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Conserved domains on  [gi|530364490|ref|XP_005245110|]
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nicastrin isoform X1 [Homo sapiens]

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)

CATH:  3.40.630.10
Gene Ontology:  GO:0042500|GO:0016485|GO:0051117|GO:0070851|GO:0030674|GO:0007219|GO:0042983
MEROPS:  M28
PubMed:  7674922|18429165|12773192

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, ...
 52-393 7.98e-170

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: 485.00  E-value: 7.98e-170
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490  52 RLLNATHQIGCQSSISGDTGVIHV-VEKEEDLQWVLTDGPNPPYMVL----LESKHFTRDLMEKLKGRtSRIAGLAVSLT 126
Cdd:cd03881    1 RSLNGTHQIGCQSNLSGEIGCSHLgVNSQEDLDLVLSKSPHPPYSVLqqvvLDPNLFNRDNVLSLKSK-KKINGVLVLIS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 127 KPSPASGFSPSVQCPNDGFGVYSnsygpefahCREIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLSQNGS 206
Cdd:cd03881   80 KTSPLKGFSPDSRCPNAQFGLYS---------NSNYNWNPNGNGLMYEDFPFPIFYLEDSTETQVLEKCYEDFNKPVNGS 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 207 APTFPLCAMQLFSHMHAVISTATCMRRSSIqstfsinPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRS 286
Cdd:cd03881  151 TPLYPLCGMELDSFMSAAINTETCLRRGSI-------PEKFCDPLGGYNVWSSLPPINTSWEVKTSKKIVLVAARMDSTS 223

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 287 FFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKF------------PV 354
Cdd:cd03881  224 FFRDVAPGADSSLSGFVALLAAAEALKKVDGKGSLKRNVVFAFFNGESWGYIGSSRFVYDMENGKFptygskddlfffPI 303

                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 530364490 355 QLENVDSFVELGQVALRTSLELWMHTDPVSQkNESVRNQ 393
Cdd:cd03881  304 SFENIDTILEVGQVGLALGAKLYAHTDGVST-NSSVTQQ 341
 
Name Accession Description Interval E-value
M28_Nicastrin cd03881
M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex; Peptidase M28 family, ...
 52-393 7.98e-170

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: 485.00  E-value: 7.98e-170
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490  52 RLLNATHQIGCQSSISGDTGVIHV-VEKEEDLQWVLTDGPNPPYMVL----LESKHFTRDLMEKLKGRtSRIAGLAVSLT 126
Cdd:cd03881    1 RSLNGTHQIGCQSNLSGEIGCSHLgVNSQEDLDLVLSKSPHPPYSVLqqvvLDPNLFNRDNVLSLKSK-KKINGVLVLIS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 127 KPSPASGFSPSVQCPNDGFGVYSnsygpefahCREIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLSQNGS 206
Cdd:cd03881   80 KTSPLKGFSPDSRCPNAQFGLYS---------NSNYNWNPNGNGLMYEDFPFPIFYLEDSTETQVLEKCYEDFNKPVNGS 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 207 APTFPLCAMQLFSHMHAVISTATCMRRSSIqstfsinPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRS 286
Cdd:cd03881  151 TPLYPLCGMELDSFMSAAINTETCLRRGSI-------PEKFCDPLGGYNVWSSLPPINTSWEVKTSKKIVLVAARMDSTS 223

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 287 FFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKF------------PV 354
Cdd:cd03881  224 FFRDVAPGADSSLSGFVALLAAAEALKKVDGKGSLKRNVVFAFFNGESWGYIGSSRFVYDMENGKFptygskddlfffPI 303

                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 530364490 355 QLENVDSFVELGQVALRTSLELWMHTDPVSQkNESVRNQ 393
Cdd:cd03881  304 SFENIDTILEVGQVGLALGAKLYAHTDGVST-NSSVTQQ 341
Ncstrn_small pfam18266
Nicastrin small lobe; This domain is part of the protein Nicastrin, a component of gamma ...
 49-223 2.17e-74

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: 228.66  E-value: 2.17e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490   49 PCVRLLNATHQIGCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGrTSRIAGLAV-SLTK 127
Cdd:pfam18266   1 PCVRLLNATGQIGCSSSRPGNVGVLHPIDSFKDLDWLLSSGPSGPYAVLLPPDLFTRDNIERLRS-SGKVAGVLVlSNTT 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490  128 PSPASGFSPSVQCPNDGFGvysnsygpeFAHC-REIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQ-CYQDHNLsQNG 205
Cdd:pfam18266  80 TEPPTGFSPDSKCPNAEFG---------LAYCnATYEWNPAGSGLLYEDFPFPIFLLSNSTETEAIREaCYENFNL-DNG 149

                         170
                  ....*....|....*...
gi 530364490  206 SAPTFPLCAMQLFSHMHA 223
Cdd:pfam18266 150 SYGGYPLCAAEFDSFMQA 167
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 254-359 1.31e-04

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: 43.20  E-value: 1.31e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 254 YNVWSMLKpinttGTLKPDDRVVVAAtRLDSRSffwNVAPGAE---SAVAsfvTQLAAAEALQKAPDvtTLPRNVMFVFF 330
Cdd:COG2234   47 RNVIAEIP-----GTDPPDEVVVLGA-HYDSVG---SIGPGADdnaSGVA---ALLELARALAALGP--KPKRTIRFVAF 112

                         90       100
                 ....*....|....*....|....*....
gi 530364490 331 QGETFDYIGSSRMVydmekGKFPVQLENV 359
Cdd:COG2234  113 GAEEQGLLGSRYYA-----ENLKAPLEKI 136
 
Name Accession Description Interval E-value
M28_Nicastrin cd03881
M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex; Peptidase M28 family, ...
 52-393 7.98e-170

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: 485.00  E-value: 7.98e-170
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490  52 RLLNATHQIGCQSSISGDTGVIHV-VEKEEDLQWVLTDGPNPPYMVL----LESKHFTRDLMEKLKGRtSRIAGLAVSLT 126
Cdd:cd03881    1 RSLNGTHQIGCQSNLSGEIGCSHLgVNSQEDLDLVLSKSPHPPYSVLqqvvLDPNLFNRDNVLSLKSK-KKINGVLVLIS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 127 KPSPASGFSPSVQCPNDGFGVYSnsygpefahCREIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLSQNGS 206
Cdd:cd03881   80 KTSPLKGFSPDSRCPNAQFGLYS---------NSNYNWNPNGNGLMYEDFPFPIFYLEDSTETQVLEKCYEDFNKPVNGS 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 207 APTFPLCAMQLFSHMHAVISTATCMRRSSIqstfsinPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRS 286
Cdd:cd03881  151 TPLYPLCGMELDSFMSAAINTETCLRRGSI-------PEKFCDPLGGYNVWSSLPPINTSWEVKTSKKIVLVAARMDSTS 223

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 287 FFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKF------------PV 354
Cdd:cd03881  224 FFRDVAPGADSSLSGFVALLAAAEALKKVDGKGSLKRNVVFAFFNGESWGYIGSSRFVYDMENGKFptygskddlfffPI 303

                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 530364490 355 QLENVDSFVELGQVALRTSLELWMHTDPVSQkNESVRNQ 393
Cdd:cd03881  304 SFENIDTILEVGQVGLALGAKLYAHTDGVST-NSSVTQQ 341
Ncstrn_small pfam18266
Nicastrin small lobe; This domain is part of the protein Nicastrin, a component of gamma ...
 49-223 2.17e-74

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: 228.66  E-value: 2.17e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490   49 PCVRLLNATHQIGCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGrTSRIAGLAV-SLTK 127
Cdd:pfam18266   1 PCVRLLNATGQIGCSSSRPGNVGVLHPIDSFKDLDWLLSSGPSGPYAVLLPPDLFTRDNIERLRS-SGKVAGVLVlSNTT 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490  128 PSPASGFSPSVQCPNDGFGvysnsygpeFAHC-REIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQ-CYQDHNLsQNG 205
Cdd:pfam18266  80 TEPPTGFSPDSKCPNAEFG---------LAYCnATYEWNPAGSGLLYEDFPFPIFLLSNSTETEAIREaCYENFNL-DNG 149

                         170
                  ....*....|....*...
gi 530364490  206 SAPTFPLCAMQLFSHMHA 223
Cdd:pfam18266 150 SYGGYPLCAAEFDSFMQA 167
Nicastrin pfam05450
Nicastrin; Nicastrin and presenilin are two major components of the gamma-secretase complex, ...
 274-393 2.64e-52

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: 174.27  E-value: 2.64e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490  274 RVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKA-PDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKF 352
Cdd:pfam05450   1 KVVLVTARMDSTSMFDGVSLGAMSSLSGFIVLLAAADALSKAlPDISNLKRNVLFAFFNGESYDYIGSQRFVYDMENGKF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 530364490  353 P--------VQLENVDSFVELGQVALRTSLELWMHTDpvSQKNESVRNQ 393
Cdd:pfam05450  81 PsdrththpISPDNIDYMLEIGQVGKATSRKFYLHVD--AARNQSVKTQ 127
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 254-387 5.31e-05

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: 43.87  E-value: 5.31e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 254 YNVWSMLKpinttGTLKPDDRVVVAAtRLDSrsffWNVAPGAESAVASFVTQLAAAEALQKAPDVTtlPRNVMFVFFQGE 333
Cdd:cd02690    2 YNVIATIK-----GSDKPDEVILIGA-HYDS----VPLSPGANDNASGVAVLLELARVLSKLQLKP--KRSIRFAFWDAE 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 530364490 334 TFDYIGSSRMVYDMekgkfPVQLENVDSFVELGQVAlRTSLELWMHTDPVSQKN 387
Cdd:cd02690   70 ELGLLGSKYYAEQL-----LSSLKNIRAALNLDMIG-GAGPDLYLQTAPGNDAL 117
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 254-359 1.31e-04

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: 43.20  E-value: 1.31e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 254 YNVWSMLKpinttGTLKPDDRVVVAAtRLDSRSffwNVAPGAE---SAVAsfvTQLAAAEALQKAPDvtTLPRNVMFVFF 330
Cdd:COG2234   47 RNVIAEIP-----GTDPPDEVVVLGA-HYDSVG---SIGPGADdnaSGVA---ALLELARALAALGP--KPKRTIRFVAF 112

                         90       100
                 ....*....|....*....|....*....
gi 530364490 331 QGETFDYIGSSRMVydmekGKFPVQLENV 359
Cdd:COG2234  113 GAEEQGLLGSRYYA-----ENLKAPLEKI 136
Peptidase_M28 pfam04389
Peptidase family M28;
264-365 2.04e-03

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 38.81  E-value: 2.04e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490  264 NTTGTLKP---DDRVVVAAtRLDSRSFfwnvAPGAE---SAVAsfvTQLAAAEALQKApdvTTLPRNVMFVFFQGETFDY 337
Cdd:pfam04389   1 NVIAKLPGkapDEVVLLSA-HYDSVGT----GPGADdnaSGVA---ALLELARVLAAG---QRPKRSVRFLFFDAEEAGL 69

                          90       100
                  ....*....|....*....|....*...
gi 530364490  338 IGSSRMVYDMEKGKfpvqleNVDSFVEL 365
Cdd:pfam04389  70 LGSHHFAKSHPPLK------KIRAVINL 91
M28_like_PA_PDZ_associated cd05663
M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ ...
 264-347 3.82e-03

M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ domain; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 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. This subfamily is composed of uncharacterized proteins, many of which contain a protease-associated (PA) domain insert which may participate in substrate binding and/or promote conformational changes, influencing the stability and accessibility of the site to substrate. Proteins in this subfamily are also associated with the PDZ domain, a widespread protein module that has been recruited to serve multiple functions during the course of evolution.


Pssm-ID: 349913 [Multi-domain]  Cd Length: 266  Bit Score: 38.59  E-value: 3.82e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530364490 264 NTTGTLKPD----DRVVVAATRLD----------SRSFFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVF 329
Cdd:cd05663   57 NVIGVLPGKgdvaDETVVVGAHYDhlgyggegslARGDESLIHNGADDNASGVAAMLELAAKLVDSDTSLALSRNLVFIA 136

                         90
                 ....*....|....*...
gi 530364490 330 FQGETFDYIGSSRMVYDM 347
Cdd:cd05663  137 FSGEELGLLGSKHFVKNP 154
 
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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