9.B.12 The Sensitivity to Sodium or Salt Stress-induced Hydrophobic Peptide (Sna) Family

The Sna family (also referred to as the SHP family or the UPF0057 family by UniProt) consists of peptides found ubiquitously in bacteria, yeast, plants and animals. There are four members of the SHP family encoded within the S. cerevisiae genome, at least eight in C. elegans and two in Synechocystis. Expression of the gene encoding one member of the SHP family, a peptide from barley or 'tall wheat grass' (L. elongatum), has been shown to be induced by both salt and low temperature stress.

Yeast (S. cerevisiae and Candida albicans) plasma membranes contain a non-essential 55 aa hydrophobic peptide (Pmp3p) with two putative TMSs and sequence similarity to a ubiquitous protein family. One plant peptide (LT16A or RC12A; gbAAF26091) is over-expressed under high salt or low temperature conditions. One C. elegans protein (pirT26079) is large (551 aas) with the region of sequence similarity at the C-terminus, while two others (pirS40492 and T16929) are small (92 aas and 77 aas) with the region of homology at the N-terminus and the C-terminus, respectively. The PMP3 gene product in yeast possibly gives rise to hyperpolarization of the membrane potential, promoting sensitivity to cytotoxic cations such as Na+ and hygromycin B. The plant homologue, RC12A, can replace Pmp3p. These results could be explained if Pmp3p forms oligomeric pores that conduct H+ or another cation.

The Plasma Membrane Proteolipid 3 (PMP3, UPF0057 family in Uniprot) family consists of abundant small hydrophobic polypeptides with two predicted transmembrane helices. Plant homologues are upregulated in response to drought/salt-stresses, and yeast deletion mutants exhibited conditional growth defects. Kwok et al. 2020 reported abundant expression of Group I PMP3 homologues (PMP3(i)hs) during normal vegetative growth in both prokaryotic and eukaryotic cells, at a level comparable to housekeeping genes. Expression of eukaryotic PMP3(i)hs is dramatically upregulated in response to membrane potential (Vm) variability (Vmvar ), whereas PMP3(i)hs deletion-knockdown led to Vm changes with conditional growth defects. Bacterial PMP3(i)h yqaE deletion led to a shift in salt sensitivity; Vmvar alternations with exogenous K+ addition downregulated prokaryotic PMP3(i)hs, suggesting that the [K+]-Vmvar axis involves a significant feedback element in prokaryotic ionic homeostasis. The eukaryotic homologues functionally suppressed the conditional growth defects in bacterial deletion mutants, demonstrating the conserved cross-kingdom membrane function. Thus, thee is a direct reciprocal relationship between PMP3(i)hs expression and Vm differentials in both prokaryotic and eukaryotic cells. Together with PMP3(i)hs ubiquitous abundance, Kwok et al. 2020 proposed that the lipid-binding selectivity and membrane protein colocalization is a key element in membrane homeostasis.



Goddard, N.J., M.A. Dunn, L. Zhang, A.J. White, P.L. Jack and M.A. Hughes (1993). Molecular analysis and spatial expression pattern of a low-temperature-specific barley gene, blt101. Plant Mol. Biol. 23: 871-879.

Gulick, P.J., W. Shen and H. An (1994). ESI3, a stress-induced gene from Lophopyrum elongatum. Plant Physiol. 104: 799-800.

Kwok, A.C.M., F. Zhang, Z. Ma, W.S. Chan, V.C. Yu, J.S.H. Tsang, and J.T.Y. Wong. (2020). Functional responses between PMP3 small membrane proteins and membrane potential. Environ Microbiol 22: 3066-3080.

Navarre, C. and A. Goffeau. (2000). Membrane hyperpolarization and salt sensitivity induced by deletion of PMP3, a highly conserved small protein of yeast plasma membrane. EMBO. J. 19: 2515-2524.

Pokrzywa, W., B. Guerriat, J. Dodzian, and P. Morsomme. (2009). Dual sorting of the Saccharomyces cerevisiae vacuolar protein Sna4p. Eukaryot. Cell. 8: 278-286.

Renard, H.F., D. Demaegd, B. Guerriat, and P. Morsomme. (2010). Efficient ER exit and vacuole targeting of yeast Sna2p require two tyrosine-based sorting motifs. Traffic 11: 931-946.

Stawiecka-Mirota, M., W. Pokrzywa, J. Morvan, T. Zoladek, R. Haguenauer-Tsapis, D. Urban-Grimal, and P. Morsomme. (2007). Targeting of Sna3p to the endosomal pathway depends on its interaction with Rsp5p and multivesicular body sorting on its ubiquitylation. Traffic 8: 1280-1296.


TC#NameOrganismal TypeExample
9.B.12.1.1Salt-stress and cold-shock-induced hydrophobic peptide, BLT101 or ESI3 Plants, bacteria, yeast, animals BLT101 of Lophopyrum elongatum (P68178)

Membrane peptide of 55 aas, plasma membrane proteolipid 3, Pmp3/Sna1. Plays a role in the regulation of membrane potential, possible by mediating a proton leak (Navarre and Goffeau 2000).


Pmp3p of Saccharomyces cerevisiae (P87284)


Pmp3 family (UPF0057) member of 87 aas.


Pmp3 family member of Bacillus anthracis


Pmp3 famiy member of 56 aas


Pmp3 family member of Bacillus subtilis


Ric1 of 58 aas


Ric1 of Chlorobaculum parvum


hydrophobic peptide of 54 aas and 2 TMSs, RCI2A or LTI6A.  It is upregulated upon drought/salt stress (Kwok et al. 2020). It might oligomerized to form a proton channel but this hypothesis has not been tested.

RCI2A of Arabidopsis thaliana (thale cress)


TC#NameOrganismal TypeExample

Uncharacterized ORF, YqaE, of 52 aas and 2 putative TMSs. The eukaryotic homologues functionally suppress the conditional growth defects in bacterial deletion mutant, demonstrating the conserved cross-kingdom membrane functions by PMP3(i)hs. There is a direct reciprocal relationship between PMP3(i)hs expression and Vm differentials in both prokaryotic and eukaryotic cells. Cumulative with the PMP3(i)hs ubiquitous abundance, their lipid-binding selectivities and membrane protein colocalization, it is a key element in membrane homeostasis (Kwok et al. 2020).


YqaE of E. coli (P0AE42)


Plasma membrane proteolipid 3, Pmp3 of 57 aas


Pmp3 of Rhizobus delemar


TC#NameOrganismal TypeExample

Uncharacterized ORF, Sna3 (YJL151c).  Targeting to the endosomal pathway depends on its interaction with Rsp5p, and multivesicular body sorting depends on ubiquitylation (Stawiecka-Mirota et al. 2007).


Sna3 of Saccharomyces cerevisiae


Vacuolar Sna4 of 140 aas with two N-terminal TMSs.  It is transported to the vauolar membrane via the alkaline phosphatase (ALP) pathway which bypasses the multivesicular bodies (MVBs) (Pokrzywa et al. 2009).


Sna4 of Saccharomyces cerevisiae


Sna2 of 79 aas.  Two tyroline-based sorting motifs are required for proper ER exit and vacuolar targeting (Renard et al. 2010).


Sna2 of Sacchaomyces cerevisiae


TC#NameOrganismal TypeExample
9.B.12.4.1Uncharacterized ORF, F47B7.1 Animals F47B7.1 of Caenorhabditis elegans