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Conserved domains on  [gi|332991916|gb|AEF01971|]
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Zn-dependent protease with chaperone function [Alteromonas naphthalenivorans]

Protein Classification

M48 family metallopeptidase( domain architecture ID 11574487)

M48 family metallopeptidase is a zinc-dependent protease, such as metalloendopeptidase OMA1 that is part of the quality control system in the inner membrane of mitochondria

EC:  3.4.24.-
Gene Ontology:  GO:0004222|GO:0046872|GO:0006508
MEROPS:  M48
PubMed:  15544561|18429165

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
M48C_Oma1_like cd07331
Peptidase M48C, integral membrane endopeptidase; This subfamily contains peptidase M48C Oma1 ...
 64-250 7.51e-89

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.


:

Pssm-ID: 320690 [Multi-domain]  Cd Length: 187  Bit Score: 261.36  E-value: 7.51e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  64 VECVANAITAKV---PNSVFDGTWEVVVFDDEQVNAFALPGGKIGVYTGLLNVAENQHQLAAVIGHEVGHVIAEHGNERM 140
Cdd:cd07331    1 VRRVAARLIAAAgddPPQSAGWDWEVHVIDSPEVNAFVLPGGKIFVFTGLLPVAKNDDELAAVLGHEIAHALARHSAERM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 141 SQSTLINMGTQAAGAALAmneVSQTAPIMAAIGLGLQVGVQLPFSRTHESEADVIGLQLMAMSGFDPRQSVNLWQNMDAA 220
Cdd:cd07331   81 SQQKLLQLLLLLLLAALG---ASLAGLALGLLGLGAQLGLLLPYSRKQELEADRIGLQLMAKAGYDPRAAVTFWEKMAAA 157

                        170       180       190
                 ....*....|....*....|....*....|
gi 332991916 221 SNGERPLELLSTHPAPQTRISNLQANMNAA 250
Cdd:cd07331  158 EGGGKPPEFLSTHPSSETRIEALEELLPEA 187
 
Name Accession Description Interval E-value
M48C_Oma1_like cd07331
Peptidase M48C, integral membrane endopeptidase; This subfamily contains peptidase M48C Oma1 ...
 64-250 7.51e-89

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.


Pssm-ID: 320690 [Multi-domain]  Cd Length: 187  Bit Score: 261.36  E-value: 7.51e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  64 VECVANAITAKV---PNSVFDGTWEVVVFDDEQVNAFALPGGKIGVYTGLLNVAENQHQLAAVIGHEVGHVIAEHGNERM 140
Cdd:cd07331    1 VRRVAARLIAAAgddPPQSAGWDWEVHVIDSPEVNAFVLPGGKIFVFTGLLPVAKNDDELAAVLGHEIAHALARHSAERM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 141 SQSTLINMGTQAAGAALAmneVSQTAPIMAAIGLGLQVGVQLPFSRTHESEADVIGLQLMAMSGFDPRQSVNLWQNMDAA 220
Cdd:cd07331   81 SQQKLLQLLLLLLLAALG---ASLAGLALGLLGLGAQLGLLLPYSRKQELEADRIGLQLMAKAGYDPRAAVTFWEKMAAA 157

                        170       180       190
                 ....*....|....*....|....*....|
gi 332991916 221 SNGERPLELLSTHPAPQTRISNLQANMNAA 250
Cdd:cd07331  158 EGGGKPPEFLSTHPSSETRIEALEELLPEA 187
COG4784 COG4784
Putative Zn-dependent protease [General function prediction only];
1-246 1.74e-43

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


Pssm-ID: 443814 [Multi-domain]  Cd Length: 488  Bit Score: 153.51  E-value: 1.74e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916   1 MKLRFTASIAAVALAVTACATSP-TGRNQVLLYSESQLEEMGDQAFSGMKEELK--ISNKAVQnSYVECVANAITAKVPN 77
Cdd:COG4784    6 RRALRLLLALALALLLAGCATNPvTGKRDLVLMSEEQEIAIGAEEHPRILAQYGgaYDDPKLQ-AYVARVGQRLAAASHR 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  78 SvfDGTWEVVVFDDEQVNAFALPGGKIGVYTGLLNVAENQHQLAAVIGHEVGHVIAEHGNERMSQSTLINMGtqaAGAAL 157
Cdd:COG4784   85 P--DLPYTFTVLDSPVVNAFALPGGYVYVTRGLLALANDEAELAAVLGHEIGHVTARHAVQRQSRATAAQIG---LGRVL 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 158 AmnEVSQTAPIMAAIGLGLQVGVqLPFSRTHESEADVIGLQLMAMSGFDPRQSVNLWQNMDA----------ASNGERPL 227
Cdd:COG4784  160 S--PVLGSAQAGQLAGAGAQLLL-ASFSRDQELEADRLGVRYLARAGYDPYAMARFLGSLKRqsafrarlagREGRRSYP 236

                        250
                 ....*....|....*....
gi 332991916 228 ELLSTHPAPQTRISNLQAN 246
Cdd:COG4784  237 DFLSTHPDTPDRVQRAVAA 255
Peptidase_M48 pfam01435
Peptidase family M48; Peptidase_M48 is the largely extracellular catalytic region of CAAX ...
 60-245 5.11e-42

Peptidase family M48; Peptidase_M48 is the largely extracellular catalytic region of CAAX prenyl protease homologs such as Human FACE-1 protease. These are metallopeptidases, with the characteriztic HExxH motif giving the two histidine-zinc-ligands and an adjacent glutamate on the next helix being the third. The whole molecule folds to form a deep groove/cleft into which the substrate can fit.


Pssm-ID: 426263 [Multi-domain]  Cd Length: 201  Bit Score: 142.57  E-value: 5.11e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916   60 QNSYVECVAN--AITAKVPnsvFDGTWEVVVFDDEQVNAFA---LPGGKIGVYTGLLNVAENQHQLAAVIGHEVGHVIAE 134
Cdd:pfam01435   3 RNAELQRVVErlAAAAGLP---LPPWYVVVIKSSPVPNAFAyglLPGGRVVVTTGLLDLLETEDELAAVLGHEIGHIKAR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  135 HGNERMSQSTLINMGTQA---AGAALAMNEVSQTAPIMAAI---GLGLQVGVQLPFSRTHESEADVIGLQLMAMSGFDPR 208
Cdd:pfam01435  80 HSVESLSIMGGLSLAQLFlalLLLGAAASGFANFGIIFLLLigpLAALLTLLLLPYSRAQEYEADRLGAELMARAGYDPR 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 332991916  209 QSVNLW---QNMDAASNGERPLELLSTHPAPQTRISNLQA 245
Cdd:pfam01435 160 ALIKLWgeiDNNGRASDGALYPELLSTHPSLVERIAALRE 199
PRK03001 PRK03001
zinc metalloprotease HtpX;
86-245 3.37e-05

zinc metalloprotease HtpX;


Pssm-ID: 179524 [Multi-domain]  Cd Length: 283  Bit Score: 44.24  E-value: 3.37e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  86 VVVFDDEQVNAFALpgGK------IGVYTGLLNVAeNQHQLAAVIGHEVGHVIaeHGNERMSQ---------STLINMGT 150
Cdd:PRK03001  87 VYLINEDQPNAFAT--GRnpehaaVAATTGILRVL-SEREIRGVMAHELAHVK--HRDILISTisatmagaiSALANFAM 161

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 151 QAAGA--------ALAMNEVSQTAPIMAAIglglqvgVQLPFSRTHESEADVIGLQLmamSGfDPRQSVNLWQNMDAASN 222
Cdd:PRK03001 162 FFGGRdengrpvnPIAGIAVAILAPLAASL-------IQMAISRAREFEADRGGARI---SG-DPQALASALDKIHRYAS 230

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 332991916 223 GER-----------------PL------ELLSTHPAPQTRISNLQA 245
Cdd:PRK03001 231 GIPfqaaeahpataqmmiinPLsggglaNLFSTHPSTEERIARLMA 276
 
Name Accession Description Interval E-value
M48C_Oma1_like cd07331
Peptidase M48C, integral membrane endopeptidase; This subfamily contains peptidase M48C Oma1 ...
 64-250 7.51e-89

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.


Pssm-ID: 320690 [Multi-domain]  Cd Length: 187  Bit Score: 261.36  E-value: 7.51e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  64 VECVANAITAKV---PNSVFDGTWEVVVFDDEQVNAFALPGGKIGVYTGLLNVAENQHQLAAVIGHEVGHVIAEHGNERM 140
Cdd:cd07331    1 VRRVAARLIAAAgddPPQSAGWDWEVHVIDSPEVNAFVLPGGKIFVFTGLLPVAKNDDELAAVLGHEIAHALARHSAERM 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 141 SQSTLINMGTQAAGAALAmneVSQTAPIMAAIGLGLQVGVQLPFSRTHESEADVIGLQLMAMSGFDPRQSVNLWQNMDAA 220
Cdd:cd07331   81 SQQKLLQLLLLLLLAALG---ASLAGLALGLLGLGAQLGLLLPYSRKQELEADRIGLQLMAKAGYDPRAAVTFWEKMAAA 157

                        170       180       190
                 ....*....|....*....|....*....|
gi 332991916 221 SNGERPLELLSTHPAPQTRISNLQANMNAA 250
Cdd:cd07331  158 EGGGKPPEFLSTHPSSETRIEALEELLPEA 187
M48C_bepA_like cd07333
Peptidase M48C Ste24p bepA-like, integral membrane protein; This family contains peptidase ...
 39-248 2.44e-46

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.


Pssm-ID: 320692 [Multi-domain]  Cd Length: 174  Bit Score: 152.65  E-value: 2.44e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  39 EMGDQAFSGMKEELKISNKAVQNSYVECVANAITAKVPNSVFDgtWEVVVFDDEQVNAFALPGGKIGVYTGLLNVAENQH 118
Cdd:cd07333    4 ELGKQFAQQIRQQLPLVEDPEVNEYVNRIGQRLAAVSPRPPFP--YRFFVVNDDSINAFATPGGYIYVNTGLILAADNEA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 119 QLAAVIGHEVGHVIAEHGNERMSQStlinmgtqaagaalamnevsqtapimaaiglglqvgvqlpFSRTHESEADVIGLQ 198
Cdd:cd07333   82 ELAGVLAHEIGHVVARHIAKQIEKS----------------------------------------YSREDEREADQLGLQ 121

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 332991916 199 LMAMSGFDPRQSVNLWQNMDAAS--NGERPLELLSTHPAPQTRISNLQANMN 248
Cdd:cd07333  122 YLTKAGYDPRGMVSFFKKLRRKEwfGGSSIPTYLSTHPAPAERIAYLEELIA 173
M48C_Oma1-like cd07324
Oma1 peptidase-like, integral membrane metallopeptidase; This family contains peptidase M48 ...
 63-245 1.32e-43

Oma1 peptidase-like, integral membrane metallopeptidase; This family contains peptidase M48 subfamily C (also known as Oma1 peptidase or mitochondrial metalloendopeptidase OMA1), including similar peptidases containing tetratricopeptide (TPR) repeats, as well as uncharacterized proteins such as E. coli bepA (formerly yfgC), ycaL and loiP (formerly yggG), considered to be putative metallopeptidases. Oma1 peptidase 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 has been proposed that in the absence of m-AAA protease, proteolysis of Oxa1 is mediated by Oma1 in an ATP-independent manner. Homologs of Oma1 are present in higher eukaryotes, eubacteria and archaebacteria, suggesting that Oma1 is the founding member of a conserved family of membrane-embedded metallopeptidases, all containing the zinc metalloprotease motif (HEXXH). M48 peptidases proteolytically remove the C-terminal three residues of farnesylated proteins.


Pssm-ID: 320683 [Multi-domain]  Cd Length: 142  Bit Score: 144.63  E-value: 1.32e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  63 YVECVANAITAKVPNSvfDGTWEVVVFDDEQVNAFALPGGKIGVYTGLLNVAENQHQLAAVIGHEVGHVIAEHGNERMSQ 142
Cdd:cd07324    1 YLNRLGDRLAAASGRP--DLPYRFFVVDDPSINAFALPGGYIFVTTGLLLLLESEDELAAVLAHEIGHVTLRHIARQLER 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 143 stlinmgtqaagaalamnevsqtapimaaiglglqvgvqlpFSRTHESEADVIGLQLMAMSGFDPRQSVNLWQNMDAAS- 221
Cdd:cd07324   79 -----------------------------------------YSRDQEREADRLGLQLLARAGYDPRGMARFFERLARQEg 117

                        170       180
                 ....*....|....*....|....*
gi 332991916 222 -NGERPLELLSTHPAPQTRISNLQA 245
Cdd:cd07324  118 lSGSRLPEFLSTHPLTAERIAALRA 142
COG4784 COG4784
Putative Zn-dependent protease [General function prediction only];
1-246 1.74e-43

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


Pssm-ID: 443814 [Multi-domain]  Cd Length: 488  Bit Score: 153.51  E-value: 1.74e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916   1 MKLRFTASIAAVALAVTACATSP-TGRNQVLLYSESQLEEMGDQAFSGMKEELK--ISNKAVQnSYVECVANAITAKVPN 77
Cdd:COG4784    6 RRALRLLLALALALLLAGCATNPvTGKRDLVLMSEEQEIAIGAEEHPRILAQYGgaYDDPKLQ-AYVARVGQRLAAASHR 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  78 SvfDGTWEVVVFDDEQVNAFALPGGKIGVYTGLLNVAENQHQLAAVIGHEVGHVIAEHGNERMSQSTLINMGtqaAGAAL 157
Cdd:COG4784   85 P--DLPYTFTVLDSPVVNAFALPGGYVYVTRGLLALANDEAELAAVLGHEIGHVTARHAVQRQSRATAAQIG---LGRVL 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 158 AmnEVSQTAPIMAAIGLGLQVGVqLPFSRTHESEADVIGLQLMAMSGFDPRQSVNLWQNMDA----------ASNGERPL 227
Cdd:COG4784  160 S--PVLGSAQAGQLAGAGAQLLL-ASFSRDQELEADRLGVRYLARAGYDPYAMARFLGSLKRqsafrarlagREGRRSYP 236

                        250
                 ....*....|....*....
gi 332991916 228 ELLSTHPAPQTRISNLQAN 246
Cdd:COG4784  237 DFLSTHPDTPDRVQRAVAA 255
Peptidase_M48 pfam01435
Peptidase family M48; Peptidase_M48 is the largely extracellular catalytic region of CAAX ...
 60-245 5.11e-42

Peptidase family M48; Peptidase_M48 is the largely extracellular catalytic region of CAAX prenyl protease homologs such as Human FACE-1 protease. These are metallopeptidases, with the characteriztic HExxH motif giving the two histidine-zinc-ligands and an adjacent glutamate on the next helix being the third. The whole molecule folds to form a deep groove/cleft into which the substrate can fit.


Pssm-ID: 426263 [Multi-domain]  Cd Length: 201  Bit Score: 142.57  E-value: 5.11e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916   60 QNSYVECVAN--AITAKVPnsvFDGTWEVVVFDDEQVNAFA---LPGGKIGVYTGLLNVAENQHQLAAVIGHEVGHVIAE 134
Cdd:pfam01435   3 RNAELQRVVErlAAAAGLP---LPPWYVVVIKSSPVPNAFAyglLPGGRVVVTTGLLDLLETEDELAAVLGHEIGHIKAR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  135 HGNERMSQSTLINMGTQA---AGAALAMNEVSQTAPIMAAI---GLGLQVGVQLPFSRTHESEADVIGLQLMAMSGFDPR 208
Cdd:pfam01435  80 HSVESLSIMGGLSLAQLFlalLLLGAAASGFANFGIIFLLLigpLAALLTLLLLPYSRAQEYEADRLGAELMARAGYDPR 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 332991916  209 QSVNLW---QNMDAASNGERPLELLSTHPAPQTRISNLQA 245
Cdd:pfam01435 160 ALIKLWgeiDNNGRASDGALYPELLSTHPSLVERIAALRE 199
M48C_Oma1_like cd07332
Peptidase M48C Ste24p, integral membrane endopeptidase; This subfamily contains peptidase M48C ...
 34-245 1.79e-38

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.


Pssm-ID: 320691 [Multi-domain]  Cd Length: 222  Bit Score: 133.85  E-value: 1.79e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  34 ESQLEEMGDQAFSGMKEELKISNK--AVQNSYVECVANAITAKVPNSVfdgTWEVVVFDDE-QVNAFALPGGKIGVYTGL 110
Cdd:cd07332   18 PSVEEKLGEQTLELLDETLLEPSElpAERQAALQQLFARLLAALPLPY---PYRLHFRDSGiGANAFALPGGTIVVTDGL 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 111 LNVAENQHQLAAVIGHEVGHVIAEHGNERMSQSTLInmgtqAAGAALAMNEVSQTAPIMAAIGLGLqvgVQLPFSRTHES 190
Cdd:cd07332   95 VELAESPEELAAVLAHEIGHVEHRHSLRQLIRSSGL-----SLLVSLLTGDVSGLSDLLAGLPALL---LSLSYSRDFER 166

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 332991916 191 EADVIGLQLMAMSGFDPRQSVNLWQNMDAASNG-ERPLELLSTHPAPQTRISNLQA 245
Cdd:cd07332  167 EADAFALELLKAAGISPEGLADFFERLEEEHGDgGSLPEWLSTHPDTEERIEAIRE 222
M48C_loiP_like cd07334
Peptidase M48C Ste24p loiP-like, integral membrane protein; This subfamily contains peptidase ...
 88-245 1.35e-24

Peptidase M48C Ste24p loiP-like, integral membrane protein; This subfamily contains peptidase M48 Ste24p protease loiP (formerly yggG)-like family are mostly uncharacterized proteins that include E. coli loiP and ycaLG, 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. LoiP has been shown to be a metallopeptidase that cleaves its targets preferentially between Phe-Phe residues. It is upregulated when bacteria are subjected to media of low osmolarity, thus yggG was named LoiP (low osmolarity induced protease). Proper membrane localization of LoiP may depend on YfgC, another putative metalloprotease in this subfamily.


Pssm-ID: 320693 [Multi-domain]  Cd Length: 215  Bit Score: 97.66  E-value: 1.35e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  88 VFDDEQVNAFALPGGKIGVYTGLLNVAENQhQLAAVIGHEVGHVIAEHGNERMSQSTLINMGTQAAGAAlAMNEVSQTAP 167
Cdd:cd07334   63 VYLTPDVNAFAMADGSVRVYSGLMDMMTDD-ELLGVIGHEIGHVKLGHSKKAMKTAYLTSAARKAAASA-SGTVGALSDS 140

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 332991916 168 IMAAIGLGLqVGVQlpFSRTHESEADVIGLQLMAMSGFDPRQSVNLWQNMdAASNGERPLELLSTHPAPQTRISNLQA 245
Cdd:cd07334  141 QLGALAEKL-INAQ--FSQKQESEADDYGYKFLKKNGYNPQAAVSALEKL-AALSGGGKSSLFSSHPDPAKRAERIRA 214
M48C_Oma1_like cd07342
M48C peptidase, integral membrane endopeptidase; This subfamily contains peptidase M48C Oma1 ...
 85-245 2.39e-19

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.


Pssm-ID: 320701 [Multi-domain]  Cd Length: 158  Bit Score: 82.31  E-value: 2.39e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  85 EVVVFDDEQVNAFAlPGGKIGVYTGLLNVAENQHQLAAVIGHEVGHVIAEHGNERMSQSTLINMGTQAAGAAlamnevsq 164
Cdd:cd07342   22 RVELGNSDGVNAYA-DGRRVQITSGMMDFAQDDDELALVVAHELAHNILGHRDRLRANGVAGGLLDGFGGNA-------- 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 165 tapimaaiglglqvgvqlPFSRTHESEADVIGLQLMAMSGFDPRQSVNLWQNMdaASNGERPLELLSTHPAPQTRISNLQ 244
Cdd:cd07342   93 ------------------AYSREFEIEADYLGLYLMARAGYDIDGAADFWRRL--GASHPVGIGRAATHPSTAERFAALE 152


                 .
gi 332991916 245 A 245
Cdd:cd07342  153 K 153
HtpX COG0501
Zn-dependent protease with chaperone function [Posttranslational modification, protein ...
 85-245 2.75e-16

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


Pssm-ID: 440267 [Multi-domain]  Cd Length: 210  Bit Score: 75.31  E-value: 2.75e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  85 EVVVFDDEQVNAFAL---PGGK-IGVYTGLLNVAeNQHQLAAVIGHEVGHVIAEHgnerMSQSTLINMGTQAAG------ 154
Cdd:COG0501   21 EVYVMDSPAPNAFATgrgPNNArIVVTDGLLELL-DRDELEAVLAHELGHIKNGD----ILLMTLASGLLGLIGflarll 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 155 -AALAMNEVSQTAPIMAAIGLGLQVG--VQLPFSRTHESEADVIGLQLM--------------AMSGFDPRQSVNLWQNM 217
Cdd:COG0501   96 pLAFGRDRDAGLLLGLLLGILAPFLAtlIQLALSRKREYEADRAAAELTgdpdalasalrklaGGNLSIPLRRAFPAQAH 175

                        170       180
                 ....*....|....*....|....*...
gi 332991916 218 DAASNGERPLELLSTHPAPQTRISNLQA 245
Cdd:COG0501  176 AFIINPLKLSSLFSTHPPLEERIARLRE 203
M48B_HtpX_like cd07338
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of ...
 85-245 4.66e-11

Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of peptidase M48 subfamily B includes uncharacterized HtpX homologs and consists of proteins smaller than Ste24p, with homology restricted to the C-terminal half of Ste24p. HtpX expression is controlled by the Cpx stress response system, which senses abnormal membrane proteins. HtpX participates in the proteolytic quality control of these misfolded proteins by undergoing self-degradation and collaborating with FtsH, a membrane-bound and ATP-dependent protease, to eliminate them. HtpX, a zinc metalloprotease with an active site motif HEXXH, has an FtsH-like topology, and is capable of introducing endoproteolytic cleavages into SecY (also an FtsH substrate). However, HtpX does not have an ATPase activity and will only act against cytoplasmic regions of a target membrane protein. Thus, HtpX and FtsH have overlapping and/or complementary functions, which are especially important at high temperature; in E. coli and Xylella fastidiosa, HtpX is heat-inducible, while in Streptococcus gordonii it is not.


Pssm-ID: 320697 [Multi-domain]  Cd Length: 216  Bit Score: 60.67  E-value: 4.66e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  85 EVVVFDDEQVNAFA----LPGGKIGVYTGLLNVAeNQHQLAAVIGHEVGHvIAEHGNERMSQSTLINMGTQAAGAAL--- 157
Cdd:cd07338   52 KVGIAEDPIPNAFAygspLTGARVAVTRGLLDIL-NRDELEAVIGHELGH-IKHRDVAIMTAIGLIPSIIYYIGRSLlfs 129

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 158 -AMNEVSQTAPIMAAIGLGL-------QVGVqLPFSRTHESEADVIGLQLMAmsgfDPRQSVNLWQNMDAASngerPLEL 229
Cdd:cd07338  130 gGSSGGRNGGGALLAVGIAAfavyflfQLLV-LGFSRLREYYADAHSAKVTG----NGRALQSALAKIAYGY----LAEI 200

                        170
                 ....*....|....*.
gi 332991916 230 LSTHPAPQTRISNLQA 245
Cdd:cd07338  201 FSTHPLPAKRIQALEK 216
M48B_HtpX_like cd07335
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This family contains ...
 85-244 2.00e-10

Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This family contains peptidase M48 subfamily B, also known as HtpX, which consists of proteins smaller than Ste24p, with homology restricted to the C-terminal half of Ste24p. HtpX, an integral membrane (IM) metallopeptidase, is widespread in bacteria and archaea, and plays a central role in protein quality control by preventing the accumulation of misfolded proteins in the membrane. Its expression is controlled by the Cpx stress response system, which senses abnormal membrane proteins. HtpX participates in the proteolytic quality control of these misfolded proteins by undergoing self-degradation and eliminating them by collaborating with FtsH, a membrane-bound and ATP-dependent protease. HtpX contains the zinc binding motif (HEXXH), has an FtsH-like topology, and is capable of introducing endoproteolytic cleavages into SecY (also an FtsH substrate). However, HtpX does not have an ATPase activity and will only act against cytoplasmic regions of a target membrane protein. Thus, HtpX and FtsH have overlapping and/or complementary functions, which are especially important at high temperature; in E. coli and Xylella fastidiosa, HtpX is heat-inducible, while in Streptococcus gordonii it is not. Mutation studies of HtpX-like M48 metalloprotease from Leptospira interrogans (LA4131) has been shown to result in altered expression of a subset of metal toxicity and stress response genes.


Pssm-ID: 320694 [Multi-domain]  Cd Length: 240  Bit Score: 59.13  E-value: 2.00e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  85 EVVVFDDEQVNAFALPGGK----IGVYTGLLNVAENQhQLAAVIGHEVGHVIaehgNERMSQSTLI------------NM 148
Cdd:cd07335   53 EVGIYPSPDVNAFATGPSRnnslVAVSTGLLDNMSED-EVEAVLAHEISHIA----NGDMVTMTLLqgvvntfviflsRI 127

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 149 GTQAAGAALAMNEVSQTAPIMAA-----IGLG-LQVGVQLPFSRTHESEADVIGLQLM---AM--------SGFDPRQSV 211
Cdd:cd07335  128 IALIIDSFLSGDENGSGIGYFLVvivleIVLGiLASLVVMWFSRKREFRADAGGAKLTgkeKMiaalerlkQISERPESE 207

                        170       180       190
                 ....*....|....*....|....*....|...
gi 332991916 212 NLWQNMDAASNGERPLELLSTHPAPQTRISNLQ 244
Cdd:cd07335  208 DDVAAAIKISRGSGFLRLFSTHPPLEERIAALE 240
M48_Ste24p_like cd07325
M48 Ste24 endopeptidase-like, integral membrane metallopeptidase; This family contains ...
 85-245 3.22e-10

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.


Pssm-ID: 320684 [Multi-domain]  Cd Length: 199  Bit Score: 58.00  E-value: 3.22e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  85 EVVVFDDEQVNAFAL-PGGK--IGVYTGLLNVAENQhQLAAVIGHEVGHVIAEHgnerMSQSTLINMGTQAAGAALAMne 161
Cdd:cd07325   33 ELYVYQSPVLNAFALgFEGRpfIVLNSGLVELLDDD-ELRFVIGHELGHIKSGH----VLYRTLLLLLLLLGELIGIL-- 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 162 vsqtaPIMAAIGLGLqvgvqLPFSRTHESEADVIGL---Q--------LMAMSG---FDPRQSVNLWQNMDAASNGERP- 226
Cdd:cd07325  106 -----LLSSALPLAL-----LAWSRAAEYSADRAGLlvcQdpeaairaLMKLAGgskLLKDVNNIEYFLEEEAQADALDg 175

                        170       180
                 ....*....|....*....|....
gi 332991916 227 -----LELLSTHPAPQTRISNLQA 245
Cdd:cd07325  176 ffkwlSELLSTHPFLVKRAAELLR 199
M48B_HtpX_like cd07337
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of ...
 86-244 2.94e-09

Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of peptidase M48 subfamily B includes uncharacterized HtpX homologs and consists of proteins smaller than Ste24p, with homology restricted to the C-terminal half of Ste24p. HtpX expression is controlled by the Cpx stress response system, which senses abnormal membrane proteins. HtpX participates in the proteolytic quality control of these misfolded proteins by undergoing self-degradation and collaborating with FtsH, a membrane-bound and ATP-dependent protease, to eliminate them. HtpX, a zinc metalloprotease with an active site motif HEXXH, has an FtsH-like topology, and is capable of introducing endoproteolytic cleavages into SecY (also an FtsH substrate). However, HtpX does not have an ATPase activity and will only act against cytoplasmic regions of a target membrane protein. Thus, HtpX and FtsH have overlapping and/or complementary functions, which are especially important at high temperature; in E. coli and Xylella fastidiosa, HtpX is heat-inducible, while in Streptococcus gordonii it is not.


Pssm-ID: 320696 [Multi-domain]  Cd Length: 203  Bit Score: 55.40  E-value: 2.94e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  86 VVVF--DDEQVNAFALPGGKIGVYTGLLNVAeNQHQLAAVIGHEVGHVIAEHGNermsQSTLINMGTQAAGAALAmnevs 163
Cdd:cd07337   59 VKLFisDDEYPNAFALGRNTICVTKGLLDLL-DYEELKGILAHELGHLSHKDTD----YLLLIFVLLLLAAIWTK----- 128

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 164 qtapIMAAIGLGLQVGVQLPFSRTHESEADV----IGLQLMAMSGFDP-RQSVNLWQNMDAAsngerpleLLSTHPAPQT 238
Cdd:cd07337  129 ----LGTLLIFVWIRLLVMFSSRKAEYRADAfavkIGYGEGLRSALDQlREYEDAPKGFLAA--------LYSTHPPTEK 196


                 ....*.
gi 332991916 239 RISNLQ 244
Cdd:cd07337  197 RIERLE 202
M48B_HtpX_like cd07339
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of ...
 93-245 1.40e-08

Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of peptidase M48 subfamily B includes uncharacterized HtpX homologs and consists of proteins smaller than Ste24p, with homology restricted to the C-terminal half of Ste24p. HtpX expression is controlled by the Cpx stress response system, which senses abnormal membrane proteins. HtpX participates in the proteolytic quality control of these misfolded proteins by undergoing self-degradation and collaborating with FtsH, a membrane-bound and ATP-dependent protease, to eliminate them. HtpX, a zinc metalloprotease with an active site motif HEXXH, has an FtsH-like topology, and is capable of introducing endoproteolytic cleavages into SecY (also an FtsH substrate). However, HtpX does not have an ATPase activity and will only act against cytoplasmic regions of a target membrane protein. Thus, HtpX and FtsH have overlapping and/or complementary functions, which are especially important at high temperature; in E. coli and Xylella fastidiosa, HtpX is heat-inducible, while in Streptococcus gordonii it is not.


Pssm-ID: 320698 [Multi-domain]  Cd Length: 229  Bit Score: 53.72  E-value: 1.40e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  93 QVNAFALPGGK---IGVYTGLLNVAeNQHQLAAVIGHEVGHVIaeHGNER-MSQSTLINMGTQAAGAA-----------L 157
Cdd:cd07339   56 VLNAFAVGSRKdaaIALTDGLLRRL-TLRELAGVLAHEVSHIR--NGDLRvMGLADLISRLTSLLSLLgqlllllnlplL 132

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 158 AMNEVSQT---------APIMAAIglglqvgVQLPFSRTHESEADvigLQLMAMSGfDP-----------RQSVNLWQNM 217
Cdd:cd07339  133 LLGEVTISwlailllilAPTLSTL-------LQLALSRTREFDAD---LDAARLTG-DPeglasalakleRYQGGWWERL 201

                        170       180
                 ....*....|....*....|....*...
gi 332991916 218 DAASNGERPLELLSTHPAPQTRISNLQA 245
Cdd:cd07339  202 LLPGRRVPEPSLLRTHPPTEERIRRLLA 229
Peptidase_M48_M56 cd05843
Peptidases M48 (Ste24 endopeptidase or htpX homolog) and M56 (in MecR1 and BlaR1), integral ...
 86-130 4.32e-07

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.


Pssm-ID: 320682 [Multi-domain]  Cd Length: 94  Bit Score: 47.06  E-value: 4.32e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 332991916  86 VVVFDDEQVNAFALPG--GKIGVYTGLLNvAENQHQLAAVIGHEVGH 130
Cdd:cd05843   20 VVVVPGSVPNAFFTGGanKRVVLTTALLE-LLSEEELAAVIAHELGH 65
M48B_HtpX_like cd07327
HtpX-like membrane-bound metallopeptidase; This family contains peptidase M48 subfamily B, ...
 86-243 3.16e-06

HtpX-like membrane-bound metallopeptidase; This family contains peptidase M48 subfamily B, also known as HtpX, which consists of proteins smaller than Ste24p, with homology restricted to the C-terminal half of Ste24p. HtpX, an integral membrane (IM) metallopeptidase, is widespread in bacteria and archaea, and plays a central role in protein quality control by preventing the accumulation of misfolded proteins in the membrane. Its expression is controlled by the Cpx stress response system, which senses abnormal membrane proteins. HtpX participates in the proteolytic quality control of these misfolded proteins by undergoing self-degradation and eliminating them by collaborating with FtsH, a membrane-bound and ATP-dependent protease. HtpX contains the zinc binding motif (HEXXH), has an FtsH-like topology, and is capable of introducing endoproteolytic cleavages into SecY (also an FtsH substrate). However, HtpX does not have an ATPase activity and will only act against cytoplasmic regions of a target membrane protein. Thus, HtpX and FtsH have overlapping and/or complementary functions, which are especially important at high temperature; in E. coli and Xylella fastidiosa, HtpX is heat-inducible, while in Streptococcus gordonii it is not. Mutation studies of HtpX-like M48 metalloprotease from Leptospira interrogans (LA4131) has been shown to result in altered expression of a subset of metal toxicity and stress response genes.


Pssm-ID: 320686 [Multi-domain]  Cd Length: 183  Bit Score: 46.48  E-value: 3.16e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  86 VVVFDDEQVNAFALpGGK-----IGVYTGLLNVAeNQHQLAAVIGHEVGHViaehGNERMSQSTLinmgtqaagaalamn 160
Cdd:cd07327   44 VAIVDTPMPNAFAT-GRNpknaaVAVTTGLLQLL-NEDELEAVLAHELSHI----KNRDVLVMTL--------------- 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 161 evsqtapimAAIglglqvgvqlpfSRTHESEADVIG---------LQ--LMAMSGF-------DPRQSVNLWQNMDAASN 222
Cdd:cd07327  103 ---------ASL------------SRYREFAADRGSakltgdplaLAsaLMKISGSmqripkrDLRQVEASAFFIIPPLS 161

                        170       180
                 ....*....|....*....|.
gi 332991916 223 GERPLELLSTHPAPQTRISNL 243
Cdd:cd07327  162 GGSLAELFSTHPPTEKRIERL 182
M48B_Htpx_like cd07340
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of ...
 70-244 4.81e-06

Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of peptidase M48 subfamily B includes uncharacterized HtpX homologs and consists of proteins smaller than Ste24p, with homology restricted to the C-terminal half of Ste24p. HtpX expression is controlled by the Cpx stress response system, which senses abnormal membrane proteins. HtpX participates in the proteolytic quality control of these misfolded proteins by undergoing self-degradation and collaborating with FtsH, a membrane-bound and ATP-dependent protease, to eliminate them. HtpX, a zinc metalloprotease with an active site motif HEXXH, has an FtsH-like topology, and is capable of introducing endoproteolytic cleavages into SecY (also an FtsH substrate). However, HtpX does not have an ATPase activity and will only act against cytoplasmic regions of a target membrane protein. Thus, HtpX and FtsH have overlapping and/or complementary functions, which are especially important at high temperature; in E. coli and Xylella fastidiosa, HtpX is heat-inducible, while in Streptococcus gordonii it is not.


Pssm-ID: 320699 [Multi-domain]  Cd Length: 246  Bit Score: 46.34  E-value: 4.81e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  70 AITAKVPnsvfdgTWEVVVFDDEQVNAFALpgGK------IGVYTGLLNvAENQHQLAAVIGHEVGHVIaeHGNERMSQ- 142
Cdd:cd07340   39 AIAAGLP------MPKVYIIDDPAPNAFAT--GRnpehavIAVTTGLLE-KLNRDELEGVIAHELSHIK--NYDIRLMTi 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 143 --------STLINMGTQAA-----GAALAMNEVSQTAPIMAAIGLGLQVG-------VQLPFSRTHESEADVIGLQLM-- 200
Cdd:cd07340  108 avvlvgiiALIADLALRSFfygggSRRRRRDGGGGGALILLILGLVLIILapifaqlIQLAISRQREYLADASAVELTrn 187

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 332991916 201 --AM-------SGFDPRQSVNlwqNMDAASNGERPL---------ELLSTHPAPQTRISNLQ 244
Cdd:cd07340  188 peGLisalekiSGDSSPLKVA---NSATAHLNLYFPnpgkkssfsSLFSTHPPIEERIKRLR 246
PRK03001 PRK03001
zinc metalloprotease HtpX;
86-245 3.37e-05

zinc metalloprotease HtpX;


Pssm-ID: 179524 [Multi-domain]  Cd Length: 283  Bit Score: 44.24  E-value: 3.37e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  86 VVVFDDEQVNAFALpgGK------IGVYTGLLNVAeNQHQLAAVIGHEVGHVIaeHGNERMSQ---------STLINMGT 150
Cdd:PRK03001  87 VYLINEDQPNAFAT--GRnpehaaVAATTGILRVL-SEREIRGVMAHELAHVK--HRDILISTisatmagaiSALANFAM 161

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 151 QAAGA--------ALAMNEVSQTAPIMAAIglglqvgVQLPFSRTHESEADVIGLQLmamSGfDPRQSVNLWQNMDAASN 222
Cdd:PRK03001 162 FFGGRdengrpvnPIAGIAVAILAPLAASL-------IQMAISRAREFEADRGGARI---SG-DPQALASALDKIHRYAS 230

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 332991916 223 GER-----------------PL------ELLSTHPAPQTRISNLQA 245
Cdd:PRK03001 231 GIPfqaaeahpataqmmiinPLsggglaNLFSTHPSTEERIARLMA 276
M56_like cd07329
Peptidase M56-like, integral membrane metallopeptidase in bacteria; This family contains ...
 85-245 7.13e-05

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.


Pssm-ID: 320688 [Multi-domain]  Cd Length: 188  Bit Score: 42.44  E-value: 7.13e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  85 EVVVFDDEQVNAFAL---PGGKIGVYTGLLNVAeNQHQLAAVIGHEVGHVIAEHGNERMSQSTLINMGTQAAGAALAMNE 161
Cdd:cd07329   13 RVYVVDSDVPNAFAVgrsRGPTVVVTTGLLDLL-DDDELEAVLAHELAHLKRRDVLVLLLFDPLLLLVVGLLLFLSLFIF 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 162 VSQTAPIMAAIGLGLQVGVQLPFSRTHESEADVIGLQLMAMSGFDPRQSVNLWQNMDAASNGERPLELLS---------- 231
Cdd:cd07329   92 ELLGFFFQPLLFLAFFALLRLAELLADALAVARTSAARRARLTGLPAALASALEKIEDASDRALEAGLVLpalaadassl 171

                        170
                 ....*....|....*..
gi 332991916 232 ---THPAPQTRISNLQA 245
Cdd:cd07329  172 ektDHPPLEERVERLLE 188
PRK04897 PRK04897
heat shock protein HtpX; Provisional
 70-131 1.28e-04

heat shock protein HtpX; Provisional


Pssm-ID: 235318 [Multi-domain]  Cd Length: 298  Bit Score: 42.63  E-value: 1.28e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 332991916  70 AITAKVPnsvfdgTWEVVVFDDEQVNAFAL---P-GGKIGVYTGLLNVAeNQHQLAAVIGHEVGHV 131
Cdd:PRK04897  90 AMVAQIP------MPRVFIIDDPSPNAFATgssPkNAAVAVTTGLLAIM-NREELEGVIGHEISHI 148
PRK03982 PRK03982
heat shock protein HtpX; Provisional
 95-243 1.76e-04

heat shock protein HtpX; Provisional


Pssm-ID: 235186 [Multi-domain]  Cd Length: 288  Bit Score: 41.91  E-value: 1.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  95 NAFAL---PG-GKIGVYTGLLNVAeNQHQLAAVIGHEVGHVIaehgnermSQSTLInmGTQAAGAALAMNEVSQ------ 164
Cdd:PRK03982  97 NAFATgrdPKhAVVAVTEGILNLL-NEDELEGVIAHELTHIK--------NRDTLI--QTIAATLAGAIMYLAQwlswgl 165

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916 165 -----------------------TAPIMAAIglglqvgVQLPFSRTHESEADVIGLQLmamSGfDPRQSVNLWQNMDAAS 221
Cdd:PRK03982 166 wfggggrddrnggnpigsllliiLAPIAATL-------IQFAISRQREFSADEGGARL---TG-NPLALANALQKLEKGV 234

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 332991916 222 NgERPLE----------------------LLSTHPAPQTRISNL 243
Cdd:PRK03982 235 R-YIPLKngnpatahmfiinpfrgqflanLFSTHPPTEERIERL 277
M56_BlaR1_MecR1_like cd07326
Peptidase M56-like including those in BlaR1 and MecR1, integral membrane metallopeptidase; ...
 86-167 4.40e-04

Peptidase M56-like including those in BlaR1 and MecR1, integral membrane metallopeptidase; 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 ?-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.


Pssm-ID: 320685 [Multi-domain]  Cd Length: 165  Bit Score: 39.98  E-value: 4.40e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  86 VVVFDDEQVNAFALPG--GKIGVYTGLLNvAENQHQLAAVIGHEVGHVIAEHgnermsqsTLINMGTQAAGAALAMNEVS 163
Cdd:cd07326   29 VRVVDHDAPLAFCLGGrrPRIVLSTGLLE-LLSPEELRAVLAHERAHLRRRD--------PLLLLLASALARALPFLPLL 99


                 ....
gi 332991916 164 QTAP 167
Cdd:cd07326  100 RRLA 103
M48_Ste24p_like cd07328
M48 Ste24 endopeptidase-like, integral membrane metallopeptidase; This family contains ...
 87-168 9.11e-03

M48 Ste24 endopeptidase-like, integral membrane metallopeptidase; This family contains peptidase M48-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.


Pssm-ID: 320687 [Multi-domain]  Cd Length: 160  Bit Score: 35.99  E-value: 9.11e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332991916  87 VVFDDEqVNAFA-----LPGGKIGVYTGL-----LNVAEnqhqLAAVIGHEVGHviaeHGNERMSQSTLINM-------- 148
Cdd:cd07328   47 VVLTAD-VNASVtelglLLGRRGLLTLGLpllaaLSPEE----LRAVLAHELGH----FANGDTRLGAWILSrraeyead 117

                         90       100
                 ....*....|....*....|....*..
gi 332991916 149 -------GTQAAGAALAMNEVSQTAPI 168
Cdd:cd07328  118 rvaarvaGSAAAASALRKLAARRPSSP 144
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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