Peptidases M48 (Ste24 endopeptidase or htpX homolog) and M56 (in MecR1 and BlaR1), integral membrane metallopeptidases; This family contains peptidase M48 (also known as Ste24 peptidase, Ste24p, Ste24 endopeptidase, a-factor converting enzyme, AFC1), M56 (also known as BlaR1 peptidase) as well as a novel family called minigluzincins. Peptidase M48 belongs to Ste24 endopeptidase family. Members of this family include Ste24 protease (peptidase M48A), protease htpX homolog (peptidase M48B), or CAAX prenyl protease 1, and mitochondrial metalloendopeptidase OMA1 (peptidase M48C). They proteolytically remove the C-terminal three residues of farnesylated proteins. They are integral membrane proteins associated with the endoplasmic reticulum and golgi, binding one zinc ion per subunit. In eukaryotes, Ste24p is required for the first NH2-terminal proteolytic processing event within the a-factor precursor, which takes place after COOH-terminal CAAX modification (C is cysteine; A is usually aliphatic; X is one of several amino acids) is complete. The Ste24p contains multiple membrane spans, a zinc metalloprotease motif (HEXXH), and a COOH-terminal ER retrieval signal (KKXX). Mutation studies have shown that the HEXXH protease motif, which is extracellular but adjacent to a transmembrane domain and therefore close to the membrane surface, is critical for Ste24p activity. Ste24p has limited homology to HtpX family of prokaryotic proteins; HtpX proteins, also part of the M48 peptidase family, are smaller and homology is restricted to the C-terminal half of Ste24p. HtpX expression is controlled by the Cpx stress response system, which senses abnormal membrane proteins; HtpX then undergoes self-degradation and collaborates with FtsH to eliminate these misfolded proteins. Peptidase M56 includes zinc metalloprotease domain in MecR1 and BlaR1. MecR1 is a transmembrane beta-lactam sensor/signal transducer protein that regulates the expression of an altered penicillin-binding protein PBP2a, which resists inactivation by beta-lactam antibiotics, in methicillin-resistant Staphylococcus aureus (MRSA). BlaR1 regulates the inducible expression of a class A beta-lactamase that hydrolytically destroys certain beta-lactam antibiotics in MRSA. Also included are a novel family of related proteins that consist of the soluble minimal scaffold similar to the catalytic domains of the integral-membrane metallopeptidase M48 and M56, thus called minigluzincins.

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gi 489959315 110 APEAFLRMIVVHELAHLKEKEHDKAFYSLCCHMEPQYHQLE 150
Cdd:cd07344   50 APPEVIDYVVVHELAHLKHMNHSPRFWALVERYMPDYKERR 90

Peptidase M48 YhfN-like, a novel minigluzincin; M48 YhfN-like protease is considered as a CaaX prenyl protease 1 homolog, with most of the sequences in this family as yet uncharacterized. It contains the zinc metalloprotease motif (HEXXH), likely exposed on the cytoplasmic side. It is probably associated with the endoplasmic reticulum (ER), regardless of whether its genes possess the conventional signal motif (KKXX) in the C-terminal. Proteins in this family proteolytically remove the C-terminal three residues of farnesylated proteins. This novel family of related proteins consist of the soluble minimal scaffold similar to the catalytic domains of the integral-membrane metallopeptidase M48 and M56, thus called minigluzincins.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 489959315 110 APEAFLRMIVVHELAHLKEKEHDKAFYSLCCHMEPQYHQLE 150
Cdd:cd07344   50 APPEVIDYVVVHELAHLKHMNHSPRFWALVERYMPDYKERR 90

YgjP-like, metallopeptidase domain; This is a conserved domain containing the catalytic zinc-metallopeptidase (HExxH) catalytic motif. Proteins containing this domain are found in some archaebacteria, as well as Helicobacter pylori. The proteins are 190-240 amino acids long, with the C terminus being the most conserved region, containing three conserved histidines. This domain is found in YgjP from E. coli, a predicted metal-dependent hydrolase that hydrolyses UTP to UMP and diphosphate in vitro; and in MJ0123 from Methanocaldococcus jannaschii (also referred to as projannalysin).

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                  ....*....|....*....|....*....|....*...
gi 489959315  110 APEAFLRMIVVHELAHLKEKEHDKAFYSLC-CHMePQY 146
Cdd:pfam01863 161 APPECIDYVVVHELCHLLEPNHSPRFWALVeRYM-PDW 197

Peptidase M48 YhfN-like, a novel minigluzincin; M48 YhfN-like protease is considered as a CaaX prenyl protease 1 homolog, with most of the sequences in this family as yet uncharacterized. It contains the zinc metalloprotease motif (HEXXH), likely exposed on the cytoplasmic side. It is probably associated with the endoplasmic reticulum (ER), regardless of whether its genes possess the conventional signal motif (KKXX) in the C-terminal. Proteins in this family proteolytically remove the C-terminal three residues of farnesylated proteins. This novel family of related proteins consist of the soluble minimal scaffold similar to the catalytic domains of the integral-membrane metallopeptidase M48 and M56, thus called minigluzincins.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 489959315 110 APEAFLRMIVVHELAHLKEKEHDKAFYSLCCHMEPQYHQLE 150
Cdd:cd07344   50 APPEVIDYVVVHELAHLKHMNHSPRFWALVERYMPDYKERR 90

YgjP-like, metallopeptidase domain; This is a conserved domain containing the catalytic zinc-metallopeptidase (HExxH) catalytic motif. Proteins containing this domain are found in some archaebacteria, as well as Helicobacter pylori. The proteins are 190-240 amino acids long, with the C terminus being the most conserved region, containing three conserved histidines. This domain is found in YgjP from E. coli, a predicted metal-dependent hydrolase that hydrolyses UTP to UMP and diphosphate in vitro; and in MJ0123 from Methanocaldococcus jannaschii (also referred to as projannalysin).

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 489959315  110 APEAFLRMIVVHELAHLKEKEHDKAFYSLC-CHMePQY 146
Cdd:pfam01863 161 APPECIDYVVVHELCHLLEPNHSPRFWALVeRYM-PDW 197