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Conserved domains on  [gi|2544591827|ref|WP_300374484|]
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M48 family metallopeptidase [Methyloprofundus sp.]

Protein Classification

M48 family metallopeptidase( domain architecture ID 11574938)

M48 family metallopeptidase similar to CAAX prenyl protease 1 which proteolytically removes the C-terminal three residues of farnesylated A-factor mating pheromone

CATH:  3.30.2010.10
EC:  3.4.24.-
Gene Ontology:  GO:0004222|GO:0046872|GO:0006508
PubMed:  26527717|7583637|8860988
SCOP:  4004609

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
M48A_Zmpste24p_like cd07343
Peptidase M48 subfamily A, a type 1 CaaX endopeptidase; This family contains peptidase family ...
 6-410 8.17e-177

Peptidase M48 subfamily A, a type 1 CaaX endopeptidase; This family contains peptidase family M48 subfamily A which includes a number of well-characterized genes such as those found in humans (ZMPSTE24, also known as farnesylated protein-converting enzyme 1 or FACE-1 or Hs Ste24), Taenia solium metacestode (TsSte24p), Arabidopsis (AtSte24) and yeast (Ste24p). Ste24p contains the zinc metalloprotease motif (HEXXH), likely exposed on the cytoplasmic side. It is thought to be intimately 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. Ste24p is involved in the post-translational processing of prelamin A to mature lamin A, a major component of the nuclear envelope. ZmpSte24 deficiency causes an accumulation of prelamin A leading to lipodystrophy and other disease phenotypes, while mutations in this gene or in that encoding its substrate, prelamin A, result in a series of human inherited diseases known as laminopathies, the most severe of which are Hutchinson Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) which arise due to unsuccessful maturation of prelamin A. Two forms of mandibuloacral dysplasia, a condition that causes a variety of abnormalities involving bone development, skin pigmentation, and fat distribution, are caused by mutations in two different genes; mutations in the LMNA gene, which normally provides instructions for making lamin A and lamin C, cause mandibuloacral dysplasia with A-type lipodystrophy (MAD-A), and mutations in the ZMPSTE24 gene cause mandibuloacral dysplasia with B-type lipodystrophy (MAD-B). Within cells, these genes are involved in maintaining the structure of the nucleus and may play a role in many cellular processes. Certain HIV protease inhibitors have been shown to inhibit the enzymatic activity of ZMPSTE24, but not enzymes involved in prelamin A processing.


:

Pssm-ID: 320702 [Multi-domain]  Cd Length: 405  Bit Score: 498.93  E-value: 8.17e-177
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827   6 YIFLIALALSYSVQFWLSRRQSAYVFKHRgQVPAAFTESITLEAHQKAADYTIAKGKLGDIDSVVGLIFLLLLTLGGGIS 85
Cdd:cd07343     1 YIILLLLVLVYLFELYLSLRQLRHLKRKL-PPPPELADVISQEEFEKAQAYSLDKSRFSIVSSLLSLLLLLLLLLFGLLP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827  86 LVFEFWTGFGWSTIMTGITALGSVFFIMSLFELPTSLYQTFVIEEKFGFNKSTVGQFIKDQFLQLALVAVIGLPLLALIL 165
Cdd:cd07343    80 LLDLLLRSLGGNEILQSLLFFLLLSLISTLLSLPFSLYSTFVIEEKFGFNKQTLGLFIKDLLKSLLLSLVLGGPLLALLL 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 166 WVMQALGNTWWIWTWAILISFSLLMSWLYPTLIAPLFNKFTPLEDGTLKERINQLLERCGFSSNGIFIMDGSKRSGHGNA 245
Cdd:cd07343   160 WIIKKFGKYWWLYAWLFVVVFSLLLMFIYPTLIAPLFNKFTPLEDGELKTKIEALAKRAGFPLKKVYVMDGSKRSTHSNA 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 246 YFTGMGNNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISLGVLGWLITENWFFTGLGVGVPSN 325
Cdd:cd07343   240 YFTGFGKNKRIVLFDTLLEQLTEDEILAVLAHELGHWKHGHILKGLILSQLLLFLGFYLFGLLLNNPSLYRAFGFFGPSD 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 326 AAALLLFMLVSPAFTTFMTPISAYFQRKFEFEADDFAAEHAQASKLISGLVKLYKENASTLTPDPLFSAFHYSHPPAAIR 405
Cdd:cd07343   320 QPALIGFLLLLSPLSFLLSPLMNALSRKFEYEADAFAVELGYGEALISALVKLSKDNLSNLTPDPLYSAFHYSHPPLLER 399


                  ....*
gi 2544591827 406 IAHLE 410
Cdd:cd07343   400 IAALE 404
 
Name Accession Description Interval E-value
M48A_Zmpste24p_like cd07343
Peptidase M48 subfamily A, a type 1 CaaX endopeptidase; This family contains peptidase family ...
 6-410 8.17e-177

Peptidase M48 subfamily A, a type 1 CaaX endopeptidase; This family contains peptidase family M48 subfamily A which includes a number of well-characterized genes such as those found in humans (ZMPSTE24, also known as farnesylated protein-converting enzyme 1 or FACE-1 or Hs Ste24), Taenia solium metacestode (TsSte24p), Arabidopsis (AtSte24) and yeast (Ste24p). Ste24p contains the zinc metalloprotease motif (HEXXH), likely exposed on the cytoplasmic side. It is thought to be intimately 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. Ste24p is involved in the post-translational processing of prelamin A to mature lamin A, a major component of the nuclear envelope. ZmpSte24 deficiency causes an accumulation of prelamin A leading to lipodystrophy and other disease phenotypes, while mutations in this gene or in that encoding its substrate, prelamin A, result in a series of human inherited diseases known as laminopathies, the most severe of which are Hutchinson Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) which arise due to unsuccessful maturation of prelamin A. Two forms of mandibuloacral dysplasia, a condition that causes a variety of abnormalities involving bone development, skin pigmentation, and fat distribution, are caused by mutations in two different genes; mutations in the LMNA gene, which normally provides instructions for making lamin A and lamin C, cause mandibuloacral dysplasia with A-type lipodystrophy (MAD-A), and mutations in the ZMPSTE24 gene cause mandibuloacral dysplasia with B-type lipodystrophy (MAD-B). Within cells, these genes are involved in maintaining the structure of the nucleus and may play a role in many cellular processes. Certain HIV protease inhibitors have been shown to inhibit the enzymatic activity of ZMPSTE24, but not enzymes involved in prelamin A processing.


Pssm-ID: 320702 [Multi-domain]  Cd Length: 405  Bit Score: 498.93  E-value: 8.17e-177
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827   6 YIFLIALALSYSVQFWLSRRQSAYVFKHRgQVPAAFTESITLEAHQKAADYTIAKGKLGDIDSVVGLIFLLLLTLGGGIS 85
Cdd:cd07343     1 YIILLLLVLVYLFELYLSLRQLRHLKRKL-PPPPELADVISQEEFEKAQAYSLDKSRFSIVSSLLSLLLLLLLLLFGLLP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827  86 LVFEFWTGFGWSTIMTGITALGSVFFIMSLFELPTSLYQTFVIEEKFGFNKSTVGQFIKDQFLQLALVAVIGLPLLALIL 165
Cdd:cd07343    80 LLDLLLRSLGGNEILQSLLFFLLLSLISTLLSLPFSLYSTFVIEEKFGFNKQTLGLFIKDLLKSLLLSLVLGGPLLALLL 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 166 WVMQALGNTWWIWTWAILISFSLLMSWLYPTLIAPLFNKFTPLEDGTLKERINQLLERCGFSSNGIFIMDGSKRSGHGNA 245
Cdd:cd07343   160 WIIKKFGKYWWLYAWLFVVVFSLLLMFIYPTLIAPLFNKFTPLEDGELKTKIEALAKRAGFPLKKVYVMDGSKRSTHSNA 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 246 YFTGMGNNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISLGVLGWLITENWFFTGLGVGVPSN 325
Cdd:cd07343   240 YFTGFGKNKRIVLFDTLLEQLTEDEILAVLAHELGHWKHGHILKGLILSQLLLFLGFYLFGLLLNNPSLYRAFGFFGPSD 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 326 AAALLLFMLVSPAFTTFMTPISAYFQRKFEFEADDFAAEHAQASKLISGLVKLYKENASTLTPDPLFSAFHYSHPPAAIR 405
Cdd:cd07343   320 QPALIGFLLLLSPLSFLLSPLMNALSRKFEYEADAFAVELGYGEALISALVKLSKDNLSNLTPDPLYSAFHYSHPPLLER 399


                  ....*
gi 2544591827 406 IAHLE 410
Cdd:cd07343   400 IAALE 404
Peptidase_M48_N pfam16491
CAAX prenyl protease N-terminal, five membrane helices; The five N-terminal five transmembrane ...
 30-204 3.15e-55

CAAX prenyl protease N-terminal, five membrane helices; The five N-terminal five transmembrane alpha-helices of peptidase_M48 family proteins including the CAAX prenyl proteases reside completely within the membrane of the endoplasmic reticulum.


Pssm-ID: 465138  Cd Length: 179  Bit Score: 180.37  E-value: 3.15e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827  30 VFKHRGQVPAAFTESITLEAHQKAADYTIAKGKLGDIDSVVGLIFLLLLTLGGGISLVFEFWTGFGW-STIMTGITALGS 108
Cdd:pfam16491   4 HLKRHRDVPEELADIIDQETFQKSQDYTLAKSRFSLVSSLFSLILLLAFLLFGGLPWLWNLSGSLLSeSEILQSLAFLLI 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 109 VFFIMSLFELPTSLYQTFVIEEKFGFNKSTVGQFIKDQFLQLALVAVIGLPLLALILWVMQALGNTWWIWTWAILISFSL 188
Cdd:pfam16491  84 LSLISTLISLPFSLYSTFVIEEKFGFNKQTPKLFITDLLKSLLLSLVLGGPLLAAILWIIQKAGDYFWLYLWLFWLVFQL 163

                         170
                  ....*....|....*.
gi 2544591827 189 LMSWLYPTLIAPLFNK 204
Cdd:pfam16491 164 LLMTIYPTLIAPLFNK 179
HtpX COG0501
Zn-dependent protease with chaperone function [Posttranslational modification, protein ...
 210-410 8.92e-53

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


Pssm-ID: 440267 [Multi-domain]  Cd Length: 210  Bit Score: 175.07  E-value: 8.92e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 210 DGTLKERINQLLERCGFSSNGIFIMDgskrSGHGNAYFTGMG-NNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVI 288
Cdd:COG0501     1 DPELYRLVEELAARAGIPMPEVYVMD----SPAPNAFATGRGpNNARIVVTDGLLELLDRDELEAVLAHELGHIKNGDIL 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 289 KMLVASSIMSLISLgvLGWLIteNWFFTGlgvgvpSNAAALLLFMLVSPAFTTFMTPISAYFQRKFEFEADDFAAEHAQ- 367
Cdd:COG0501    77 LMTLASGLLGLIGF--LARLL--PLAFGR------DRDAGLLLGLLLGILAPFLATLIQLALSRKREYEADRAAAELTGd 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2544591827 368 ASKLISGLVKLYKENASTLTPDPL-------------FSAFHYSHPPAAIRIAHLE 410
Cdd:COG0501   147 PDALASALRKLAGGNLSIPLRRAFpaqahafiinplkLSSLFSTHPPLEERIARLR 202
PRK02391 PRK02391
heat shock protein HtpX; Provisional
 244-410 1.57e-12

heat shock protein HtpX; Provisional


Pssm-ID: 179418 [Multi-domain]  Cd Length: 296  Bit Score: 67.65  E-value: 1.57e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMGNNKRIVFFDT-LAESLDDDEMEAVLAHELGHFKRKHVIKMLVASsimsliSLGVLGWLITENWFFTGLGVGV 322
Cdd:PRK02391  105 NAFATGRSPKNAVVCVTTgLMRRLDPDELEAVLAHELSHVKNRDVAVMTIAS------FLSTIAFLIVRWGFYFGGFGGR 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 323 PSN--AAALLLFMLVSP---AFTTFMT-PISAYfqRkfEFEADDFAAE-HAQASKLISGLVKLYKE-------------- 381
Cdd:PRK02391  179 GGGggGGGILVVILVSLvvwAISFLLIrALSRY--R--EFAADRGAAIiTGRPSALASALMKISGRmdrvptedlreaeg 254

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 2544591827 382 -NASTLTPDP-------LFSafhySHPPAAIRIAHLE 410
Cdd:PRK02391  255 mNAFFIIPALsggslgrLFS----THPPLEKRIAQLE 287
 
Name Accession Description Interval E-value
M48A_Zmpste24p_like cd07343
Peptidase M48 subfamily A, a type 1 CaaX endopeptidase; This family contains peptidase family ...
 6-410 8.17e-177

Peptidase M48 subfamily A, a type 1 CaaX endopeptidase; This family contains peptidase family M48 subfamily A which includes a number of well-characterized genes such as those found in humans (ZMPSTE24, also known as farnesylated protein-converting enzyme 1 or FACE-1 or Hs Ste24), Taenia solium metacestode (TsSte24p), Arabidopsis (AtSte24) and yeast (Ste24p). Ste24p contains the zinc metalloprotease motif (HEXXH), likely exposed on the cytoplasmic side. It is thought to be intimately 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. Ste24p is involved in the post-translational processing of prelamin A to mature lamin A, a major component of the nuclear envelope. ZmpSte24 deficiency causes an accumulation of prelamin A leading to lipodystrophy and other disease phenotypes, while mutations in this gene or in that encoding its substrate, prelamin A, result in a series of human inherited diseases known as laminopathies, the most severe of which are Hutchinson Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) which arise due to unsuccessful maturation of prelamin A. Two forms of mandibuloacral dysplasia, a condition that causes a variety of abnormalities involving bone development, skin pigmentation, and fat distribution, are caused by mutations in two different genes; mutations in the LMNA gene, which normally provides instructions for making lamin A and lamin C, cause mandibuloacral dysplasia with A-type lipodystrophy (MAD-A), and mutations in the ZMPSTE24 gene cause mandibuloacral dysplasia with B-type lipodystrophy (MAD-B). Within cells, these genes are involved in maintaining the structure of the nucleus and may play a role in many cellular processes. Certain HIV protease inhibitors have been shown to inhibit the enzymatic activity of ZMPSTE24, but not enzymes involved in prelamin A processing.


Pssm-ID: 320702 [Multi-domain]  Cd Length: 405  Bit Score: 498.93  E-value: 8.17e-177
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827   6 YIFLIALALSYSVQFWLSRRQSAYVFKHRgQVPAAFTESITLEAHQKAADYTIAKGKLGDIDSVVGLIFLLLLTLGGGIS 85
Cdd:cd07343     1 YIILLLLVLVYLFELYLSLRQLRHLKRKL-PPPPELADVISQEEFEKAQAYSLDKSRFSIVSSLLSLLLLLLLLLFGLLP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827  86 LVFEFWTGFGWSTIMTGITALGSVFFIMSLFELPTSLYQTFVIEEKFGFNKSTVGQFIKDQFLQLALVAVIGLPLLALIL 165
Cdd:cd07343    80 LLDLLLRSLGGNEILQSLLFFLLLSLISTLLSLPFSLYSTFVIEEKFGFNKQTLGLFIKDLLKSLLLSLVLGGPLLALLL 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 166 WVMQALGNTWWIWTWAILISFSLLMSWLYPTLIAPLFNKFTPLEDGTLKERINQLLERCGFSSNGIFIMDGSKRSGHGNA 245
Cdd:cd07343   160 WIIKKFGKYWWLYAWLFVVVFSLLLMFIYPTLIAPLFNKFTPLEDGELKTKIEALAKRAGFPLKKVYVMDGSKRSTHSNA 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 246 YFTGMGNNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISLGVLGWLITENWFFTGLGVGVPSN 325
Cdd:cd07343   240 YFTGFGKNKRIVLFDTLLEQLTEDEILAVLAHELGHWKHGHILKGLILSQLLLFLGFYLFGLLLNNPSLYRAFGFFGPSD 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 326 AAALLLFMLVSPAFTTFMTPISAYFQRKFEFEADDFAAEHAQASKLISGLVKLYKENASTLTPDPLFSAFHYSHPPAAIR 405
Cdd:cd07343   320 QPALIGFLLLLSPLSFLLSPLMNALSRKFEYEADAFAVELGYGEALISALVKLSKDNLSNLTPDPLYSAFHYSHPPLLER 399


                  ....*
gi 2544591827 406 IAHLE 410
Cdd:cd07343   400 IAALE 404
Peptidase_M48_N pfam16491
CAAX prenyl protease N-terminal, five membrane helices; The five N-terminal five transmembrane ...
 30-204 3.15e-55

CAAX prenyl protease N-terminal, five membrane helices; The five N-terminal five transmembrane alpha-helices of peptidase_M48 family proteins including the CAAX prenyl proteases reside completely within the membrane of the endoplasmic reticulum.


Pssm-ID: 465138  Cd Length: 179  Bit Score: 180.37  E-value: 3.15e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827  30 VFKHRGQVPAAFTESITLEAHQKAADYTIAKGKLGDIDSVVGLIFLLLLTLGGGISLVFEFWTGFGW-STIMTGITALGS 108
Cdd:pfam16491   4 HLKRHRDVPEELADIIDQETFQKSQDYTLAKSRFSLVSSLFSLILLLAFLLFGGLPWLWNLSGSLLSeSEILQSLAFLLI 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 109 VFFIMSLFELPTSLYQTFVIEEKFGFNKSTVGQFIKDQFLQLALVAVIGLPLLALILWVMQALGNTWWIWTWAILISFSL 188
Cdd:pfam16491  84 LSLISTLISLPFSLYSTFVIEEKFGFNKQTPKLFITDLLKSLLLSLVLGGPLLAAILWIIQKAGDYFWLYLWLFWLVFQL 163

                         170
                  ....*....|....*.
gi 2544591827 189 LMSWLYPTLIAPLFNK 204
Cdd:pfam16491 164 LLMTIYPTLIAPLFNK 179
HtpX COG0501
Zn-dependent protease with chaperone function [Posttranslational modification, protein ...
 210-410 8.92e-53

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


Pssm-ID: 440267 [Multi-domain]  Cd Length: 210  Bit Score: 175.07  E-value: 8.92e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 210 DGTLKERINQLLERCGFSSNGIFIMDgskrSGHGNAYFTGMG-NNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVI 288
Cdd:COG0501     1 DPELYRLVEELAARAGIPMPEVYVMD----SPAPNAFATGRGpNNARIVVTDGLLELLDRDELEAVLAHELGHIKNGDIL 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 289 KMLVASSIMSLISLgvLGWLIteNWFFTGlgvgvpSNAAALLLFMLVSPAFTTFMTPISAYFQRKFEFEADDFAAEHAQ- 367
Cdd:COG0501    77 LMTLASGLLGLIGF--LARLL--PLAFGR------DRDAGLLLGLLLGILAPFLATLIQLALSRKREYEADRAAAELTGd 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2544591827 368 ASKLISGLVKLYKENASTLTPDPL-------------FSAFHYSHPPAAIRIAHLE 410
Cdd:COG0501   147 PDALASALRKLAGGNLSIPLRRAFpaqahafiinplkLSSLFSTHPPLEERIARLR 202
M48A_Ste24p cd07330
Peptidase M48 CaaX prenyl protease type 1, an integral membrane, Zn-dependent protein; This ...
 106-410 7.71e-52

Peptidase M48 CaaX prenyl protease type 1, an integral membrane, Zn-dependent protein; This family of M48 CaaX prenyl protease 1-like family includes a number of well characterized genes such as those found in Taenia solium metacestode (TsSte24p), Arabidopsis (AtSte24), yeast Ste24p and human (Hs Ste24p) as well as several uncharacterized genes such as YhfN, some of which also containing tetratricopeptide (TPR) repeats. All members of this family contain the zinc metalloprotease motif (HEXXH), likely exposed on the cytoplasmic side. They are thought to be intimately associated with the endoplasmic reticulum (ER), regardless of whether their 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. The gene ZmpSte24, also known as FACE-1 in humans, a member of this family, is involved in the post-translational processing of prelamin A to mature lamin A, a major component of the nuclear envelope. ZmpSte24 deficiency causes an accumulation of prelamin A leading to lipodystrophy and other disease phenotypes while mutations in the protein lead to diseases of lamin processing (laminopathies), such as premature aging disease progeria and metabolic disorders. Some of these mutations map to the peptide-binding site.


Pssm-ID: 320689 [Multi-domain]  Cd Length: 285  Bit Score: 175.32  E-value: 7.71e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 106 LGSVFFIMSLFELPTSLYQTFVIEEKFGFNKSTVGQFIKDQFLQLALVAVIGLPLLALILWVMQALGNTWWIWTWaILIS 185
Cdd:cd07330    10 LLVFTGLMVLVELPFGWVARFRVEERFGYMRETRSLWSKRTVALLTVGLLVALPVSALLLPFEEPGGGAWWLGEW-LAWL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 186 FSLLMSW-LYPTLIAPLFNKFTPLEDGTLKERINQLLERCGFSSNGIFIMDGSKRSG-HGNAYFTGMGNNKRIVFFDTLA 263
Cdd:cd07330    89 FYLFWRWkLSPFYAQFWKRRSRPLANGELRERIESMMNREGFGCAEILKVELSGGSMiHANAYFPGSGKRRRVVVFADAL 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 264 ESL-DDDEMEAVLAHELGHFKRKHVIKMLvassimsLISLGVLGWLitenwfftglgvgvpsnAAALLLFMLVSPAFTTF 342
Cdd:cd07330   169 VSLmTPDELLAVIAHELGHVKHHHHLFRL-------AASQAVSFIV-----------------CALFILIYPLRFLLNFF 224

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2544591827 343 MtpisayfqRKFEFEADDFAAEHAQASKLISGLVKLYKENASTLTPDPLFSAFHYSHPPAAIRIAHLE 410
Cdd:cd07330   225 A--------RRFEYQADAYAAKLAGADALISALVKLHRDNLTTLTPSRLYSLWHYSHPHAAMRVAHLL 284
Peptidase_M48 pfam01435
Peptidase family M48; Peptidase_M48 is the largely extracellular catalytic region of CAAX ...
 207-410 2.55e-39

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: 139.87  E-value: 2.55e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 207 PLEDGTLKERINQLLERCGFSSNGIFImDGSKRSGHGNAYFTGMGNNKRIVFFDTLAESL-DDDEMEAVLAHELGHFKRK 285
Cdd:pfam01435   1 PLRNAELQRVVERLAAAAGLPLPPWYV-VVIKSSPVPNAFAYGLLPGGRVVVTTGLLDLLeTEDELAAVLGHEIGHIKAR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 286 HVIKMLVASSIMSLISLGVLGWLITenWFFTGLgvgvpSNAAALLLFMLVSPAFTtfMTPISAYFQRKFEFEADDFAAEH 365
Cdd:pfam01435  80 HSVESLSIMGGLSLAQLFLALLLLG--AAASGF-----ANFGIIFLLLIGPLAAL--LTLLLLPYSRAQEYEADRLGAEL 150

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 2544591827 366 AQASKL-ISGLVKLYKENA--STLTPDPLFSAFHYSHPPAAIRIAHLE 410
Cdd:pfam01435 151 MARAGYdPRALIKLWGEIDnnGRASDGALYPELLSTHPSLVERIAALR 198
M48A_Ste24p-like cd07345
Peptidase M48 subfamily A-like, putative CaaX prenyl protease; This family contains peptidase ...
 87-410 3.06e-21

Peptidase M48 subfamily A-like, putative CaaX prenyl protease; This family contains peptidase family M48 subfamily A-like CaaX prenyl protease 1, most of which are uncharacterized. Some of these contain tetratricopeptide (TPR) repeats at the C-terminus. Proteins in this family contain the zinc metalloprotease motif (HEXXH), likely exposed on the cytoplasmic side. They are thought to be possibly associated with the endoplasmic reticulum (ER), regardless of whether their genes possess the conventional signal motif (KKXX) in the C-terminal. These proteins putatively remove the C-terminal three residues of farnesylated proteins proteolytically.


Pssm-ID: 320704 [Multi-domain]  Cd Length: 346  Bit Score: 93.88  E-value: 3.06e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827  87 VFEFWTGFGWSTIMTGITALGSVFFIMSL-FELPTSLYQTFV------IEEKFGFNKSTVGQFIKDQFLQLALvavIGLP 159
Cdd:cd07345     9 FAIDIYALDLKYYLSFIPLFGSSPTLLALlFLLLFLLLLLLVwyaaypVYKKLFSGLESRRAYVLSNLRFLLP---ILLP 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 160 LLALILWVMQ----------ALGNTWW--IWTWAILISFSLLMSWLYPTLIAPLfnkfTPLEDGTLKERINQLLERCGFS 227
Cdd:cd07345    86 WLLLSLLQDLlsllplailkNLLSSSLglLGFLLLFLLLLLLFPPLLIRLIWGC----KPLPPGPLRDRLEAFCRRAGFK 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 228 SNGIFIMDgSKRSGHGNAYFTGMGNNKRIVFF-DTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISLGVLG 306
Cdd:cd07345   162 VADILVWP-LFEGRVATAGVMGILPRFRYILItDALLDSLSPEELEAVLAHEIGHVKKRHLLLYLLFFLGFILLLALLSL 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 307 WLITENWFFTGLGVGVPSNAAALLLFMLVSPAFTTFMTP----ISAYFQRKFEFEADDFAAEHA-QASKLISGLVKLYKE 381
Cdd:cd07345   241 LLSLLLLLLLPLLILLLGSSAEILLTLLLALPLLLLLVLyfrfVFGFFSRNFERQADLYALRALgSAEPLISALEKIAEL 320

                         330       340
                  ....*....|....*....|....*....
gi 2544591827 382 NASTLTpdpLFSAFHYShppAAIRIAHLE 410
Cdd:cd07345   321 SGNSRD---KPSWHHFS---IAQRIAFLE 343
M48C_Oma1_like cd07332
Peptidase M48C Ste24p, integral membrane endopeptidase; This subfamily contains peptidase M48C ...
 255-410 8.49e-19

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: 84.55  E-value: 8.49e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 255 RIVFFDTLAESLD-DDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISLGVLGwlitenwFFTGLGVGVPSNAAALLlfm 333
Cdd:cd07332    87 TIVVTDGLVELAEsPEELAAVLAHEIGHVEHRHSLRQLIRSSGLSLLVSLLTG-------DVSGLSDLLAGLPALLL--- 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 334 lvspafttfmtpiSAYFQRKFEFEADDFAAEHAQASK-----LISGLVKLYKENASTLTPDPLFSafhySHPPAAIRIAH 408
Cdd:cd07332   157 -------------SLSYSRDFEREADAFALELLKAAGispegLADFFERLEEEHGDGGSLPEWLS----THPDTEERIEA 219


                  ..
gi 2544591827 409 LE 410
Cdd:cd07332   220 IR 221
M48B_HtpX_like cd07335
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This family contains ...
 244-410 1.86e-17

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: 81.09  E-value: 1.86e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMGNNKRIVFFDT-LAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMS--LISLGVLGWLITENWFFTGLGV 320
Cdd:cd07335    63 NAFATGPSRNNSLVAVSTgLLDNMSEDEVEAVLAHEISHIANGDMVTMTLLQGVVNtfVIFLSRIIALIIDSFLSGDENG 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 321 GVPSNaaaLLLFMLVSPAFTTFMTPISAYFQRKFEFEADDFAAEHAQASKLISGLVKLyKENASTLTPDP---------- 390
Cdd:cd07335   143 SGIGY---FLVVIVLEIVLGILASLVVMWFSRKREFRADAGGAKLTGKEKMIAALERL-KQISERPESEDdvaaaikisr 218

                         170       180
                  ....*....|....*....|....*.
gi 2544591827 391 ------LFSafhySHPPAAIRIAHLE 410
Cdd:cd07335   219 gsgflrLFS----THPPLEERIAALE 240
M48B_HtpX_like cd07338
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of ...
 160-410 8.08e-17

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: 78.78  E-value: 8.08e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 160 LLALILWVMQalgntWWIWTWAIlisfsllmSWLYPTLiaplfnKFTPLEDGTLKERINQLLERCGFSSNGIFIMDGskr 239
Cdd:cd07338     1 IFALIINLIQ-----WLISPYII--------NWVYRAR------EPPDPEYPWLQEIVEEVARRAGIKPPKVGIAED--- 58

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 240 sGHGNAYFTGMG-NNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLIslGVLGWLItenwFFTGL 318
Cdd:cd07338    59 -PIPNAFAYGSPlTGARVAVTRGLLDILNRDELEAVIGHELGHIKHRDVAIMTAIGLIPSII--YYIGRSL----LFSGG 131

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 319 GVGVPSNAAALLLFMLVSPAFTTFMTPISAYFQRKFEFEADDFAAEHAQA-SKLISGLVKLYKenastLTPDPLFSafhy 397
Cdd:cd07338   132 SSGGRNGGGALLAVGIAAFAVYFLFQLLVLGFSRLREYYADAHSAKVTGNgRALQSALAKIAY-----GYLAEIFS---- 202

                         250
                  ....*....|...
gi 2544591827 398 SHPPAAIRIAHLE 410
Cdd:cd07338   203 THPLPAKRIQALE 215
M48_Ste24p_like cd07325
M48 Ste24 endopeptidase-like, integral membrane metallopeptidase; This family contains ...
 240-410 6.01e-14

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: 69.95  E-value: 6.01e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 240 SGHGNAYFTGMGNNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISLGVLGWLitenwfftglg 319
Cdd:cd07325    39 SPVLNAFALGFEGRPFIVLNSGLVELLDDDELRFVIGHELGHIKSGHVLYRTLLLLLLLLGELIGILLL----------- 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 320 vgvpSNAAALLLFmlvspafttfmtpisaYFQRKFEFEADDFAAEHAQ---AS-----KLISGLVKLYKEN--------- 382
Cdd:cd07325   108 ----SSALPLALL----------------AWSRAAEYSADRAGLLVCQdpeAAiralmKLAGGSKLLKDVNnieyfleee 167

                         170       180       190
                  ....*....|....*....|....*....|.
gi 2544591827 383 ASTLTPDPLFSAFH---YSHPPAAIRIAHLE 410
Cdd:cd07325   168 AQADALDGFFKWLSellSTHPFLVKRAAELL 198
M48B_HtpX_like cd07337
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of ...
 181-410 2.22e-13

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: 68.49  E-value: 2.22e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 181 AILISFSLLMSWLYPTLIAPLFNKFTPLEDGTLKERINQLLERCGfSSNGI-------FIMDgSKRSghgNAYFTGmgnN 253
Cdd:cd07337     5 AILIGISPFGESILRALSGCRIRRGARKPTRRELEEINPELEDKA-RRLGPdpekvklFISD-DEYP---NAFALG---R 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 254 KRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLIslgvlgwlitenWFFTGLGVgvpsnaaALLLFM 333
Cdd:cd07337    77 NTICVTKGLLDLLDYEELKGILAHELGHLSHKDTDYLLLIFVLLLLA------------AIWTKLGT-------LLIFVW 137

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2544591827 334 LVspafttfmtPISAYFQRKFEFEADDFAAEHAQASKLISGLVKLykeNASTLTPDPLFSAFHYSHPPAAIRIAHLE 410
Cdd:cd07337   138 IR---------LLVMFSSRKAEYRADAFAVKIGYGEGLRSALDQL---REYEDAPKGFLAALYSTHPPTEKRIERLE 202
PRK02391 PRK02391
heat shock protein HtpX; Provisional
 244-410 1.57e-12

heat shock protein HtpX; Provisional


Pssm-ID: 179418 [Multi-domain]  Cd Length: 296  Bit Score: 67.65  E-value: 1.57e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMGNNKRIVFFDT-LAESLDDDEMEAVLAHELGHFKRKHVIKMLVASsimsliSLGVLGWLITENWFFTGLGVGV 322
Cdd:PRK02391  105 NAFATGRSPKNAVVCVTTgLMRRLDPDELEAVLAHELSHVKNRDVAVMTIAS------FLSTIAFLIVRWGFYFGGFGGR 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 323 PSN--AAALLLFMLVSP---AFTTFMT-PISAYfqRkfEFEADDFAAE-HAQASKLISGLVKLYKE-------------- 381
Cdd:PRK02391  179 GGGggGGGILVVILVSLvvwAISFLLIrALSRY--R--EFAADRGAAIiTGRPSALASALMKISGRmdrvptedlreaeg 254

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 2544591827 382 -NASTLTPDP-------LFSafhySHPPAAIRIAHLE 410
Cdd:PRK02391  255 mNAFFIIPALsggslgrLFS----THPPLEKRIAQLE 287
M56_like cd07329
Peptidase M56-like, integral membrane metallopeptidase in bacteria; This family contains ...
 244-410 3.24e-12

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: 64.78  E-value: 3.24e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMGNNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISLGVLGWLITEN-----WFFTGL 318
Cdd:cd07329    23 NAFAVGRSRGPTVVVTTGLLDLLDDDELEAVLAHELAHLKRRDVLVLLLFDPLLLLVVGLLLFLSLFIFellgfFFQPLL 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 319 GVGVpsnAAALLLFMLVSPAFTTFMTPisayfqrkfefeADDFAAEHAQASKLISGLVKLYKENAS---------TLTPD 389
Cdd:cd07329   103 FLAF---FALLRLAELLADALAVARTS------------AARRARLTGLPAALASALEKIEDASDRaleaglvlpALAAD 167

                         170       180
                  ....*....|....*....|.
gi 2544591827 390 PLFSAFHySHPPAAIRIAHLE 410
Cdd:cd07329   168 ASSLEKT-DHPPLEERVERLL 187
Peptidase_M48_M56 cd05843
Peptidases M48 (Ste24 endopeptidase or htpX homolog) and M56 (in MecR1 and BlaR1), integral ...
 213-283 7.78e-12

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: 61.31  E-value: 7.78e-12
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2544591827 213 LKERINQLLERCG-FSSNGIFIMDGSkrsgHGNAYFTGmGNNKRIVFFDTLAESLDDDEMEAVLAHELGHFK 283
Cdd:cd05843     1 LKKIRQEILLSAGaFPLDKVVVVPGS----VPNAFFTG-GANKRVVLTTALLELLSEEELAAVIAHELGHFK 67
M48B_HtpX_like cd07336
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of ...
 262-410 6.87e-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: 320695 [Multi-domain]  Cd Length: 266  Bit Score: 62.51  E-value: 6.87e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 262 LAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISlgvlgwLITENWFFTGL-----GVGVPSNAAALLLFMLVS 336
Cdd:cd07336   103 ILRLLDKDELEGVLAHELAHIKNRDILISTIAATIAGAIS------MLANMAQWGAIfggrgGRDRGGNPIGALLLAILA 176

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 337 P-AFTTFMTPISayfqRKFEFEADDFAAE---HAQAskLISGLVKLykENASTLTPDP---------------------- 390
Cdd:cd07336   177 PiAATLIQLAIS----RSREYLADETGARisgNPLA--LASALEKL--ERGAQRHPPMeanpatahlfivnplsggglak 248

                         170       180
                  ....*....|....*....|
gi 2544591827 391 LFSafhySHPPAAIRIAHLE 410
Cdd:cd07336   249 LFS----THPPTEERIARLR 264
M48B_Htpx_like cd07340
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of ...
 244-410 3.49e-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: 320699 [Multi-domain]  Cd Length: 246  Bit Score: 57.12  E-value: 3.49e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMGNNKRIVFFDT-LAESLDDDEMEAVLAHELGHFKRKHVIKMLVAS---SIMSLISLGVLGWLITENWFFTGLG 319
Cdd:cd07340    58 NAFATGRNPEHAVIAVTTgLLEKLNRDELEGVIAHELSHIKNYDIRLMTIAVvlvGIIALIADLALRSFFYGGGSRRRRR 137

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 320 VGVPSNAAALLLFMLVSPAFTTFMTP-ISAYFQRKFEFEADDFAAE---HAQAskLISGLVKL--------YKENASTLT 387
Cdd:cd07340   138 DGGGGGALILLILGLVLIILAPIFAQlIQLAISRQREYLADASAVEltrNPEG--LISALEKIsgdssplkVANSATAHL 215

                         170       180       190
                  ....*....|....*....|....*....|.
gi 2544591827 388 PDPLFSAFHYS--------HPPAAIRIAHLE 410
Cdd:cd07340   216 NLYFPNPGKKSsfsslfstHPPIEERIKRLR 246
PRK05457 PRK05457
protease HtpX;
244-410 4.53e-09

protease HtpX;


Pssm-ID: 235478 [Multi-domain]  Cd Length: 284  Bit Score: 57.11  E-value: 4.53e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMGNNKRIVFFDT-LAESLDDDEMEAVLAHELGHfkrkhvikmlVASS---IMSLISlGVL-----------GWL 308
Cdd:PRK05457  106 NAFATGASKNNSLVAVSTgLLQNMSRDEVEAVLAHEISH----------IANGdmvTMTLIQ-GVVntfviflsriiAQI 174

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 309 ITENWFFTGLGVGVPSNAAALLLFMLvspaFTTFMTPISAYFQRKFEFEADDFAAEHAQASKLISGLVKLYKENASTLtP 388
Cdd:PRK05457  175 VDRFVSGNEEGNGIGYFIVSIVLEIV----FGILASIIVMWFSRHREFRADAGGAKLAGREKMIAALQRLKTSYEPQL-P 249

                         170       180       190
                  ....*....|....*....|....*....|..
gi 2544591827 389 DPL----------FSAFHYSHPPAAIRIAHLE 410
Cdd:PRK05457  250 GSMaafgingksgLSELFMSHPPLEKRIAALR 281
PRK03072 PRK03072
heat shock protein HtpX; Provisional
 266-410 1.91e-08

heat shock protein HtpX; Provisional


Pssm-ID: 235102 [Multi-domain]  Cd Length: 288  Bit Score: 55.43  E-value: 1.91e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 266 LDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLIS-LGVLGWLITenwFFTGLGVGVPSNAAALLLFMLVSP-AFTTFM 343
Cdd:PRK03072  122 LNERELRGVLGHELSHVYNRDILISSVAGALASVITyLANMAMFAG---MFGGRRDNDGPNPLALLLVSLLGPiAATVIQ 198

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 344 TPISayfqRKFEFEADDFAAE-----HAQASKL--ISGLVKlykenASTLTPDP---------------------LFSaf 395
Cdd:PRK03072  199 LAIS----RSREYQADESGAEltgdpLALASALrkISGGVQ-----AAPLPPEPqlasqahlmianpfraggigrLFS-- 267

                         170
                  ....*....|....*
gi 2544591827 396 hySHPPAAIRIAHLE 410
Cdd:PRK03072  268 --THPPMADRIARLE 280
PRK03001 PRK03001
zinc metalloprotease HtpX;
244-410 1.96e-08

zinc metalloprotease HtpX;


Pssm-ID: 179524 [Multi-domain]  Cd Length: 283  Bit Score: 55.03  E-value: 1.96e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMG-NNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISLgvlgwLITENWFFTGLG-VG 321
Cdd:PRK03001   96 NAFATGRNpEHAAVAATTGILRVLSEREIRGVMAHELAHVKHRDILISTISATMAGAISA-----LANFAMFFGGRDeNG 170

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 322 VPSNAAALLLFMLVSP-AFTTFMTPISayfqRKFEFEADDFAAE---HAQAskLISGLVKLYK--------------ENA 383
Cdd:PRK03001  171 RPVNPIAGIAVAILAPlAASLIQMAIS----RAREFEADRGGARisgDPQA--LASALDKIHRyasgipfqaaeahpATA 244

                         170       180       190
                  ....*....|....*....|....*....|.
gi 2544591827 384 STLTPDPL----FSAFHYSHPPAAIRIAHLE 410
Cdd:PRK03001  245 QMMIINPLsgggLANLFSTHPSTEERIARLM 275
M56_BlaR1_MecR1_like cd07326
Peptidase M56-like including those in BlaR1 and MecR1, integral membrane metallopeptidase; ...
 255-409 2.45e-08

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: 53.08  E-value: 2.45e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 255 RIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLislgvLGWLitenwfftglgvgvpsnaaalllfml 334
Cdd:cd07326    48 RIVLSTGLLELLSPEELRAVLAHERAHLRRRDPLLLLLASALARA-----LPFL-------------------------- 96

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2544591827 335 vspafttfmtPISAYFQRKF----EFEADDFAAEHAQASKLISGLVKLykENASTLTPDPLFSAFHYSHPPAAiRIAHL 409
Cdd:cd07326    97 ----------PLLRRLAAAYrllrELAADDAAARRVGPRALASALLKL--ARAGAPAAPAGALAFAGAAVNEA-RIRRL 162
PRK02870 PRK02870
heat shock protein HtpX; Provisional
 262-413 4.30e-08

heat shock protein HtpX; Provisional


Pssm-ID: 235081 [Multi-domain]  Cd Length: 336  Bit Score: 54.34  E-value: 4.30e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 262 LAESLDDDEMEAVLAHELGHFkRKHVIKMLVASSIMSLISLgvlgwLITENWFFTGLGVGVPSNAAALLLFML----VSP 337
Cdd:PRK02870  164 LLEKLDRDELQAVMAHELSHI-RHGDIRLTLCVGVLSNIML-----IVADFLFYSFMGNRRNSGANRARMIILilryVLP 237

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 338 AFTTFMTpisAYFQRKFEFEADDFAAEHAQASK-LISGLVKL------------YKE-------------NASTLTPDPL 391
Cdd:PRK02870  238 ILTVLLM---LFLSRTREYMADAGAVELMRDNEpMARALQKIsndhaqndeqyaYKHtdhestrraaylfDPAGISPGSL 314

                         170       180
                  ....*....|....*....|..
gi 2544591827 392 FSAFHySHPPAAIRIAHLEPKL 413
Cdd:PRK02870  315 SDAFS-THPSIENRLAALGGKL 335
M48_Ste24p_like cd07328
M48 Ste24 endopeptidase-like, integral membrane metallopeptidase; This family contains ...
 262-410 1.78e-07

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: 50.63  E-value: 1.78e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 262 LAESLDDDEMEAVLAHELGHFKRKHvikMLVASSIMSlislgvlgwlitenwfftglgvgvpsnaaalllfmlvspaftt 341
Cdd:cd07328    76 LLAALSPEELRAVLAHELGHFANGD---TRLGAWILS------------------------------------------- 109

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2544591827 342 fmtpisayfqRKFEFEADDFAAEHAQASKLISGLVKLykenaSTLTPDPLFSafhySHPPAAIRIAHLE 410
Cdd:cd07328   110 ----------RRAEYEADRVAARVAGSAAAASALRKL-----AARRPSSPDD----THPPLAERLAALG 159
M48B_HtpX_like cd07327
HtpX-like membrane-bound metallopeptidase; This family contains peptidase M48 subfamily B, ...
 244-410 8.36e-07

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: 48.79  E-value: 8.36e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMG-NNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASsimslISlgvlgwlitenwfftglgvgv 322
Cdd:cd07327    53 NAFATGRNpKNAAVAVTTGLLQLLNEDELEAVLAHELSHIKNRDVLVMTLAS-----LS--------------------- 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 323 psnaaalllfmlvspafttfmtpisayfqRKFEFEADDFAAE-HAQASKLISGLVKLYKENASTLTPDP----------- 390
Cdd:cd07327   107 -----------------------------RYREFAADRGSAKlTGDPLALASALMKISGSMQRIPKRDLrqveasaffii 157

                         170       180       190
                  ....*....|....*....|....*....|
gi 2544591827 391 ----------LFSafhySHPPAAIRIAHLE 410
Cdd:cd07327   158 pplsggslaeLFS----THPPTEKRIERLR 183
M48C_Oma1-like cd07324
Oma1 peptidase-like, integral membrane metallopeptidase; This family contains peptidase M48 ...
 244-410 1.41e-06

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: 47.56  E-value: 1.41e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMGNnkrIVFFD-TLAESLDDDEMEAVLAHELGHFKRKHVIKMLVAssimslislgvlgwlitenwfftglgvgv 322
Cdd:cd07324    31 NAFALPGGY---IFVTTgLLLLLESEDELAAVLAHEIGHVTLRHIARQLER----------------------------- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 323 psnaaalllfmlvspafttfmtpisayFQRKFEFEADDFAAEHAQAS-----KLISGLVKLYKENASTLTPDPLFSAfhy 397
Cdd:cd07324    79 ---------------------------YSRDQEREADRLGLQLLARAgydprGMARFFERLARQEGLSGSRLPEFLS--- 128

                         170
                  ....*....|...
gi 2544591827 398 SHPPAAIRIAHLE 410
Cdd:cd07324   129 THPLTAERIAALR 141
PRK03982 PRK03982
heat shock protein HtpX; Provisional
 244-409 1.60e-06

heat shock protein HtpX; Provisional


Pssm-ID: 235186 [Multi-domain]  Cd Length: 288  Bit Score: 49.23  E-value: 1.60e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMGNNKRIVFFDT-LAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISlgVLGWLITENWFFTGLGV-- 320
Cdd:PRK03982   97 NAFATGRDPKHAVVAVTEgILNLLNEDELEGVIAHELTHIKNRDTLIQTIAATLAGAIM--YLAQWLSWGLWFGGGGRdd 174

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 321 GVPSNAAALLLFMLVSP-AFTTFMTPISayfqRKFEFEADDFAAE-----HAQASKL--ISGLVKLYK-ENASTLTP--- 388
Cdd:PRK03982  175 RNGGNPIGSLLLIILAPiAATLIQFAIS----RQREFSADEGGARltgnpLALANALqkLEKGVRYIPlKNGNPATAhmf 250

                         170       180       190
                  ....*....|....*....|....*....|.
gi 2544591827 389 --DP--------LFSafhySHPPAAIRIAHL 409
Cdd:PRK03982  251 iiNPfrgqflanLFS----THPPTEERIERL 277
M48B_HtpX_like cd07339
Peptidase M48 subfamily B HtpX-like membrane-bound metallopeptidase; This HtpX family of ...
 244-409 3.54e-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: 320698 [Multi-domain]  Cd Length: 229  Bit Score: 47.94  E-value: 3.54e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 244 NAYFTGMGNNKRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLIS-LGVLGWLITE-NWFFTGLG-V 320
Cdd:cd07339    58 NAFAVGSRKDAAIALTDGLLRRLTLRELAGVLAHEVSHIRNGDLRVMGLADLISRLTSlLSLLGQLLLLlNLPLLLLGeV 137

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 321 GVPSnaaALLLFMLVSPAfttfmtpISAYFQ----RKFEFEADDFAAE---HAQAskLISGLVKLYKENASTLT------ 387
Cdd:cd07339   138 TISW---LAILLLILAPT-------LSTLLQlalsRTREFDADLDAARltgDPEG--LASALAKLERYQGGWWErlllpg 205

                         170       180
                  ....*....|....*....|...
gi 2544591827 388 -PDPLFSAFHySHPPAAIRIAHL 409
Cdd:cd07339   206 rRVPEPSLLR-THPPTEERIRRL 227
M48C_loiP_like cd07334
Peptidase M48C Ste24p loiP-like, integral membrane protein; This subfamily contains peptidase ...
 262-410 3.89e-06

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: 47.58  E-value: 3.89e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 262 LAESLDDDEMEAVLAHELGHFKRKHVIKMLVASsimslislgvlgwLITENWFftgLGVGVPSNAAALL----LFMLVSP 337
Cdd:cd07334    85 LMDMMTDDELLGVIGHEIGHVKLGHSKKAMKTA-------------YLTSAAR---KAAASASGTVGALsdsqLGALAEK 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 338 AfttfmtpISAYFQRKFEFEADDFAAE-------HAQAskLISGLVKL---YKENASTltpdpLFSafhySHPPAAIRIA 407
Cdd:cd07334   149 L-------INAQFSQKQESEADDYGYKflkkngyNPQA--AVSALEKLaalSGGGKSS-----LFS----SHPDPAKRAE 210


                  ...
gi 2544591827 408 HLE 410
Cdd:cd07334   211 RIR 213
MecR1 COG4219
Signal transducer regulating beta-lactamase production, contains metallopeptidase domain ...
 181-299 5.69e-06

Signal transducer regulating beta-lactamase production, contains metallopeptidase domain [Signal transduction mechanisms];


Pssm-ID: 443363 [Multi-domain]  Cd Length: 337  Bit Score: 48.12  E-value: 5.69e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 181 AILISFSLLMSWLYptlIAPLFNKFTPLEDGTLKERINQLLERCGFSSNGIFIMdgskrSGHGNAYFTgMGNNKRIVFFD 260
Cdd:COG4219     5 VLLLLLRLLISLLR---LRRLLRRARPVTDEELLELLERLARRLGIRRPVRLLE-----SDRITSPFS-FGLLRPVILLP 75

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2544591827 261 TLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSL 299
Cdd:COG4219    76 AGLEELSEEELEAILAHELAHIRRRDLLDNLLAELLLAL 114
M48C_Oma1_like cd07331
Peptidase M48C, integral membrane endopeptidase; This subfamily contains peptidase M48C Oma1 ...
 247-410 1.13e-05

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: 45.65  E-value: 1.13e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 247 FTGMgnnkrivfFDTLAeslDDDEMEAVLAHELGHFKRKHVIKMLvasSIMSLISLGVLGWLITENWFFTGLGVGVPSNA 326
Cdd:cd07331    47 FTGL--------LPVAK---NDDELAAVLGHEIAHALARHSAERM---SQQKLLQLLLLLLLAALGASLAGLALGLLGLG 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 327 AALLLFMLvspafttfmtpisayFQRKFEFEAD----DFAAE----HAQASKLisgLVKLYKENASTLTPDpLFSafhyS 398
Cdd:cd07331   113 AQLGLLLP---------------YSRKQELEADriglQLMAKagydPRAAVTF---WEKMAAAEGGGKPPE-FLS----T 169

                         170
                  ....*....|..
gi 2544591827 399 HPPAAIRIAHLE 410
Cdd:cd07331   170 HPSSETRIEALE 181
PRK04897 PRK04897
heat shock protein HtpX; Provisional
 231-410 1.20e-05

heat shock protein HtpX; Provisional


Pssm-ID: 235318 [Multi-domain]  Cd Length: 298  Bit Score: 46.87  E-value: 1.20e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 231 IFIMDGSKRsghgNAYFTGMGNNKRIVFFDT-LAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISLGVlgwLI 309
Cdd:PRK04897  100 VFIIDDPSP----NAFATGSSPKNAAVAVTTgLLAIMNREELEGVIGHEISHIRNYDIRLSTIAVALASAITLLS---DI 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 310 TENWFFTGLGVGVPS---NAAALLLFMLVSPAFTTFMTPISAY-----FQRKFEFEADDFAAE---HAQAskLISGLVKL 378
Cdd:PRK04897  173 AGRMMWWGGGSRRRDddrDGGGLQIILLIVSLLLLILAPLAATliqlaISRQREYLADASSVEltrNPQG--LISALEKI 250

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 2544591827 379 -----YKENASTLTP-----DPL----FSAFHYSHPPAAIRIAHLE 410
Cdd:PRK04897  251 snsqpMKHPVDDASAalyisDPLkkkgLSKLFDTHPPIEERIERLK 296
PRK01345 PRK01345
heat shock protein HtpX; Provisional
 219-410 1.88e-04

heat shock protein HtpX; Provisional


Pssm-ID: 234944 [Multi-domain]  Cd Length: 317  Bit Score: 43.08  E-value: 1.88e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 219 QLLERCGFSSNGIFIMDgskrSGHGNAYFTGMGNNKRIVFFDT-LAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIM 297
Cdd:PRK01345   75 DLARRAGLPMPKVYIID----NPQPNAFATGRNPENAAVAATTgLLQRLSPEEVAGVMAHELAHVKNRDTLTMTITATLA 150

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 298 SLIS-LGVLGwlitenwFFTGLGVGVPSNAAAL---LLFMLVSP--AFTTFMTpISayfqRKFEFEADDFAAEHA-QASK 370
Cdd:PRK01345  151 GAISmLANFA-------FFFGGNRENNNGPLGLvgtLAAMIVAPlaAMLVQMA-IS----RTREYAADRRGAEICgNPLW 218

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2544591827 371 LISGLVKLykENASTLTP------------------------DPLFSafhySHPPAAIRIAHLE 410
Cdd:PRK01345  219 LASALGKI--ERGAHGVPneeaernpatahmfiinplsgegmDNLFS----THPATENRIAALQ 276
M48C_bepA_like cd07333
Peptidase M48C Ste24p bepA-like, integral membrane protein; This family contains peptidase ...
 244-294 2.97e-04

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: 41.32  E-value: 2.97e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2544591827 244 NAyFTGMGNNkriVFFDT-LAESLD-DDEMEAVLAHELGHFKRKHVIKMLVAS 294
Cdd:cd07333    58 NA-FATPGGY---IYVNTgLILAADnEAELAGVLAHEIGHVVARHIAKQIEKS 106
PRK01265 PRK01265
heat shock protein HtpX; Provisional
 254-343 3.60e-04

heat shock protein HtpX; Provisional


Pssm-ID: 234931 [Multi-domain]  Cd Length: 324  Bit Score: 42.42  E-value: 3.60e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2544591827 254 KRIVFFDTLAESLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSLISLgvLGWLITENWFFTGLGVGVPSNAAALLL-- 331
Cdd:PRK01265  123 KRIAITLPLLKILNRDEIKAVAGHELGHLKHRDVELLMAIGLIPTLIYY--LGYSLFWGGMFGGGGGGRGNNGGLLFLig 200

                          90
                  ....*....|....
gi 2544591827 332 --FMLVSPAFTTFM 343
Cdd:PRK01265  201 iaLMAVSFVFNLLV 214
M56_BlaR1_MecR1_like cd07341
Peptidase M56-like including those in BlaR1 and MecR1, integral membrane metallopeptidase; ...
 265-299 4.53e-03

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: 320700 [Multi-domain]  Cd Length: 187  Bit Score: 38.08  E-value: 4.53e-03
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2544591827 265 SLDDDEMEAVLAHELGHFKRKHVIKMLVASSIMSL 299
Cdd:cd07341    77 EGSPEELRAILLHELAHIRRRDLLVNLLQRLLEAL 111
Peptidase_M56 pfam05569
BlaR1 peptidase M56; Production of beta-Lactamase and penicillin-binding protein 2a (which ...
 255-307 8.79e-03

BlaR1 peptidase M56; Production of beta-Lactamase and penicillin-binding protein 2a (which mediate staphylococcal resistance to beta-lactam antibiotics) is regulated by a signal-transducing integral membrane protein and a transcriptional repressor. The signal transducer is a fusion protein with penicillin-binding and zinc metalloprotease domains. 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. homologs to this peptidase domain, which corresponds to Merops family M56, are also found in a number of other bacterial genome sequences.


Pssm-ID: 428523  Cd Length: 296  Bit Score: 37.84  E-value: 8.79e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2544591827 255 RIVFFDTLAESLDDDEMEAVLAHELGHFKRK-HVIKMLVAssimsliSLGVLGW 307
Cdd:pfam05569 177 RIVLPADFDTRLSGEEIDYILAHELSHLKRGdLIINLLVA-------VLQCLHW 223
 
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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