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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1085855443  83 LGDAILVSAETFPEVQNAVDEVRAALQYDRRVDIFVIPNLSP-----RIQLKSYFGIRALLIEGgaiadmttpASRSQLL 157
Cdd:cd07325     1 LGNSVRVTPRQFPELHALLVEACRILGLKKVPELYVYQSPVLnafalGFEGRPFIVLNSGLVEL---------LDDDELR 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1085855443 158 FLLGTYFGAFKAKHD--RSAVVELTLDSAGIRRLLAPFVAP-----WLRTTVYTGDQIAYACSGDFGASISAVHRVLVGR 230
Cdd:cd07325    72 FVIGHELGHIKSGHVlyRTLLLLLLLLGELIGILLLSSALPlallaWSRAAEYSADRAGLLVCQDPEAAIRALMKLAGGS 151

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1085855443 231 ELSPQL----AAAGLILQADRVSKSWVlRVAEMLRPEPHATNRFLNLVR 275
Cdd:cd07325   152 KLLKDVnnieYFLEEEAQADALDGFFK-WLSELLSTHPFLVKRAAELLR 199

M48 Ste24 endopeptidase-like, integral membrane metallopeptidase; This family contains peptidase M48 family Ste24p-like proteins that are as yet uncharacterized, but probably function as intracellular, membrane-associated zinc metalloproteases; they all contain the HEXXH Zn-binding motif, which is critical for Ste24p activity. They likely remove the C-terminal three residues of farnesylated proteins proteolytically and are possibly associated with the endoplasmic reticulum and golgi. Some members also contain ankyrin domains which occur in very diverse families of proteins and mediate protein-protein interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1085855443  83 LGDAILVSAETFPEVQNAVDEVRAALQYDRRVDIFVIPNLSP-----RIQLKSYFGIRALLIEGgaiadmttpASRSQLL 157
Cdd:cd07325     1 LGNSVRVTPRQFPELHALLVEACRILGLKKVPELYVYQSPVLnafalGFEGRPFIVLNSGLVEL---------LDDDELR 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1085855443 158 FLLGTYFGAFKAKHD--RSAVVELTLDSAGIRRLLAPFVAP-----WLRTTVYTGDQIAYACSGDFGASISAVHRVLVGR 230
Cdd:cd07325    72 FVIGHELGHIKSGHVlyRTLLLLLLLLGELIGILLLSSALPlallaWSRAAEYSADRAGLLVCQDPEAAIRALMKLAGGS 151

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1085855443 231 ELSPQL----AAAGLILQADRVSKSWVlRVAEMLRPEPHATNRFLNLVR 275
Cdd:cd07325   152 KLLKDVnnieYFLEEEAQADALDGFFK-WLSELLSTHPFLVKRAAELLR 199

M48 Ste24 endopeptidase-like, integral membrane metallopeptidase; This family contains peptidase M48 family Ste24p-like proteins that are as yet uncharacterized, but probably function as intracellular, membrane-associated zinc metalloproteases; they all contain the HEXXH Zn-binding motif, which is critical for Ste24p activity. They likely remove the C-terminal three residues of farnesylated proteins proteolytically and are possibly associated with the endoplasmic reticulum and golgi. Some members also contain ankyrin domains which occur in very diverse families of proteins and mediate protein-protein interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1085855443  83 LGDAILVSAETFPEVQNAVDEVRAALQYDRRVDIFVIPNLSP-----RIQLKSYFGIRALLIEGgaiadmttpASRSQLL 157
Cdd:cd07325     1 LGNSVRVTPRQFPELHALLVEACRILGLKKVPELYVYQSPVLnafalGFEGRPFIVLNSGLVEL---------LDDDELR 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1085855443 158 FLLGTYFGAFKAKHD--RSAVVELTLDSAGIRRLLAPFVAP-----WLRTTVYTGDQIAYACSGDFGASISAVHRVLVGR 230
Cdd:cd07325    72 FVIGHELGHIKSGHVlyRTLLLLLLLLGELIGILLLSSALPlallaWSRAAEYSADRAGLLVCQDPEAAIRALMKLAGGS 151

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1085855443 231 ELSPQL----AAAGLILQADRVSKSWVlRVAEMLRPEPHATNRFLNLVR 275
Cdd:cd07325   152 KLLKDVnnieYFLEEEAQADALDGFFK-WLSELLSTHPFLVKRAAELLR 199