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Conserved domains on  [gi|1843978404|ref|NP_001369695|]
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procathepsin L isoform 4 precursor [Homo sapiens]

Protein Classification

C1 family peptidase( domain architecture ID 11276840)

C1 family peptidase (also called papain family protein) is a papain-like cysteine peptidase that catalyzes the hydrolysis of peptide bonds in substrates using a catalytic dyad of Cys and His residues

CATH:  3.90.70.10
EC:  3.4.22.-
Gene Ontology:  GO:0008234|GO:0006508
MEROPS:  C1
PubMed:  12887050|11517925
SCOP:  4000859

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Peptidase_C1 pfam00112
Papain family cysteine protease;
114-260 3.41e-86

Papain family cysteine protease;


:

Pssm-ID: 425470 [Multi-domain]  Cd Length: 214  Bit Score: 255.93  E-value: 3.41e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 114 APRSVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSGpqGNEGCNGGLMDYAFQYVQDN 193
Cdd:pfam00112   1 LPESFDWREKGAVTPVKDQGQCGSCWAFSAVGALEGRYCIKTGKLVSLSEQQLVDCDT--FNNGCNGGLPDNAFEYIKKN 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1843978404 194 GGLDSEESYPYEATEESCKYNP-KYSVANDTGFVDIPKQ-EKALMKAVATVGPISVAIDAGHESFLFYK 260
Cdd:pfam00112  79 GGIVTESDYPYTAKDGTCKFKKsNSKVAKIKGYGDVPYNdEEALQAALAKNGPVSVAIDAYERDFQLYK 147
Inhibitor_I29 smart00848
Cathepsin propeptide inhibitor domain (I29); This domain is found at the N-terminus of some C1 ...
 29-87 2.32e-16

Cathepsin propeptide inhibitor domain (I29); This domain is found at the N-terminus of some C1 peptidases such as Cathepsin L where it acts as a propeptide. There are also a number of proteins that are composed solely of multiple copies of this domain such as the peptidase inhibitor salarin. This family is classified as I29 by MEROPS. Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties.


:

Pssm-ID: 214853 [Multi-domain]  Cd Length: 57  Bit Score: 71.12  E-value: 2.32e-16
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404   29 WTKWKAMHNRLYGMNEEGWRR-AVWEKNMKMIELHNQEYregKHSFTMAMNAFGDMTSEE 87
Cdd:smart00848   1 FEQWKKKHGKSYSSEEEEARRfAIFKENLKKIEEHNKKY---EHSYKLGVNQFSDLTPEE 57
 
Name Accession Description Interval E-value
Peptidase_C1 pfam00112
Papain family cysteine protease;
114-260 3.41e-86

Papain family cysteine protease;


Pssm-ID: 425470 [Multi-domain]  Cd Length: 214  Bit Score: 255.93  E-value: 3.41e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 114 APRSVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSGpqGNEGCNGGLMDYAFQYVQDN 193
Cdd:pfam00112   1 LPESFDWREKGAVTPVKDQGQCGSCWAFSAVGALEGRYCIKTGKLVSLSEQQLVDCDT--FNNGCNGGLPDNAFEYIKKN 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1843978404 194 GGLDSEESYPYEATEESCKYNP-KYSVANDTGFVDIPKQ-EKALMKAVATVGPISVAIDAGHESFLFYK 260
Cdd:pfam00112  79 GGIVTESDYPYTAKDGTCKFKKsNSKVAKIKGYGDVPYNdEEALQAALAKNGPVSVAIDAYERDFQLYK 147
Peptidase_C1A cd02248
Peptidase C1A subfamily (MEROPS database nomenclature); composed of cysteine peptidases (CPs) ...
 115-264 2.82e-81

Peptidase C1A subfamily (MEROPS database nomenclature); composed of cysteine peptidases (CPs) similar to papain, including the mammalian CPs (cathepsins B, C, F, H, L, K, O, S, V, X and W). Papain is an endopeptidase with specific substrate preferences, primarily for bulky hydrophobic or aromatic residues at the S2 subsite, a hydrophobic pocket in papain that accommodates the P2 sidechain of the substrate (the second residue away from the scissile bond). Most members of the papain subfamily are endopeptidases. Some exceptions to this rule can be explained by specific details of the catalytic domains like the occluding loop in cathepsin B which confers an additional carboxydipeptidyl activity and the mini-chain of cathepsin H resulting in an N-terminal exopeptidase activity. Papain-like CPs have different functions in various organisms. Plant CPs are used to mobilize storage proteins in seeds. Parasitic CPs act extracellularly to help invade tissues and cells, to hatch or to evade the host immune system. Mammalian CPs are primarily lysosomal enzymes with the exception of cathepsin W, which is retained in the endoplasmic reticulum. They are responsible for protein degradation in the lysosome. Papain-like CPs are synthesized as inactive proenzymes with N-terminal propeptide regions, which are removed upon activation. In addition to its inhibitory role, the propeptide is required for proper folding of the newly synthesized enzyme and its stabilization in denaturing pH conditions. Residues within the propeptide region also play a role in the transport of the proenzyme to lysosomes or acidified vesicles. Also included in this subfamily are proteins classified as non-peptidase homologs, which lack peptidase activity or have missing active site residues.


Pssm-ID: 239068 [Multi-domain]  Cd Length: 210  Bit Score: 243.30  E-value: 2.82e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 115 PRSVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSGPqGNEGCNGGLMDYAFQYVQdNG 194
Cdd:cd02248     1 PESVDWREKGAVTPVKDQGSCGSCWAFSTVGALEGAYAIKTGKLVSLSEQQLVDCSTS-GNNGCNGGNPDNAFEYVK-NG 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1843978404 195 GLDSEESYPYEATEESCKYNPKYSVANDTGFVDIPK-QEKALMKAVATVGPISVAIDAGHeSFLFYKEaGV 264
Cdd:cd02248    79 GLASESDYPYTGKDGTCKYNSSKVGAKITGYSNVPPgDEEALKAALANYGPVSVAIDASS-SFQFYKG-GI 147
Pept_C1 smart00645
Papain family cysteine protease;
114-206 6.81e-58

Papain family cysteine protease;


Pssm-ID: 214761 [Multi-domain]  Cd Length: 175  Bit Score: 182.78  E-value: 6.81e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404  114 APRSVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSGPqGNEGCNGGLMDYAFQYVQDN 193
Cdd:smart00645   1 LPESFDWRKKGAVTPVKDQGQCGSCWAFSATGALEGRYCIKTGKLVSLSEQQLVDCSGG-GNCGCNGGLPDNAFEYIKKN 79

                           90
                   ....*....|...
gi 1843978404  194 GGLDSEESYPYEA 206
Cdd:smart00645  80 GGLETESCYPYTG 92
PTZ00203 PTZ00203
cathepsin L protease; Provisional
 6-259 1.56e-46

cathepsin L protease; Provisional


Pssm-ID: 185513 [Multi-domain]  Cd Length: 348  Bit Score: 159.10  E-value: 1.56e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404   6 ILAAFCLGIASA-----TLTFDHSLEAQWTKWKAMHNRLYG-MNEEGWRRAVWEKNMKMIELHNQEYREGKHSFTmamnA 79
Cdd:PTZ00203   10 AVAVVCVVLAAAcaparAIYVGTPAAALFEEFKRTYQRAYGtLTEEQQRLANFERNLELMREHQARNPHARFGIT----K 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404  80 FGDMTSEEF-RQVMNG---FQNRKPRKGKVFQEPL--FYEAPRSVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFR 153
Cdd:PTZ00203   86 FFDLSEAEFaARYLNGaayFAAAKQHAGQHYRKARadLSAVPDAVDWREKGAVTPVKNQGACGSCWAFSAVGNIESQWAV 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 154 KTGRLISLSEQNLVDCSgpQGNEGCNGGLMDYAFQYVQDN--GGLDSEESYPYEATEES---CKYNPKYSV-ANDTGFVD 227
Cdd:PTZ00203  166 AGHKLVRLSEQQLVSCD--HVDNGCGGGLMLQAFEWVLRNmnGTVFTEKSYPYVSGNGDvpeCSNSSELAPgARIDGYVS 243

                         250       260       270
                  ....*....|....*....|....*....|..
gi 1843978404 228 IPKQEKALMKAVATVGPISVAIDAghESFLFY 259
Cdd:PTZ00203  244 MESSERVMAAWLAKNGPISIAVDA--SSFMSY 273
COG4870 COG4870
Cysteine protease, C1A family [Posttranslational modification, protein turnover, chaperones];
113-260 3.54e-22

Cysteine protease, C1A family [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 443898 [Multi-domain]  Cd Length: 426  Bit Score: 94.82  E-value: 3.54e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 113 EAPRSVDWRekGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLIS---LSEQNLVDC---SGPQGNEGCNGGLMDYA 186
Cdd:COG4870     3 ALPSSVDLR--GYVTPVKDQGSLGSCWAFATAAALESYLKKQAGAPGTsldLSELFLYNQarnGDGTEGTDDGGSSLRDA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 187 FQYVQDNgGLDSEESYPYEATEESCKYNPK-YSVAND---TGFVDIPKQE-----KALMKAVATVGPISVAIdAGHESFL 257
Cdd:COG4870    81 LKLLRWS-GVVPESDWPYDDSDFTSQPSAAaYADARNykiQDYYRLPGGGgatdlDAIKQALAEGGPVVFGF-YVYESFY 158


                  ...
gi 1843978404 258 FYK 260
Cdd:COG4870   159 NYT 161
Inhibitor_I29 smart00848
Cathepsin propeptide inhibitor domain (I29); This domain is found at the N-terminus of some C1 ...
 29-87 2.32e-16

Cathepsin propeptide inhibitor domain (I29); This domain is found at the N-terminus of some C1 peptidases such as Cathepsin L where it acts as a propeptide. There are also a number of proteins that are composed solely of multiple copies of this domain such as the peptidase inhibitor salarin. This family is classified as I29 by MEROPS. Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties.


Pssm-ID: 214853 [Multi-domain]  Cd Length: 57  Bit Score: 71.12  E-value: 2.32e-16
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404   29 WTKWKAMHNRLYGMNEEGWRR-AVWEKNMKMIELHNQEYregKHSFTMAMNAFGDMTSEE 87
Cdd:smart00848   1 FEQWKKKHGKSYSSEEEEARRfAIFKENLKKIEEHNKKY---EHSYKLGVNQFSDLTPEE 57
Inhibitor_I29 pfam08246
Cathepsin propeptide inhibitor domain (I29); This domain is found at the N-terminus of some C1 ...
 29-88 3.29e-14

Cathepsin propeptide inhibitor domain (I29); This domain is found at the N-terminus of some C1 peptidases such as Cathepsin L where it acts as a propeptide. There are also a number of proteins that are composed solely of multiple copies of this domain such as the peptidase inhibitor salarin Swiss:Q70SU8. This family is classified as I29 by MEROPS.


Pssm-ID: 462410 [Multi-domain]  Cd Length: 58  Bit Score: 65.74  E-value: 3.29e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1843978404  29 WTKWKAMHNRLYG-MNEEGWRRAVWEKNMKMIELHNQEyreGKHSFTMAMNAFGDMTSEEF 88
Cdd:pfam08246   1 FDDWMKKYGKSYRsEEEELYRFQIFKENLKRIEEHNSN---GNVTYKLGLNKFADLTDEEF 58
 
Name Accession Description Interval E-value
Peptidase_C1 pfam00112
Papain family cysteine protease;
114-260 3.41e-86

Papain family cysteine protease;


Pssm-ID: 425470 [Multi-domain]  Cd Length: 214  Bit Score: 255.93  E-value: 3.41e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 114 APRSVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSGpqGNEGCNGGLMDYAFQYVQDN 193
Cdd:pfam00112   1 LPESFDWREKGAVTPVKDQGQCGSCWAFSAVGALEGRYCIKTGKLVSLSEQQLVDCDT--FNNGCNGGLPDNAFEYIKKN 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1843978404 194 GGLDSEESYPYEATEESCKYNP-KYSVANDTGFVDIPKQ-EKALMKAVATVGPISVAIDAGHESFLFYK 260
Cdd:pfam00112  79 GGIVTESDYPYTAKDGTCKFKKsNSKVAKIKGYGDVPYNdEEALQAALAKNGPVSVAIDAYERDFQLYK 147
Peptidase_C1A cd02248
Peptidase C1A subfamily (MEROPS database nomenclature); composed of cysteine peptidases (CPs) ...
 115-264 2.82e-81

Peptidase C1A subfamily (MEROPS database nomenclature); composed of cysteine peptidases (CPs) similar to papain, including the mammalian CPs (cathepsins B, C, F, H, L, K, O, S, V, X and W). Papain is an endopeptidase with specific substrate preferences, primarily for bulky hydrophobic or aromatic residues at the S2 subsite, a hydrophobic pocket in papain that accommodates the P2 sidechain of the substrate (the second residue away from the scissile bond). Most members of the papain subfamily are endopeptidases. Some exceptions to this rule can be explained by specific details of the catalytic domains like the occluding loop in cathepsin B which confers an additional carboxydipeptidyl activity and the mini-chain of cathepsin H resulting in an N-terminal exopeptidase activity. Papain-like CPs have different functions in various organisms. Plant CPs are used to mobilize storage proteins in seeds. Parasitic CPs act extracellularly to help invade tissues and cells, to hatch or to evade the host immune system. Mammalian CPs are primarily lysosomal enzymes with the exception of cathepsin W, which is retained in the endoplasmic reticulum. They are responsible for protein degradation in the lysosome. Papain-like CPs are synthesized as inactive proenzymes with N-terminal propeptide regions, which are removed upon activation. In addition to its inhibitory role, the propeptide is required for proper folding of the newly synthesized enzyme and its stabilization in denaturing pH conditions. Residues within the propeptide region also play a role in the transport of the proenzyme to lysosomes or acidified vesicles. Also included in this subfamily are proteins classified as non-peptidase homologs, which lack peptidase activity or have missing active site residues.


Pssm-ID: 239068 [Multi-domain]  Cd Length: 210  Bit Score: 243.30  E-value: 2.82e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 115 PRSVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSGPqGNEGCNGGLMDYAFQYVQdNG 194
Cdd:cd02248     1 PESVDWREKGAVTPVKDQGSCGSCWAFSTVGALEGAYAIKTGKLVSLSEQQLVDCSTS-GNNGCNGGNPDNAFEYVK-NG 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1843978404 195 GLDSEESYPYEATEESCKYNPKYSVANDTGFVDIPK-QEKALMKAVATVGPISVAIDAGHeSFLFYKEaGV 264
Cdd:cd02248    79 GLASESDYPYTGKDGTCKYNSSKVGAKITGYSNVPPgDEEALKAALANYGPVSVAIDASS-SFQFYKG-GI 147
Pept_C1 smart00645
Papain family cysteine protease;
114-206 6.81e-58

Papain family cysteine protease;


Pssm-ID: 214761 [Multi-domain]  Cd Length: 175  Bit Score: 182.78  E-value: 6.81e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404  114 APRSVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSGPqGNEGCNGGLMDYAFQYVQDN 193
Cdd:smart00645   1 LPESFDWRKKGAVTPVKDQGQCGSCWAFSATGALEGRYCIKTGKLVSLSEQQLVDCSGG-GNCGCNGGLPDNAFEYIKKN 79

                           90
                   ....*....|...
gi 1843978404  194 GGLDSEESYPYEA 206
Cdd:smart00645  80 GGLETESCYPYTG 92
PTZ00203 PTZ00203
cathepsin L protease; Provisional
 6-259 1.56e-46

cathepsin L protease; Provisional


Pssm-ID: 185513 [Multi-domain]  Cd Length: 348  Bit Score: 159.10  E-value: 1.56e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404   6 ILAAFCLGIASA-----TLTFDHSLEAQWTKWKAMHNRLYG-MNEEGWRRAVWEKNMKMIELHNQEYREGKHSFTmamnA 79
Cdd:PTZ00203   10 AVAVVCVVLAAAcaparAIYVGTPAAALFEEFKRTYQRAYGtLTEEQQRLANFERNLELMREHQARNPHARFGIT----K 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404  80 FGDMTSEEF-RQVMNG---FQNRKPRKGKVFQEPL--FYEAPRSVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFR 153
Cdd:PTZ00203   86 FFDLSEAEFaARYLNGaayFAAAKQHAGQHYRKARadLSAVPDAVDWREKGAVTPVKNQGACGSCWAFSAVGNIESQWAV 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 154 KTGRLISLSEQNLVDCSgpQGNEGCNGGLMDYAFQYVQDN--GGLDSEESYPYEATEES---CKYNPKYSV-ANDTGFVD 227
Cdd:PTZ00203  166 AGHKLVRLSEQQLVSCD--HVDNGCGGGLMLQAFEWVLRNmnGTVFTEKSYPYVSGNGDvpeCSNSSELAPgARIDGYVS 243

                         250       260       270
                  ....*....|....*....|....*....|..
gi 1843978404 228 IPKQEKALMKAVATVGPISVAIDAghESFLFY 259
Cdd:PTZ00203  244 MESSERVMAAWLAKNGPISIAVDA--SSFMSY 273
PTZ00021 PTZ00021
falcipain-2; Provisional
 36-267 1.05e-44

falcipain-2; Provisional


Pssm-ID: 240232 [Multi-domain]  Cd Length: 489  Bit Score: 157.24  E-value: 1.05e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404  36 HNRLYGMNEEGWRR-AVWEKNMKMIELHNQE----YREGkhsftmaMNAFGDMTSEEFRQVMNGFQNRKP-RKGKVFQEP 109
Cdd:PTZ00021  176 HGKKYQTPDEMQQRyLSFVENLAKINAHNNKenvlYKKG-------MNRFGDLSFEEFKKKYLTLKSFDFkSNGKKSPRV 248

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 110 LFYEA------PR-------SVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSgpQGNE 176
Cdd:PTZ00021  249 INYDDvikkykPKdatfdhaKYDWRLHNGVTPVKDQKNCGSCWAFSTVGVVESQYAIRKNELVSLSEQELVDCS--FKNN 326

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 177 GCNGGLMDYAFQYVQDNGGLDSEESYPYEA-TEESCKY---NPKYSVANdtgFVDIPkqEKALMKAVATVGPISVAIdAG 252
Cdd:PTZ00021  327 GCYGGLIPNAFEDMIELGGLCSEDDYPYVSdTPELCNIdrcKEKYKIKS---YVSIP--EDKFKEAIRFLGPISVSI-AV 400

                         250
                  ....*....|....*
gi 1843978404 253 HESFLFYKEaGVKNG 267
Cdd:PTZ00021  401 SDDFAFYKG-GIFDG 414
PTZ00200 PTZ00200
cysteine proteinase; Provisional
 19-267 1.14e-33

cysteine proteinase; Provisional


Pssm-ID: 240310 [Multi-domain]  Cd Length: 448  Bit Score: 126.73  E-value: 1.14e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404  19 LTFDHSLE----AQWTKWKAMHNRLYGMNEEGWRRAVWEKNmKMIELHNQEyreGKHSFTMAMNAFGDMTSEEFRQVmng 94
Cdd:PTZ00200  112 ISDDPKLEfevyLEFEEFNKKYNRKHATHAERLNRFLTFRN-NYLEVKSHK---GDEPYSKEINKFSDLTEEEFRKL--- 184

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404  95 FQNRKPRKGKVFQEPLFYEAPRSV------------------------------DWREKGYVTPVKNQG-QCGSCWAFSA 143
Cdd:PTZ00200  185 FPVIKVPPKSNSTSHNNDFKARHVsnptylknlkkakntdedvkdpskitgeglDWRRADAVTKVKDQGlNCGSCWAFSS 264

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 144 TGALEGQMFRKTGRLISLSEQNLVDCSgpQGNEGCNGGLMDYAFQYVQdNGGLDSEESYPYEATEESCKY--NPKYSVAN 221
Cdd:PTZ00200  265 VGSVESLYKIYRDKSVDLSEQELVNCD--TKSQGCSGGYPDTALEYVK-NKGLSSSSDVPYLAKDGKCVVssTKKVYIDS 341

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1843978404 222 DTGFVDIPKQEKALmkavaTVGPISVAIdAGHESFLFYKeAGVKNG 267
Cdd:PTZ00200  342 YLVAKGKDVLNKSL-----VISPTVVYI-AVSRELLKYK-SGVYNG 380
Peptidase_C1 cd02619
C1 Peptidase family (MEROPS database nomenclature), also referred to as the papain family; ...
 117-267 5.55e-24

C1 Peptidase family (MEROPS database nomenclature), also referred to as the papain family; composed of two subfamilies of cysteine peptidases (CPs), C1A (papain) and C1B (bleomycin hydrolase). Papain-like enzymes are mostly endopeptidases with some exceptions like cathepsins B, C, H and X, which are exopeptidases. Papain-like CPs have different functions in various organisms. Plant CPs are used to mobilize storage proteins in seeds while mammalian CPs are primarily lysosomal enzymes responsible for protein degradation in the lysosome. Papain-like CPs are synthesized as inactive proenzymes with N-terminal propeptide regions, which are removed upon activation. Bleomycin hydrolase (BH) is a CP that detoxifies bleomycin by hydrolysis of an amide group. It acts as a carboxypeptidase on its C-terminus to convert itself into an aminopeptidase and peptide ligase. BH is found in all tissues in mammals as well as in many other eukaryotes. It forms a hexameric ring barrel structure with the active sites imbedded in the central channel. Some members of the C1 family are proteins classified as non-peptidase homologs which lack peptidase activity or have missing active site residues.


Pssm-ID: 239110 [Multi-domain]  Cd Length: 223  Bit Score: 96.43  E-value: 5.55e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 117 SVDWREKgYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGR--LISLSEQNLVDCSGPQ---GNEGCNGGLMDYAFQYVQ 191
Cdd:cd02619     1 SVDLRPL-RLTPVKNQGSRGSCWAFASAYALESAYRIKGGEdeYVDLSPQYLYICANDEclgINGSCDGGGPLSALLKLV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 192 DNGGLDSEESYPYEATEESCKYNP----KYSVANDTGFVDI-PKQEKALMKAVATVGPISVAIDAgHESFLFYKEAGVKN 266
Cdd:cd02619    80 ALKGIPPEEDYPYGAESDGEEPKSeaalNAAKVKLKDYRRVlKNNIEDIKEALAKGGPVVAGFDV-YSGFDRLKEGIIYE 158


                  .
gi 1843978404 267 G 267
Cdd:cd02619   159 E 159
COG4870 COG4870
Cysteine protease, C1A family [Posttranslational modification, protein turnover, chaperones];
113-260 3.54e-22

Cysteine protease, C1A family [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 443898 [Multi-domain]  Cd Length: 426  Bit Score: 94.82  E-value: 3.54e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 113 EAPRSVDWRekGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLIS---LSEQNLVDC---SGPQGNEGCNGGLMDYA 186
Cdd:COG4870     3 ALPSSVDLR--GYVTPVKDQGSLGSCWAFATAAALESYLKKQAGAPGTsldLSELFLYNQarnGDGTEGTDDGGSSLRDA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 187 FQYVQDNgGLDSEESYPYEATEESCKYNPK-YSVAND---TGFVDIPKQE-----KALMKAVATVGPISVAIdAGHESFL 257
Cdd:COG4870    81 LKLLRWS-GVVPESDWPYDDSDFTSQPSAAaYADARNykiQDYYRLPGGGgatdlDAIKQALAEGGPVVFGF-YVYESFY 158


                  ...
gi 1843978404 258 FYK 260
Cdd:COG4870   159 NYT 161
Peptidase_C1A_CathepsinC cd02621
Cathepsin C; also known as Dipeptidyl Peptidase I (DPPI), an atypical papain-like cysteine ...
 115-261 2.40e-20

Cathepsin C; also known as Dipeptidyl Peptidase I (DPPI), an atypical papain-like cysteine peptidase with chloride dependency and dipeptidyl aminopeptidase activity, resulting from its tetrameric structure which limits substrate access. Each subunit of the tetramer is composed of three peptides: the heavy and light chains, which together adopts the papain fold and forms the catalytic domain; and the residual propeptide region, which forms a beta barrel and points towards the substrate's N-terminus. The subunit composition is the result of the unique characteristic of procathepsin C maturation involving the cleavage of the catalytic domain and the non-autocatalytic excision of an activation peptide within its propeptide region. By removing N-terminal dipeptide extensions, cathepsin C activates granule serine peptidases (granzymes) involved in cell-mediated apoptosis, inflammation and tissue remodelling. Loss-of-function mutations in cathepsin C are associated with Papillon-Lefevre and Haim-Munk syndromes, rare diseases characterized by hyperkeratosis and early-onset periodontitis. Cathepsin C is widely expressed in many tissues with high levels in lung, kidney and placenta. It is also highly expressed in cytotoxic lymphocytes and mature myeloid cells.


Pssm-ID: 239112 [Multi-domain]  Cd Length: 243  Bit Score: 87.06  E-value: 2.40e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 115 PRSVDWREKG----YVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLIS------LSEQNLVDCSgpQGNEGCNGGLMD 184
Cdd:cd02621     2 PKSFDWGDVNngfnYVSPVRNQGGCGSCYAFASVYALEARIMIASNKTDPlgqqpiLSPQHVLSCS--QYSQGCDGGFPF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 185 YAFQYVQDNgGLDSEESYPYEA-TEESCKYNPKYSV---ANDTGFVDI---PKQEKALMKAVATVGPISVAIDAgHESFL 257
Cdd:cd02621    80 LVGKFAEDF-GIVTEDYFPYTAdDDRPCKASPSECRryyFSDYNYVGGcygCTNEDEMKWEIYRNGPIVVAFEV-YSDFD 157


                  ....
gi 1843978404 258 FYKE 261
Cdd:cd02621   158 FYKE 161
Peptidase_C1A_CathepsinB cd02620
Cathepsin B group; composed of cathepsin B and similar proteins, including tubulointerstitial ...
 115-264 7.58e-20

Cathepsin B group; composed of cathepsin B and similar proteins, including tubulointerstitial nephritis antigen (TIN-Ag). Cathepsin B is a lysosomal papain-like cysteine peptidase which is expressed in all tissues and functions primarily as an exopeptidase through its carboxydipeptidyl activity. Together with other cathepsins, it is involved in the degradation of proteins, proenzyme activation, Ag processing, metabolism and apoptosis. Cathepsin B has been implicated in a number of human diseases such as cancer, rheumatoid arthritis, osteoporosis and Alzheimer's disease. The unique carboxydipeptidyl activity of cathepsin B is attributed to the presence of an occluding loop in its active site which favors the binding of the C-termini of substrate proteins. Some members of this group do not possess the occluding loop. TIN-Ag is an extracellular matrix basement protein which was originally identified as a target Ag involved in anti-tubular basement membrane antibody-mediated interstitial nephritis. It plays a role in renal tubulogenesis and is defective in hereditary tubulointerstitial disorders. TIN-Ag is exclusively expressed in kidney tissues.


Pssm-ID: 239111 [Multi-domain]  Cd Length: 236  Bit Score: 85.40  E-value: 7.58e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 115 PRSVDWREK--GYVT--PVKNQGQCGSCWAFSATGAL--------EGQMfrktgrLISLSEQNLVDCSGPQGNeGCNGGL 182
Cdd:cd02620     1 PESFDAREKwpNCISigEIRDQGNCGSCWAFSAVEAFsdrlciqsNGKE------NVLLSAQDLLSCCSGCGD-GCNGGY 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 183 MDYAFQYVQDNgGLDSEESYPYEA--------------TEESC------KYNPKYSvaNDTGFVD----IPKQEKALMKA 238
Cdd:cd02620    74 PDAAWKYLTTT-GVVTGGCQPYTIppcghhpegpppccGTPYCtpkcqdGCEKTYE--EDKHKGKsaysVPSDETDIMKE 150

                         170       180
                  ....*....|....*....|....*.
gi 1843978404 239 VATVGPISVAIDAgHESFLFYKEaGV 264
Cdd:cd02620   151 IMTNGPVQAAFTV-YEDFLYYKS-GV 174
Peptidase_C1A_CathepsinX cd02698
Cathepsin X; the only papain-like lysosomal cysteine peptidase exhibiting carboxymonopeptidase ...
 115-259 1.10e-19

Cathepsin X; the only papain-like lysosomal cysteine peptidase exhibiting carboxymonopeptidase activity. It can also act as a carboxydipeptidase, like cathepsin B, but has been shown to preferentially cleave substrates through a monopeptidyl carboxypeptidase pathway. The propeptide region of cathepsin X, the shortest among papain-like peptidases, is covalently attached to the active site cysteine in the inactive form of the enzyme. Little is known about the biological function of cathepsin X. Some studies point to a role in early tumorigenesis. A more recent study indicates that cathepsin X expression is restricted to immune cells suggesting a role in phagocytosis and the regulation of the immune response.


Pssm-ID: 239149  Cd Length: 239  Bit Score: 85.16  E-value: 1.10e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 115 PRSVDWRE---KGYVTPVKNQ---GQCGSCWAFSATGALEGQMF--RK-TGRLISLSEQNLVDCSGpQGNegCNGGLMDY 185
Cdd:cd02698     2 PKSWDWRNvngVNYVSPTRNQhipQYCGSCWAHGSTSALADRINiaRKgAWPSVYLSVQVVIDCAG-GGS--CHGGDPGG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 186 AFQYVQDNGGLDsEESYPYEATEESC-KYN-----------------PKYSVAnDTGFVdipKQEKALMKAVATVGPISV 247
Cdd:cd02698    79 VYEYAHKHGIPD-ETCNPYQAKDGECnPFNrcgtcnpfgecfaiknyTLYFVS-DYGSV---SGRDKMMAEIYARGPISC 153

                         170
                  ....*....|..
gi 1843978404 248 AIDAgHESFLFY 259
Cdd:cd02698   154 GIMA-TEALENY 164
Inhibitor_I29 smart00848
Cathepsin propeptide inhibitor domain (I29); This domain is found at the N-terminus of some C1 ...
 29-87 2.32e-16

Cathepsin propeptide inhibitor domain (I29); This domain is found at the N-terminus of some C1 peptidases such as Cathepsin L where it acts as a propeptide. There are also a number of proteins that are composed solely of multiple copies of this domain such as the peptidase inhibitor salarin. This family is classified as I29 by MEROPS. Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties.


Pssm-ID: 214853 [Multi-domain]  Cd Length: 57  Bit Score: 71.12  E-value: 2.32e-16
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404   29 WTKWKAMHNRLYGMNEEGWRR-AVWEKNMKMIELHNQEYregKHSFTMAMNAFGDMTSEE 87
Cdd:smart00848   1 FEQWKKKHGKSYSSEEEEARRfAIFKENLKKIEEHNKKY---EHSYKLGVNQFSDLTPEE 57
Inhibitor_I29 pfam08246
Cathepsin propeptide inhibitor domain (I29); This domain is found at the N-terminus of some C1 ...
 29-88 3.29e-14

Cathepsin propeptide inhibitor domain (I29); This domain is found at the N-terminus of some C1 peptidases such as Cathepsin L where it acts as a propeptide. There are also a number of proteins that are composed solely of multiple copies of this domain such as the peptidase inhibitor salarin Swiss:Q70SU8. This family is classified as I29 by MEROPS.


Pssm-ID: 462410 [Multi-domain]  Cd Length: 58  Bit Score: 65.74  E-value: 3.29e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1843978404  29 WTKWKAMHNRLYG-MNEEGWRRAVWEKNMKMIELHNQEyreGKHSFTMAMNAFGDMTSEEF 88
Cdd:pfam08246   1 FDDWMKKYGKSYRsEEEELYRFQIFKENLKRIEEHNSN---GNVTYKLGLNKFADLTDEEF 58
PTZ00049 PTZ00049
cathepsin C-like protein; Provisional
 129-236 2.94e-08

cathepsin C-like protein; Provisional


Pssm-ID: 240244 [Multi-domain]  Cd Length: 693  Bit Score: 54.19  E-value: 2.94e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 129 VKNQGQCGSCWAFSATGAL----EGQMFRKTG-RLIS-----LSEQNLVDCSGPqgNEGCNGGLmDYAFQYVQDNGGLDS 198
Cdd:PTZ00049  400 VTNQLLCGSCYIASQMYAFkrriEIALTKNLDkKYLNnfddlLSIQTVLSCSFY--DQGCNGGF-PYLVSKMAKLQGIPL 476

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1843978404 199 EESYPYEATEESCKYnPKYSVANDTGFVDIPKQEKALM 236
Cdd:PTZ00049  477 DKVFPYTATEQTCPY-QVDQSANSMNGSANLRQINAVF 513
PTZ00364 PTZ00364
dipeptidyl-peptidase I precursor; Provisional
 115-204 1.84e-04

dipeptidyl-peptidase I precursor; Provisional


Pssm-ID: 240381 [Multi-domain]  Cd Length: 548  Bit Score: 42.57  E-value: 1.84e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404 115 PRSVDWREKG---YVTPVKNQG---QCGSCWAFSATGALEGQMF------RKTGRLISLSEQNLVDCSgpQGNEGCNGGL 182
Cdd:PTZ00364  206 PAAWSWGDVGgasFLPAAPPASpgrGCNSSYVEAALAAMMARVMvasnrtDPLGQQTFLSARHVLDCS--QYGQGCAGGF 283

                          90       100
                  ....*....|....*....|....
gi 1843978404 183 MDYAFQYVQDNGGLdSEESY--PY 204
Cdd:PTZ00364  284 PEEVGKFAETFGIL-TTDSYyiPY 306
PTZ00462 PTZ00462
Serine-repeat antigen protein; Provisional
 129-211 1.35e-03

Serine-repeat antigen protein; Provisional


Pssm-ID: 185641 [Multi-domain]  Cd Length: 1004  Bit Score: 40.04  E-value: 1.35e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843978404  129 VKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSGPQGNEGCNGGLMDYAF-QYVQDNGGLDSEESYPYEAT 207
Cdd:PTZ00462   547 IEDQGNCAISWIFASKYHLETIKCMKGYEPHAISALYIANCSKGEHKDRCDEGSNPLEFlQIIEDNGFLPADSNYLYNYT 626


                   ....*.
gi 1843978404  208 E--ESC 211
Cdd:PTZ00462   627 KvgEDC 632
 
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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