TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
1.A.23.1.1









Minor K+-dependent MscS-type mechanosensitive channel protein, designated KefA, AefA or MscK, (Edwards et al. 2012). A molecular dynamics study of gating has been published (Sotomayor and Schulten 2004). It suggested that when restraining the backbone of the protein, the channel remained in the open form and the simulation revealed intermittent permeation of water molecules through the channel. Abolishing the restraints under constant pressure conditions led to spontaneous closure of the transmembrane channel, whereas abolishing the restraints when surface tension (20 dyn/cm) was applied led to channel widening. The large balloon-shaped cytoplasmic domain of MscS exhibited spontaneous diffusion of ions through its side openings. Interaction between the transmembrane domain and the cytoplasmic domain of MscS was observed and involved formation of salt bridges between residues Asp62 and Arg128; this interaction may be essential for the gating of MscS. K+ and Cl- ions showed distinctively different distributions in and around the channel (Sotomayor and Schulten 2004).

Bacteria
Proteobacteria
KefA (AefA) of E. coli
1.A.23.1.2









The putative osmoadaptation receptor, BspA
Bacteria
Proteobacteria
BspA of Erwinia (Pectobacterium) chrysanthemi
1.A.23.1.3









Mini conductance (300 pS) mechanosensitive channel, YjeP or MscM (1107aas; 13 TMSs in a 1 + 12 TMS arrangement).  Encoded in an operon with phosphatidyl serine decarboxylase (Moraes and Reithmeier 2012). Protects against hypoosmotic shock (Edwards et al. 2012).

Bacteria
Proteobacteria
YjeP of E. coli (P39285)
1.A.23.1.4









Uncharacterized protein of 571 aas and 6 TMSs.

Bacteria
Proteobacteria
UP of Bdellovibrio exovorus
1.A.23.1.5









Mechanosensitive ion channel, MscS, of 952 aas and 10 TMSs.

Bacteria
Proteobacteria
MscS of Legionella sp.
1.A.23.2.1









Major MscS channel protein, YggB. Seven residues, mostly hydrophobic, in the first and second transmembrane helices are lipid-sensing residues (Malcolm et al., 2011).  X-ray structures are available (Lai et al. 2013).  The cytoplasmic cage domain senses macromolecular crowding (Rowe et al. 2014). A gating mechanism has been proposed (Malcolm et al. 2015).  The thermodynamics of K+ leak have been studied (Koprowski et al. 2015).  In the MscS crystal structure (PDB 2OAU ), a narrow, hydrophobic opening is visible in the crystal structure, and a vapor lock, created by hydrophobic seals consisting of L105 and L109, is the barrier to water and ions (Rasmussen et al. 2015). The voltage dependence of inactivation occurs independently of the positive charges of R46, R54, and R74 (Nomura et al. 2016). The closed-to-open transition may involve rotation and tilt of the pore-lining helices (Edwards et al. 2005).

Bacteria
Proteobacteria
YggB of E. coli (P0C0S1)
1.A.23.2.2









MscS protein.  The x-ray structure at 4.2 Å is available (Lai et al. 2013).

Bacteria
Proteobacteria
MscS of Helicobacter pylori
1.A.23.2.3









MscS mechanosensitive channel of 462 aas and 5 TMSs.

Bacteria
Candidatus Peregrinibacteria
MscS channel of Candidatus Peribacter riflensis
1.A.23.2.4









Putative small conductance mechanosensetive channel protein of 261 aas and 3 TMSs

Viruses
Phycodnaviridae
MscS homologue of Aureococcus anophagefferens virus
1.A.23.3.1









The YkuT osmolyte efflux channel
Bacteria
Firmicutes
YkuT of Bacillus subtilis
1.A.23.3.2









Mechanosensitive NaCl-inducible RpoS-dependent channel (1,000 pS), YbiO (741 aas; 10TMSs).  Protects agains hypoosmotic shock (Edwards et al. 2012).

Bacteria
Proteobacteria
YbiO of E. coli (P75783)
1.A.23.3.3









Mechanosensitive channel, small conductance, YggB, GluE or MscCG (533 aas; 6-7 TMSs).  Mediates glutamate efflux (Becker et al. 2013).  The pore domain is in the N-terminus.  The C-terminus includes three subdomains, the periplasmic loop, the fourth transmembrane segment, and the cytoplasmic loop, all of which are important for MscCG function, in particular for glutamate excretion (Becker and Krämer 2015). Deletion of the encoding gene results in a 10% increase in lysine production and a decrease in cell mass yield (Xiao et al. 2020).

 

Bacteria
Actinobacteria
YggB or MscCG of Corynebacterium glutamicum (P42531)
1.A.23.3.4









MscCG2 of 334 aas and 4 TMSs in a 3 + 1 arrangement.  It functions as an L-glutamate exporter and an osmotic safety valve (Wang et al. 2018). It is 23% identical to MscCG (TC# 1.A.23.3.3) in the same organism. MscCG2-mediated L-glutamate excretion was activated by biotin limitation or penicillin treatment, and constitutive L-glutamate excretion was triggered by a gain-of-function mutation (A151V). It was not induced by glutamate producing conditions (Wang et al. 2018).

Bacteria
Actinobacteria
MscCG2 of Corynebacterium glutamicum
1.A.23.3.5









Small-conductance mechanosensitive channel Msc1 of 533 aas and 5 TMSs in a 4 (N-terminus) + 1 TMS (near the C-terminus) with two smaller peaks of hydrophobicity between these that could be TMSs. This system as well as a second Msc protein, Msc2, are able to export L-glutamate and other metabolites (Kawasaki and Martinac 2020).

Bacteria
Actinobacteria
Msc1 of Corynebacterium glutamicum
1.A.23.4.1









The MscMJ mechanosensitive channel
Archaea
Euryarchaeota
MscMJ of Methanococcus jannaschii
1.A.23.4.2









The MscMJLR mechanosensitive channel
Archaea
Euryarchaeota
MscMJLR of Methanococcus jannaschii
1.A.23.4.3









Mechanosensative cation-selective channel with a conductance of 100 pS, YnaI (344aas; 4TMSs).  Protects against hypoosmotic shock (Edwards et al. 2012).  The structure has been solved by cryo-electron microscopy to a resolution of 13 A (Böttcher et al. 2015). While the cytosolic vestibule is structurally similar to that in MscS, additional density is seen in the transmembrane region, consistent with the presence of two additional TMSs predicted for YnaI. The location of this density suggests that the extra TMSs are tilted, which could induce local membrane curvature extending the tension-sensing paddles seen in MscS. Off-center lipid-accessible cavities are seen that resemble gaps between the sensor paddles in MscS. The conservation of the tapered shape and the cavities in YnaI suggest a mechanism similar to that of MscS (Böttcher et al. 2015). The voltage dependence of inactivation occurs independently of the positive charges of R46, R54, and R74 (Nomura et al. 2016). A 3.8 Å structure by cryoEM revealed a heptamer structural fold similar to previously studied MscS channels. The ion-selective filter is formed by seven hydrophobic methionines (Met158) in the transmembrane pore (Yu et al. 2017). Details of the gating transition for MscS have been predicted (Zhu et al. 2018). YnaI has a gating mechanism based on flexible pore helices (Flegler et al. 2020), and thus, MscS-like channels of different sizes have a common core architecture but show different gating mechanisms and fine-tuned conductive properties.

Bacteria
Proteobacteria
YnaI of E. coli (P0AEB5)
1.A.23.4.4









Plant plastid mechanosensitive channel MscS-like-2 (Msl2) (controls plastid organellar morphology, as does Msl3) (Haswell and Meyerowitz, 2006Haswell et al., 2008). It functions as do the bacterial homologues, but is essential for leaf growth, chloroplast integrity and normal starch accumulation (Jensen and Haswell 2012).  msl2 msl3 double mutant seedlings exhibit several hallmarks of drought or environmental osmotic stress, including solute accumulation, elevated levels of the compatible osmolyte proline (Pro), and accumulation of the stress hormone abscisic acid (ABA). Furthermore, msl2 msl3 mutants expressed Pro and ABA metabolism genes in a pattern normally seen under drought or osmotic stress. Pro accumulation in the msl2 msl3 mutant was suppressed by conditions that reduce plastid osmotic stress leading to the conclusion that these channels function like their bacterial homologues (Wilson et al. 2014).

Eukaryota
Viridiplantae
Msl2 of Arabidopsis thaliana (Q56X46)
1.A.23.4.5









MscM (YbdG) is a distant member of the MscS family. It displays miniconductance (MscM) activity (Schumann et al., 2010; Edwards et al. 2012).

Bacteria
Proteobacteria
MscM (YbdG) of E. coli (P0AAT4)
1.A.23.4.6









Mechanosensitive channel, MscS

Archaea
Crenarchaeota
MscS of Sulfolobus islandicus (C4KE93)
1.A.23.4.7









Mechanosensitive ion channel protein 8 (Mechanosensitive channel of small conductance-like 8) (MscS-Like protein 8) is a pollen-specific, membrane tension-gated ion channel required for pollen to survive the hypoosmotic shock of rehydration and for full male fertility. It negatively regulates pollen germination but is required for cellular integrity during germination and tube growth. MSL8 thus senses and responds to changes in membrane tension associated with pollen hydration and germination (Hamilton et al. 2015).

Eukaryota
Viridiplantae
MSL8 of Arabidopsis thaliana
1.A.23.4.8









Mechanosensitive ion channel protein 5 (Mechanosensitive channel of small conductance-like 5) (MscS-Like protein 5)
Eukaryota
Viridiplantae
MSL5 of Arabidopsis thaliana
1.A.23.4.9









Putative small conductance mechanosensitive channel; Calcium channel, MacS

Eukaryota
Fungi
MacS of Mycosphaerella graminicola (Zymoseptoria tritici)
1.A.23.4.10









Uncharacterized MscS homologue

Bacteria
Proteobacteria
MscS homologue of Helicobacter pylori
1.A.23.4.11









Mitochondrial mechanosensitive ion channel protein 1, MscS-like channel, MSL1, of 497 aas and 5 TMSs. As the sole member of the Arabidopsis MSL family, localized in the mitochondrial inner membrane, MSL1 is essential for maintaining the normal membrane potential of mitochondria. Li et al. 2020 reported a cryoelectron microscopy (cryo-EM) structure of AtMSL1 at 3.3 Å. The overall architecture of AtMSL1 is similar to MscS, but the transmembrane domain of AtMSL1 is larger. Structural differences are observed in both the transmembrane and the matrix domain, and the carboxyl-terminus of AtMSL1 is more flexible while the beta-barrel structure observed in MscS is absent. The side portals in AtMSL1 are significantly smaller, and enlarging the size of the portal by mutagenesis can increase the channel conductance (Li et al. 2020).

Eukaryota
Viridiplantae
MSL1 of Arabidopsis thaliana
1.A.23.4.12









Uncharacterized MscS channel of 351 aas and 4 N-terminal TMSs.

Bacteria
Proteobacteria
UP of Bdellovibrio bacteriovorus
1.A.23.4.13









MscS channel of 553 aas and 6 TMSs.

Eukaryota
Entamoebidae
MscS of Entamoeba histolytica
1.A.23.4.14









Mechanosensitive channel-like 10, Msl10 of 734 aas and 5 or more TMSs.  Functions in triggering cell death in a process that is independent of its channel activity (Maksaev et al. 2018).

Eukaryota
Viridiplantae
Mscl10 of Arabidopsis thaliana (Mouse-ear cress)
1.A.23.4.15









Plasma membrane small conductance mechanosensitive channel, MSL4, of 881 aas and 5 putative TMSs (Hamilton et al. 2015). 

Eukaryota
Viridiplantae
MSL4 of Arabidopsis thaliana
1.A.23.5.1









The cyclic nucleotide-binding MscS homologue, MT2508 (the C-terminal domain is the CAP_ED domain CD00038). It lacks mechanosensitivity but is ligand-gated by cyclic nucleotides (Caldwell et al., 2010).

Bacteria
Actinobacteria
MscS homologue, MT2508 of Mycobacterium tuberculosis (P71915)
1.A.23.6.1









Chloroplast mechanosensitive channel, Msc1 (anions are preferred over cations) (Nakayama et al., 2007).
Eukaryota
Viridiplantae
Msc1 of Chlamydomonas reinhardtii (A3KE12)
1.A.23.7.1









MscS homologue

Bacteria
Actinobacteria
MscS homologue of Streptomyces coelicolor
1.A.23.7.2









MscS homologue

Bacteria
Proteobacteria
MscS of Myxococcus xanthus
1.A.23.8.1









CmpX of 274 aas and 5 TMSs in a 1 + 4 arrangement. CmpX regulates virulence and controls biofilm formation in P. aeruginosa (Bhagirath et al. 2017). It also modulates intra-cellular c-di-GMP levels. A cmpX knockout showed decreased promoter activity of exoS (PA1362) and increased activity of the small RNA, RsmY. As compared to the wild-type PAO1, the cmpX mutant had elevated intracellular c-di-GMP levels as well as increased expression of wspR (PA3702), a c-di-GMP synthase. Transcription of the major outer membrane porin gene oprF (PA1777) and sigma factor sigX (PA1776) was decreased in the cmpX mutant. The cmpX knockout mutant had increased sensitivity to membrane detergents and antibiotics such as lauryl sulfobetaine, tobramycin, and vancomycin (Bhagirath et al. 2017).

Bacteria
Proteobacteria
CmpX of Pseudomonas aeruginosa
1.A.23.8.2









CmpX protein of 227 aas and 5 TMSs

Bacteria
Candidatus Wolfebacteria
CmpX of Candidatus Wolfebacteria bacterium
1.A.23.8.3









Uncharacterized protein of 439 aas and 9 TMSs in a 5 + 4 arrangement.

Bacteria
Proteobacteria
UP of Brevundimonas viscosa
1.A.23.8.4









Mechanosensitive ion channel protein MscS of 254 aas and 5 TM

Archaea
Euryarchaeota
MscS of Haloterrigena daqingensis
1.A.23.8.5









Uncharacterized protein of 486 aas and 11 TMSs.

Bacteria
Proteobacteria
UP of Hydrogenophaga taeniospiralis