Protein: Endoribonuclease MazF6 (EC 3.1.27.-) (Toxin MazF6) (mRNA interferase MazF-mt3) (P9WII3)
Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Function: Toxic component of a type II toxin-antitoxin (TA) system. Upon expression in E.coli and in M.smegmatis partially inhibits cell growth and colony formation; its toxic effect is neutralized by coexpression with cognate antitoxin MazE6. Acts as an mRNA interferase on ssRNA, cleaving between the second and third bases in the sequences CUCCU and UUCCU. Further experiments demonstrate that it digests between the first and second bases of UCCUU, yielding a 5'-hydroxyl end; digests M.tuberculosis mRNA (in coding as well as the 5'- and 3'-UTR regions) and 23S rRNA, digests E.coli 16S rRNA both alone and in the 70S ribosome but no data for M.tuberculosis 16S rRNA cleavage was presented. 23S and 16S rRNA digestion occurs in predicted single-stranded regions, the 16S rRNA UCCUU site is in the anti-Shine-Dalgarno site and would cleave off the last 7 nucleotides. Non-cognate antitoxins VapB27 and VapB40 partially neutralize toxicity in vivo.
Subcellular location: Secreted. Note=Following 6 weeks of nutrient starvation. {ECO:0000269|PubMed:23345537}.
InterPro domains:
- IPR003477: mRNA interferase PemK-like (family) [1-114]
- IPR011067: Plasmid maintenance toxin/Cell growth inhibitor (homologous_superfamily) [1-114]
Sequence:
MVISRAEIYWADLGPPSGSQPAKRRPVLVIQSDPYNASRLATVIAAVITSNTALAAMPGNVFLPATTTRLPRDSVVNVTAIVTLNKTDLTDRVGEVPASLMHEVDRGLRRVLDL
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140640 (catalytic activity, acting on a nucleic acid), GO:0016787 (hydrolase activity), GO:0005515 (protein binding), GO:0140098 (catalytic activity, acting on RNA), GO:0016788 (hydrolase activity, acting on ester bonds), GO:0004518 (nuclease activity), GO:0004540 (ribonuclease activity), GO:0004519 (endonuclease activity), GO:0004521 (RNA endonuclease activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0065007 (biological regulation), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0035821 (modulation of process of another organism), GO:0071704 (organic substance metabolic process), GO:0045927 (positive regulation of growth), GO:0044403 (biological process involved in symbiotic interaction), GO:0009056 (catabolic process), GO:0009892 (negative regulation of metabolic process), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0045926 (negative regulation of growth), GO:0048523 (negative regulation of cellular process), GO:0040008 (regulation of growth), GO:0044238 (primary metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0044248 (cellular catabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0051701 (biological process involved in interaction with host), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0044003 (modulation by symbiont of host process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:1901575 (organic substance catabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0034655 (nucleobase-containing compound catabolic process), GO:0044270 (cellular nitrogen compound catabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051246 (regulation of protein metabolic process), GO:0019439 (aromatic compound catabolic process), GO:0051248 (negative regulation of protein metabolic process), GO:0046700 (heterocycle catabolic process), GO:0010468 (regulation of gene expression), GO:0009057 (macromolecule catabolic process), GO:0034248 (regulation of amide metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0044265 (cellular macromolecule catabolic process), GO:1901361 (organic cyclic compound catabolic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010629 (negative regulation of gene expression), GO:0034249 (negative regulation of amide metabolic process), GO:0017148 (negative regulation of translation), GO:0016070 (RNA metabolic process), GO:2001141 (regulation of RNA biosynthetic process), GO:0006402 (mRNA catabolic process), GO:0006355 (regulation of DNA-templated transcription), GO:0006401 (RNA catabolic process), GO:2000112 (regulation of cellular macromolecule biosynthetic process), GO:0006417 (regulation of translation), GO:1902679 (negative regulation of RNA biosynthetic process), GO:2000113 (negative regulation of cellular macromolecule biosynthetic process), GO:0010608 (post-transcriptional regulation of gene expression), GO:0045892 (negative regulation of DNA-templated transcription), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:0016071 (mRNA metabolic process), GO:0034661 (ncRNA catabolic process), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0034660 (ncRNA metabolic process), GO:0016075 (rRNA catabolic process), GO:0016072 (rRNA metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0071944 (cell periphery), GO:0016020 (membrane), GO:0005886 (plasma membrane)