Peptidase M48C, integral membrane endopeptidase; This subfamily contains peptidase M48C Oma1 (also called mitochondrial metalloendopeptidase OMA1) protease homologs that are mostly uncharacterized. Oma1 is part of the quality control system in the inner membrane of mitochondria, with its catalytic site facing the matrix space. It cleaves and thereby promotes the turnover of mistranslated or misfolded membrane proteins. Oma1 can cleave the misfolded multi-pass membrane protein Oxa1, thus exerting a function similar to the ATP-dependent m-AAA protease for quality control of inner membrane proteins; it cleaves a misfolded polytopic membrane protein at multiple sites. It has been proposed that in the absence of m-AAA protease, proteolysis of Oxa1 is mediated by Oma1 in an ATP-independent manner. Oma1 is part of highly conserved mitochondrial metallopeptidases, with homologs present in higher eukaryotes, eubacteria and archaebacteria, all containing the zinc binding motif (HEXXH). It forms a high molecular mass complex in the inner membrane, possibly a homo-hexamer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039768458 265 HLTQCNRDVPGISET-NWVVHVVDSPAVNAFVLPNGQVFIFTGLLNSVTDVHQLSFLLGHEIAHAVLGHA---------- 333
Cdd:cd07331     7 RLIAAAGDDPPQSAGwDWEVHVIDSPEVNAFVLPGGKIFVFTGLLPVAKNDDELAAVLGHEIAHALARHSaermsqqkll 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039768458 334 ----------------------------YMFDRPYSRTLEAEADKVGLQLAAKA 359
Cdd:cd07331    87 qlllllllaalgaslaglalgllglgaqLGLLLPYSRKQELEADRIGLQLMAKA 140

Peptidase M48C, integral membrane endopeptidase; This subfamily contains peptidase M48C Oma1 (also called mitochondrial metalloendopeptidase OMA1) protease homologs that are mostly uncharacterized. Oma1 is part of the quality control system in the inner membrane of mitochondria, with its catalytic site facing the matrix space. It cleaves and thereby promotes the turnover of mistranslated or misfolded membrane proteins. Oma1 can cleave the misfolded multi-pass membrane protein Oxa1, thus exerting a function similar to the ATP-dependent m-AAA protease for quality control of inner membrane proteins; it cleaves a misfolded polytopic membrane protein at multiple sites. It has been proposed that in the absence of m-AAA protease, proteolysis of Oxa1 is mediated by Oma1 in an ATP-independent manner. Oma1 is part of highly conserved mitochondrial metallopeptidases, with homologs present in higher eukaryotes, eubacteria and archaebacteria, all containing the zinc binding motif (HEXXH). It forms a high molecular mass complex in the inner membrane, possibly a homo-hexamer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039768458 265 HLTQCNRDVPGISET-NWVVHVVDSPAVNAFVLPNGQVFIFTGLLNSVTDVHQLSFLLGHEIAHAVLGHA---------- 333
Cdd:cd07331     7 RLIAAAGDDPPQSAGwDWEVHVIDSPEVNAFVLPGGKIFVFTGLLPVAKNDDELAAVLGHEIAHALARHSaermsqqkll 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039768458 334 ----------------------------YMFDRPYSRTLEAEADKVGLQLAAKA 359
Cdd:cd07331    87 qlllllllaalgaslaglalgllglgaqLGLLLPYSRKQELEADRIGLQLMAKA 140

Putative Zn-dependent protease [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039768458 277 SETNWVVHVVDSPAVNAFVLPNGQVFIFTGLLNSVTDVHQLSFLLGHEIAH-------------------------AVLG 331
Cdd:COG4784    85 PDLPYTFTVLDSPVVNAFALPGGYVYVTRGLLALANDEAELAAVLGHEIGHvtarhavqrqsrataaqiglgrvlsPVLG 164

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1039768458 332 HAYMFD----------RPYSRTLEAEADKVGLQLAAKA 359
Cdd:COG4784   165 SAQAGQlagagaqlllASFSRDQELEADRLGVRYLARA 202

Peptidase M48C, integral membrane endopeptidase; This subfamily contains peptidase M48C Oma1 (also called mitochondrial metalloendopeptidase OMA1) protease homologs that are mostly uncharacterized. Oma1 is part of the quality control system in the inner membrane of mitochondria, with its catalytic site facing the matrix space. It cleaves and thereby promotes the turnover of mistranslated or misfolded membrane proteins. Oma1 can cleave the misfolded multi-pass membrane protein Oxa1, thus exerting a function similar to the ATP-dependent m-AAA protease for quality control of inner membrane proteins; it cleaves a misfolded polytopic membrane protein at multiple sites. It has been proposed that in the absence of m-AAA protease, proteolysis of Oxa1 is mediated by Oma1 in an ATP-independent manner. Oma1 is part of highly conserved mitochondrial metallopeptidases, with homologs present in higher eukaryotes, eubacteria and archaebacteria, all containing the zinc binding motif (HEXXH). It forms a high molecular mass complex in the inner membrane, possibly a homo-hexamer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039768458 265 HLTQCNRDVPGISET-NWVVHVVDSPAVNAFVLPNGQVFIFTGLLNSVTDVHQLSFLLGHEIAHAVLGHA---------- 333
Cdd:cd07331     7 RLIAAAGDDPPQSAGwDWEVHVIDSPEVNAFVLPGGKIFVFTGLLPVAKNDDELAAVLGHEIAHALARHSaermsqqkll 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039768458 334 ----------------------------YMFDRPYSRTLEAEADKVGLQLAAKA 359
Cdd:cd07331    87 qlllllllaalgaslaglalgllglgaqLGLLLPYSRKQELEADRIGLQLMAKA 140

Peptidase M48C Ste24p bepA-like, integral membrane protein; This family contains peptidase M48C Ste24p protease bepA (formerly yfgC)-like proteins considered to be putative metallopeptidases, containing a zinc-binding motif, HEXXH, and a COOH-terminal ER retrieval signal (KKXX). 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. 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. Several members of this family also contain tetratricopeptide (TPR) repeat motifs, which are involved in a variety of functions including protein-protein interactions. BepA has been shown to possess protease activity and is responsible for the degradation of incorrectly folded LptD, an essential outer-membrane protein (OMP) involved in OM transport and assembly of lipopolysaccharide. Overexpression of the bepA protease causes abnormal biofilm architecture.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039768458 280 NWVVHVVDSPAVNAFVLPNGQVFIFTGLLNSVTDVHQLSFLLGHEIAHAVLGH-AYMFDRPYSRTLEAEADKVGLQLAAK 358
Cdd:cd07333    46 PYRFFVVNDDSINAFATPGGYIYVNTGLILAADNEAELAGVLAHEIGHVVARHiAKQIEKSYSREDEREADQLGLQYLTK 125

                  .
gi 1039768458 359 A 359
Cdd:cd07333   126 A 126

Peptidase M48C Ste24p, integral membrane endopeptidase; This subfamily contains peptidase M48C Oma1 (also called mitochondrial metalloendopeptidase OMA1) protease homologs that are mostly uncharacterized. Oma1 is part of the quality control system in the inner membrane of mitochondria, with its catalytic site facing the matrix space. It cleaves and thereby promotes the turnover of mistranslated or misfolded membrane proteins. Oma1 can cleave the misfolded multi-pass membrane protein Oxa1, thus exerting a function similar to the ATP-dependent m-AAA protease for quality control of inner membrane proteins; it cleaves a misfolded polytopic membrane protein at multiple sites. It has been proposed that in the absence of m-AAA protease, proteolysis of Oxa1 is mediated by Oma1 in an ATP-independent manner. Oma1 is part of highly conserved mitochondrial metallopeptidases, with homologs present in higher eukaryotes, eubacteria and archaebacteria, all containing the zinc binding motif (HEXXH). It forms a high molecular mass complex in the inner membrane, possibly a homo-hexamer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039768458 283 VHVVDSPA-VNAFVLPNGQVFIFTGLLNSVTDVHQLSFLLGHEIAHAVLGH----------------------------- 332
Cdd:cd07332    69 LHFRDSGIgANAFALPGGTIVVTDGLVELAESPEELAAVLAHEIGHVEHRHslrqlirssglsllvslltgdvsglsdll 148

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039768458 333 ----AYMFDRPYSRTLEAEADKVGLQLAAKA 359
Cdd:cd07332   149 aglpALLLSLSYSRDFEREADAFALELLKAA 179

M48C peptidase, integral membrane endopeptidase; This subfamily contains peptidase M48C Oma1 (also called mitochondrial metalloendopeptidase OMA1) protease homologs that are mostly uncharacterized. Oma1 is part of the quality control system in the inner membrane of mitochondria, with its catalytic site facing the matrix space. It cleaves and thereby promotes the turnover of mistranslated or misfolded membrane proteins. Oma1 can cleave the misfolded multi-pass membrane protein Oxa1, thus exerting a function similar to the ATP-dependent m-AAA protease for quality control of inner membrane proteins; it cleaves a misfolded polytopic membrane protein at multiple sites. It has been proposed that in the absence of m-AAA protease, proteolysis of Oxa1 is mediated by Oma1 in an ATP-independent manner. Oma1 is part of highly conserved mitochondrial metallopeptidases, with homologs present in higher eukaryotes, eubacteria and archaebacteria, all containing the zinc binding motif (HEXXH). It forms a high molecular mass complex in the inner membrane, possibly a homo-hexamer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039768458 283 VHVVDSPAVNAFVlpNGQ-VFIFTGLLNSVTDVHQLSFLLGHEIAHAVLGHA----------YMFD-----RPYSRTLEA 346
Cdd:cd07342    23 VELGNSDGVNAYA--DGRrVQITSGMMDFAQDDDELALVVAHELAHNILGHRdrlrangvagGLLDgfggnAAYSREFEI 100

                          90
                  ....*....|...
gi 1039768458 347 EADKVGLQLAAKA 359
Cdd:cd07342   101 EADYLGLYLMARA 113

Zn-dependent protease with chaperone function [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039768458 283 VHVVDSPAVNAFV----LPNGQVFIFTGLLNSVTDvHQLSFLLGHEIAHAVLGHA 333
Cdd:COG0501    22 VYVMDSPAPNAFAtgrgPNNARIVVTDGLLELLDR-DELEAVLAHELGHIKNGDI 75

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1039768458 282 VVHVVDSPAVNAFVLP--NGQVFIFTGLLNSVTDvHQLSFLLGHEIAHAVLgHAYMFD 337
Cdd:cd05843    19 KVVVVPGSVPNAFFTGgaNKRVVLTTALLELLSE-EELAAVIAHELGHFKA-HEYQAD 74

Peptidase M56-like, integral membrane metallopeptidase in bacteria; This family contains peptidase M56, which includes zinc metalloprotease domain in MecR1 as well as 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. Both, MecR1 and BlaR1, are transmembrane proteins that consist of four transmembrane helices, a cytoplasmic zinc protease domain, and the soluble C-terminal extracellular sensor domain, and are highly similar in sequence and function. The signal for protein expression is transmitted by site-specific proteolytic cleavage of both the transducer, which auto-activates, and the repressor, which is inactivated, unblocking gene transcription. All members contain the zinc metalloprotease motif (HEXXH). Homologs of this peptidase domain are also found in a number of other bacterial genome sequences, most of which are as yet uncharacterized.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039768458 282 VVHVVDSPAVNAFVL---PNGQVFIFTGLLNSVTDvHQLSFLLGHEIAHAVLGHA 333
Cdd:cd07329    13 RVYVVDSDVPNAFAVgrsRGPTVVVTTGLLDLLDD-DELEAVLAHELAHLKRRDV 66