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Conserved domains on  [gi|1622826021|ref|XP_028701997|]
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nicastrin isoform X1 [Macaca mulatta]

Protein Classification

nicastrin( domain architecture ID 10133853)

nicastrin is an essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein)

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
M28_Nicastrin cd03881
M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex; Peptidase M28 family, ...
2-560 0e+00

M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex; Peptidase M28 family, nicastrin subfamily. Nicastrin is a main component of the gamma-secretase complex, which also contains presenilin, Pen-2 and Aph-1. Its extracellular domain sequence resembles aminopeptidases, but certain catalytic residues are not conserved. It is mainly localized to the endoplasmic reticulum and Golgi. It is highly glycosylated (Mr 120 kDa) and is essential for substrate recognition of the N-terminus of gamma-secretase substrates derived from APP and Notch. Nicastrin facilitates substrate cleavage by the catalytic presenilin subunit in the gamma-secretase complex. One conserved glutamate is especially important, probably because this residue forms an ion pair with the amino terminus of the substrate. This substrate-binding domain is often called the DAP domain (named after DYIGS, the amino acid stretch that modulates amyloid precursor protein (APP) processing, and Peptidase homologous region). The sequence of the substrate N-terminus is apparently not critical for the interaction, but a free amino group is. Thus, nicastrin can be considered a kind of gatekeeper for the gamma-secretase complex: type I membrane proteins that have not shed their ectodomains cannot interact properly with nicastrin and do not gain access to the active site. Dysfunction of gamma-secretase is thought to cause Alzheimer's disease, with most mutations derived from Alzheimer's disease mapping to the catalytic subunit presenilin 1 (PS1).


:

Pssm-ID: 349877 [Multi-domain]  Cd Length: 519  Bit Score: 604.41  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021   2 VLLESKLFTRDLMEKLKGRtSRIAGLAVSLTKPNPASGFSPSVQCPNDGFGVYSnsygpefahCREIQWNSLGNGLAYED 81
Cdd:cd03881    50 VVLDPNLFNRDNVLSLKSK-KKINGVLVLISKTSPLKGFSPDSRCPNAQFGLYS---------NSNYNWNPNGNGLMYED 119
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021  82 FSFPIFLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIqstfsinPEIVCDPLSDYN 161
Cdd:cd03881   120 FPFPIFYLEDSTETQVLEKCYEDFNKPVNGSTPLYPLCGMELDSFMSAAINTETCLRRGSI-------PEKFCDPLGGYN 192
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 162 VWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETF 241
Cdd:cd03881   193 VWSSLPPINTSWEVKTSKKIVLVAARMDSTSFFRDVAPGADSSLSGFVALLAAAEALKKVDGKGSLKRNVVFAFFNGESW 272
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 242 DYIGSSRMVYDMEKGKF------------PVQLENVDSFVELGQVALRTSLELWMHTDPVSQkNDSVRNQVEDLLVTLEK 309
Cdd:cd03881   273 GYIGSSRFVYDMENGKFptygskddlfffPISFENIDTILEVGQVGLALGAKLYAHTDGVST-NSSVTQQLLDALSNSLK 351
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 310 SGAgvpAVILRRPNQSQPLPPSSLQRFLRA-RNISGVVLADHSGAFHNKYYQSIYDTAENINVsypewlspeedlnfvtD 388
Cdd:cd03881   352 SLA---FTILSAPASSPGLPPSSLMSFLRAdPNIPGVVLTDHDKAFTNKYYHSIYDDAENVNV----------------D 412
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 389 TAKALADVATVLGRALYELAGGtnfsdtvqadpqtvtrllygflikannswfqsilrqdlrsylgdgplqhyiavssptN 468
Cdd:cd03881   413 TASSVAEVASVVARSLYTLAGG---------------------------------------------------------N 435
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 469 TTYVVQYALANLTGTVVNLTREQCQDPSKvpsenkdlyeysWVQGPLNSNETDRLPRCVRSTARLARALSPAF---ELSQ 545
Cdd:cd03881   436 TTRFVGYFLANLTGTVTNATNDVCQNPCK------------NVDEVCIGAGTSRLGECVKSTTRYSPALSPAFkfnEPSD 503
                         570
                  ....*....|....*.
gi 1622826021 546 WSST-EYSTWTESRWK 560
Cdd:cd03881   504 WMSTnRYSTWTESFWI 519
 
Name Accession Description Interval E-value
M28_Nicastrin cd03881
M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex; Peptidase M28 family, ...
2-560 0e+00

M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex; Peptidase M28 family, nicastrin subfamily. Nicastrin is a main component of the gamma-secretase complex, which also contains presenilin, Pen-2 and Aph-1. Its extracellular domain sequence resembles aminopeptidases, but certain catalytic residues are not conserved. It is mainly localized to the endoplasmic reticulum and Golgi. It is highly glycosylated (Mr 120 kDa) and is essential for substrate recognition of the N-terminus of gamma-secretase substrates derived from APP and Notch. Nicastrin facilitates substrate cleavage by the catalytic presenilin subunit in the gamma-secretase complex. One conserved glutamate is especially important, probably because this residue forms an ion pair with the amino terminus of the substrate. This substrate-binding domain is often called the DAP domain (named after DYIGS, the amino acid stretch that modulates amyloid precursor protein (APP) processing, and Peptidase homologous region). The sequence of the substrate N-terminus is apparently not critical for the interaction, but a free amino group is. Thus, nicastrin can be considered a kind of gatekeeper for the gamma-secretase complex: type I membrane proteins that have not shed their ectodomains cannot interact properly with nicastrin and do not gain access to the active site. Dysfunction of gamma-secretase is thought to cause Alzheimer's disease, with most mutations derived from Alzheimer's disease mapping to the catalytic subunit presenilin 1 (PS1).


Pssm-ID: 349877 [Multi-domain]  Cd Length: 519  Bit Score: 604.41  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021   2 VLLESKLFTRDLMEKLKGRtSRIAGLAVSLTKPNPASGFSPSVQCPNDGFGVYSnsygpefahCREIQWNSLGNGLAYED 81
Cdd:cd03881    50 VVLDPNLFNRDNVLSLKSK-KKINGVLVLISKTSPLKGFSPDSRCPNAQFGLYS---------NSNYNWNPNGNGLMYED 119
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021  82 FSFPIFLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIqstfsinPEIVCDPLSDYN 161
Cdd:cd03881   120 FPFPIFYLEDSTETQVLEKCYEDFNKPVNGSTPLYPLCGMELDSFMSAAINTETCLRRGSI-------PEKFCDPLGGYN 192
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 162 VWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETF 241
Cdd:cd03881   193 VWSSLPPINTSWEVKTSKKIVLVAARMDSTSFFRDVAPGADSSLSGFVALLAAAEALKKVDGKGSLKRNVVFAFFNGESW 272
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 242 DYIGSSRMVYDMEKGKF------------PVQLENVDSFVELGQVALRTSLELWMHTDPVSQkNDSVRNQVEDLLVTLEK 309
Cdd:cd03881   273 GYIGSSRFVYDMENGKFptygskddlfffPISFENIDTILEVGQVGLALGAKLYAHTDGVST-NSSVTQQLLDALSNSLK 351
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 310 SGAgvpAVILRRPNQSQPLPPSSLQRFLRA-RNISGVVLADHSGAFHNKYYQSIYDTAENINVsypewlspeedlnfvtD 388
Cdd:cd03881   352 SLA---FTILSAPASSPGLPPSSLMSFLRAdPNIPGVVLTDHDKAFTNKYYHSIYDDAENVNV----------------D 412
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 389 TAKALADVATVLGRALYELAGGtnfsdtvqadpqtvtrllygflikannswfqsilrqdlrsylgdgplqhyiavssptN 468
Cdd:cd03881   413 TASSVAEVASVVARSLYTLAGG---------------------------------------------------------N 435
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 469 TTYVVQYALANLTGTVVNLTREQCQDPSKvpsenkdlyeysWVQGPLNSNETDRLPRCVRSTARLARALSPAF---ELSQ 545
Cdd:cd03881   436 TTRFVGYFLANLTGTVTNATNDVCQNPCK------------NVDEVCIGAGTSRLGECVKSTTRYSPALSPAFkfnEPSD 503
                         570
                  ....*....|....*.
gi 1622826021 546 WSST-EYSTWTESRWK 560
Cdd:cd03881   504 WMSTnRYSTWTESFWI 519
Nicastrin pfam05450
Nicastrin; Nicastrin and presenilin are two major components of the gamma-secretase complex, ...
180-405 5.25e-95

Nicastrin; Nicastrin and presenilin are two major components of the gamma-secretase complex, which executes the intramembrane proteolysis of type I integral membrane proteins such as the amyloid precursor protein (APP) and Notch. Nicastrin is synthesized in fibroblasts and neurons as an endoglycosidase-H-sensitive glycosylated precursor protein (immature nicastrin) and is then modified by complex glycosylation in the Golgi apparatus and by sialylation in the trans-Golgi network (mature nicastrin). A region featured in this family has a fold similar to human transferrin receptor (TfR) and a bacterial aminopeptidase. It is implicated in the pathogenesis of Alzheimer's disease.


Pssm-ID: 310213 [Multi-domain]  Cd Length: 227  Bit Score: 290.99  E-value: 5.25e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 180 RVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKA-PDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKF 258
Cdd:pfam05450   1 KVVLVTARMDSTSMFDGVSLGAMSSLSGFIVLLAAADALSKAlPDISNLKRNVLFAFFNGESYDYIGSQRFVYDMENGKF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 259 P--------VQLENVDSFVELGQVALRTSLELWMHTDpvSQKNDSVRNQVEDLLVTLEKSGAGVPAVILRRPNQSQPLPP 330
Cdd:pfam05450  81 PsdrththpISPDNIDYMLEIGQVGKATSRKFYLHVD--AARNQSVKTQTLDLLDRIEKSLRSGNFKVLPASTSNPGLPP 158
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622826021 331 SSLQRFLRAR-NISGVVLADHSGAFHNKYYQSIYDTAENINvsypewlSPEEDLNFVTDTAKALADVATVLGRALY 405
Cdd:pfam05450 159 SSLQSFLRANpNFSAVVLADRPTEFENRFYHSILDDAENIN-------SDTEDLNEKDSQQMSVVNAASLVARALY 227
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
160-408 7.09e-08

Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein turnover, chaperones, Amino acid transport and metabolism];


Pssm-ID: 441835 [Multi-domain]  Cd Length: 257  Bit Score: 53.98  E-value: 7.09e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 160 YNVWSMLKpinttGTLKPDDRVVVAAtRLDSRSffwNVAPGAE---SAVAsfvTQLAAAEALQKAPDvtTLPRNVMFVFF 236
Cdd:COG2234    47 RNVIAEIP-----GTDPPDEVVVLGA-HYDSVG---SIGPGADdnaSGVA---ALLELARALAALGP--KPKRTIRFVAF 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 237 QGETFDYIGSSRMVydmekGKFPVQLENVDSFVELGQV-ALRTSLELWMHTDpvsQKNDSVRNQVEDLlvtLEKSGAGVP 315
Cdd:COG2234   113 GAEEQGLLGSRYYA-----ENLKAPLEKIVAVLNLDMIgRGGPRNYLYVDGD---GGSPELADLLEAA---AKAYLPGLG 181
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 316 AVilrrPNQSQPLPPSSLQRFLRARNISGVVLADHSGAFHnKYYQSIYDTAENINvsypewlspeedlnfvtdtAKALAD 395
Cdd:COG2234   182 VD----PPEETGGYGRSDHAPFAKAGIPALFLFTGAEDYH-PDYHTPSDTLDKID-------------------LDALAK 237
                         250
                  ....*....|...
gi 1622826021 396 VATVLGRALYELA 408
Cdd:COG2234   238 VAQLLAALVYELA 250
 
Name Accession Description Interval E-value
M28_Nicastrin cd03881
M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex; Peptidase M28 family, ...
2-560 0e+00

M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex; Peptidase M28 family, nicastrin subfamily. Nicastrin is a main component of the gamma-secretase complex, which also contains presenilin, Pen-2 and Aph-1. Its extracellular domain sequence resembles aminopeptidases, but certain catalytic residues are not conserved. It is mainly localized to the endoplasmic reticulum and Golgi. It is highly glycosylated (Mr 120 kDa) and is essential for substrate recognition of the N-terminus of gamma-secretase substrates derived from APP and Notch. Nicastrin facilitates substrate cleavage by the catalytic presenilin subunit in the gamma-secretase complex. One conserved glutamate is especially important, probably because this residue forms an ion pair with the amino terminus of the substrate. This substrate-binding domain is often called the DAP domain (named after DYIGS, the amino acid stretch that modulates amyloid precursor protein (APP) processing, and Peptidase homologous region). The sequence of the substrate N-terminus is apparently not critical for the interaction, but a free amino group is. Thus, nicastrin can be considered a kind of gatekeeper for the gamma-secretase complex: type I membrane proteins that have not shed their ectodomains cannot interact properly with nicastrin and do not gain access to the active site. Dysfunction of gamma-secretase is thought to cause Alzheimer's disease, with most mutations derived from Alzheimer's disease mapping to the catalytic subunit presenilin 1 (PS1).


Pssm-ID: 349877 [Multi-domain]  Cd Length: 519  Bit Score: 604.41  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021   2 VLLESKLFTRDLMEKLKGRtSRIAGLAVSLTKPNPASGFSPSVQCPNDGFGVYSnsygpefahCREIQWNSLGNGLAYED 81
Cdd:cd03881    50 VVLDPNLFNRDNVLSLKSK-KKINGVLVLISKTSPLKGFSPDSRCPNAQFGLYS---------NSNYNWNPNGNGLMYED 119
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021  82 FSFPIFLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIqstfsinPEIVCDPLSDYN 161
Cdd:cd03881   120 FPFPIFYLEDSTETQVLEKCYEDFNKPVNGSTPLYPLCGMELDSFMSAAINTETCLRRGSI-------PEKFCDPLGGYN 192
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 162 VWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETF 241
Cdd:cd03881   193 VWSSLPPINTSWEVKTSKKIVLVAARMDSTSFFRDVAPGADSSLSGFVALLAAAEALKKVDGKGSLKRNVVFAFFNGESW 272
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 242 DYIGSSRMVYDMEKGKF------------PVQLENVDSFVELGQVALRTSLELWMHTDPVSQkNDSVRNQVEDLLVTLEK 309
Cdd:cd03881   273 GYIGSSRFVYDMENGKFptygskddlfffPISFENIDTILEVGQVGLALGAKLYAHTDGVST-NSSVTQQLLDALSNSLK 351
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 310 SGAgvpAVILRRPNQSQPLPPSSLQRFLRA-RNISGVVLADHSGAFHNKYYQSIYDTAENINVsypewlspeedlnfvtD 388
Cdd:cd03881   352 SLA---FTILSAPASSPGLPPSSLMSFLRAdPNIPGVVLTDHDKAFTNKYYHSIYDDAENVNV----------------D 412
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 389 TAKALADVATVLGRALYELAGGtnfsdtvqadpqtvtrllygflikannswfqsilrqdlrsylgdgplqhyiavssptN 468
Cdd:cd03881   413 TASSVAEVASVVARSLYTLAGG---------------------------------------------------------N 435
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 469 TTYVVQYALANLTGTVVNLTREQCQDPSKvpsenkdlyeysWVQGPLNSNETDRLPRCVRSTARLARALSPAF---ELSQ 545
Cdd:cd03881   436 TTRFVGYFLANLTGTVTNATNDVCQNPCK------------NVDEVCIGAGTSRLGECVKSTTRYSPALSPAFkfnEPSD 503
                         570
                  ....*....|....*.
gi 1622826021 546 WSST-EYSTWTESRWK 560
Cdd:cd03881   504 WMSTnRYSTWTESFWI 519
Nicastrin pfam05450
Nicastrin; Nicastrin and presenilin are two major components of the gamma-secretase complex, ...
180-405 5.25e-95

Nicastrin; Nicastrin and presenilin are two major components of the gamma-secretase complex, which executes the intramembrane proteolysis of type I integral membrane proteins such as the amyloid precursor protein (APP) and Notch. Nicastrin is synthesized in fibroblasts and neurons as an endoglycosidase-H-sensitive glycosylated precursor protein (immature nicastrin) and is then modified by complex glycosylation in the Golgi apparatus and by sialylation in the trans-Golgi network (mature nicastrin). A region featured in this family has a fold similar to human transferrin receptor (TfR) and a bacterial aminopeptidase. It is implicated in the pathogenesis of Alzheimer's disease.


Pssm-ID: 310213 [Multi-domain]  Cd Length: 227  Bit Score: 290.99  E-value: 5.25e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 180 RVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKA-PDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKF 258
Cdd:pfam05450   1 KVVLVTARMDSTSMFDGVSLGAMSSLSGFIVLLAAADALSKAlPDISNLKRNVLFAFFNGESYDYIGSQRFVYDMENGKF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 259 P--------VQLENVDSFVELGQVALRTSLELWMHTDpvSQKNDSVRNQVEDLLVTLEKSGAGVPAVILRRPNQSQPLPP 330
Cdd:pfam05450  81 PsdrththpISPDNIDYMLEIGQVGKATSRKFYLHVD--AARNQSVKTQTLDLLDRIEKSLRSGNFKVLPASTSNPGLPP 158
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622826021 331 SSLQRFLRAR-NISGVVLADHSGAFHNKYYQSIYDTAENINvsypewlSPEEDLNFVTDTAKALADVATVLGRALY 405
Cdd:pfam05450 159 SSLQSFLRANpNFSAVVLADRPTEFENRFYHSILDDAENIN-------SDTEDLNEKDSQQMSVVNAASLVARALY 227
Ncstrn_small pfam18266
Nicastrin small lobe; This domain is part of the protein Nicastrin, a component of gamma ...
1-129 1.42e-40

Nicastrin small lobe; This domain is part of the protein Nicastrin, a component of gamma secretase present in Homo sapiens. Gamma-secretase is thought to contribute to Alzheimer's disease development by generating beta-amyloid peptides. This domain is the known as the small lobe which forms the 'lid'. The lid is an extended surface loop that covers the hydrophilic pocket that is thought to be responsible for substrate recruitment. On substrate binding, the large lobe is thought to rotate relative to the small lobe.


Pssm-ID: 465690  Cd Length: 167  Bit Score: 145.08  E-value: 1.42e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021   1 MVLLESKLFTRDLMEKLKGrTSRIAGLAV-SLTKPNPASGFSPSVQCPNDGFGvysnsygpeFAHC-REIQWNSLGNGLA 78
Cdd:pfam18266  47 AVLLPPDLFTRDNIERLRS-SGKVAGVLVlSNTTTEPPTGFSPDSKCPNAEFG---------LAYCnATYEWNPAGSGLL 116
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1622826021  79 YEDFSFPIFLLEDENETKVIKQ-CYQDHNLsQNGSAPTFPLCAMQLFSHMHA 129
Cdd:pfam18266 117 YEDFPFPIFLLSNSTETEAIREaCYENFNL-DNGSYGGYPLCAAEFDSFMQA 167
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
160-407 7.10e-12

M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also called aminopeptidase Y family) contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. The aminopeptidases in this family are also called bacterial leucyl aminopeptidases, but are able to release a variety of N-terminal amino acids. IAP aminopeptidase and aminopeptidase Y preferentially release basic amino acids while glutamate carboxypeptidase II preferentially releases C-terminal glutamates. Plasma glutamate carboxypeptidase (PGCP) and glutamate carboxypeptidase II (NAALADase) hydrolyze dipeptides. Several members of the M28 peptidase family have PA domain inserts which may participate in substrate binding and/or in promoting conformational changes, which influence the stability and accessibility of the site to substrate. These include prostate-specific membrane antigen (PSMA), yeast aminopeptidase S (SGAP), human transferrin receptors (TfR1 and TfR2), plasma glutamate carboxypeptidase (PGCP) and several predicted aminopeptidases where relatively little is known about them. Also included in the M28 family are glutaminyl cyclases (QC), which are involved in N-terminal glutamine cyclization of many endocrine peptides. Nicastrin and nicalin belong to this family but lack the amino-acid conservation required for catalytically active aminopeptidases.


Pssm-ID: 349868 [Multi-domain]  Cd Length: 202  Bit Score: 65.06  E-value: 7.10e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 160 YNVWSMLKpinttGTLKPDDRVVVAAtRLDSrsffWNVAPGAESAVASFVTQLAAAEALQKAPDVTtlPRNVMFVFFQGE 239
Cdd:cd02690     2 YNVIATIK-----GSDKPDEVILIGA-HYDS----VPLSPGANDNASGVAVLLELARVLSKLQLKP--KRSIRFAFWDAE 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 240 TFDYIGSSRMVYDMekgkfPVQLENVDSFVELGQVAlRTSLELWMHTDPVSQKNdsvrnqVEDLLVTLEKSGAGVPAVIL 319
Cdd:cd02690    70 ELGLLGSKYYAEQL-----LSSLKNIRAALNLDMIG-GAGPDLYLQTAPGNDAL------VEKLLRALAHELENVVYTVV 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 320 rrpNQSQPLPPSSLQRFLRARNISGVVLADHSGAFhNKYYQSIYDTAENINvsypewlspeedlnfvtdtAKALADVATV 399
Cdd:cd02690   138 ---YKEDGGTGGSDHRPFLARGIPAASLIQSESYN-FPYYHTTQDTLENID-------------------KDTLKRAGDI 194

                  ....*...
gi 1622826021 400 LGRALYEL 407
Cdd:cd02690   195 LASFLYRL 202
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
160-408 7.09e-08

Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein turnover, chaperones, Amino acid transport and metabolism];


Pssm-ID: 441835 [Multi-domain]  Cd Length: 257  Bit Score: 53.98  E-value: 7.09e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 160 YNVWSMLKpinttGTLKPDDRVVVAAtRLDSRSffwNVAPGAE---SAVAsfvTQLAAAEALQKAPDvtTLPRNVMFVFF 236
Cdd:COG2234    47 RNVIAEIP-----GTDPPDEVVVLGA-HYDSVG---SIGPGADdnaSGVA---ALLELARALAALGP--KPKRTIRFVAF 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 237 QGETFDYIGSSRMVydmekGKFPVQLENVDSFVELGQV-ALRTSLELWMHTDpvsQKNDSVRNQVEDLlvtLEKSGAGVP 315
Cdd:COG2234   113 GAEEQGLLGSRYYA-----ENLKAPLEKIVAVLNLDMIgRGGPRNYLYVDGD---GGSPELADLLEAA---AKAYLPGLG 181
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 316 AVilrrPNQSQPLPPSSLQRFLRARNISGVVLADHSGAFHnKYYQSIYDTAENINvsypewlspeedlnfvtdtAKALAD 395
Cdd:COG2234   182 VD----PPEETGGYGRSDHAPFAKAGIPALFLFTGAEDYH-PDYHTPSDTLDKID-------------------LDALAK 237
                         250
                  ....*....|...
gi 1622826021 396 VATVLGRALYELA 408
Cdd:COG2234   238 VAQLLAALVYELA 250
Peptidase_M28 pfam04389
Peptidase family M28;
170-370 2.69e-05

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 45.35  E-value: 2.69e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 170 NTTGTLKP---DDRVVVAAtRLDSRSFfwnvAPGAE---SAVAsfvTQLAAAEALQKApdvTTLPRNVMFVFFQGETFDY 243
Cdd:pfam04389   1 NVIAKLPGkapDEVVLLSA-HYDSVGT----GPGADdnaSGVA---ALLELARVLAAG---QRPKRSVRFLFFDAEEAGL 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622826021 244 IGSSRMVYDMEKGKfpvqleNVDSFVELGQVALRTSLELWMHTDPVSqkndsvrnqvEDLLVTLEKSGAGVPAVILRRPN 323
Cdd:pfam04389  70 LGSHHFAKSHPPLK------KIRAVINLDMIGSGGPALLFQSGPKGS----------SLLEKYLKAAAKPYGVTLAEDPF 133
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1622826021 324 QSQPLPPSSLQRFLRARNISGVVLADHsgAFHNKYYQSiYDTAENIN 370
Cdd:pfam04389 134 QERGGPGRSDHAPFIKAGIPGLDLAFT--DFGYRYHTP-ADTIDNID 177
 
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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