Table 1.
Representation of Known Small Proteins in HMPI-II Data
| Abundant in HMPI-II Samples | Identified at Low Levels in HMPI-II Samples | Not Identified in HMPI-II Samples |
|---|---|---|
| Ribosomal proteins | CydX (Escherichia coli) | MciZ (Bacillus subtilis) |
| AgrD (Gram+ bacteria) | AcrZ (Escherichia coli) | MgrB (Escherichia coli) |
| ComC (Streptococcus) | Hok (Escherichia coli) | SpoVM (Bacillus subtilis) |
| Phenol soluble modulin (Staphylococcus) | KdpF (Escherichia coli) | BacSp222 (Staphylococcus pseudintermedius) |
| TisB (Escherichia coli) | AimP (Bacillus subtilis phages) | |
| SgrT (Escherichia coli) | FbpA/B/C (Bacillus subtilis) | |
| MntS (Escherichia coli) | MgtR (Salmonella typhimurium) | |
| PmrR (Salmonella enterica) | Prli42 (Listeria monocytogenes) | |
| SidA (Caulobacter crescentus) | CmpA (Bacillus subtilis) | |
| MgtS (Escherichia coli) | PepA1 (Staphylococcus aureus) | |
| Blr (Escherichia coli) | Listeriolysin S (Listeria monocytogenes) | |
| Streptolysin (Streptococcus pyogenes) | ||
| SdaA (Bacillus subtilis) |
Known proteins were queried against CDD-assigned domains of all ~444,054 representatives whenever they had an assigned domain and against all protein sequences of the ~444,054 representatives using BLASTp (Camacho et al., 2009) when the known protein was not assigned a known domain (Table S2). Only 12 of the 29 small proteins have an assigned protein domain (AcrZ, CydX, KdpF, AgrD, ComC, MciZ, MgrB, SpoVM, SgrT, Hok, TisB, phenol-soluble modulins as well as small ribosomal proteins). Approximately 3.5% of small proteins that were assigned a domain (3,930/113,693) were homologous to the extensively studied quorum-sensing small protein, Staphylococcal AgrD. ComC, a quorum-sensing signal that enables Streptococci to regulate DNA uptake and genetic transformation in response to population density as well as environmental queues such as antibiotic stress (Moreno-Gámez et al., 2017), was found in ~2% (2,176/113,693) of small proteins. Homologs of AgrD and ComC were clustered into 153 and 19 clusters, respectively, suggesting rapid evolution of these proteins, in line with what has been previously documented (Hyatt et al., 2012; Allan et al., 2007). CydX (YbgT) is a small protein required for the function of cytochrome bd oxidase (Sun et al., 2012). KdpF is part of the high-affinity ATP-driven potassium transport system (Gassel et al., 1999). Hok (Chukwudi and Good, 2015) and TisB (Steinbrecher et al., 2012) are toxins. AcrZ is a multidrug efflux pump accessory protein (Hobbs et al., 2012). SgrT is a regulator of glucose metabolism (Lloyd et al., 2017). MntS that takes part in manganese chaperoning (Martin et al., 2015). PmrR, is a regulator of a membrane-bound enzyme (Kato et al., 2012). SidAisan inhibitor of cell division (Modell et al., 2011). MgtS (formerly known as YneM) modulates intracellular Mg2+ levels to maintain cellular integrity upon Mg2+ limitation (Wang et al., 2017). Blr is involved in B-lactamase resistance (Karimova et al., 2012). Names of organisms in parentheses indicate the model organism in which small protein was mainly studied.