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Conserved domains on  [gi|665506030|ref|NP_001287859|]
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N-acetylated-alpha-linked acidic dipeptidase 2 isoform 2 [Homo sapiens]

Protein Classification

M28 family metallopeptidase( domain architecture ID 10114706)

M28 family metallopeptidase is a zinc-dependent peptidase that may be an aminopeptidase or a carboxypeptidase with co-catalytic zinc ions; contains a protease-associated (PA) domain insert which may participate in substrate binding and/or promote conformational changes; similar to Homo sapiens glutamate carboxypeptidase 2, N-acetylated-alpha-linked acidic dipeptidase 2 and N-acetylated-alpha-linked acidic dipeptidase-like protein

CATH:  3.40.630.10
EC:  3.4.-.-
Gene Ontology:  GO:0008237|GO:0016020|GO:0006508|GO:0008270
MEROPS:  M28
PubMed:  7674922|10493853|16381862
SCOP:  3000662|3000955|3000375

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 298-552 5.99e-124

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: 370.41  E-value: 5.99e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 298 KVRMHVYNInkitRIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIARSFGKLMSKGWRPRRTIIFAS 377
Cdd:cd08022   50 DVELEEYDV----PIWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFAS 125

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 378 WDAEEFGLLGSTEWAEENVKILQERSIAYINSDSSIEGnYTLRVDCTPLLYQLVYKLTKEIPSPDDGFESKSlyeswlek 457
Cdd:cd08022  126 WDAEEYGLIGSTEWVEENADWLQERAVAYLNVDVAVSG-STLRAAGSPLLQNLLREAAKEVQDPDEGATLKY-------- 196

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 458 DPSPENKNLPRINKLGSGSDFEAYFQRLGIASGRARYTKNKKtdkySSYPVYHTIYETFELVEKFYDPTFKKQLSVAQLR 537
Cdd:cd08022  197 LPSWWDDTGGEIGNLGSGSDYTPFLDHLGIASIDFGFSGGPT----DPYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVW 272

                        250
                 ....*....|....*
gi 665506030 538 GALVYELVDSKIIPF 552
Cdd:cd08022  273 GLLALRLADDPILPF 287
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 110-296 4.16e-84

PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to the peptidase M28 family. GCPII is also known N-acetylated-alpha-linked acidic dipeptidase (NAALDase1), folate hydrolase or prostate-specific membrane antigen (PSMA). GCPII is found in various human tissues including prostate, small intestine, and the central nervous system. In the brain, GCPII is known as NAALDase1, it functions as a NAALDase hydrolyzing the neuropeptide N-acetyl-L-aspartyl-L-glutamate (alpha-NAAG), to release free glutamate. In the small intestine, GCPII releases the terminal glutamate from poly-gamma-glutamated folates. GCPII (PSMA) is a useful cancer marker; its expression is markedly increased in prostate cancer and in tumor-associated neovasculature. GCPIII hydrolyzes alpha-NAAG with a lower efficiency than does GCPII; NAALADase L is not able to hydrolyze alpha-NAAG. The GCPII PA domain (referred to as the apical domain) participates in substrate binding and may act as a protein-protein interaction domain.


:

Pssm-ID: 239036  Cd Length: 220  Bit Score: 264.92  E-value: 4.16e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 110 PNETNANYISIVDEHETEIFKTsYLEPPPDgyenvTNIVPPYNAFSAQGMPEGDLVYVNYARTEDFFKLEReMGINCTGK 189
Cdd:cd02121    1 PVKRSLILTKPDGATGKLIEDT-VLEEPPS-----PDVVPPFHAYSASGNVTAELVYANYGSPEDFEYLED-LGIDVKGK 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 190 IVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPEV---QPYPKGWNLPGTAAQRGNVLNL-NGAGDPLTPGYPAK 265
Cdd:cd02121   74 IVIARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYITGengKTYPDGPARPPSGVQRGSVLFMsIGPGDPLTPGYPSK 153

                        170       180       190
                 ....*....|....*....|....*....|.
gi 665506030 266 EYTFRLDVEEGVGIPRIPVHPIGYNDAEILL 296
Cdd:cd02121  154 PGAERRDKEESKGLPKIPSLPISYRDAQPLL 184
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 584-704 1.73e-42

Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the transferrin receptor as shown in its crystal structure.


:

Pssm-ID: 461238  Cd Length: 116  Bit Score: 149.66  E-value: 1.73e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030  584 VSFDSLFSAVKNFSEAASDFHKR---LIQVDLNNPIAVRMMNDQLMLLERAFIDPLGLPGKLFYRHIIFAPSSHNKYAGE 660
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWakkWEDIKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 665506030  661 SFPGIYDAIFDIenkansrlAWKEVKKHISIAAFTIQAAAGTLK 704
Cdd:pfam04253  81 TFPGIRDAIEAG--------DWELAQKQISIVAKAIQSAAETLK 116
 
Name Accession Description Interval E-value
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 298-552 5.99e-124

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: 370.41  E-value: 5.99e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 298 KVRMHVYNInkitRIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIARSFGKLMSKGWRPRRTIIFAS 377
Cdd:cd08022   50 DVELEEYDV----PIWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFAS 125

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 378 WDAEEFGLLGSTEWAEENVKILQERSIAYINSDSSIEGnYTLRVDCTPLLYQLVYKLTKEIPSPDDGFESKSlyeswlek 457
Cdd:cd08022  126 WDAEEYGLIGSTEWVEENADWLQERAVAYLNVDVAVSG-STLRAAGSPLLQNLLREAAKEVQDPDEGATLKY-------- 196

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 458 DPSPENKNLPRINKLGSGSDFEAYFQRLGIASGRARYTKNKKtdkySSYPVYHTIYETFELVEKFYDPTFKKQLSVAQLR 537
Cdd:cd08022  197 LPSWWDDTGGEIGNLGSGSDYTPFLDHLGIASIDFGFSGGPT----DPYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVW 272

                        250
                 ....*....|....*
gi 665506030 538 GALVYELVDSKIIPF 552
Cdd:cd08022  273 GLLALRLADDPILPF 287
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 110-296 4.16e-84

PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to the peptidase M28 family. GCPII is also known N-acetylated-alpha-linked acidic dipeptidase (NAALDase1), folate hydrolase or prostate-specific membrane antigen (PSMA). GCPII is found in various human tissues including prostate, small intestine, and the central nervous system. In the brain, GCPII is known as NAALDase1, it functions as a NAALDase hydrolyzing the neuropeptide N-acetyl-L-aspartyl-L-glutamate (alpha-NAAG), to release free glutamate. In the small intestine, GCPII releases the terminal glutamate from poly-gamma-glutamated folates. GCPII (PSMA) is a useful cancer marker; its expression is markedly increased in prostate cancer and in tumor-associated neovasculature. GCPIII hydrolyzes alpha-NAAG with a lower efficiency than does GCPII; NAALADase L is not able to hydrolyze alpha-NAAG. The GCPII PA domain (referred to as the apical domain) participates in substrate binding and may act as a protein-protein interaction domain.


Pssm-ID: 239036  Cd Length: 220  Bit Score: 264.92  E-value: 4.16e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 110 PNETNANYISIVDEHETEIFKTsYLEPPPDgyenvTNIVPPYNAFSAQGMPEGDLVYVNYARTEDFFKLEReMGINCTGK 189
Cdd:cd02121    1 PVKRSLILTKPDGATGKLIEDT-VLEEPPS-----PDVVPPFHAYSASGNVTAELVYANYGSPEDFEYLED-LGIDVKGK 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 190 IVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPEV---QPYPKGWNLPGTAAQRGNVLNL-NGAGDPLTPGYPAK 265
Cdd:cd02121   74 IVIARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYITGengKTYPDGPARPPSGVQRGSVLFMsIGPGDPLTPGYPSK 153

                        170       180       190
                 ....*....|....*....|....*....|.
gi 665506030 266 EYTFRLDVEEGVGIPRIPVHPIGYNDAEILL 296
Cdd:cd02121  154 PGAERRDKEESKGLPKIPSLPISYRDAQPLL 184
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 584-704 1.73e-42

Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the transferrin receptor as shown in its crystal structure.


Pssm-ID: 461238  Cd Length: 116  Bit Score: 149.66  E-value: 1.73e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030  584 VSFDSLFSAVKNFSEAASDFHKR---LIQVDLNNPIAVRMMNDQLMLLERAFIDPLGLPGKLFYRHIIFAPSSHNKYAGE 660
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWakkWEDIKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 665506030  661 SFPGIYDAIFDIenkansrlAWKEVKKHISIAAFTIQAAAGTLK 704
Cdd:pfam04253  81 TFPGIRDAIEAG--------DWELAQKQISIVAKAIQSAAETLK 116
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 310-547 4.66e-35

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: 133.72  E-value: 4.66e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 310 TRIYNVVGTIRGSVEPDRYVILGGHRDSWVF---GAIDPTSGVAVLQEIARSFGKLmskGWRPRRTIIFASWDAEEFGLL 386
Cdd:COG2234   44 GDSRNVIAEIPGTDPPDEVVVLGAHYDSVGSigpGADDNASGVAALLELARALAAL---GPKPKRTIRFVAFGAEEQGLL 120

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 387 GSTEWAeENVKILQERSIAYINSDSSIEGNYTLRVDctpllyqlvykLTKEIPSPddgfESKSLYESWLEKDPSPENKNL 466
Cdd:COG2234  121 GSRYYA-ENLKAPLEKIVAVLNLDMIGRGGPRNYLY-----------VDGDGGSP----ELADLLEAAAKAYLPGLGVDP 184

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 467 PRINKLGSGSDFeAYFQRLGIASGRARytknkkTDKYSSYPVYHTIYETFELVekfyDPTFKKQlsVAQLRGALVYELVD 546
Cdd:COG2234  185 PEETGGYGRSDH-APFAKAGIPALFLF------TGAEDYHPDYHTPSDTLDKI----DLDALAK--VAQLLAALVYELAN 251


                 .
gi 665506030 547 S 547
Cdd:COG2234  252 A 252
Peptidase_M28 pfam04389
Peptidase family M28;
314-517 3.50e-25

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 103.13  E-value: 3.50e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030  314 NVVGTIRGSvEPDRYVILGGHRDSWVF--GAIDPTSGVAVLQEIARSFGKlmskGWRPRRTIIFASWDAEEFGLLGSTEW 391
Cdd:pfam04389   1 NVIAKLPGK-APDEVVLLSAHYDSVGTgpGADDNASGVAALLELARVLAA----GQRPKRSVRFLFFDAEEAGLLGSHHF 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030  392 AEENvkILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLTKEIPSPddgfeskslYESWLEKDPSPENKNLprink 471
Cdd:pfam04389  76 AKSH--PPLKKIRAVINLDMIGSGGPALLFQSGPKGSSLLEKYLKAAAKP---------YGVTLAEDPFQERGGP----- 139

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 665506030  472 lgSGSDFEAyFQRLGIASGRARYTKNKktdkyssyPVYHTIYETFE 517
Cdd:pfam04389 140 --GRSDHAP-FIKAGIPGLDLAFTDFG--------YRYHTPADTID 174
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
 161-251 9.53e-15

PA domain; The PA (Protease associated) domain is found as an insert domain in diverse proteases. The PA domain is also found in a plant vacuolar sorting receptor Swiss:O22925 and members of the RZF family Swiss:O43567. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors.


Pssm-ID: 460499 [Multi-domain]  Cd Length: 91  Bit Score: 70.24  E-value: 9.53e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030  161 EGDLV-----YVNYARTEDFfkleremgiNCTGKIVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPE----VQP 231
Cdd:pfam02225   1 TGPLVlapgcYAGDGIPADF---------DVKGKIVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVEGLGGPPgaggNEL 71

                          90       100
                  ....*....|....*....|
gi 665506030  232 YPKGWNLPGTAAQRGNVLNL 251
Cdd:pfam02225  72 YPDGIYIPAVGVSRADGEAL 91
PRK08262 PRK08262
M20 family peptidase;
338-404 5.56e-04

M20 family peptidase;


Pssm-ID: 236208 [Multi-domain]  Cd Length: 486  Bit Score: 43.01  E-value: 5.56e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 665506030 338 WVFGAIDPTSGVAVLQEIARSfgkLMSKGWRPRRTIIFASWDAEEFGLLGstewAEENVKILQERSI 404
Cdd:PRK08262 148 WGRGALDDKGSLVAILEAAEA---LLAQGFQPRRTIYLAFGHDEEVGGLG----ARAIAELLKERGV 207
 
Name Accession Description Interval E-value
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 298-552 5.99e-124

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: 370.41  E-value: 5.99e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 298 KVRMHVYNInkitRIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIARSFGKLMSKGWRPRRTIIFAS 377
Cdd:cd08022   50 DVELEEYDV----PIWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFAS 125

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 378 WDAEEFGLLGSTEWAEENVKILQERSIAYINSDSSIEGnYTLRVDCTPLLYQLVYKLTKEIPSPDDGFESKSlyeswlek 457
Cdd:cd08022  126 WDAEEYGLIGSTEWVEENADWLQERAVAYLNVDVAVSG-STLRAAGSPLLQNLLREAAKEVQDPDEGATLKY-------- 196

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 458 DPSPENKNLPRINKLGSGSDFEAYFQRLGIASGRARYTKNKKtdkySSYPVYHTIYETFELVEKFYDPTFKKQLSVAQLR 537
Cdd:cd08022  197 LPSWWDDTGGEIGNLGSGSDYTPFLDHLGIASIDFGFSGGPT----DPYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVW 272

                        250
                 ....*....|....*
gi 665506030 538 GALVYELVDSKIIPF 552
Cdd:cd08022  273 GLLALRLADDPILPF 287
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 110-296 4.16e-84

PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to the peptidase M28 family. GCPII is also known N-acetylated-alpha-linked acidic dipeptidase (NAALDase1), folate hydrolase or prostate-specific membrane antigen (PSMA). GCPII is found in various human tissues including prostate, small intestine, and the central nervous system. In the brain, GCPII is known as NAALDase1, it functions as a NAALDase hydrolyzing the neuropeptide N-acetyl-L-aspartyl-L-glutamate (alpha-NAAG), to release free glutamate. In the small intestine, GCPII releases the terminal glutamate from poly-gamma-glutamated folates. GCPII (PSMA) is a useful cancer marker; its expression is markedly increased in prostate cancer and in tumor-associated neovasculature. GCPIII hydrolyzes alpha-NAAG with a lower efficiency than does GCPII; NAALADase L is not able to hydrolyze alpha-NAAG. The GCPII PA domain (referred to as the apical domain) participates in substrate binding and may act as a protein-protein interaction domain.


Pssm-ID: 239036  Cd Length: 220  Bit Score: 264.92  E-value: 4.16e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 110 PNETNANYISIVDEHETEIFKTsYLEPPPDgyenvTNIVPPYNAFSAQGMPEGDLVYVNYARTEDFFKLEReMGINCTGK 189
Cdd:cd02121    1 PVKRSLILTKPDGATGKLIEDT-VLEEPPS-----PDVVPPFHAYSASGNVTAELVYANYGSPEDFEYLED-LGIDVKGK 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 190 IVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPEV---QPYPKGWNLPGTAAQRGNVLNL-NGAGDPLTPGYPAK 265
Cdd:cd02121   74 IVIARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYITGengKTYPDGPARPPSGVQRGSVLFMsIGPGDPLTPGYPSK 153

                        170       180       190
                 ....*....|....*....|....*....|.
gi 665506030 266 EYTFRLDVEEGVGIPRIPVHPIGYNDAEILL 296
Cdd:cd02121  154 PGAERRDKEESKGLPKIPSLPISYRDAQPLL 184
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 307-551 2.85e-77

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: 249.14  E-value: 2.85e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 307 NKITRIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIARSFGKLMSK-GWRPRRTIIFASWDAEEFGL 385
Cdd:cd03874   52 EEYSPITNVVGKIEGIEQPDRAIIIGAHRDSWGYGAGYPNSGTAVLLEIARLFQQLKKKfGWKPLRTIYFISWDGSEFGL 131

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 386 LGSTEWAEENVKILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLTKEIPSPDDGFESKSLYEswlekdpspenkn 465
Cdd:cd03874  132 AGSTELGEDRKASLKDEVYAYINIDQLVIGNSELDVDAHPLLQSLFRKASKKVKFPGNEDWWKHSPN------------- 198

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 466 lPRINKLGSGSDFEAYFQRLGIASGRARYTKNKktdkySSYPVYHTIYETFELVEKFYDPTFKKQLSVAQLRGALVYELV 545
Cdd:cd03874  199 -AKVSNLHQYGDWTPFLNHLGIPVAVFSFKNDR-----NASYPINSSYDTFEWLEKFLDPDFELHSTLAEFVGLLVLSLA 272


                 ....*.
gi 665506030 546 DSKIIP 551
Cdd:cd03874  273 EDPLLP 278
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
 285-553 9.25e-43

M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) subfamily. TfRs 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). While related in sequence to peptidase M28 glutamate carboxypeptidase II (also called prostate-specific membrane antigen or PSMA), TfR lacks the metal ion coordination centers and protease activity of that group.


Pssm-ID: 349946 [Multi-domain]  Cd Length: 285  Bit Score: 156.38  E-value: 9.25e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 285 HPIGYNDAEILLRKVR--------MHVYNiNKITRIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIA 356
Cdd:cd09848   22 HEAGSSGDENLANYIMnefknlklMKVWT-DEHYKIHNIFGVIKGFVEPDRYVVIGAQRDAWGPGAAKSGVGTALLLELA 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 357 RSFGKLMSK-GWRPRRTIIFASWDAEEFGLLGSTEWAEENVKILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLT 435
Cdd:cd09848  101 RTFSDMVKNdGFKPRRSIVFASWSAGDFGSVGATEWLEGYLSSLHLKAFTYISLDGAVLGDDSFKASASPLLYTLIESTM 180

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 436 KEIPSPDDGfeskslYESWLEKDPSPENKNlprINKLGSGSDFEAYFQRLGIASGRARYTKNkktdkYSSYPVYHTIYET 515
Cdd:cd09848  181 KQVKSPVHS------GQSYYETRSSWWASI---VEPLGLDSAAYPFLAFSGIPSVSFHFTED-----DEDYPFLGTKEDT 246

                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 665506030 516 FELVEKFYDP-TFKKQLSVAQLRGALVYELVDSKIIPFN 553
Cdd:cd09848  247 KENLDKFTNGeLWEVAAAAAEVAGQMALRLVHDHLLPLD 285
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 584-704 1.73e-42

Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the transferrin receptor as shown in its crystal structure.


Pssm-ID: 461238  Cd Length: 116  Bit Score: 149.66  E-value: 1.73e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030  584 VSFDSLFSAVKNFSEAASDFHKR---LIQVDLNNPIAVRMMNDQLMLLERAFIDPLGLPGKLFYRHIIFAPSSHNKYAGE 660
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWakkWEDIKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 665506030  661 SFPGIYDAIFDIenkansrlAWKEVKKHISIAAFTIQAAAGTLK 704
Cdd:pfam04253  81 TFPGIRDAIEAG--------DWELAQKQISIVAKAIQSAAETLK 116
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 310-547 4.66e-35

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: 133.72  E-value: 4.66e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 310 TRIYNVVGTIRGSVEPDRYVILGGHRDSWVF---GAIDPTSGVAVLQEIARSFGKLmskGWRPRRTIIFASWDAEEFGLL 386
Cdd:COG2234   44 GDSRNVIAEIPGTDPPDEVVVLGAHYDSVGSigpGADDNASGVAALLELARALAAL---GPKPKRTIRFVAFGAEEQGLL 120

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 387 GSTEWAeENVKILQERSIAYINSDSSIEGNYTLRVDctpllyqlvykLTKEIPSPddgfESKSLYESWLEKDPSPENKNL 466
Cdd:COG2234  121 GSRYYA-ENLKAPLEKIVAVLNLDMIGRGGPRNYLY-----------VDGDGGSP----ELADLLEAAAKAYLPGLGVDP 184

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 467 PRINKLGSGSDFeAYFQRLGIASGRARytknkkTDKYSSYPVYHTIYETFELVekfyDPTFKKQlsVAQLRGALVYELVD 546
Cdd:COG2234  185 PEETGGYGRSDH-APFAKAGIPALFLF------TGAEDYHPDYHTPSDTLDKI----DLDALAK--VAQLLAALVYELAN 251


                 .
gi 665506030 547 S 547
Cdd:COG2234  252 A 252
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 312-517 9.97e-29

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: 113.98  E-value: 9.97e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 312 IYNVVGTIRGSVEPDRYVILGGHRDSWVF--GAIDPTSGVAVLQEIARSFGKLmskGWRPRRTIIFASWDAEEFGLLGST 389
Cdd:cd02690    1 GYNVIATIKGSDKPDEVILIGAHYDSVPLspGANDNASGVAVLLELARVLSKL---QLKPKRSIRFAFWDAEELGLLGSK 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 390 EWAEENvKILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLTKEIpspddgfesKSLYESWLEKDPSPENKNLPRi 469
Cdd:cd02690   78 YYAEQL-LSSLKNIRAALNLDMIGGAGPDLYLQTAPGNDALVEKLLRAL---------AHELENVVYTVVYKEDGGTGG- 146

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 665506030 470 nklgsgSDFEaYFQRLGIASGRARytknkkTDKYSSYPVYHTIYETFE 517
Cdd:cd02690  147 ------SDHR-PFLARGIPAASLI------QSESYNFPYYHTTQDTLE 181
Peptidase_M28 pfam04389
Peptidase family M28;
314-517 3.50e-25

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 103.13  E-value: 3.50e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030  314 NVVGTIRGSvEPDRYVILGGHRDSWVF--GAIDPTSGVAVLQEIARSFGKlmskGWRPRRTIIFASWDAEEFGLLGSTEW 391
Cdd:pfam04389   1 NVIAKLPGK-APDEVVLLSAHYDSVGTgpGADDNASGVAALLELARVLAA----GQRPKRSVRFLFFDAEEAGLLGSHHF 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030  392 AEENvkILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLTKEIPSPddgfeskslYESWLEKDPSPENKNLprink 471
Cdd:pfam04389  76 AKSH--PPLKKIRAVINLDMIGSGGPALLFQSGPKGSSLLEKYLKAAAKP---------YGVTLAEDPFQERGGP----- 139

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 665506030  472 lgSGSDFEAyFQRLGIASGRARYTKNKktdkyssyPVYHTIYETFE 517
Cdd:pfam04389 140 --GRSDHAP-FIKAGIPGLDLAFTDFG--------YRYHTPADTID 174
PA_TfR cd02128
PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This ...
 117-298 3.39e-24

PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This group contains various PA domain-containing proteins similar to human TfR1 and TfR2. TfR1 and TfR2 are type II membrane proteins, belonging to the peptidase M28 family. TfR1 is homodimeric, widely expressed, and a key player in the uptake of iron-loaded transferrin (Tf) into cells. The TfR1 homodimer binds two molecules of Tf and this complex is internalized. In addition to its role in iron uptake, TfR1 may participate in cell growth and proliferation. TfR2 also binds Tf but with a significantly lower affinity than does TfR1. TfR2 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. HFE and TfR2 interact in cells. By one model for serum iron sensing, at low or basal iron concentrations, HFE and TFR1 form a complex at the plasma membrane; at increased Tf, Tf competes with HFE for binding of TfR1, resulting in HFE disassociating from TfR1 and associating with TfR2 . The TfR1-TfR2 association might initiate a signal cascade leading to the induction of hepcidin (a small peptide hormone that controls systemic iron levels). Human mutations in TfR2 are associated with a form of hemochromatosis (HFE3). The significance of the PA domain to TfRs has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239043 [Multi-domain]  Cd Length: 183  Bit Score: 100.17  E-value: 3.39e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 117 YISIVDEHETEifktsYLEPPPDGYEnvtnivppynAFSAQGMPEGDLVYVNYARTEDFFKLeREMGINCTGKIVIARYG 196
Cdd:cd02128    1 SVIIGDAGRLN-----ELVENPGGYV----------AYSAAGTVTGKLVYANYGRKKDFEDL-QSVGVSVNGSVVLVRAG 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 197 KIFRGNKVKNAMLAGAIGIILYSDPADYfaPEVqpypkgwnlPGTAAQRGNVlNLnGAGDPLTPGYPAKEYTFRLDVEEG 276
Cdd:cd02128   65 KISFAEKVANAEKLGAVGVLIYPDPADF--PID---------PSETALFGHV-HL-GTGDPYTPGFPSFNHTQFPPSQSS 131

                        170       180
                 ....*....|....*....|..
gi 665506030 277 vGIPRIPVHPIGYNDAEILLRK 298
Cdd:cd02128  132 -GLPNIPAQTISAAAAAKLLSK 152
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
 170-410 2.91e-21

M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate carboxypeptidase (PGCP; blood plasma glutamate carboxypeptidase; EC 3.4.17.21) subfamily. PGCP is a 56kDa glutamate carboxypeptidase that is mainly produced in mammalian placenta and kidney, the majority of which is thought to be secreted into the bloodstream. Similar proteins are also found in other species, including bacteria. These proteins contain protease-associated (PA) domain inserts between the first and second strands of the central beta sheet in the protease-like domain. The PA domains may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. The exact physiological substrates of PGCP are unknown, although this enzyme may play an important role in the hydrolysis of circulating peptides. Its closest homolog encodes an important brain glutamate carboxypeptidase II (NAALADase) identical to the prostate-specific membrane antigen (PSMA), which serves as a marker for prostatic cancer metastasis. Hypermethylation of PGCP gene has been associated with human bronchial epithelial (HBE) cell immortalization and lung cancer. PGCP also provides an attractive target for serological analysis in hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) patients.


Pssm-ID: 349879 [Multi-domain]  Cd Length: 425  Bit Score: 96.99  E-value: 2.91e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 170 ARTEDFFKLEREMGiNCTGKIVI-----ARYGK--IFRGNKVKNAMLAGAIGIILYSdpadyfapeVQPYpkGWNLPGTA 242
Cdd:cd03883  109 VVVFSFEELQAKAD-EVKGKIVVynqpfKGYGEtvKYRGQGAVEAAKYGAVAVLIRS---------ITPF--SIYSPHTG 176

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 243 AQRgnvlnlngagdpltpgypakeytfrldveEGVGIPRIPVHPIGYNDAEILLR------KVRMHVYNINKI---TRIY 313
Cdd:cd03883  177 IMR-----------------------------YQDGVTKIPAAAITVEDAEMLSRmaargqKIVIELKMEAKTypdATSR 227

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 314 NVVGTIRGSVEPDRYVILGGHRDSWVF--GAIDPTSGVAVLQEIARSFGKLmskGWRPRRTIIFASWDAEEFGLLGSTEW 391
Cdd:cd03883  228 NVIAEITGSKYPDEVVLVGGHLDSWDVgtGAMDDGGGVAISWEALKLIKDL---GLKPKRTIRVVLWTGEEQGLVGAKAY 304

                        250
                 ....*....|....*....
gi 665506030 392 AEENVKILQERSIAyINSD 410
Cdd:cd03883  305 AEAHKDELENHVFA-MESD 322
M28_like cd03877
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
 313-410 1.33e-16

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: 78.82  E-value: 1.33e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 313 YNVVGTIRGSVEPDRYVILGGHRDSWVF-----------GAIDPTSGVAVLQEIARSFgklmSKGWRPRRTIIFASWDAE 381
Cdd:cd03877    2 HNVVGVLEGSDLPDETIVIGAHYDHLGIgggdsgdkiynGADDNASGVAAVLELARYF----AKQKTPKRSIVFAAFTAE 77

                         90       100
                 ....*....|....*....|....*....
gi 665506030 382 EFGLLGSTEWAeENVKILQERSIAYINSD 410
Cdd:cd03877   78 EKGLLGSKYFA-ENPKFPLDKIVAMLNLD 105
M28_like cd08015
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 313-411 4.97e-16

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: 77.64  E-value: 4.97e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 313 YNVVGTIRGSVEPDRYVILGGHRDSW--VFGAIDPTSGVAVLQEIARSFGKLMSKgwrPRRTIIFASWDAEEFGLLGSTE 390
Cdd:cd08015    2 YNVIAEIPGSDKKDEVVILGAHLDSWhgATGATDNGAGTAVMMEAMRILKAIGSK---PKRTIRVALWGSEEQGLHGSRA 78

                         90       100
                 ....*....|....*....|....*....
gi 665506030 391 WAE---ENVKILQERSI-----AYINSDS 411
Cdd:cd08015   79 YVEkhfGDPPTMQLQRDhkkisAYFNLDN 107
M28_like_PA cd05660
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ...
 256-411 3.56e-15

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: 76.63  E-value: 3.56e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 256 DPLTPG------YPAKEYTfRLDVEEGVGIPripvhpiGYndaeilLRKVRMhVYNINKITRiYNVVGTIRGSVEPDRYV 329
Cdd:cd05660   13 APGSEGekktvdYLAEQFK-ELGLKPAGSDG-------SY------LQAVPL-VSKIEYSTS-HNVVAILPGSKLPDEYI 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 330 ILGGHRDSW----------VF-GAIDPTSGVAVLQEIARSFGKlmsKGWRPRRTIIFASWDAEEFGLLGSTEWAE-ENVK 397
Cdd:cd05660   77 VLSAHWDHLgigppiggdeIYnGAVDNASGVAAVLELARVFAA---QDQRPKRSIVFLAVTAEEKGLLGSRYYAAnPIFP 153

                        170
                 ....*....|....
gi 665506030 398 IlqERSIAYINSDS 411
Cdd:cd05660  154 L--DKIVANLNIDM 165
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
 145-298 9.15e-15

PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. Proteins into which the PA domain is inserted include the following: i) various signal peptide peptidases including, hSPPL2a and 2b which catalyze the intramembrane proteolysis of tumor necrosis factor alpha, ii) various proteins containing a C3H2C3 RING finger including, Arabidopsis ReMembR-H2 protein and various E3 ubiquitin ligases such as human GRAIL (gene related to anergy in lymphocytes), iii) EDEM3 (ER-degradation-enhancing mannosidase-like 3 protein), iv) various plant vacuolar sorting receptors such as Pisum sativum BP-80, v) glutamate carboxypeptidase II (GCPII), vi) yeast aminopeptidase Y, vii) Vibrio metschnikovii VapT, a sodium dodecyl sulfate (SDS) resistant extracellular alkaline serine protease, viii) lactocepin (a cell envelope-associated protease from Lactobacillus paracasei subsp. paracasei NCDO 151), ix) various subtilisin-like proteases such as melon Cucumisin, and x) human TfR (transferrin receptor) 1 and 2.


Pssm-ID: 238300 [Multi-domain]  Cd Length: 126  Bit Score: 71.39  E-value: 9.15e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 145 TNIVPPYNAFSAQGMPEGDLVYVNYARTEDFfkleremGINCTGKIVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADy 224
Cdd:cd00538   11 GSALLFNPPSSPVGVVAGPLVGCGYGTTDDS-------GADVKGKIVLVRRGGCSFSEKVKNAQKAGAKAVIIYNNGDD- 82

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665506030 225 fapevqPYPKGWNlpgtaaqrgnvlnlngagdpltpgypakeytfrldVEEGVGIPRIPVHPIGYNDAEILLRK 298
Cdd:cd00538   83 ------PGPQMGS-----------------------------------VGLESTDPSIPTVGISYADGEALLSL 115
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
 161-251 9.53e-15

PA domain; The PA (Protease associated) domain is found as an insert domain in diverse proteases. The PA domain is also found in a plant vacuolar sorting receptor Swiss:O22925 and members of the RZF family Swiss:O43567. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors.


Pssm-ID: 460499 [Multi-domain]  Cd Length: 91  Bit Score: 70.24  E-value: 9.53e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030  161 EGDLV-----YVNYARTEDFfkleremgiNCTGKIVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPE----VQP 231
Cdd:pfam02225   1 TGPLVlapgcYAGDGIPADF---------DVKGKIVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVEGLGGPPgaggNEL 71

                          90       100
                  ....*....|....*....|
gi 665506030  232 YPKGWNLPGTAAQRGNVLNL 251
Cdd:pfam02225  72 YPDGIYIPAVGVSRADGEAL 91
M28_like cd05642
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 310-393 6.65e-14

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: 73.68  E-value: 6.65e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 310 TRIYNVVGTIRGSVEPDRYVILGGHRDSWVF----------GAIDPTSGVAVLQEIARSFGKlmskgWRPRRTIIFASWD 379
Cdd:cd05642   86 VNISNVVATLKGSEDPDRVYVVSGHYDSRVSdvmdyesdapGANDDASGVAVSMELARIFAK-----HRPKATIVFTAVA 160

                         90
                 ....*....|....
gi 665506030 380 AEEFGLLGSTEWAE 393
Cdd:cd05642  161 GEEQGLYGSTFLAQ 174
PA_hNAALADL2_like cd02131
PA_hNAALADL2_like: Protease-associated domain containing proteins like human N-acetylated ...
 150-296 6.03e-12

PA_hNAALADL2_like: Protease-associated domain containing proteins like human N-acetylated alpha-linked acidic dipeptidase-like 2 protein (hNAALADL2). This group contains various PA domain-containing proteins similar to hNAALADL2. The function of hNAALADL2 is unknown. This gene has been mapped to a chromosomal region associated with Cornelia de Lange syndrome. The significance of the PA domain to hNAALADL2 has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239046  Cd Length: 153  Bit Score: 64.19  E-value: 6.03e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 150 PYNAFSAQGMPEGDLVYVNYARTEDFFKLEREMgiNCTGKIVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADyfapev 229
Cdd:cd02131    5 SYAAYSAKGTLQAEVVDVQYGSVEDLRRIRDNM--NVTNQIALLKLGQAPLLYKLSLLEEAGFGGVLLYVDPCD------ 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 665506030 230 qpYPKGWNLpgtaAQRGNVLNLNGAGDPLTPGYPAKEYTFRldvEEGVGIPRIPVHPIGYNDAEILL 296
Cdd:cd02131   77 --LPKTRHT----WHQAFMVSLNPGGDPSTPGYPSADQSCR---QCRGNLTSLLVQPISAYLAKKLL 134
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 313-399 9.13e-12

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: 66.50  E-value: 9.13e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 313 YNVVGTIRGSVEPDRYVILGGHRDS---WVF------GAIDPTSGVAVLQEIARSfgkLMSKGWRPRRTIIFASWDAEEF 383
Cdd:cd03879   75 PSIIATIPGSEKSDEIVVIGAHQDSingSNPsngrapGADDDGSGTVTILEALRV---LLESGFQPKNTIEFHWYAAEEG 151

                         90       100
                 ....*....|....*....|
gi 665506030 384 GLLGS----TEWAEENVKIL 399
Cdd:cd03879  152 GLLGSqaiaTQYKSEGKNVK 171
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
 291-408 5.31e-11

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: 64.15  E-value: 5.31e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 291 DAEILLRKVRMHVYNINKITRIYNVVGTIRGSV-EPDRYVILGGHRDSWV--FGAIDPTSGVAVLQEIARSFGKlmsKGW 367
Cdd:cd03875   58 DDTGSGSFNFLSSGMTLVYFEVTNIVVRISGKNsNSLPALLLNAHFDSVPtsPGATDDGMGVAVMLEVLRYLSK---SGH 134

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 665506030 368 RPRRTIIFASWDAEEFGLLGST-----EWAEENVKilqersiAYIN 408
Cdd:cd03875  135 QPKRDIIFLFNGAEENGLLGAHafitqHPWAKNVR-------AFIN 173
M28_SGAP_like cd03876
M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family ...
 288-490 4.85e-10

M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family M28; Streptomyces griseus Aminopeptidase (SGAP, Leucine aminopeptidase (LAP), aminopeptidase S, Mername-AA022 peptidase) subfamily. SGAP is a di-zinc exopeptidase with high preference towards large hydrophobic amino-terminal residues, with Leu being the most efficiently cleaved. It can accommodate all except Pro and Glu residues in the P1' position. It is a monomeric (30 kDa), calcium-activated and calcium-stabilized enzyme; its activation by calcium correlates with substrate specificity and it has thermal stability only in the presence of calcium. Although SGAP contains a calcium binding site, it is not conserved in many members of this subfamily. SGAP is present in the extracellular fluid of S. griseus cultures.


Pssm-ID: 349873 [Multi-domain]  Cd Length: 289  Bit Score: 61.16  E-value: 4.85e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 288 GYND-AEILLRKVR-MHVYNINK------ITRIYNVVGTIRGSvEPDRYVILGGHRDSwVF---GAIDPTSGVAVLQEIA 356
Cdd:cd03876   31 GYNAsVDYVKNELKaAGYYDVTLqpftslYRTTYNVIAETKGG-DPNNVVMLGAHLDS-VSagpGINDNGSGSAALLEVA 108

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 357 RSFGKlmskgWRPRRTIIFASWDAEEFGLLGSTEWA-----EENVKILqersiAYINSD---SSIEGNYTLRVDCTplly 428
Cdd:cd03876  109 LALAK-----FKVKNAVRFAWWTAEEFGLLGSKFYVnnlssEERSKIR-----LYLNFDmiaSPNYGYFIYDGDGS---- 174

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665506030 429 qlvyklTKEIPSPDDGFESKSLYESWLEKdpspenKNLPRINKLGSG-SDFEAyFQRLGIASG 490
Cdd:cd03876  175 ------AFNLTGPPGSAEIERLFEAYFTS------LGLPSTPTEFDGrSDYAP-FIEAGIPAG 224
M28_like cd05640
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
 270-394 7.87e-09

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: 57.46  E-value: 7.87e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 270 RLDVEEGVGIPRIPVHP-IGYNDAEILLRKV-RMHVYNINKITRIY------NVVGTIRGSVEPDRYVILGGHRDSW--V 339
Cdd:cd05640    2 RAHLEQLVRMERNPHDPsAFLAAAAEYIAQElVGSGYNVTSHFFSHqegvyaNLIADLPGSYSQDKLILIGAHYDTVpgS 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 340 FGAIDPTSGVAVLQEIARSFGKLmskgwRPRRTIIFASWDAEEF-----GLLGSTEWAEE 394
Cdd:cd05640   82 PGADDNASGVAALLELARLLATL-----DPNHTLRFVAFDLEEYpffarGLMGSHAYAED 136
M28_like_PA cd05661
M28 Zn-peptidase containing a PA domain insert; Peptidase family M28 (also called ...
 313-543 9.81e-09

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: 56.81  E-value: 9.81e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 313 YNVVGTIR--GSVEPDRYVILGGHRDSWVF--GAIDPTSGVAVLQEIARSFGKLMSKgwrprRTIIFASWDAEEFGLLGS 388
Cdd:cd05661   61 HNVIATKKpdNNKNNNDIIIVTSHYDSVVKapGANDNASGTAVTLELARVFKKVKTD-----KELRFIAFGAEENGLLGS 135

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 389 TEWAEENVKILQERSIAYIN------SDSSIEGNYTLRVDCTPllyQLVYKLTKEipspddgfeskslyeswlekdpspE 462
Cdd:cd05661  136 KYYVASLSEDEIKRTIGVFNldmvgtSDAKAGDLYAYTIDGKP---NLVTDSGAA------------------------A 188

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 463 NKNLPRINKLGSG--SDFEAyFQRLGIASgrARYTKNKKTDKYSSyPVYHTIYETFELVEKfydptfKKQLSVAQLRGAL 540
Cdd:cd05661  189 SKRLSGVLPLVQQgsSDHVP-FHEAGIPA--ALFIHMDPETEPVE-PWYHTPNDTVENISK------ERLDNALDIVGTA 258


                 ...
gi 665506030 541 VYE 543
Cdd:cd05661  259 VYQ 261
M28_like_PA_PDZ_associated cd05663
M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ ...
 284-410 1.33e-08

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: 56.69  E-value: 1.33e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 284 VHPIGYNDAEillrkvrMHVYNINKITrIYNVVGTI-RGSVEPDRYVILGGHRDSWVFG----------------AIDPT 346
Cdd:cd05663   35 LEPGLDNGTY-------FQPFEFTTGT-GRNVIGVLpGKGDVADETVVVGAHYDHLGYGgegslargdeslihngADDNA 106

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665506030 347 SGVAVLQEIARSFGKLMSKGWRPRRtIIFASWDAEEFGLLGSTEWAeENVKILQERSIAYINSD 410
Cdd:cd05663  107 SGVAAMLELAAKLVDSDTSLALSRN-LVFIAFSGEELGLLGSKHFV-KNPPFPIKNTVYMINMD 168
M28_like cd05662
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
 314-410 4.70e-08

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: 54.78  E-value: 4.70e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 314 NVVGTIRGSVEPDRYVILGGHRD------SWVF-GAIDPTSGVAVLQEIARSFgklmsKGWRPRRTIIFASWDAEEFGLL 386
Cdd:cd05662   64 NVLAVIKGSEPPTKWRVVSAHYDhlgirgGKIYnGADDNASGVAALLALAEYF-----KKHPPKHNVIFAATDAEEPGLR 138

                         90       100
                 ....*....|....*....|....*
gi 665506030 387 GSTEWAEEnvKILQERSIAY-INSD 410
Cdd:cd05662  139 GSYAFVEA--LKVPRAQIELnINLD 161
PA_C5a_like cd02133
PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a ...
 163-218 1.14e-05

PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a peptidase. This group contains various PA domain-containing proteins similar to S. pyogenes C5a, including, i) Vpr, a minor extracellular serine protease from Bacillus subtilis, ii) a large molecular mass collagenolytic protease from Geobacillus collagenovorans MO-1, and iii) PrtS, a cell envelope protease from Streptococcus thermophilus CNRZ 385. Proteins in this group belong to the peptidase S8 family. C5a peptidase is a cell surface serine protease which specifically inactivates C5a [a chemotactic peptide, which attracts polymorphonuclear leukocytes (PMNs)], by cleaving it to release a 7-residue carboxy-terminal fragment which contains the PMN binding site. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239048 [Multi-domain]  Cd Length: 143  Bit Score: 45.74  E-value: 1.14e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 665506030 163 DLVYVNYARTEDFFKLEREmginctGKIV-IARyGKIFRGNKVKNAMLAGAIGIILY 218
Cdd:cd02133   29 ELVDAGLGTPEDFEGKDVK------GKIAlIQR-GEITFVEKIANAKAAGAVGVIIY 78
PRK08262 PRK08262
M20 family peptidase;
338-404 5.56e-04

M20 family peptidase;


Pssm-ID: 236208 [Multi-domain]  Cd Length: 486  Bit Score: 43.01  E-value: 5.56e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 665506030 338 WVFGAIDPTSGVAVLQEIARSfgkLMSKGWRPRRTIIFASWDAEEFGLLGstewAEENVKILQERSI 404
Cdd:PRK08262 148 WGRGALDDKGSLVAILEAAEA---LLAQGFQPRRTIYLAFGHDEEVGGLG----ARAIAELLKERGV 207
PA_M28_1_3 cd04822
PA_M28_1_3: Protease-associated (PA) domain, peptidase family M28, subfamily-1, subgroup 3. A ...
 153-259 5.86e-04

PA_M28_1_3: Protease-associated (PA) domain, peptidase family M28, subfamily-1, subgroup 3. A subgroup of PA-domain containing proteins belonging to the peptidase family M28. Family M28 contains aminopeptidases and carboxypeptidases, and has co-catalytic zinc ions. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. Proteins into which the PA domain is inserted include the following members of the peptidase family M28: i) prostate-specific membrane antigen (PSMA), ii) yeast aminopeptidase Y, and ii) human TfR (transferrin receptor)1 and human TfR2. The proteins listed above belong to other subgroups; relatively little is known about proteins in this subgroup.


Pssm-ID: 240126 [Multi-domain]  Cd Length: 151  Bit Score: 40.90  E-value: 5.86e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 153 AFSAQGMPEGDLVYVNYARTEDFFKLEREMGINCTGKIV-IARY-------GKIFRGN----------KVKNAMLAGAIG 214
Cdd:cd04822   13 AFSRSGAVTAPVVFAGYGITAPELGYDDYAGLDVKGKIVlVLRHepqeddaNSRFNGPgltrhaglryKATNARRHGAAA 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 665506030 215 IILYSDPAD--YFAPEVQPYPkGWNLP--GTAAQRGNVLNLNGAGDPLT 259
Cdd:cd04822   93 VIVVNGPNShsGDADRLPRFG-GTAPQrvDIAAADPWFTAAEAAGKDLT 140
PA_subtilisin_like cd02120
PA_subtilisin_like: Protease-associated domain containing subtilisin-like proteases. This ...
 187-223 1.22e-03

PA_subtilisin_like: Protease-associated domain containing subtilisin-like proteases. This group contains various PA domain-containing subtilisin-like proteases including melon cucumisin, Arabidopsis thaliana Ara12, a nodule specific serine protease from Alnus glutinosa ag12, members of the tomato P69 family, and tomato LeSBT2. These proteins belong to the peptidase S8 family. Cucumisin from the juice of melon fruits is a thermostable serine peptidase, with a broad substrate specificity for oligopeptides and proteins. A. thaliana Ara12 is a thermostable, extracellular serine protease, found chiefly in silique tissue and stem tissue. Ara12 is stimulated by Ca2+ ions. A. glutinosa ag12 is expressed at high levels in the nodules, and at low levels in the shoot tips; it is implicated in both symbiotic and non-symbiotic processes in plant development. The tomato P69 protease family is comprised of various protein isoforms of approximately 69KDa. These isoforms accumulate extracellularly. Some of the P69 genes are tightly regulated in a tissue specific fashion, and by environmental and developmental signals. For example: infection with avirulent bacteria activates transcription of the genes for the P69 B and C isoforms, the P69 E transcript was detected only in roots, and the P69F transcript only in hydathodes. The Tomato LeSBT2 subtilase transcript was not detected in flowers and roots, but was present in cotyledons and leaves. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239035 [Multi-domain]  Cd Length: 126  Bit Score: 39.32  E-value: 1.22e-03
                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 665506030 187 TGKIVIARYGKIF-RGNKVKNAMLAGAIGIILYSDPAD 223
Cdd:cd02120   51 KGKIVLCDRGGNTsRVAKGDAVKAAGGAGMILANDPTD 88
PRK09133 PRK09133
hypothetical protein; Provisional
 314-430 1.75e-03

hypothetical protein; Provisional


Pssm-ID: 236388 [Multi-domain]  Cd Length: 472  Bit Score: 41.53  E-value: 1.75e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 314 NVVGTIRGSvEPDRYVILGGH-------RDSWV---F------------GAIDPTSGVAVLqeIArSFGKLMSKGWRPRR 371
Cdd:PRK09133  90 NLVARLRGT-DPKKPILLLAHmdvveakREDWTrdpFklveengyfygrGTSDDKADAAIW--VA-TLIRLKREGFKPKR 165

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 665506030 372 TIIFASWDAEEFGLLGSTEWAEENVKILQERSIAyINSDssieGNYTLRVDCTPLLYQL 430
Cdd:PRK09133 166 DIILALTGDEEGTPMNGVAWLAENHRDLIDAEFA-LNEG----GGGTLDEDGKPVLLTV 219
Zinc_peptidase_like cd03873
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ...
 314-394 2.78e-03

Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and signaling pathways throughout all kingdoms of life. This hierarchy contains zinc peptidases that correspond to the MH clan in the MEROPS database, which contains 4 families (M18, M20, M28, M42). The peptidase M20 family includes carboxypeptidases such as the glutamate carboxypeptidase from Pseudomonas, the thermostable carboxypeptidase Ss1 of broad specificity from archaea and yeast Gly-X carboxypeptidase. The dipeptidases include bacterial dipeptidase, peptidase V (PepV), a non-specific eukaryotic dipeptidase, and two Xaa-His dipeptidases (carnosinases). There is also the bacterial aminopeptidase, peptidase T (PepT) that acts only on tripeptide substrates and has therefore been termed a tripeptidase. Peptidase family M28 contains aminopeptidases and carboxypeptidases, and has co-catalytic zinc ions. However, several enzymes in this family utilize other first row transition metal ions such as cobalt and manganese. 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. Glutamate carboxypeptidase II and plasma glutamate carboxypeptidase hydrolyze dipeptides. Peptidase families M18 and M42 contain metallo-aminopeptidases. M18 is widely distributed in bacteria and eukaryotes. However, only yeast aminopeptidase I and mammalian aspartyl aminopeptidase have been characterized in detail. Some M42 (also known as glutamyl aminopeptidase) enzymes exhibit aminopeptidase specificity while others also have acylaminoacyl-peptidase activity (i.e. hydrolysis of acylated N-terminal residues).


Pssm-ID: 349870 [Multi-domain]  Cd Length: 200  Bit Score: 39.72  E-value: 2.78e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665506030 314 NVVGTIRGSvEPDRYVILGGHRDS-------WVF----------------GAIDPTSGVAVLQEIARSFGKlmsKGWRPR 370
Cdd:cd03873    1 NLIARLGGG-EGGKSVALGAHLDVvpagegdNRDppfaedteeegrlygrGALDDKGGVAAALEALKRLKE---NGFKPK 76

                         90       100
                 ....*....|....*....|....
gi 665506030 371 RTIIFASWDAEEFGLLGSTEWAEE 394
Cdd:cd03873   77 GTIVVAFTADEEVGSGGGKGLLSK 100
 
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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