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Conserved domains on  [gi|17508877|ref|NP_492553|]
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Nicalin [Caenorhabditis elegans]

Protein Classification

nicalin-like protein( domain architecture ID 10133856)

nicalin-like protein, similar to Human nicalin which regulates assembly and stability of the nicalin-nodal modulator (NOMO) membrane protein complex

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
M28_nicalin_like cd03882
M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin ...
 121-424 1.01e-114

M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin (nicastrin-like protein) subfamily. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated gamma-secretase, and forms a complex with Nomo (nodal modulator) pM5. Similar to Nicastrin, Nicalin lacks the amino-acid conservation required for catalytically active aminopeptidases. Functional studies in zebrafish embryos and cultured human cells reveal that nicalin and Nomo collaborate to antagonize the Nodal/TGFbeta signaling pathway. Thus, nicastrin and nicalin are both associated with protein complexes involved in cell fate decisions during early embryonic development.


:

Pssm-ID: 349878  Cd Length: 296  Bit Score: 342.42  E-value: 1.01e-114
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 121 FIDLEAKLLSAKTDLAVYVAPFNDDAVSILHDVNTRSEKAPTALQHLLQSLSGNTISITSSDQSPELPPSYKPLNIVGRL 200
Cdd:cd03882   1 FMELEAELLNTKTNVPVYFAPENEELLSIYEDVKSSSAAAQSAAEVLIRSLSANGFKIVVSGNSPKAISDWKITTIEGRL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 201 SS--GDRAAPTIAFVAHYDTQSAVPGVSPGADSNGSGIVALLELLAVLSKFYDSPSTRPPYNILFIWTAAGKLNYQGTRH 278
Cdd:cd03882  81 TGlgDGEKLPTIVIVAHYDTFGVAPWLSSGADSNGSGVAALLELMRLFSRLYSNPRTRAKYNLLFLLTGGGKLNYQGTKH 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 279 WIDEYQKGFdsadyaksglsrkDDRVDLAICIEAIGRKTGGFFMHAGKTPSENSVAAQLLRRLNSIS--PKKNIELVTKK 356
Cdd:cd03882 161 WLESNLDHF-------------LDNVEFVLCLDSIGSKDSDLYLHVSKPPKEGTHIQQFLEELKSVAkaPDKNLTVVHKK 227

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17508877 357 ISLT-TVSAWEHEKFNIKRMPAITLSTLPSPSDPARNSILDLPSALDEDELIDNIRLIGEAVLGYILDL 424
Cdd:cd03882 228 INLAdTKLAWEHERFSIKRLPAFTLSHLESHRSPLRNSIFDTRSSVDEDKLKRNTKIIAEALARYIYNL 296
 
Name Accession Description Interval E-value
M28_nicalin_like cd03882
M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin ...
 121-424 1.01e-114

M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin (nicastrin-like protein) subfamily. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated gamma-secretase, and forms a complex with Nomo (nodal modulator) pM5. Similar to Nicastrin, Nicalin lacks the amino-acid conservation required for catalytically active aminopeptidases. Functional studies in zebrafish embryos and cultured human cells reveal that nicalin and Nomo collaborate to antagonize the Nodal/TGFbeta signaling pathway. Thus, nicastrin and nicalin are both associated with protein complexes involved in cell fate decisions during early embryonic development.


Pssm-ID: 349878  Cd Length: 296  Bit Score: 342.42  E-value: 1.01e-114
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 121 FIDLEAKLLSAKTDLAVYVAPFNDDAVSILHDVNTRSEKAPTALQHLLQSLSGNTISITSSDQSPELPPSYKPLNIVGRL 200
Cdd:cd03882   1 FMELEAELLNTKTNVPVYFAPENEELLSIYEDVKSSSAAAQSAAEVLIRSLSANGFKIVVSGNSPKAISDWKITTIEGRL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 201 SS--GDRAAPTIAFVAHYDTQSAVPGVSPGADSNGSGIVALLELLAVLSKFYDSPSTRPPYNILFIWTAAGKLNYQGTRH 278
Cdd:cd03882  81 TGlgDGEKLPTIVIVAHYDTFGVAPWLSSGADSNGSGVAALLELMRLFSRLYSNPRTRAKYNLLFLLTGGGKLNYQGTKH 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 279 WIDEYQKGFdsadyaksglsrkDDRVDLAICIEAIGRKTGGFFMHAGKTPSENSVAAQLLRRLNSIS--PKKNIELVTKK 356
Cdd:cd03882 161 WLESNLDHF-------------LDNVEFVLCLDSIGSKDSDLYLHVSKPPKEGTHIQQFLEELKSVAkaPDKNLTVVHKK 227

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17508877 357 ISLT-TVSAWEHEKFNIKRMPAITLSTLPSPSDPARNSILDLPSALDEDELIDNIRLIGEAVLGYILDL 424
Cdd:cd03882 228 INLAdTKLAWEHERFSIKRLPAFTLSHLESHRSPLRNSIFDTRSSVDEDKLKRNTKIIAEALARYIYNL 296
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 195-417 8.64e-11

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: 62.46  E-value: 8.64e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 195 NIVGRLSSGDRAAPTIAFVAHYDTqsaVPGVSPGADSNGSGIVALLELLAVLSKFYDspstRPPYNILFIWTAAGKLNYQ 274
Cdd:COG2234  48 NVIAEIPGTDPPDEVVVLGAHYDS---VGSIGPGADDNASGVAALLELARALAALGP----KPKRTIRFVAFGAEEQGLL 120

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 275 GTRHWIDEyqkgfdsadyaksgLSRKDDRVDLAICIEAIGRKTGGFFMHAGkTPSENSVAAQLLRRLNSiSPKKNIElVT 354
Cdd:COG2234 121 GSRYYAEN--------------LKAPLEKIVAVLNLDMIGRGGPRNYLYVD-GDGGSPELADLLEAAAK-AYLPGLG-VD 183

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17508877 355 KKISLTTVSAWEHEKFNIKRMPAITLSTLPSPSDPARNSILDLPSALDEDELIDNIRLIGEAV 417
Cdd:COG2234 184 PPEETGGYGRSDHAPFAKAGIPALFLFTGAEDYHPDYHTPSDTLDKIDLDALAKVAQLLAALV 246
Nicastrin pfam05450
Nicastrin; Nicastrin and presenilin are two major components of the gamma-secretase complex, ...
 208-405 4.92e-08

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: 53.70  E-value: 4.92e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877   208 PTIAFVAHYDTQSAVPGVSPGADSNGSGIVALLELLAVLSKFYDsPSTRPPYNILFIWTAAGKLNYQGTRHWIDEYQKGF 287
Cdd:pfam05450   1 KVVLVTARMDSTSMFDGVSLGAMSSLSGFIVLLAAADALSKALP-DISNLKRNVLFAFFNGESYDYIGSQRFVYDMENGK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877   288 DSADYAKSGLSRKDDrVDLAICIEAIGRKTGG-FFMHAGKTPSEnSVAAQLLRRLNSIS------PKKNIELVTKKISLT 360
Cdd:pfam05450  80 FPSDRTHTHPISPDN-IDYMLEIGQVGKATSRkFYLHVDAARNQ-SVKTQTLDLLDRIEkslrsgNFKVLPASTSNPGLP 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 17508877   361 TVSAWEHEKFNIKrMPAITLSTLPSPSDPAR-NSILDLPSALDEDE 405
Cdd:pfam05450 158 PSSLQSFLRANPN-FSAVVLADRPTEFENRFyHSILDDAENINSDT 202
 
Name Accession Description Interval E-value
M28_nicalin_like cd03882
M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin ...
 121-424 1.01e-114

M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin (nicastrin-like protein) subfamily. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated gamma-secretase, and forms a complex with Nomo (nodal modulator) pM5. Similar to Nicastrin, Nicalin lacks the amino-acid conservation required for catalytically active aminopeptidases. Functional studies in zebrafish embryos and cultured human cells reveal that nicalin and Nomo collaborate to antagonize the Nodal/TGFbeta signaling pathway. Thus, nicastrin and nicalin are both associated with protein complexes involved in cell fate decisions during early embryonic development.


Pssm-ID: 349878  Cd Length: 296  Bit Score: 342.42  E-value: 1.01e-114
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 121 FIDLEAKLLSAKTDLAVYVAPFNDDAVSILHDVNTRSEKAPTALQHLLQSLSGNTISITSSDQSPELPPSYKPLNIVGRL 200
Cdd:cd03882   1 FMELEAELLNTKTNVPVYFAPENEELLSIYEDVKSSSAAAQSAAEVLIRSLSANGFKIVVSGNSPKAISDWKITTIEGRL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 201 SS--GDRAAPTIAFVAHYDTQSAVPGVSPGADSNGSGIVALLELLAVLSKFYDSPSTRPPYNILFIWTAAGKLNYQGTRH 278
Cdd:cd03882  81 TGlgDGEKLPTIVIVAHYDTFGVAPWLSSGADSNGSGVAALLELMRLFSRLYSNPRTRAKYNLLFLLTGGGKLNYQGTKH 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 279 WIDEYQKGFdsadyaksglsrkDDRVDLAICIEAIGRKTGGFFMHAGKTPSENSVAAQLLRRLNSIS--PKKNIELVTKK 356
Cdd:cd03882 161 WLESNLDHF-------------LDNVEFVLCLDSIGSKDSDLYLHVSKPPKEGTHIQQFLEELKSVAkaPDKNLTVVHKK 227

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17508877 357 ISLT-TVSAWEHEKFNIKRMPAITLSTLPSPSDPARNSILDLPSALDEDELIDNIRLIGEAVLGYILDL 424
Cdd:cd03882 228 INLAdTKLAWEHERFSIKRLPAFTLSHLESHRSPLRNSIFDTRSSVDEDKLKRNTKIIAEALARYIYNL 296
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 195-420 1.93e-21

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: 92.41  E-value: 1.93e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 195 NIVGRLSSGDRAAPTIAFVAHYDTqsavPGVSPGADSNGSGIVALLELLAVLSKFYdspsTRPPYNILFIWTAAGKLNYQ 274
Cdd:cd02690   3 NVIATIKGSDKPDEVILIGAHYDS----VPLSPGANDNASGVAVLLELARVLSKLQ----LKPKRSIRFAFWDAEELGLL 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 275 GTRHWIDEYqkgfdsadyaksgLSRKDDrVDLAICIEAIGRKTGGFFMHagKTPSENSVAAQLLRRLNsiSPKKNIELVT 354
Cdd:cd02690  75 GSKYYAEQL-------------LSSLKN-IRAALNLDMIGGAGPDLYLQ--TAPGNDALVEKLLRALA--HELENVVYTV 136

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 17508877 355 KKISLTTVSAWEHEKFNIKRMPAITLSTLPSPSDPARNSILDLPSALDEDELIDNIRLIGEAVLGY 420
Cdd:cd02690 137 VYKEDGGTGGSDHRPFLARGIPAASLIQSESYNFPYYHTTQDTLENIDKDTLKRAGDILASFLYRL 202
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 195-417 8.64e-11

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: 62.46  E-value: 8.64e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 195 NIVGRLSSGDRAAPTIAFVAHYDTqsaVPGVSPGADSNGSGIVALLELLAVLSKFYDspstRPPYNILFIWTAAGKLNYQ 274
Cdd:COG2234  48 NVIAEIPGTDPPDEVVVLGAHYDS---VGSIGPGADDNASGVAALLELARALAALGP----KPKRTIRFVAFGAEEQGLL 120

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 275 GTRHWIDEyqkgfdsadyaksgLSRKDDRVDLAICIEAIGRKTGGFFMHAGkTPSENSVAAQLLRRLNSiSPKKNIElVT 354
Cdd:COG2234 121 GSRYYAEN--------------LKAPLEKIVAVLNLDMIGRGGPRNYLYVD-GDGGSPELADLLEAAAK-AYLPGLG-VD 183

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17508877 355 KKISLTTVSAWEHEKFNIKRMPAITLSTLPSPSDPARNSILDLPSALDEDELIDNIRLIGEAV 417
Cdd:COG2234 184 PPEETGGYGRSDHAPFAKAGIPALFLFTGAEDYHPDYHTPSDTLDKIDLDALAKVAQLLAALV 246
Nicastrin pfam05450
Nicastrin; Nicastrin and presenilin are two major components of the gamma-secretase complex, ...
 208-405 4.92e-08

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: 53.70  E-value: 4.92e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877   208 PTIAFVAHYDTQSAVPGVSPGADSNGSGIVALLELLAVLSKFYDsPSTRPPYNILFIWTAAGKLNYQGTRHWIDEYQKGF 287
Cdd:pfam05450   1 KVVLVTARMDSTSMFDGVSLGAMSSLSGFIVLLAAADALSKALP-DISNLKRNVLFAFFNGESYDYIGSQRFVYDMENGK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877   288 DSADYAKSGLSRKDDrVDLAICIEAIGRKTGG-FFMHAGKTPSEnSVAAQLLRRLNSIS------PKKNIELVTKKISLT 360
Cdd:pfam05450  80 FPSDRTHTHPISPDN-IDYMLEIGQVGKATSRkFYLHVDAARNQ-SVKTQTLDLLDRIEkslrsgNFKVLPASTSNPGLP 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 17508877   361 TVSAWEHEKFNIKrMPAITLSTLPSPSDPAR-NSILDLPSALDEDE 405
Cdd:pfam05450 158 PSSLQSFLRANPN-FSAVVLADRPTEFENRFyHSILDDAENINSDT 202
Peptidase_M28 pfam04389
Peptidase family M28;
195-325 9.73e-05

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 43.43  E-value: 9.73e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877   195 NIVGRLSSGDRAApTIAFVAHYDTqsavPGVSPGADSNGSGIVALLELLAVLSKFYdspstRPPYNILFIWTAAGKLNYQ 274
Cdd:pfam04389   1 NVIAKLPGKAPDE-VVLLSAHYDS----VGTGPGADDNASGVAALLELARVLAAGQ-----RPKRSVRFLFFDAEEAGLL 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 17508877   275 GTRHwideyqkgfdsadYAKSGLSRKddRVDLAICIEAIGRKTGGFFMHAG 325
Cdd:pfam04389  71 GSHH-------------FAKSHPPLK--KIRAVINLDMIGSGGPALLFQSG 106
M28_like cd05643
M28 Zn-peptidase-like; Peptidase family M28 (also called aminopeptidase Y family), ...
 184-430 2.43e-04

M28 Zn-peptidase-like; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They typically 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 protein subfamily conserves some of the metal-coordinating residues of the typically co-catalytic M28 family which might suggest binding of a single metal ion.


Pssm-ID: 349895 [Multi-domain]  Cd Length: 290  Bit Score: 43.16  E-value: 2.43e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 184 SPELPPSYKPLNivGRLSS---------GDRAAPTIAFVAHydtqsaVPGVSPGADSNGSGIVALLELLAVLSKFYDSps 254
Cdd:cd05643  53 TPQSPISWELIE--GELNEtlpilyaiiGKETPPEIAFVAH------LCHPKPGANDNASGSALLLEVARVLAKLILN-- 122

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 255 tRPPYNILFIWTAagklNYQGTRHWIDEyqkgfdsadyaksgLSRKDDRVDLAICIEAIGR---KTGGFFMHAGKTPSEN 331
Cdd:cd05643 123 -RPKRGICFLWVP----EYTGTAAYFAQ--------------HPDRLKKIIAVINLDMVGEdqtKTGSTLMLVPTPLSFP 183

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 332 SVAAQLLrrLNSISPKKNIELVTKKISLTTVSAW-EHEKFNIKRMPAITLSTLPspsDPARNSILDLPSALDEDELidni 410
Cdd:cd05643 184 SYLNEEL--AQKLSNFTGSSLPAVRYGKEPYEGGsDHDVFSDPGIPAVMFNTWP---DRYYHTSDDTPDKLDPETL---- 254

                       250       260
                ....*....|....*....|
gi 17508877 411 RLIGEAVLGYILDLPESGPS 430
Cdd:cd05643 255 KNVGAAVLLTAYALANGEEE 274
M28_Nicastrin cd03881
M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex; Peptidase M28 family, ...
 190-345 3.61e-04

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: 43.18  E-value: 3.61e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 190 SYKPLNIVGRLSSGDRAaptIAFVAHYDTQSAVPGVSPGADSNGSGIVALLELLAVLSKFydSPSTRPPYNILFIWTAAG 269
Cdd:cd03881 196 SLPPINTSWEVKTSKKI---VLVAARMDSTSFFRDVAPGADSSLSGFVALLAAAEALKKV--DGKGSLKRNVVFAFFNGE 270

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 270 KLNYQGTRHWIDEYQKG-FDSADYAKSGLSR--KDDRVDLAICIEAIGRKTGG-FFMHAGKTPSENSVAAQLLRRLNSIS 345
Cdd:cd03881 271 SWGYIGSSRFVYDMENGkFPTYGSKDDLFFFpiSFENIDTILEVGQVGLALGAkLYAHTDGVSTNSSVTQQLLDALSNSL 350
M28_like cd05662
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
 191-376 3.71e-04

M28 Zn-Peptidases; 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 that do not contain a protease-associated (PA) domain.


Pssm-ID: 349912 [Multi-domain]  Cd Length: 268  Bit Score: 42.45  E-value: 3.71e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 191 YKPLNIVGRLSSGDRAAPTIAFVAHYDTQSAVPG-VSPGADSNGSGIVALLELLAVLSKfydspsTRPPYNILFIWTAAG 269
Cdd:cd05662  60 RQGVNVLAVIKGSEPPTKWRVVSAHYDHLGIRGGkIYNGADDNASGVAALLALAEYFKK------HPPKHNVIFAATDAE 133

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 270 KLNYQGTRHWIDEyqkgfdsadyaksgLSRKDDRVDLAICIEAIGRKTGGFFMHAGktPSENSVAAQLLRRLNSISPK-- 347
Cdd:cd05662 134 EPGLRGSYAFVEA--------------LKVPRAQIELNINLDMISRPERNELYVEG--ASQFPQLTSILENVKGTCIKal 197

                       170       180       190
                ....*....|....*....|....*....|.
gi 17508877 348 --KNIELVTKKISLTTVSawEHEKFNIKRMP 376
Cdd:cd05662 198 hpKDTDGSIGSIDWTRAS--DHYPFHKAKIP 226
M28_like cd05640
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
 194-314 5.35e-04

M28 Zn-peptidase; uncharacterized subfamily; 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.


Pssm-ID: 349893 [Multi-domain]  Cd Length: 281  Bit Score: 42.05  E-value: 5.35e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 194 LNIVGRLSSGDRAAPTIAFVAHYDTqsaVPGvSPGADSNGSGIvallELLAVLSKFYDspSTRPPYNILFIWTAagklny 273
Cdd:cd05640  53 ANLIADLPGSYSQDKLILIGAHYDT---VPG-SPGADDNASGV----AALLELARLLA--TLDPNHTLRFVAFD------ 116

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 17508877 274 qgtrhwIDEYQKGFD----SADYAKSgLSRKDDRVDLAICIEAIG 314
Cdd:cd05640 117 ------LEEYPFFARglmgSHAYAED-LLRPLTPIVGMLSLEMIG 154
M28_like cd03877
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
 195-267 2.89e-03

M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; 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. Some 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: 349874 [Multi-domain]  Cd Length: 206  Bit Score: 39.15  E-value: 2.89e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17508877 195 NIVGRLSSGDRAAPTIAFVAHYDTQSAVPGVS-----PGADSNGSGIVALLELLAvlsKFYDSPstRPPYNILFI-WTA 267
Cdd:cd03877   3 NVVGVLEGSDLPDETIVIGAHYDHLGIGGGDSgdkiyNGADDNASGVAAVLELAR---YFAKQK--TPKRSIVFAaFTA 76
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 154-236 7.56e-03

M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; Aeromonas (Vibrio) proteolytica aminopeptidase (AAP; leucine aminopeptidase from Vibrio proteolyticus; Bacterial leucyl aminopeptidase; E.C. 3.4.11.10) subfamily. AAP is a small (32kDa), heat stable leucine aminopeptidase and is active as a monomer. Similar forms of the enzyme have been isolated from Escherichia coli and Staphylococcus thermophilus. Leucine aminopeptidases, in general, play important roles in many biological processes such as protein catabolism, hormone degradation, regulation of migration and cell proliferation, as well as HIV infection and proliferation. AAP is a broad-specificity enzyme, utilizing two zinc(II) ions in its active site to remove N-terminal amino acids, with preference for large hydrophobic amino acids in the P1 position of the substrate, Leu being the most efficiently cleaved. It can accommodate all residues, except Pro, Asp and Glu in the P1' position.


Pssm-ID: 349875 [Multi-domain]  Cd Length: 286  Bit Score: 38.38  E-value: 7.56e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508877 154 NTRSEKAPTALQH---LLQSLSGNTISITSSDQSPEL-PPSYKPLNIVGRLSSGDRAAPTIAFVAHYDT---QSAVPGVS 226
Cdd:cd03879  31 NNRYYKSQTGVESaewLLDQVQAIIASSGRSGATVEQfTHSFPQPSIIATIPGSEKSDEIVVIGAHQDSingSNPSNGRA 110

                        90
                ....*....|
gi 17508877 227 PGADSNGSGI 236
Cdd:cd03879 111 PGADDDGSGT 120
 
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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