These data strongly support the BI-D1870 hypothesis that M60-like/Paclitaxel PF13402 containing proteins play important roles in colonisation of the invertebrate digestive tract and vertebrate mucosal surfaces by a broad diversity of mutualistic and pathogenic microbes. Consistent with this hypothesis entries positive for the PF13402 profile were also positive for a pattern characteristic of some Znmetallopeptidases or hit by the M60-enhancin domain with enhancin being a Znmetallopeptidase that is a well established baculovirus virulence factor. However the majority of the 523 entries positive for the PF13402 profile were not positive for either of these two sequence features despite possessing the pattern HEXXHX E. These observations prompted us to search the MEROPS peptidase database with the PF13402 profile. Significant hits included 38 entries and these are all members of the family M60-enhancin peptidase, with the three most significant hits being from Bacillus cereus and Akkermansia muciniphila, a mucin degrading bacterium from the human gut. The Zn-metallopeptidase domain of the M60-enhancin annotated peptidases in MEROPS overlapped with the new domain and included the shared HEXXHX E pattern. Of these 38 MEROPS entries, 35 were identified as having the M60-enhancin/PF03272 domain by InterProScan. The three most significant hits for the PF13402 profile corresponded to the three entries negative for the M60-enhancin/PF03272 profile. Plotting the difference of the HMMER search bit scores between profiles PF13402 and PF03272 against the PSI-Blast scores indicated that the PF13402 profile correlated better with the PSI-Blast profiles than the PF03272 profile does. The most significant hits for the M60-enhancin/PF03272 profile corresponded to the least significant hits for the PF13402 and PSI-Blast profiles, consistent with the characterisation of a new protein domain. The difference of the HMMER search bit scores between profiles PF13402 and PF03272 defined a total of 415 entries positive for the PF13402 profile. The remaining entries positive for the PF03272 profile were from two Fungi, bacteria and baculoviruses of which 48 taxa also encoded one or more entries positive for the PF13402 profile. Taken together these different considerations strongly support the hypothesis that the newly defined M60-like/PF13402 domain corresponds to a novel Zn-metallopeptidase sub-family related to the M60-enhancin/PF03272 member of the MA clan as defined in the MEROPS database. The 415 proteins with most significant hits for the M60-like/ PF13402 profile were derived from 256 taxa across bacteria and eukaryotes. The majority of these taxa are microorganisms, including both bacteria and eukaryotes, known to be mutualists, commensals or pathogens of animal hosts. Indeed, a highly significant positive association between the M60-like/PF13402 domain distribution and animal host-adapted microorganisms was observed; with the strongest association observed for microbes able to thrive on vertebrate mucosa.
The information available so far studying mitochondria from rat liver treated
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