxin"
FT /evidence="ECO:0000269|PubMed:25450593"
FT BINDING 116
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="ligand shared with antitoxin"
FT /evidence="ECO:0000269|PubMed:25450593"
FT STRAND 1..3
FT /evidence="ECO:0007829|PDB:4CHG"
FT HELIX 5..13
FT /evidence="ECO:0007829|PDB:4CHG"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:4CHG"
FT HELIX 18..28
FT /evidence="ECO:0007829|PDB:4CHG"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:4CHG"
FT HELIX 37..44
FT /evidence="ECO:0007829|PDB:4CHG"
FT HELIX 50..61
FT /evidence="ECO:0007829|PDB:4CHG"
FT STRAND 63..66
FT /evidence="ECO:0007829|PDB:4CHG"
FT HELIX 72..86
FT /evidence="ECO:0007829|PDB:4CHG"
FT HELIX 94..106
FT /evidence="ECO:0007829|PDB:4CHG"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:4CHG"
FT HELIX 116..124
FT /evidence="ECO:0007829|PDB:4CHG"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:4CHG"
SQ SEQUENCE 132 AA; 14731 MW; CEBE78B1A25BDEFC CRC64;
MIVDTSVWIA YLSTSESLAS RWLADRIAAD STVIVPEVVM MELLIGKTDE DTAALRRRLL
QRFAIEPLAP VRDAEDAAAI HRRCRRGGDT VRSLIDCQVA AMALRIGVAV AHRDRDYEAI
RTHCGLRTEP LF
