TCDB is operated by the Saier Lab Bioinformatics Group

9.B.149 The M50 Peptidase (M50-P) Family

The M50 Peptidase (S2P-M50) family includes proteins frequently of 700-800 aas in length with six N-terminal or centrally located TMSs. However, other members of the family are relatively small (300-400 aas).  They are integral membrane zinc metaloprotease that cleave transmembrane domains in proteins. They are frequently encoded in gene clusters with lantibiotic biosynthetic enzymes and ABC transporters. For example, Streptomyces griseus encodes in the following order: an ABC-2 type transporter, an ABC-type ATPase (see TC#3.A.1.105.11), a S2P-M50 peptidase with a CBS domain (see 9.B.149.1.1), a lantibiotic synthesis protein and a lantibiotic dehydratase. Other M50 peptidases include Membrane Fusion Protein (MFP; TC# 8.A.1) domains or may have an MFP encoded in the same operon. Still others include ABC-type ATPase domains fused to them, indicating a close relationship with the transporter. Peptidase processing of bacteriocins is known in some cases to occur during transport, and the peptidase and transporter presumably form a complex in the membrane. Many bacteriocin-producing Gram-positive bacteria have ABC exporters that function with an essential MFP (Harley et al. 2000). 

References associated with 9.B.149 family:

Akiyama, Y., K. Kanehara, and K. Ito. (2004). RseP (YaeL), an Escherichia coli RIP protease, cleaves transmembrane sequences. EMBO. J. 23: 4434-4442. 15496982
Alba, B.M., J.A. Leeds, C. Onufryk, C.Z. Lu, and C.A. Gross. (2002). DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response. Genes Dev. 16: 2156-2168. 12183369
Flores, S.K., Y. Deng, Z. Cheng, X. Zhang, S. Tao, A. Saliba, I. Chu, N. Burnichon, A.P. Gimenez-Roqueplo, E. Wang, R.C.T. Aguiar, and P.L.M. Dahia. (2020). Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking. J Clin Endocrinol Metab 105:. 32575117
Harley, K.T., G.M. Djordjevic, T.T. Tseng, and M.H. Saier. (2000). Membrane-fusion protein homologues in gram-positive bacteria. Mol. Microbiol. 36: 516-517. 10792737
Kanehara, K., K. Ito, and Y. Akiyama. (2002). YaeL (EcfE) activates the sigma(E) pathway of stress response through a site-2 cleavage of anti-sigma(E), RseA. Genes Dev. 16: 2147-2155. 12183368
Koide, K., K. Ito, and Y. Akiyama. (2008). Substrate recognition and binding by RseP, an Escherichia coli intramembrane protease. J. Biol. Chem. 283: 9562-9570. 18268014
Yokoyama, T., T. Niinae, K. Tsumagari, K. Imami, Y. Ishihama, Y. Hizukuri, and Y. Akiyama. (2021). The Escherichia coli S2P intramembrane protease RseP regulates ferric citrate uptake by cleaving the sigma factor regulator FecR. J. Biol. Chem. 100673. [Epub: Ahead of Print] 33865858
Yu, Y.T. and L. Kroos. (2000). Evidence that SpoIVFB is a novel type of membrane metalloprotease governing intercompartmental communication during Bacillus subtilis sporulation. J. Bacteriol. 182: 3305-3309. 10809718