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Conserved domains on  [gi|1393428373|ref|NP_001350628|]
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legumain isoform 3 precursor [Homo sapiens]

Protein Classification

C13 family peptidase( domain architecture ID 15870986)

C13 family peptidase similar to human legumain that has a strict specificity for hydrolysis of asparaginyl bonds

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Peptidase_C13 pfam01650
Peptidase C13 family; Members of this family are asparaginyl peptidases. The blood fluke ...
29-285 1.82e-160

Peptidase C13 family; Members of this family are asparaginyl peptidases. The blood fluke parasite Schistosoma mansoni has at least five Clan CA cysteine peptidases in its digestive tract including cathepsins B (2 isoforms), C, F and L. All have been recombinantly expressed as active enzymes, albeit in various stages of activation. In addition, a Clan CD peptidase, termed asparaginyl endopeptidase or 'legumain' has been identified. This has formerly been characterized as a 'haemoglobinase', but this term is probably incorrect. Two cDNAs have been described for Schistosoma mansoni legumain; one encodes an active enzyme whereas the active site cysteine residue encoded by the second cDNA is substituted by an asparagine residue. Both forms have been recombinantly expressed.


:

Pssm-ID: 396290  Cd Length: 257  Bit Score: 450.20  E-value: 1.82e-160
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428373  29 HWVVIVAGSNGWYNYRHQADACHAYQIIHRNGIPDEQIVVMMYDDIAYSEDNPTPGIVINRPNGTDVYQGVPKDYTGEDV 108
Cdd:pfam01650   1 LWAVLVAGSNGYYNYRHQADVCHAYQLLKKFGIKDENIIVMMYDDIANNPENPFPGKIFNKPNGTDVYKGVPKDYTGNDV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428373 109 TPQNFLAVLRGDAEAVkgiGSGKVLKSGPQDHVFIYFTDHGSTGILVFPNED-LHVKDLNETIHYMYKHKMYRKMVFYIE 187
Cdd:pfam01650  81 TPRNFLAVLLGDKSAL---GSGKVLKSGPNDNVFIYFTDHGAPGVLGFPELDyLYAKDLAEALKKMHARGKYKKLVFYVE 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428373 188 ACESGSMMNHLPDNINVYATTAANPRESSYACYY-DEKRSTYLGDWYSVNWMEDSDVEDLTKETLHKQYHLVKSHTNTSH 266
Cdd:pfam01650 158 ACESGSMFEGLPKDINVYATTAANADESSYGCYCpDPEDGTYLGDLFSVNWMEDSDDHDLSKETLEQQFELVKNRTTGSH 237
                         250
                  ....*....|....*....
gi 1393428373 267 VMQYGNKTISTMKVMQFQG 285
Cdd:pfam01650 238 VMQYGDKSLPQLPLSLFQG 256
legumain_C super family cl41234
C-terminal prodomain of legumain; This family contains the C-terminal propeptide of legumain, ...
309-342 3.75e-06

C-terminal prodomain of legumain; This family contains the C-terminal propeptide of legumain, a lysosomal endopeptidase with a specificity for hydrolysis of asparaginyl bonds. Legumain (also called vacuolar processing enzyme or VPE in plants, and asparaginyl endopeptidase or AEP in animals) is synthesized as a precursor with both N- and C-terminal propeptides. Prolegumain is directed to the lysosome or plant vacuole, where activation occurs at least partially by autolysis. The N-terminal catalytic domain is a cysteine protease from the C13 family. The C-terminal prodomain can be organized into an activation peptide (AP), spanning a helical region, and a C-terminal death domain-like fold, denoted as legumain stabilization and activity modulation (LSAM) domain. The C-terminal prodomain binds over the active site and inhibits the catalytic domain. During activation, the C-terminal prodomain is autocatalytically cleaved. This process is induced by pH changes. Human legumain has been shown to process the tetanus toxin generating the fragments found in class II antigen presentation. Legumain from plant seeds is thought to be responsible for the post-translational processing of seed proteins prior to storage. Legumain is highly expressed in some cancers such as colorectal cancer (CRC) and uveal melanoma (UM); it is associated with poor outcome in CRC and upregulation of legumain is associated with malignant behavior of UM. Thus, legumain may be used as a negative prognostic factor as well as a therapeutic target.


The actual alignment was detected with superfamily member cd21115:

Pssm-ID: 411051  Cd Length: 119  Bit Score: 45.36  E-value: 3.75e-06
                          10        20        30
                  ....*....|....*....|....*....|....
gi 1393428373 309 DVPLTIMKRKLMNTNDLEESRQLTEEIQRHLDDK 342
Cdd:cd21115     1 DVPLAILKRKLKKANDPEEKEELKKELEKLLQKR 34
 
Name Accession Description Interval E-value
Peptidase_C13 pfam01650
Peptidase C13 family; Members of this family are asparaginyl peptidases. The blood fluke ...
29-285 1.82e-160

Peptidase C13 family; Members of this family are asparaginyl peptidases. The blood fluke parasite Schistosoma mansoni has at least five Clan CA cysteine peptidases in its digestive tract including cathepsins B (2 isoforms), C, F and L. All have been recombinantly expressed as active enzymes, albeit in various stages of activation. In addition, a Clan CD peptidase, termed asparaginyl endopeptidase or 'legumain' has been identified. This has formerly been characterized as a 'haemoglobinase', but this term is probably incorrect. Two cDNAs have been described for Schistosoma mansoni legumain; one encodes an active enzyme whereas the active site cysteine residue encoded by the second cDNA is substituted by an asparagine residue. Both forms have been recombinantly expressed.


Pssm-ID: 396290  Cd Length: 257  Bit Score: 450.20  E-value: 1.82e-160
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428373  29 HWVVIVAGSNGWYNYRHQADACHAYQIIHRNGIPDEQIVVMMYDDIAYSEDNPTPGIVINRPNGTDVYQGVPKDYTGEDV 108
Cdd:pfam01650   1 LWAVLVAGSNGYYNYRHQADVCHAYQLLKKFGIKDENIIVMMYDDIANNPENPFPGKIFNKPNGTDVYKGVPKDYTGNDV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428373 109 TPQNFLAVLRGDAEAVkgiGSGKVLKSGPQDHVFIYFTDHGSTGILVFPNED-LHVKDLNETIHYMYKHKMYRKMVFYIE 187
Cdd:pfam01650  81 TPRNFLAVLLGDKSAL---GSGKVLKSGPNDNVFIYFTDHGAPGVLGFPELDyLYAKDLAEALKKMHARGKYKKLVFYVE 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428373 188 ACESGSMMNHLPDNINVYATTAANPRESSYACYY-DEKRSTYLGDWYSVNWMEDSDVEDLTKETLHKQYHLVKSHTNTSH 266
Cdd:pfam01650 158 ACESGSMFEGLPKDINVYATTAANADESSYGCYCpDPEDGTYLGDLFSVNWMEDSDDHDLSKETLEQQFELVKNRTTGSH 237
                         250
                  ....*....|....*....
gi 1393428373 267 VMQYGNKTISTMKVMQFQG 285
Cdd:pfam01650 238 VMQYGDKSLPQLPLSLFQG 256
legumain_C cd21115
C-terminal prodomain of legumain; This family contains the C-terminal propeptide of legumain, ...
309-342 3.75e-06

C-terminal prodomain of legumain; This family contains the C-terminal propeptide of legumain, a lysosomal endopeptidase with a specificity for hydrolysis of asparaginyl bonds. Legumain (also called vacuolar processing enzyme or VPE in plants, and asparaginyl endopeptidase or AEP in animals) is synthesized as a precursor with both N- and C-terminal propeptides. Prolegumain is directed to the lysosome or plant vacuole, where activation occurs at least partially by autolysis. The N-terminal catalytic domain is a cysteine protease from the C13 family. The C-terminal prodomain can be organized into an activation peptide (AP), spanning a helical region, and a C-terminal death domain-like fold, denoted as legumain stabilization and activity modulation (LSAM) domain. The C-terminal prodomain binds over the active site and inhibits the catalytic domain. During activation, the C-terminal prodomain is autocatalytically cleaved. This process is induced by pH changes. Human legumain has been shown to process the tetanus toxin generating the fragments found in class II antigen presentation. Legumain from plant seeds is thought to be responsible for the post-translational processing of seed proteins prior to storage. Legumain is highly expressed in some cancers such as colorectal cancer (CRC) and uveal melanoma (UM); it is associated with poor outcome in CRC and upregulation of legumain is associated with malignant behavior of UM. Thus, legumain may be used as a negative prognostic factor as well as a therapeutic target.


Pssm-ID: 411051  Cd Length: 119  Bit Score: 45.36  E-value: 3.75e-06
                          10        20        30
                  ....*....|....*....|....*....|....
gi 1393428373 309 DVPLTIMKRKLMNTNDLEESRQLTEEIQRHLDDK 342
Cdd:cd21115     1 DVPLAILKRKLKKANDPEEKEELKKELEKLLQKR 34
 
Name Accession Description Interval E-value
Peptidase_C13 pfam01650
Peptidase C13 family; Members of this family are asparaginyl peptidases. The blood fluke ...
29-285 1.82e-160

Peptidase C13 family; Members of this family are asparaginyl peptidases. The blood fluke parasite Schistosoma mansoni has at least five Clan CA cysteine peptidases in its digestive tract including cathepsins B (2 isoforms), C, F and L. All have been recombinantly expressed as active enzymes, albeit in various stages of activation. In addition, a Clan CD peptidase, termed asparaginyl endopeptidase or 'legumain' has been identified. This has formerly been characterized as a 'haemoglobinase', but this term is probably incorrect. Two cDNAs have been described for Schistosoma mansoni legumain; one encodes an active enzyme whereas the active site cysteine residue encoded by the second cDNA is substituted by an asparagine residue. Both forms have been recombinantly expressed.


Pssm-ID: 396290  Cd Length: 257  Bit Score: 450.20  E-value: 1.82e-160
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428373  29 HWVVIVAGSNGWYNYRHQADACHAYQIIHRNGIPDEQIVVMMYDDIAYSEDNPTPGIVINRPNGTDVYQGVPKDYTGEDV 108
Cdd:pfam01650   1 LWAVLVAGSNGYYNYRHQADVCHAYQLLKKFGIKDENIIVMMYDDIANNPENPFPGKIFNKPNGTDVYKGVPKDYTGNDV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428373 109 TPQNFLAVLRGDAEAVkgiGSGKVLKSGPQDHVFIYFTDHGSTGILVFPNED-LHVKDLNETIHYMYKHKMYRKMVFYIE 187
Cdd:pfam01650  81 TPRNFLAVLLGDKSAL---GSGKVLKSGPNDNVFIYFTDHGAPGVLGFPELDyLYAKDLAEALKKMHARGKYKKLVFYVE 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428373 188 ACESGSMMNHLPDNINVYATTAANPRESSYACYY-DEKRSTYLGDWYSVNWMEDSDVEDLTKETLHKQYHLVKSHTNTSH 266
Cdd:pfam01650 158 ACESGSMFEGLPKDINVYATTAANADESSYGCYCpDPEDGTYLGDLFSVNWMEDSDDHDLSKETLEQQFELVKNRTTGSH 237
                         250
                  ....*....|....*....
gi 1393428373 267 VMQYGNKTISTMKVMQFQG 285
Cdd:pfam01650 238 VMQYGDKSLPQLPLSLFQG 256
legumain_C cd21115
C-terminal prodomain of legumain; This family contains the C-terminal propeptide of legumain, ...
309-342 3.75e-06

C-terminal prodomain of legumain; This family contains the C-terminal propeptide of legumain, a lysosomal endopeptidase with a specificity for hydrolysis of asparaginyl bonds. Legumain (also called vacuolar processing enzyme or VPE in plants, and asparaginyl endopeptidase or AEP in animals) is synthesized as a precursor with both N- and C-terminal propeptides. Prolegumain is directed to the lysosome or plant vacuole, where activation occurs at least partially by autolysis. The N-terminal catalytic domain is a cysteine protease from the C13 family. The C-terminal prodomain can be organized into an activation peptide (AP), spanning a helical region, and a C-terminal death domain-like fold, denoted as legumain stabilization and activity modulation (LSAM) domain. The C-terminal prodomain binds over the active site and inhibits the catalytic domain. During activation, the C-terminal prodomain is autocatalytically cleaved. This process is induced by pH changes. Human legumain has been shown to process the tetanus toxin generating the fragments found in class II antigen presentation. Legumain from plant seeds is thought to be responsible for the post-translational processing of seed proteins prior to storage. Legumain is highly expressed in some cancers such as colorectal cancer (CRC) and uveal melanoma (UM); it is associated with poor outcome in CRC and upregulation of legumain is associated with malignant behavior of UM. Thus, legumain may be used as a negative prognostic factor as well as a therapeutic target.


Pssm-ID: 411051  Cd Length: 119  Bit Score: 45.36  E-value: 3.75e-06
                          10        20        30
                  ....*....|....*....|....*....|....
gi 1393428373 309 DVPLTIMKRKLMNTNDLEESRQLTEEIQRHLDDK 342
Cdd:cd21115     1 DVPLAILKRKLKKANDPEEKEELKKELEKLLQKR 34
 
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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