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Conserved domains on  [gi|528515194|ref|XP_005161646|]
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nicalin-1 isoform X1 [Danio rerio]

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 ...
 120-437 3.48e-156

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: 448.74  E-value: 3.48e-156
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 120 FMELEPELLATETIVPVYFALEDEELLSIYTQTQISSSSQGSssAAEVLLHTATANGFQMVTSGAQSKAVSDWAITSLEG 199
Cdd:cd03882    1 FMELEAELLNTKTNVPVYFAPENEELLSIYEDVKSSSAAAQS--AAEVLIRSLSANGFKIVVSGNSPKAISDWKITTIEG 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 200 RLTGSG-GEDLPTIVLVAHYDSFGVAPWLSYGADSNGSGVAILLELARLFSRLYSYKRTHAGYNLLFFLSGGGKFNYQGT 278
Cdd:cd03882   79 RLTGLGdGEKLPTIVIVAHYDTFGVAPWLSSGADSNGSGVAALLELMRLFSRLYSNPRTRAKYNLLFLLTGGGKLNYQGT 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 279 KRWLEDNLDHTdasllQDNVAFVLCLDTLGNSD-NLHLHVSKPPKEGSPQYTLLKELETVVahQHPDLKFAMVHKKINLA 357
Cdd:cd03882  159 KHWLESNLDHF-----LDNVEFVLCLDSIGSKDsDLYLHVSKPPKEGTHIQQFLEELKSVA--KAPDKNLTVVHKKINLA 231

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 358 DDTLAWEHERFGIRRLPAFTLSHLESHRSPARHSIMDMRSVspslegageattgphVDLGKLSRNTKVIAETLARVIYNL 437
Cdd:cd03882  232 DTKLAWEHERFSIKRLPAFTLSHLESHRSPLRNSIFDTRSS---------------VDEDKLKRNTKIIAEALARYIYNL 296
 
Name Accession Description Interval E-value
M28_nicalin_like cd03882
M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin ...
 120-437 3.48e-156

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: 448.74  E-value: 3.48e-156
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 120 FMELEPELLATETIVPVYFALEDEELLSIYTQTQISSSSQGSssAAEVLLHTATANGFQMVTSGAQSKAVSDWAITSLEG 199
Cdd:cd03882    1 FMELEAELLNTKTNVPVYFAPENEELLSIYEDVKSSSAAAQS--AAEVLIRSLSANGFKIVVSGNSPKAISDWKITTIEG 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 200 RLTGSG-GEDLPTIVLVAHYDSFGVAPWLSYGADSNGSGVAILLELARLFSRLYSYKRTHAGYNLLFFLSGGGKFNYQGT 278
Cdd:cd03882   79 RLTGLGdGEKLPTIVIVAHYDTFGVAPWLSSGADSNGSGVAALLELMRLFSRLYSNPRTRAKYNLLFLLTGGGKLNYQGT 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 279 KRWLEDNLDHTdasllQDNVAFVLCLDTLGNSD-NLHLHVSKPPKEGSPQYTLLKELETVVahQHPDLKFAMVHKKINLA 357
Cdd:cd03882  159 KHWLESNLDHF-----LDNVEFVLCLDSIGSKDsDLYLHVSKPPKEGTHIQQFLEELKSVA--KAPDKNLTVVHKKINLA 231

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 358 DDTLAWEHERFGIRRLPAFTLSHLESHRSPARHSIMDMRSVspslegageattgphVDLGKLSRNTKVIAETLARVIYNL 437
Cdd:cd03882  232 DTKLAWEHERFSIKRLPAFTLSHLESHRSPLRNSIFDTRSS---------------VDEDKLKRNTKIIAEALARYIYNL 296
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 164-433 2.59e-15

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: 75.94  E-value: 2.59e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 164 AAEVLLHTATANGFQMVTSGAQSKAVSDWAITSLEGRLTGSGGEDlPTIVLVAHYDSFGVapwLSYGADSNGSGVAILLE 243
Cdd:COG2234   16 AAAAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPD-EVVVLGAHYDSVGS---IGPGADDNASGVAALLE 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 244 LARLFSRL-YSYKRThagynLLFFLSGGGKFNYQGTKRWLEdnlDHTDAsllQDNVAFVLCLDTLGNSDNLHlHVSKPPK 322
Cdd:COG2234   92 LARALAALgPKPKRT-----IRFVAFGAEEQGLLGSRYYAE---NLKAP---LEKIVAVLNLDMIGRGGPRN-YLYVDGD 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 323 EGSPQytLLKELETVVAHQHPDLKFAMvhkkINLADDTLAWEHERFGIRRLPAFTLSHLESHRSPARHSIMDmrsvspSL 402
Cdd:COG2234  160 GGSPE--LADLLEAAAKAYLPGLGVDP----PEETGGYGRSDHAPFAKAGIPALFLFTGAEDYHPDYHTPSD------TL 227

                        250       260       270
                 ....*....|....*....|....*....|.
gi 528515194 403 EgageattgpHVDLGKLSRNTKVIAETLARV 433
Cdd:COG2234  228 D---------KIDLDALAKVAQLLAALVYEL 249
Peptidase_M28 pfam04389
Peptidase family M28;
199-311 9.01e-12

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 64.23  E-value: 9.01e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194  199 GRLTGSGGEDlpTIVLVAHYDSFGVAPwlsyGADSNGSGVAILLELARLFSRLYSYKRThagynLLFFLSGGGKFNYQGT 278
Cdd:pfam04389   4 AKLPGKAPDE--VVLLSAHYDSVGTGP----GADDNASGVAALLELARVLAAGQRPKRS-----VRFLFFDAEEAGLLGS 72

                          90       100       110
                  ....*....|....*....|....*....|...
gi 528515194  279 KRWLEDNLDhtdasllQDNVAFVLCLDTLGNSD 311
Cdd:pfam04389  73 HHFAKSHPP-------LKKIRAVINLDMIGSGG 98
 
Name Accession Description Interval E-value
M28_nicalin_like cd03882
M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin ...
 120-437 3.48e-156

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: 448.74  E-value: 3.48e-156
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 120 FMELEPELLATETIVPVYFALEDEELLSIYTQTQISSSSQGSssAAEVLLHTATANGFQMVTSGAQSKAVSDWAITSLEG 199
Cdd:cd03882    1 FMELEAELLNTKTNVPVYFAPENEELLSIYEDVKSSSAAAQS--AAEVLIRSLSANGFKIVVSGNSPKAISDWKITTIEG 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 200 RLTGSG-GEDLPTIVLVAHYDSFGVAPWLSYGADSNGSGVAILLELARLFSRLYSYKRTHAGYNLLFFLSGGGKFNYQGT 278
Cdd:cd03882   79 RLTGLGdGEKLPTIVIVAHYDTFGVAPWLSSGADSNGSGVAALLELMRLFSRLYSNPRTRAKYNLLFLLTGGGKLNYQGT 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 279 KRWLEDNLDHTdasllQDNVAFVLCLDTLGNSD-NLHLHVSKPPKEGSPQYTLLKELETVVahQHPDLKFAMVHKKINLA 357
Cdd:cd03882  159 KHWLESNLDHF-----LDNVEFVLCLDSIGSKDsDLYLHVSKPPKEGTHIQQFLEELKSVA--KAPDKNLTVVHKKINLA 231

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 358 DDTLAWEHERFGIRRLPAFTLSHLESHRSPARHSIMDMRSVspslegageattgphVDLGKLSRNTKVIAETLARVIYNL 437
Cdd:cd03882  232 DTKLAWEHERFSIKRLPAFTLSHLESHRSPLRNSIFDTRSS---------------VDEDKLKRNTKIIAEALARYIYNL 296
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 194-394 2.62e-40

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: 145.18  E-value: 2.62e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 194 ITSLEGRLTGSGGEDlPTIVLVAHYDSFGVAPwlsyGADSNGSGVAILLELARLFSRLysYKRTHAGYNLLFFlsGGGKF 273
Cdd:cd02690    1 GYNVIATIKGSDKPD-EVILIGAHYDSVPLSP----GANDNASGVAVLLELARVLSKL--QLKPKRSIRFAFW--DAEEL 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 274 NYQGTKRWLEDNLDHtdasllQDNVAFVLCLDTLGnSDNLHLHVSKPPKEGSPQYTLLKELETVVAHQHPDlkfamvhKK 353
Cdd:cd02690   72 GLLGSKYYAEQLLSS------LKNIRAALNLDMIG-GAGPDLYLQTAPGNDALVEKLLRALAHELENVVYT-------VV 137

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 528515194 354 INLADDTLAWEHERFGIRRLPAFTLSHLESHRSPARHSIMD 394
Cdd:cd02690  138 YKEDGGTGGSDHRPFLARGIPAASLIQSESYNFPYYHTTQD 178
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 164-433 2.59e-15

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: 75.94  E-value: 2.59e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 164 AAEVLLHTATANGFQMVTSGAQSKAVSDWAITSLEGRLTGSGGEDlPTIVLVAHYDSFGVapwLSYGADSNGSGVAILLE 243
Cdd:COG2234   16 AAAAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPD-EVVVLGAHYDSVGS---IGPGADDNASGVAALLE 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 244 LARLFSRL-YSYKRThagynLLFFLSGGGKFNYQGTKRWLEdnlDHTDAsllQDNVAFVLCLDTLGNSDNLHlHVSKPPK 322
Cdd:COG2234   92 LARALAALgPKPKRT-----IRFVAFGAEEQGLLGSRYYAE---NLKAP---LEKIVAVLNLDMIGRGGPRN-YLYVDGD 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 323 EGSPQytLLKELETVVAHQHPDLKFAMvhkkINLADDTLAWEHERFGIRRLPAFTLSHLESHRSPARHSIMDmrsvspSL 402
Cdd:COG2234  160 GGSPE--LADLLEAAAKAYLPGLGVDP----PEETGGYGRSDHAPFAKAGIPALFLFTGAEDYHPDYHTPSD------TL 227

                        250       260       270
                 ....*....|....*....|....*....|.
gi 528515194 403 EgageattgpHVDLGKLSRNTKVIAETLARV 433
Cdd:COG2234  228 D---------KIDLDALAKVAQLLAALVYEL 249
Peptidase_M28 pfam04389
Peptidase family M28;
199-311 9.01e-12

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 64.23  E-value: 9.01e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194  199 GRLTGSGGEDlpTIVLVAHYDSFGVAPwlsyGADSNGSGVAILLELARLFSRLYSYKRThagynLLFFLSGGGKFNYQGT 278
Cdd:pfam04389   4 AKLPGKAPDE--VVLLSAHYDSVGTGP----GADDNASGVAALLELARVLAAGQRPKRS-----VRFLFFDAEEAGLLGS 72

                          90       100       110
                  ....*....|....*....|....*....|...
gi 528515194  279 KRWLEDNLDhtdasllQDNVAFVLCLDTLGNSD 311
Cdd:pfam04389  73 HHFAKSHPP-------LKKIRAVINLDMIGSGG 98
M28_like cd05640
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
 164-328 3.65e-10

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: 60.92  E-value: 3.65e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 164 AAEVLLHTATANGFQmVTSgaQSKAVSDWAITSLEGRLTGSGGEDlPTIVLVAHYDSFGVAPwlsyGADSNGSGVAILLE 243
Cdd:cd05640   25 AAEYIAQELVGSGYN-VTS--HFFSHQEGVYANLIADLPGSYSQD-KLILIGAHYDTVPGSP----GADDNASGVAALLE 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 244 LARLFSRLysykRTHAGYNLLFFLSGggkfNYQGTKRWLEDNLDHTDASLLQDN-VAFVLCLDTLGNSDNLHLHVSKPPK 322
Cdd:cd05640   97 LARLLATL----DPNHTLRFVAFDLE----EYPFFARGLMGSHAYAEDLLRPLTpIVGMLSLEMIGYYDPFPHSQAYPAG 168


                 ....*.
gi 528515194 323 EGSPQY 328
Cdd:cd05640  169 FELHFY 174
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 194-334 1.13e-08

M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor (TfR) and prostate-specific membrane antigen (PSMA, also called glutamate carboxypeptidase or GCP-II) subfamily. TfR and PSMA are homodimeric type II transmembrane proteins containing three distinct domains: protease-like, apical or protease-associated (PA) and helical domains. The protease-like domain is a large extracellular portion (ectodomain). In TfR, it contains a binding site for the transferrin molecule and has 28% identity to membrane glutamate carboxypeptidase II (mGCP-II or PSMA). The PA domain is inserted between the first and second strands of the central beta sheet in the protease-like domain. TfR1 is widely expressed, and is a key player in the uptake of iron-loaded transferrin (Tf) into cells. The TfR1 homodimer binds two molecules of Tf and the complex is then internalized. TfR1 may also participate in cell growth and proliferation. TfR2 binds Tf but with a significantly lower affinity than TfR1. It is expressed chiefly in hepatocytes, hematopoietic cells, and duodenal crypt cells; its expression overlaps with that of hereditary hemochromatosis protein (HFE). TfR2 is involved in iron homeostasis; in humans, mutations in TfR2 are associated with a form of hemochromatosis (HFE3). PSMA is over-expressed predominantly in prostate cancer (PCa) as well as in the neovasculature of most solid tumors, but not in the vasculature of normal tissues. PSMA is considered a biomarker for PCa and possibly for use as an imaging and therapeutic target. The extracellular domain of PSMA possesses two unique enzymatic functions: N-acetylated, alpha-linked acidic dipeptidase (NAALADase) which cleaves terminal glutamate from the neurodipeptide N-acetyl-aspartyl-glutamate (NAAG), and folate hydrolase (FOLH) which cleaves the terminal glutamates from gamma-linked polyglutamates (carboxypeptidase). A mutation in this gene may be associated with impaired intestinal absorption of dietary folates, resulting in low blood folate levels and consequent hyperhomocysteinemia. Expression of this protein in the brain may be involved in a number of pathological conditions associated with glutamate excitotoxicity. This gene likely arose from a duplication event of a nearby chromosomal region. Alternative splicing gives rise to multiple transcript variants. While related in sequence to peptidase M28 GCP-II, TfR lacks the metal ion coordination centers and protease activity.


Pssm-ID: 349871 [Multi-domain]  Cd Length: 278  Bit Score: 56.54  E-value: 1.13e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 194 ITSLEGRLTGSGGEDLpTIVLVAHYDSFGvapwlsYGADSNGSGVAILLELARLFSRLysykRTHAGY----NLLFFLSG 269
Cdd:cd03874   57 ITNVVGKIEGIEQPDR-AIIIGAHRDSWG------YGAGYPNSGTAVLLEIARLFQQL----KKKFGWkplrTIYFISWD 125

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528515194 270 GGKFNYQGTKRWLEDNLDhtdasLLQDNVAFVLCLDTLGnSDNLHLHVskppkEGSPqytLLKEL 334
Cdd:cd03874  126 GSEFGLAGSTELGEDRKA-----SLKDEVYAYINIDQLV-IGNSELDV-----DAHP---LLQSL 176
M28_like cd03877
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
 199-265 1.19e-07

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: 52.24  E-value: 1.19e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528515194 199 GRLTGSggeDLP--TIVLVAHYDSFGVAPWLSY-----GADSNGSGVAILLELARLFSRLYSYKRthagyNLLF 265
Cdd:cd03877    6 GVLEGS---DLPdeTIVIGAHYDHLGIGGGDSGdkiynGADDNASGVAAVLELARYFAKQKTPKR-----SIVF 71
M28_like_PA_PDZ_associated cd05663
M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ ...
 199-385 1.57e-07

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: 52.84  E-value: 1.57e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 199 GRLTGSGGEDLPTIVLVAHYDSFG------VAPWLSY----GADSNGSGVAILLELA-RLFSRLYSYKRTHagyNLLFFL 267
Cdd:cd05663   60 GVLPGKGDVADETVVVGAHYDHLGyggegsLARGDESlihnGADDNASGVAAMLELAaKLVDSDTSLALSR---NLVFIA 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 268 SGGGKFNYQGTKRWLEdnldhtDASLLQDNVAFVLCLDTLGNSDNLHLHV----SKPPKEGspqytLLKELETVVahqhp 343
Cdd:cd05663  137 FSGEELGLLGSKHFVK------NPPFPIKNTVYMINMDMVGRLRDNKLIVqgtgTSPGWEQ-----LVQARNKAT----- 200

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 528515194 344 DLKFAMVHkkinlaDDTLAWEHERFGIRRLPA---FTLSHLESHR 385
Cdd:cd05663  201 GFKLILDP------TGYGPSDHTSFYLDDVPVlhfFTGAHSDYHR 239
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
 200-250 4.34e-07

M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic reticulum metallopeptidase 1 (ERMP1; Felix-ina, FXNA or Fxna peptidase; KIAA1815) subfamily. ERMP1 is a multi-pass membrane protein located in the endoplasmic reticulum membrane. In humans, Fxna may play a crucial role in processing proteins required for the organization of somatic cells and oocytes into discrete follicular structures, although which proteins are hydrolyzed has not yet been determined. Another member of this subfamily is the 24-kDa vacuolar protein (VP24) which is probably involved in the formation of intravacuolar pigmented globules (cyanoplasts) in highly anthocyanin-containing vacuoles; however, the biological function of the C-terminal region which includes the putative transmembrane metallopeptidase domain is unknown.


Pssm-ID: 349872 [Multi-domain]  Cd Length: 307  Bit Score: 51.82  E-value: 4.34e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 528515194 200 RLTGSGGEDLPTIVLVAHYDSfgVAPwlSYGADSNGSGVAILLELARLFSR 250
Cdd:cd03875   85 RISGKNSNSLPALLLNAHFDS--VPT--SPGATDDGMGVAVMLEVLRYLSK 131
M28_Nicastrin cd03881
M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex; Peptidase M28 family, ...
 210-337 6.52e-06

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: 48.96  E-value: 6.52e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 210 PTIVLVAHYDSFGVAPWLSYGADSNGSGVAILLELARLFSRL---YSYKRthagyNLLFFLSGGGKFNYQGTKRWLEDNL 286
Cdd:cd03881  211 KIVLVAARMDSTSFFRDVAPGADSSLSGFVALLAAAEALKKVdgkGSLKR-----NVVFAFFNGESWGYIGSSRFVYDME 285

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528515194 287 DHTDASLL-----------QDNVAFVLCLDTLG--NSDNLHLHVSKPPKEGSPQYTLLKELETV 337
Cdd:cd03881  286 NGKFPTYGskddlfffpisFENIDTILEVGQVGlaLGAKLYAHTDGVSTNSSVTQQLLDALSNS 349
M28_like_PA cd05660
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ...
 199-249 7.35e-06

M28 Zn-peptidase 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 containing 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.


Pssm-ID: 349910 [Multi-domain]  Cd Length: 290  Bit Score: 48.13  E-value: 7.35e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 528515194 199 GRLTGSGGEDlPTIVLVAHYDSFGVAPWLS----Y-GADSNGSGVAILLELARLFS 249
Cdd:cd05660   64 AILPGSKLPD-EYIVLSAHWDHLGIGPPIGgdeiYnGAVDNASGVAAVLELARVFA 118
Nicastrin pfam05450
Nicastrin; Nicastrin and presenilin are two major components of the gamma-secretase complex, ...
 210-319 1.68e-05

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: 46.39  E-value: 1.68e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194  210 PTIVLVAHYDSFGVAPWLSYGADSNGSGVAILLELARLFSRLYSyKRTHAGYNLLFFLSGGGKFNYQGTKRWLEDNLDHT 289
Cdd:pfam05450   1 KVVLVTARMDSTSMFDGVSLGAMSSLSGFIVLLAAADALSKALP-DISNLKRNVLFAFFNGESYDYIGSQRFVYDMENGK 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 528515194  290 DAS-------LLQDNVAFVLCLDTLGN--SDNLHLHVSK 319
Cdd:pfam05450  80 FPSdrththpISPDNIDYMLEIGQVGKatSRKFYLHVDA 118
M28_like_PA cd05661
M28 Zn-peptidase containing a PA domain insert; Peptidase family M28 (also called ...
 210-251 2.04e-05

M28 Zn-peptidase containing a 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 containing 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.


Pssm-ID: 349911 [Multi-domain]  Cd Length: 262  Bit Score: 46.41  E-value: 2.04e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 528515194 210 PTIVLVAHYDSFGVAPwlsyGADSNGSGVAILLELARLFSRL 251
Cdd:cd05661   77 DIIIVTSHYDSVVKAP----GANDNASGTAVTLELARVFKKV 114
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 199-335 6.09e-05

M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific membrane antigen (PSMA, also called glutamate carboxypeptidase II or GCP-II)-like subfamily. PSMA is a homodimeric type II transmembrane protein containing three distinct domains: protease-like, apical or protease-associated (PA) and helical domains. The protease-like domain is a large extracellular portion (ectodomain). PSMA is over-expressed predominantly in prostate cancer (PCa) as well as in the neovasculature of most solid tumors, but not in the vasculature of the normal tissues. PSMA is considered a biomarker for PCa and possibly for use as an imaging and therapeutic target. The extracellular domain of PSMA possesses two unique enzymatic functions: N-acetylated, alpha-linked acidic dipeptidase (NAALADase) which cleaves terminal glutamate from the neurodipeptide N-acetyl-aspartyl-glutamate (NAAG), and folate hydrolase (FOLH) which cleaves the terminal glutamates from gamma-linked polyglutamates (carboxypeptidase). A mutation in this gene may be associated with impaired intestinal absorption of dietary folates, resulting in low blood folate levels and consequent hyperhomocysteinemia. Expression of this protein in the brain may be involved in a number of pathological conditions associated with glutamate excitotoxicity. Inhibition of GCP-II has been shown to be effective in preclinical models of neurological disorders associated with excessive activation of glutamatergic systems. This gene likely arose from a duplication event of a nearby chromosomal region. Alternative splicing gives rise to multiple transcript variants.


Pssm-ID: 349942 [Multi-domain]  Cd Length: 287  Bit Score: 45.30  E-value: 6.09e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 199 GRLTGSGGEDlPTIVLVAHYDSfgvapWlSYGA-DSNgSGVAILLELARLFSRL----YSYKRThagynlLFFLS-GGGK 272
Cdd:cd08022   65 GTIRGSEEPD-EYIILGNHRDA-----W-VFGAgDPN-SGTAVLLEVARALGTLlkkgWRPRRT------IIFASwDAEE 130

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528515194 273 FNYQGTKRWLEDNLDhtdasLLQDNVAFVLCLDTLGNsdNLHLHVSkppkeGSPQ-----YTLLKELE 335
Cdd:cd08022  131 YGLIGSTEWVEENAD-----WLQERAVAYLNVDVAVS--GSTLRAA-----GSPLlqnllREAAKEVQ 186
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 192-247 6.23e-05

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: 44.93  E-value: 6.23e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528515194 192 WAITSLEGRLTGSGgEDLPTIVLVAHYDS-------FGVAPwlsyGADSNGSGVAILLELARL 247
Cdd:cd03879   72 FPQPSIIATIPGSE-KSDEIVVIGAHQDSingsnpsNGRAP----GADDDGSGTVTILEALRV 129
M28_like cd05662
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
 206-265 3.01e-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: 42.84  E-value: 3.01e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528515194 206 GEDLPT--IVLVAHYDSFGVAPWLSY-GADSNGSGVAILLELArlfsrlySYKRTHA-GYNLLF 265
Cdd:cd05662   71 GSEPPTkwRVVSAHYDHLGIRGGKIYnGADDNASGVAALLALA-------EYFKKHPpKHNVIF 127
M28_like cd05642
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 164-310 4.88e-04

M28 Zn-peptidase-like; 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: 349894 [Multi-domain]  Cd Length: 347  Bit Score: 42.48  E-value: 4.88e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 164 AAEVLLHTATANGFQMVTSGAQSKAVSDWAITSLE-----GRLTGSggEDlPT--IVLVAHYDSFGVAPwLSY-----GA 231
Cdd:cd05642   53 AEEFREYAAASGGRMTVEVPSYVQGPASRIPFPVNisnvvATLKGS--ED-PDrvYVVSGHYDSRVSDV-MDYesdapGA 128

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 528515194 232 DSNGSGVAILLELARLFSRlYSYKRThagynLLFFLSGGGKFNYQGTKrWLEDNLDHTDAsllqdNVAFVLCLDTLGNS 310
Cdd:cd05642  129 NDDASGVAVSMELARIFAK-HRPKAT-----IVFTAVAGEEQGLYGST-FLAQTYRNNSV-----NVEGMLNNDIVGSS 195
M28_like cd08015
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 201-312 3.33e-03

M28 Zn-peptidase-like; 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: 349937 [Multi-domain]  Cd Length: 218  Bit Score: 39.12  E-value: 3.33e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 201 LTGSGGEDlPTIVLVAHYDSFGVAPwlsyGADSNGSGVAILLELARLFSRLYSY-KRThagynLLFFLSGGGKFNYQGTK 279
Cdd:cd08015    8 IPGSDKKD-EVVILGAHLDSWHGAT----GATDNGAGTAVMMEAMRILKAIGSKpKRT-----IRVALWGSEEQGLHGSR 77

                         90       100       110
                 ....*....|....*....|....*....|...
gi 528515194 280 RWLEDNLDHTDASLLQDNVAFVlclDTLGNSDN 312
Cdd:cd08015   78 AYVEKHFGDPPTMQLQRDHKKI---SAYFNLDN 107
M28_like cd05643
M28 Zn-peptidase-like; Peptidase family M28 (also called aminopeptidase Y family), ...
 205-322 5.71e-03

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: 38.92  E-value: 5.71e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515194 205 GGEDLPTIVLVAHYdsFGVAPwlsyGADSNGSGVAILLELARLFSRLYSyKRTHAGYNLLFFLSgggkfnYQGTKRWLED 284
Cdd:cd05643   79 GKETPPEIAFVAHL--CHPKP----GANDNASGSALLLEVARVLAKLIL-NRPKRGICFLWVPE------YTGTAAYFAQ 145

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 528515194 285 NLDHtdasllQDNVAFVLCLDTLGNSDN-----LHLHVSKPPK 322
Cdd:cd05643  146 HPDR------LKKIIAVINLDMVGEDQTktgstLMLVPTPLSF 182
 
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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