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Conserved domains on  [gi|1072989427|ref|XP_018445417|]
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probable glutamate carboxypeptidase LAMP1 [Raphanus sativus]

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 ...
 301-525 5.75e-135

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: 397.76  E-value: 5.75e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 301 IENVIGVIEGEEEPDRYVILGNHRDAWTFGAVDPNSGTAVLLEIAQRLDKLQKRGWKPRRTIILCNWDAEEYALIGSTEW 380
Cdd:cd08022    60 IWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFASWDAEEYGLIGSTEW 139

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 381 VEENREMLASRAVAYLNVDCAVSGPGFRVSATPQLDDLIKQAAKEVQDPDNTTQTVYESWIGSSNSDEIGRLgGGGSDYA 460
Cdd:cd08022   140 VEENADWLQERAVAYLNVDVAVSGSTLRAAGSPLLQNLLREAAKEVQDPDEGATLKYLPSWWDDTGGEIGNL-GSGSDYT 218

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1072989427 461 SFVQHVGVPAVDMLFGGG----YPVYHSMYDDFTWMEKFGDPMFQRHVAIASVLGLVALRLADDEFLPF 525
Cdd:cd08022   219 PFLDHLGIASIDFGFSGGptdpYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVWGLLALRLADDPILPF 287
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 93-275 9.35e-65

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: 213.31  E-value: 9.35e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427  93 PVHRSLVLTttpkdsaNPTTTTFALEQEHVGDNPHADEVTPTFHGYAKSGNVSGPAAYANYGRVEDF----AAGGNFSGA 168
Cdd:cd02121     1 PVKRSLILT-------KPDGATGKLIEDTVLEEPPSPDVVPPFHAYSASGNVTAELVYANYGSPEDFeyleDLGIDVKGK 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 169 VAVARYGKIYRGDIVRNAYEAGAVGVVIYTDKRDYGG-----EECFPESRWMPPSGVQVGTVY---NGLGDPTTPGWASV 240
Cdd:cd02121    74 IVIARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYitgenGKTYPDGPARPPSGVQRGSVLfmsIGPGDPLTPGYPSK 153

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1072989427 241 NGCERLSEEDvelSGDAPGIPSLPISAADAEVILK 275
Cdd:cd02121   154 PGAERRDKEE---SKGLPKIPSLPISYRDAQPLLK 185
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 550-668 6.79e-36

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: 130.78  E-value: 6.79e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 550 IDLSPLIKSIQDLYTAAQEINIE----KEEGVKGALRVREVNDRLMMAERALTDRDGLSERPWYKHLVYGPSKYDDYGSK 625
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWakkwEDIKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1072989427 626 SFPGVDDAIDnakrvntKASWEHVQHEVWRVSRAIRHASLVLR 668
Cdd:pfam04253  81 TFPGIRDAIE-------AGDWELAQKQISIVAKAIQSAAETLK 116
 
Name Accession Description Interval E-value
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 301-525 5.75e-135

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: 397.76  E-value: 5.75e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 301 IENVIGVIEGEEEPDRYVILGNHRDAWTFGAVDPNSGTAVLLEIAQRLDKLQKRGWKPRRTIILCNWDAEEYALIGSTEW 380
Cdd:cd08022    60 IWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFASWDAEEYGLIGSTEW 139

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 381 VEENREMLASRAVAYLNVDCAVSGPGFRVSATPQLDDLIKQAAKEVQDPDNTTQTVYESWIGSSNSDEIGRLgGGGSDYA 460
Cdd:cd08022   140 VEENADWLQERAVAYLNVDVAVSGSTLRAAGSPLLQNLLREAAKEVQDPDEGATLKYLPSWWDDTGGEIGNL-GSGSDYT 218

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1072989427 461 SFVQHVGVPAVDMLFGGG----YPVYHSMYDDFTWMEKFGDPMFQRHVAIASVLGLVALRLADDEFLPF 525
Cdd:cd08022   219 PFLDHLGIASIDFGFSGGptdpYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVWGLLALRLADDPILPF 287
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 93-275 9.35e-65

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: 213.31  E-value: 9.35e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427  93 PVHRSLVLTttpkdsaNPTTTTFALEQEHVGDNPHADEVTPTFHGYAKSGNVSGPAAYANYGRVEDF----AAGGNFSGA 168
Cdd:cd02121     1 PVKRSLILT-------KPDGATGKLIEDTVLEEPPSPDVVPPFHAYSASGNVTAELVYANYGSPEDFeyleDLGIDVKGK 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 169 VAVARYGKIYRGDIVRNAYEAGAVGVVIYTDKRDYGG-----EECFPESRWMPPSGVQVGTVY---NGLGDPTTPGWASV 240
Cdd:cd02121    74 IVIARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYitgenGKTYPDGPARPPSGVQRGSVLfmsIGPGDPLTPGYPSK 153

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1072989427 241 NGCERLSEEDvelSGDAPGIPSLPISAADAEVILK 275
Cdd:cd02121   154 PGAERRDKEE---SKGLPKIPSLPISYRDAQPLLK 185
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 303-521 2.37e-39

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: 145.66  E-value: 2.37e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 303 NVIGVIEGEEEPDRYVILGNHRDAWTF---GAVDPNSGTAVLLEIAQRLdklQKRGWKPRRTIILCNWDAEEYALIGSTE 379
Cdd:COG2234    48 NVIAEIPGTDPPDEVVVLGAHYDSVGSigpGADDNASGVAALLELARAL---AALGPKPKRTIRFVAFGAEEQGLLGSRY 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 380 WVEENREMLAsRAVAYLNVDC-AVSGPGFRVSAT-----PQLDDLIKQAAKEVQDpdnttqtvyeswiGSSNSDEIGRLG 453
Cdd:COG2234   125 YAENLKAPLE-KIVAVLNLDMiGRGGPRNYLYVDgdggsPELADLLEAAAKAYLP-------------GLGVDPPEETGG 190

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 454 GGGSDYASFVQHvGVPAVDMLFGG--GYPVYHSMYDDftwMEKFGDPMFQRHVAIasvLGLVALRLADDE 521
Cdd:COG2234   191 YGRSDHAPFAKA-GIPALFLFTGAedYHPDYHTPSDT---LDKIDLDALAKVAQL---LAALVYELANAD 253
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 550-668 6.79e-36

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: 130.78  E-value: 6.79e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 550 IDLSPLIKSIQDLYTAAQEINIE----KEEGVKGALRVREVNDRLMMAERALTDRDGLSERPWYKHLVYGPSKYDDYGSK 625
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWakkwEDIKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1072989427 626 SFPGVDDAIDnakrvntKASWEHVQHEVWRVSRAIRHASLVLR 668
Cdd:pfam04253  81 TFPGIRDAIE-------AGDWELAQKQISIVAKAIQSAAETLK 116
Peptidase_M28 pfam04389
Peptidase family M28;
303-489 2.70e-30

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 117.77  E-value: 2.70e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 303 NVIGVIEGEEePDRYVILGNHRDAWTF--GAVDPNSGTAVLLEIAQRLdklqKRGWKPRRTIILCNWDAEEYALIGSTEW 380
Cdd:pfam04389   1 NVIAKLPGKA-PDEVVLLSAHYDSVGTgpGADDNASGVAALLELARVL----AAGQRPKRSVRFLFFDAEEAGLLGSHHF 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 381 VEENREMlaSRAVAYLNVD-CAVSGPGFRVSATPQLDDLIKQAAKEVQDPdnTTQTVYESWIGSSNSDeigrlggGGSDY 459
Cdd:pfam04389  76 AKSHPPL--KKIRAVINLDmIGSGGPALLFQSGPKGSSLLEKYLKAAAKP--YGVTLAEDPFQERGGP-------GRSDH 144

                         170       180       190
                  ....*....|....*....|....*....|
gi 1072989427 460 ASFVQhVGVPAVDMLFGGGYPVYHSMYDDF 489
Cdd:pfam04389 145 APFIK-AGIPGLDLAFTDFGYRYHTPADTI 173
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
 144-224 7.72e-11

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: 59.06  E-value: 7.72e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 144 VSGPAAYANYGRVEDFaaggNFSGAVAVARYGKIYRGDIVRNAYEAGAVGVVIYTDKRD------YGGEECFPESRWMPP 217
Cdd:pfam02225   5 VLAPGCYAGDGIPADF----DVKGKIVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVEGlggppgAGGNELYPDGIYIPA 80


                  ....*..
gi 1072989427 218 SGVQVGT 224
Cdd:pfam02225  81 VGVSRAD 87
 
Name Accession Description Interval E-value
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 301-525 5.75e-135

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: 397.76  E-value: 5.75e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 301 IENVIGVIEGEEEPDRYVILGNHRDAWTFGAVDPNSGTAVLLEIAQRLDKLQKRGWKPRRTIILCNWDAEEYALIGSTEW 380
Cdd:cd08022    60 IWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFASWDAEEYGLIGSTEW 139

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 381 VEENREMLASRAVAYLNVDCAVSGPGFRVSATPQLDDLIKQAAKEVQDPDNTTQTVYESWIGSSNSDEIGRLgGGGSDYA 460
Cdd:cd08022   140 VEENADWLQERAVAYLNVDVAVSGSTLRAAGSPLLQNLLREAAKEVQDPDEGATLKYLPSWWDDTGGEIGNL-GSGSDYT 218

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1072989427 461 SFVQHVGVPAVDMLFGGG----YPVYHSMYDDFTWMEKFGDPMFQRHVAIASVLGLVALRLADDEFLPF 525
Cdd:cd08022   219 PFLDHLGIASIDFGFSGGptdpYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVWGLLALRLADDPILPF 287
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 288-524 2.63e-78

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: 251.06  E-value: 2.63e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 288 LNLSYVGRSVIAEIENVIGVIEGEEEPDRYVILGNHRDAWTFGAVDPNSGTAVLLEIAQRLDKL-QKRGWKPRRTIILCN 366
Cdd:cd03874    44 NGLFEVELEEYSPITNVVGKIEGIEQPDRAIIIGAHRDSWGYGAGYPNSGTAVLLEIARLFQQLkKKFGWKPLRTIYFIS 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 367 WDAEEYALIGSTEWVEENREMLASRAVAYLNVDCAVSGPG-FRVSATPQLDDLIKQAAKEVQDPDNTTQTVYESWIGSSN 445
Cdd:cd03874   124 WDGSEFGLAGSTELGEDRKASLKDEVYAYINIDQLVIGNSeLDVDAHPLLQSLFRKASKKVKFPGNEDWWKHSPNAKVSN 203

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 446 SdeigrlgGGGSDYASFVQHVGVPAVDMLF---GGGYPVYHSMYDDFTWMEKFGDPMFQRHVAIASVLGLVALRLADDEF 522
Cdd:cd03874   204 L-------HQYGDWTPFLNHLGIPVAVFSFkndRNASYPINSSYDTFEWLEKFLDPDFELHSTLAEFVGLLVLSLAEDPL 276


                  ..
gi 1072989427 523 LP 524
Cdd:cd03874   277 LP 278
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 93-275 9.35e-65

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: 213.31  E-value: 9.35e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427  93 PVHRSLVLTttpkdsaNPTTTTFALEQEHVGDNPHADEVTPTFHGYAKSGNVSGPAAYANYGRVEDF----AAGGNFSGA 168
Cdd:cd02121     1 PVKRSLILT-------KPDGATGKLIEDTVLEEPPSPDVVPPFHAYSASGNVTAELVYANYGSPEDFeyleDLGIDVKGK 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 169 VAVARYGKIYRGDIVRNAYEAGAVGVVIYTDKRDYGG-----EECFPESRWMPPSGVQVGTVY---NGLGDPTTPGWASV 240
Cdd:cd02121    74 IVIARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYitgenGKTYPDGPARPPSGVQRGSVLfmsIGPGDPLTPGYPSK 153

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1072989427 241 NGCERLSEEDvelSGDAPGIPSLPISAADAEVILK 275
Cdd:cd02121   154 PGAERRDKEE---SKGLPKIPSLPISYRDAQPLLK 185
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
 300-526 6.61e-52

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: 181.03  E-value: 6.61e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 300 EIENVIGVIEGEEEPDRYVILGNHRDAWTFGAVDPNSGTAVLLEIAQRL-DKLQKRGWKPRRTIILCNWDAEEYALIGST 378
Cdd:cd09848    55 KIHNIFGVIKGFVEPDRYVVIGAQRDAWGPGAAKSGVGTALLLELARTFsDMVKNDGFKPRRSIVFASWSAGDFGSVGAT 134

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 379 EWVEENREMLASRAVAYLNVDCAVSGPG-FRVSATPQLDDLIKQAAKEVQDPDNTTQTVYESwiGSSNSDEIGRLGGGGS 457
Cdd:cd09848   135 EWLEGYLSSLHLKAFTYISLDGAVLGDDsFKASASPLLYTLIESTMKQVKSPVHSGQSYYET--RSSWWASIVEPLGLDS 212

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1072989427 458 DYASFVQHVGVPAVDMLFGGG---YPVYHSMYDDFTWMEKFGdpmfQRHV-----AIASVLGLVALRLADDEFLPFN 526
Cdd:cd09848   213 AAYPFLAFSGIPSVSFHFTEDdedYPFLGTKEDTKENLDKFT----NGELwevaaAAAEVAGQMALRLVHDHLLPLD 285
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 303-521 2.37e-39

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: 145.66  E-value: 2.37e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 303 NVIGVIEGEEEPDRYVILGNHRDAWTF---GAVDPNSGTAVLLEIAQRLdklQKRGWKPRRTIILCNWDAEEYALIGSTE 379
Cdd:COG2234    48 NVIAEIPGTDPPDEVVVLGAHYDSVGSigpGADDNASGVAALLELARAL---AALGPKPKRTIRFVAFGAEEQGLLGSRY 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 380 WVEENREMLAsRAVAYLNVDC-AVSGPGFRVSAT-----PQLDDLIKQAAKEVQDpdnttqtvyeswiGSSNSDEIGRLG 453
Cdd:COG2234   125 YAENLKAPLE-KIVAVLNLDMiGRGGPRNYLYVDgdggsPELADLLEAAAKAYLP-------------GLGVDPPEETGG 190

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 454 GGGSDYASFVQHvGVPAVDMLFGG--GYPVYHSMYDDftwMEKFGDPMFQRHVAIasvLGLVALRLADDE 521
Cdd:COG2234   191 YGRSDHAPFAKA-GIPALFLFTGAedYHPDYHTPSDT---LDKIDLDALAKVAQL---LAALVYELANAD 253
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 550-668 6.79e-36

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: 130.78  E-value: 6.79e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 550 IDLSPLIKSIQDLYTAAQEINIE----KEEGVKGALRVREVNDRLMMAERALTDRDGLSERPWYKHLVYGPSKYDDYGSK 625
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWakkwEDIKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1072989427 626 SFPGVDDAIDnakrvntKASWEHVQHEVWRVSRAIRHASLVLR 668
Cdd:pfam04253  81 TFPGIRDAIE-------AGDWELAQKQISIVAKAIQSAAETLK 116
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 301-489 1.05e-30

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: 119.37  E-value: 1.05e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 301 IENVIGVIEGEEEPDRYVILGNHRDAWTF--GAVDPNSGTAVLLEIAQRLDKLQKrgwKPRRTIILCNWDAEEYALIGST 378
Cdd:cd02690     1 GYNVIATIKGSDKPDEVILIGAHYDSVPLspGANDNASGVAVLLELARVLSKLQL---KPKRSIRFAFWDAEELGLLGSK 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 379 EWVEENREMLaSRAVAYLNVDCAVSGPG-----FRVSATPQLDDLIKQAAKEVQDPdnTTQTVYESWIGSsnsdeigrlg 453
Cdd:cd02690    78 YYAEQLLSSL-KNIRAALNLDMIGGAGPdlylqTAPGNDALVEKLLRALAHELENV--VYTVVYKEDGGT---------- 144

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1072989427 454 gGGSDYASFVQhVGVPAVDMLFGGGY--PVYHSMYDDF 489
Cdd:cd02690   145 -GGSDHRPFLA-RGIPAASLIQSESYnfPYYHTTQDTL 180
Peptidase_M28 pfam04389
Peptidase family M28;
303-489 2.70e-30

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 117.77  E-value: 2.70e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 303 NVIGVIEGEEePDRYVILGNHRDAWTF--GAVDPNSGTAVLLEIAQRLdklqKRGWKPRRTIILCNWDAEEYALIGSTEW 380
Cdd:pfam04389   1 NVIAKLPGKA-PDEVVLLSAHYDSVGTgpGADDNASGVAALLELARVL----AAGQRPKRSVRFLFFDAEEAGLLGSHHF 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 381 VEENREMlaSRAVAYLNVD-CAVSGPGFRVSATPQLDDLIKQAAKEVQDPdnTTQTVYESWIGSSNSDeigrlggGGSDY 459
Cdd:pfam04389  76 AKSHPPL--KKIRAVINLDmIGSGGPALLFQSGPKGSSLLEKYLKAAAKP--YGVTLAEDPFQERGGP-------GRSDH 144

                         170       180       190
                  ....*....|....*....|....*....|
gi 1072989427 460 ASFVQhVGVPAVDMLFGGGYPVYHSMYDDF 489
Cdd:pfam04389 145 APFIK-AGIPGLDLAFTDFGYRYHTPADTI 173
PA_TfR cd02128
PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This ...
 122-274 9.48e-22

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: 93.23  E-value: 9.48e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 122 VGDNPHADEVTPTFHG---YAKSGNVSGPAAYANYGRVEDF----AAGGNFSGAVAVARYGKIYRGDIVRNAYEAGAVGV 194
Cdd:cd02128     4 IGDAGRLNELVENPGGyvaYSAAGTVTGKLVYANYGRKKDFedlqSVGVSVNGSVVLVRAGKISFAEKVANAEKLGAVGV 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 195 VIYTDKRDYGGeecfpesrwMPPSGVQVGTVYNGLGDPTTPGWASVNGCERLSeedVELSGdAPGIPSLPISAADAEVIL 274
Cdd:cd02128    84 LIYPDPADFPI---------DPSETALFGHVHLGTGDPYTPGFPSFNHTQFPP---SQSSG-LPNIPAQTISAAAAAKLL 150
M28_like cd03877
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
 302-489 2.50e-19

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: 86.91  E-value: 2.50e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 302 ENVIGVIEGEEEPDRYVILGNHRDAWTF-----------GAVDPNSGTAVLLEIAQRLdKLQKrgwKPRRTIILCNWDAE 370
Cdd:cd03877     2 HNVVGVLEGSDLPDETIVIGAHYDHLGIgggdsgdkiynGADDNASGVAAVLELARYF-AKQK---TPKRSIVFAAFTAE 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 371 EYALIGSTEWVeENREMLASRAVAYLNVD-CAVSGPGFRVSAT----PQLDDLIKQAAKEVQDPDNTTQTVyeswigssn 445
Cdd:cd03877    78 EKGLLGSKYFA-ENPKFPLDKIVAMLNLDmIGRLGRSKDVYLIgsgsSELENLLKKANKAAGRVLSKDPLP--------- 147

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1072989427 446 sdeigRLGGGGSDYASFVQhVGVPAVdMLFGGGYPVYHSMYDDF 489
Cdd:cd03877   148 -----EWGFFRSDHYPFAK-AGVPAL-YFFTGLHDDYHKPSDDY 184
M28_like cd08015
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 303-470 3.85e-17

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: 80.72  E-value: 3.85e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 303 NVIGVIEGEEEPDRYVILGNHRDAW--TFGAVDPNSGTAVLLEiAQRLdkLQKRGWKPRRTIILCNWDAEEYALIGSTEW 380
Cdd:cd08015     3 NVIAEIPGSDKKDEVVILGAHLDSWhgATGATDNGAGTAVMME-AMRI--LKAIGSKPKRTIRVALWGSEEQGLHGSRAY 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 381 VEEN----REMLASRAV----AYLNVDCA------VSGPGFrVSATPQLDDLIKQAakevqdPDNTTQTVYESwigssns 446
Cdd:cd08015    80 VEKHfgdpPTMQLQRDHkkisAYFNLDNGtgrirgIYLQGN-LAAYPIFSAWLYPF------HDLGATTVIER------- 145

                         170       180
                  ....*....|....*....|....
gi 1072989427 447 deigrlGGGGSDYASFVQhVGVPA 470
Cdd:cd08015   146 ------NTGGTDHAAFDA-VGIPA 162
M28_like_PA_PDZ_associated cd05663
M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ ...
 300-489 2.70e-15

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: 76.34  E-value: 2.70e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 300 EIENVIGVIEGEEEP-DRYVILGNHRDAWTFG----------------AVDPNSGTAVLLEIAQRLdKLQKRGWKPRRTI 362
Cdd:cd05663    54 TGRNVIGVLPGKGDVaDETVVVGAHYDHLGYGgegslargdeslihngADDNASGVAAMLELAAKL-VDSDTSLALSRNL 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 363 ILCNWDAEEYALIGSTEWVeENREMLASRAVAYLNVD---------CAVSGPGfrvsATPQLDDLIKQAAKevqdPDNTT 433
Cdd:cd05663   133 VFIAFSGEELGLLGSKHFV-KNPPFPIKNTVYMINMDmvgrlrdnkLIVQGTG----TSPGWEQLVQARNK----ATGFK 203

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1072989427 434 QTVYESwigssnsdeigrlGGGGSDYASFVQHvGVPAVDmLFGGGYPVYHSMYDDF 489
Cdd:cd05663   204 LILDPT-------------GYGPSDHTSFYLD-DVPVLH-FFTGAHSDYHRPSDDS 244
M28_like_PA cd05660
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ...
 299-479 7.49e-14

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: 72.39  E-value: 7.49e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 299 AEIENVIGVIEGEEEPDRYVILGNHRDAWTF-----------GAVDPNSGTAVLLEIAQRLDKLQKRgwkPRRTIILCNW 367
Cdd:cd05660    57 STSHNVVAILPGSKLPDEYIVLSAHWDHLGIgppiggdeiynGAVDNASGVAAVLELARVFAAQDQR---PKRSIVFLAV 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 368 DAEEYALIGSTEWVeENREMLASRAVAYLNVDC-AVSGPGFRV----SATPQLDDLIKQAAKEVQ---DPDNTTQtvyes 439
Cdd:cd05660   134 TAEEKGLLGSRYYA-ANPIFPLDKIVANLNIDMiGRIGPTKDVlligSGSSELENILKEAAKAVGrvvDYDPNPE----- 207

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1072989427 440 wigssnSDEIGRlggggSDYASFVQHvGVPAVdmLFGGGY 479
Cdd:cd05660   208 ------NGSFYR-----SDHYNFAKK-GVPVL--FFFGGY 233
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
 303-514 8.78e-13

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: 70.80  E-value: 8.78e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 303 NVIGVIEGEEEPDRYVILGNHRDAWTF--GAVDPNSGTAVLLEiAQRLdkLQKRGWKPRRTIILCNWDAEEYALIGSTEW 380
Cdd:cd03883   228 NVIAEITGSKYPDEVVLVGGHLDSWDVgtGAMDDGGGVAISWE-ALKL--IKDLGLKPKRTIRVVLWTGEEQGLVGAKAY 304

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 381 VEENREMLASRAVAYLNVDCAVSGPGFRVSATPQLDDLIKQAAKEVQdPDNTTQTVYEswigssnsdeigrlGGGGSDyA 460
Cdd:cd03883   305 AEAHKDELENHVFAMESDIGTFTPYGLQFTGSDTARAIVKEVMKLLS-PLGITQVLPK--------------AGVGPD-I 368

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1072989427 461 SFVQHVGVPAVDmLFGGGYPVY---HSMYDDFTWMEKfgDPMFQRHVAIASVLGLVA 514
Cdd:cd03883   369 SFLKAAGVPGAS-LIQDNSDYFdyhHTAGDTMDVMDP--KQLDQNVAAWASLAYVIA 422
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
 122-275 8.51e-12

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: 62.92  E-value: 8.51e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 122 VGDNPHADEVTPTFHGYAKSGNVSGPAAYANYGRVEDFAAggNFSGAVAVARYGKIYRGDIVRNAYEAGAVGVVIYTDKr 201
Cdd:cd00538     4 LATTGYAGSALLFNPPSSPVGVVAGPLVGCGYGTTDDSGA--DVKGKIVLVRRGGCSFSEKVKNAQKAGAKAVIIYNNG- 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1072989427 202 dyggeecfpesrwmPPSGVQVGTVYNGLGDPTtpgwasvngcerlseedvelsgdapgIPSLPISAADAEVILK 275
Cdd:cd00538    81 --------------DDPGPQMGSVGLESTDPS--------------------------IPTVGISYADGEALLS 114
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
 290-489 5.42e-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: 5.42e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 290 LSYVGRSVIAEIENVIGVIEGEE-EPDRYVILGNHRDAW--TFGAVDPNSGTAVLLEIAQRldkLQKRGWKPRRTIILcN 366
Cdd:cd03875    68 LSSGMTLVYFEVTNIVVRISGKNsNSLPALLLNAHFDSVptSPGATDDGMGVAVMLEVLRY---LSKSGHQPKRDIIF-L 143

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 367 W-DAEEYALIGSTEWVeeNREMLASRAVAYLNVDCAVSGpG----FRvsATPQLddLIKQAAKEVQDPDNTT--QTVYES 439
Cdd:cd03875   144 FnGAEENGLLGAHAFI--TQHPWAKNVRAFINLEAAGAG-GrailFQ--TGPPW--LVEAYYSAAKHPFASViaQDVFQS 216

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1072989427 440 wigssnsdeigRLGGGGSDYASFVQHVGVPAVDMLF-GGGYpVYHSMYDDF 489
Cdd:cd03875   217 -----------GLIPSDTDYRVFRDYGGLPGLDIAFyKNRY-VYHTKYDTA 255
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
 144-224 7.72e-11

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: 59.06  E-value: 7.72e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 144 VSGPAAYANYGRVEDFaaggNFSGAVAVARYGKIYRGDIVRNAYEAGAVGVVIYTDKRD------YGGEECFPESRWMPP 217
Cdd:pfam02225   5 VLAPGCYAGDGIPADF----DVKGKIVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVEGlggppgAGGNELYPDGIYIPA 80


                  ....*..
gi 1072989427 218 SGVQVGT 224
Cdd:pfam02225  81 VGVSRAD 87
M28_SGAP_like cd03876
M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family ...
 290-470 2.81e-09

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: 58.85  E-value: 2.81e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 290 LSYVGRSVIAEIEnvigviEGEeePDRYVILGNHRDAWTFGA--VDPNSGTAVLLEIAQRLDKlqkrgWKPRRTIILCNW 367
Cdd:cd03876    59 LYRTTYNVIAETK------GGD--PNNVVMLGAHLDSVSAGPgiNDNGSGSAALLEVALALAK-----FKVKNAVRFAWW 125

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 368 DAEEYALIGSTEWVEENREMLASRAVAYLNVDCAVSgPGFRVsatpqlddlikqaakEVQDPDNTTQTVyeswIGSSNSD 447
Cdd:cd03876   126 TAEEFGLLGSKFYVNNLSSEERSKIRLYLNFDMIAS-PNYGY---------------FIYDGDGSAFNL----TGPPGSA 185

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1072989427 448 EIGRL----------------GGGGSDYASFVQhVGVPA 470
Cdd:cd03876   186 EIERLfeayftslglpstpteFDGRSDYAPFIE-AGIPA 223
M28_like cd05662
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
 302-489 4.95e-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: 4.95e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 302 ENVIGVIEGEEEPDRYVILGNHRDAWTF-------GAVDPNSGTAVLLEIAQRLDKLQkrgwkPRRTIILCNWDAEEYAL 374
Cdd:cd05662    63 VNVLAVIKGSEPPTKWRVVSAHYDHLGIrggkiynGADDNASGVAALLALAEYFKKHP-----PKHNVIFAATDAEEPGL 137

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 375 IGSTEWVEENREMLASRAVAyLNVDCA---------VSGPgfrvSATPQLDDLIKQ------AAKEVQDPDNTTQTVyeS 439
Cdd:cd05662   138 RGSYAFVEALKVPRAQIELN-INLDMIsrpernelyVEGA----SQFPQLTSILENvkgtciKALHPKDTDGSIGSI--D 210

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1072989427 440 WIGSsnsdeigrlggggSDYASFVQhVGVPAVdmLFG-GGYPVYHSMYDDF 489
Cdd:cd05662   211 WTRA-------------SDHYPFHK-AKIPWL--YFGvEDHPDYHKPTDDF 245
M28_like cd05642
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 292-451 1.83e-07

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: 53.65  E-value: 1.83e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 292 YVGRSVI--AEIENVIGVIEGEEEPDRYVILGNHRDAWTF----------GAVDPNSGTAVLLEIAQRLDKlqkrgWKPR 359
Cdd:cd05642    77 GPASRIPfpVNISNVVATLKGSEDPDRVYVVSGHYDSRVSdvmdyesdapGANDDASGVAVSMELARIFAK-----HRPK 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 360 RTIILCNWDAEEYALIGSTEWVEENREmlASRAV-AYLNVDCAVSGPGFRVSATPQLDDLIKQAAKEVQDPDNTTQTVYe 438
Cdd:cd05642   152 ATIVFTAVAGEEQGLYGSTFLAQTYRN--NSVNVeGMLNNDIVGSSTGDDGTKDPHTIRLFAQGTPAVESSEQAESRLS- 228

                         170
                  ....*....|....*.
gi 1072989427 439 swIGSSN---SDEIGR 451
Cdd:cd05642   229 --IGGENdspARNLGR 242
PA_C5a_like cd02133
PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a ...
 149-200 2.83e-07

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: 50.36  E-value: 2.83e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1072989427 149 AYANYGRVEDFAaGGNFSGAVAVarygkIYRGDI-----VRNAYEAGAVGVVIYTDK 200
Cdd:cd02133    31 VDAGLGTPEDFE-GKDVKGKIAL-----IQRGEItfvekIANAKAAGAVGVIIYNNV 81
M28_like cd05640
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
 302-488 3.45e-07

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: 52.45  E-value: 3.45e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 302 ENVIGVIEGEEEPDRYVILGNHRDAW--TFGAVDPNSGTAVLLEIAQRLDKLQkrgwkPRRTIILCNWDAEEY-----AL 374
Cdd:cd05640    53 ANLIADLPGSYSQDKLILIGAHYDTVpgSPGADDNASGVAALLELARLLATLD-----PNHTLRFVAFDLEEYpffarGL 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 375 IGSTEWVEENRE-------MLASRAVAYLNVDCA--VSGPGFRVSATPQLDDLI---------------KQAAKEVQDPD 430
Cdd:cd05640   128 MGSHAYAEDLLRpltpivgMLSLEMIGYYDPFPHsqAYPAGFELHFYPHMGDFIavvgrlrsrklvrafKRAFRMLSDFP 207

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1072989427 431 ----NTTQTVYeswigssNSDEIGRlggggSDYASFVQHvGVPAVdMLFGG---GYPVYHSMYDD 488
Cdd:cd05640   208 veslNLPFNGP-------GVPPFRR-----SDHSSFWDH-GYPAI-MVTDTafyRNPQYHLPCDT 258
M28_like_PA cd05661
M28 Zn-peptidase containing a PA domain insert; Peptidase family M28 (also called ...
 318-487 3.86e-07

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: 51.80  E-value: 3.86e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 318 VILGNHRDAWTF--GAVDPNSGTAVLLEIAQRLDKLQkrGWKPRRTIilcNWDAEEYALIGSTEWVEENREMLASRAVAY 395
Cdd:cd05661    79 IIVTSHYDSVVKapGANDNASGTAVTLELARVFKKVK--TDKELRFI---AFGAEENGLLGSKYYVASLSEDEIKRTIGV 153

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 396 LNVDCAvsgpgfrVSATPQLDDLIkqaakeVQDPDNTTQTVYESWIGSSN--SDEIGRLGGGGSDYASFvQHVGVPAVDM 473
Cdd:cd05661   154 FNLDMV-------GTSDAKAGDLY------AYTIDGKPNLVTDSGAAASKrlSGVLPLVQQGSSDHVPF-HEAGIPAALF 219

                         170
                  ....*....|....*....
gi 1072989427 474 LFGGGY-----PVYHSMYD 487
Cdd:cd05661   220 IHMDPEtepvePWYHTPND 238
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 303-389 1.35e-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: 47.24  E-value: 1.35e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 303 NVIGVIEGEEEPDRYVILGNHRDA---WTF------GAVDPNSGTAVLLEiAQRLdkLQKRGWKPRRTIILCNWDAEEYA 373
Cdd:cd03879    76 SIIATIPGSEKSDEIVVIGAHQDSingSNPsngrapGADDDGSGTVTILE-ALRV--LLESGFQPKNTIEFHWYAAEEGG 152

                          90       100
                  ....*....|....*....|
gi 1072989427 374 LIGS----TEWVEENREMLA 389
Cdd:cd03879   153 LLGSqaiaTQYKSEGKNVKA 172
M28_like cd05643
M28 Zn-peptidase-like; Peptidase family M28 (also called aminopeptidase Y family), ...
 298-523 2.46e-04

M28 Zn-peptidase-like; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They typically have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This protein subfamily conserves some of the metal-coordinating residues of the typically co-catalytic M28 family which might suggest binding of a single metal ion.


Pssm-ID: 349895 [Multi-domain]  Cd Length: 290  Bit Score: 43.55  E-value: 2.46e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 298 IAEIENVIGVIEGEEePDRYVILGNHRDAWTFGAVDPNSGTAVLLEIAQRLDKLQKRgwKPRRTIILCnWDAEeyaLIGS 377
Cdd:cd05643    67 LNETLPILYAIIGKE-TPPEIAFVAHLCHPKPGANDNASGSALLLEVARVLAKLILN--RPKRGICFL-WVPE---YTGT 139

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 378 TEWVEENREMLAsRAVAYLNVDC-----AVSGPGFRVSATP-----QLDDLIKQAAKevqdpdNTTQTVYES-WIGSSNS 446
Cdd:cd05643   140 AAYFAQHPDRLK-KIIAVINLDMvgedqTKTGSTLMLVPTPlsfpsYLNEELAQKLS------NFTGSSLPAvRYGKEPY 212

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1072989427 447 DeigrlggGGSDYASFVQHvGVPAVdMLfgGGYP--VYHSMYDDftwMEKFgDPMFQRHVAIASVLGLVALRLADDEFL 523
Cdd:cd05643   213 E-------GGSDHDVFSDP-GIPAV-MF--NTWPdrYYHTSDDT---PDKL-DPETLKNVGAAVLLTAYALANGEEEMA 276
PA_ScAPY_like cd02130
PA_ScAPY_like: Protease-associated domain containing proteins like Saccharomyces cerevisiae ...
 125-197 3.28e-04

PA_ScAPY_like: Protease-associated domain containing proteins like Saccharomyces cerevisiae aminopeptidase Y (ScAPY). This group contains various PA domain-containing proteins similar to the S. cerevisiae APY, including Trichophyton rubrum leucine aminopeptidase 1(LAP1). Proteins in this group belong to the peptidase M28 family. ScAPY hydrolyzes amino acid-4-methylcoumaryl-7-amides (MCAs). ScAPY more rapidly hydrolyzes dipeptidyl-MCAs. Hydrolysis of amino acid-MCAs or dipeptides is stimulated by Co2+ while the hydrolysis of dipeptidyl-MCAs, tripeptides, and longer peptides is inhibited by Co2+. ScAPY is vacuolar and is activated by proteolytic processing. LAP1 is a secreted leucine aminopeptidase. 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: 239045 [Multi-domain]  Cd Length: 122  Bit Score: 40.70  E-value: 3.28e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1072989427 125 NPHADEVTPTFhgYAKSGNVSGPAAYA-NYG-RVEDFAAggNFSGAVAVARYGKIYRGDIVRNAYEAGAVGVVIY 197
Cdd:cd02130     5 NGEAIPTTAFT--YSPAGEVTGPLVVVpNLGcDAADYPA--SVAGNIALIERGECPFGDKSALAGAAGAAAAIIY 75
Zinc_peptidase_like cd03873
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ...
 297-484 4.68e-04

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: 42.03  E-value: 4.68e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 297 VIAEIENVIGVIEGEEEPDRYVILGNHRDAWTFGAVDPNSGTAVLLEIAQRLdklQKRGWKPRRTIILCNWDAEEYALIG 376
Cdd:cd03873    17 LGAHLDVVPAGEGDNRDPPFAEDTEEEGRLYGRGALDDKGGVAAALEALKRL---KENGFKPKGTIVVAFTADEEVGSGG 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 377 STEWVEENREMLASRAVAYLNVD-CAVSGPG-FRVSATPQLdDLIKQAAKEVQDPDnttqtVYESWIgssnsdeigrlgG 454
Cdd:cd03873    94 GKGLLSKFLLAEDLKVDAAFVIDaTAGPILQkGVVIRNPLV-DALRKAAREVGGKP-----QRASVI------------G 155

                         170       180       190
                  ....*....|....*....|....*....|
gi 1072989427 455 GGSDyASFVQHVGVPAVdMLFGGGYPVYHS 484
Cdd:cd03873   156 GGTD-GRLFAELGIPGV-TLGPPGDKGAHS 183
PA_2 cd04819
PA_2: Protease-associated (PA) domain subgroup 2. A subgroup of PA-domain containing proteins. ...
 121-214 9.29e-04

PA_2: Protease-associated (PA) domain subgroup 2. A subgroup of PA-domain containing proteins. 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 in this group contain a C-terminal RING-finger domain. Proteins into which the PA domain is inserted include the following: i) various signal peptide peptidases: such as hSPPL2a and 2b, ii) various E3 ubiquitin ligases similar to human GRAIL (gene related to anergy in lymphocytes) protein, iii) various proteins containing a RING finger motif such as Arabidopsis ReMembR-H2 protein, iv) EDEM3 (ER-degradation-enhancing mannosidase-like 3 protein), v) various plant vacuolar sorting receptors such as Pisum sativum BP-80, vi) prostate-specific membrane antigen (PSMA), vii) yeast aminopeptidase Y viii) Vibrio metschnikovii VapT, a sodium dodecyl sulfate (SDS) resistant extracellular alkaline serine protease, ix) various subtilisin-like proteases such as Cucumisin from the juice of melon fruits, and x) 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: 240123 [Multi-domain]  Cd Length: 127  Bit Score: 39.68  E-value: 9.29e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 121 HVGDNPHADEVTPtfhgYAKSGNVSGPAAYANYGRVEDFAaGGNFSGAVAVARYGK--IYRGDIVRNAYEAGAVGVVIYT 198
Cdd:cd04819     4 SGGDLAFDAIALP----RSPSGEAKGEPVDAGYGLPKDFD-GLDLEGKIAVVKRDDpdVDRKEKYAKAVAAGAAAFVVVN 78

                          90       100
                  ....*....|....*....|...
gi 1072989427 199 DKR-------DYGGEECFPESRW 214
Cdd:cd04819    79 TVPgvlpatgDEGTEDGPPSPIP 101
M20_peptT_like cd05683
M20 Peptidase T like enzymes specifically cleave tripeptides; Peptidase M20 family, PeptT ...
 382-484 4.24e-03

M20 Peptidase T like enzymes specifically cleave tripeptides; Peptidase M20 family, PeptT (tripeptide aminopeptidase; tripeptidase)-like subfamily. This group includes bacterial tripeptidases as well as predicted tripeptidases. Peptidase T acts only on tripeptide substrates, and is thus called a tripeptidase. It catalyzes the release of N-terminal amino acids with hydrophobic side chains from tripeptides with high specificity; dipeptides, tetrapeptides or tripeptides with the N-terminus blocked are not cleaved. Tripeptidases are known to function at the final stage of proteolysis in lactococcal bacteria and release amino acids from tripeptides produced during the digestion of milk proteins such as casein.


Pssm-ID: 349932 [Multi-domain]  Cd Length: 368  Bit Score: 40.13  E-value: 4.24e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 382 EENREMLASRAVAYLNVDCAVSGPGFRVSATPQLDDLIKQAAKEVQDPDNTTQTvyeswigssnsdeigrlgGGGSDyAS 461
Cdd:cd05683   264 KETFETTAKEKGAHAEVEVETSYPGFKINEDEEVVKLAKRAANNLGLEINTTYS------------------GGGSD-AN 324

                          90       100
                  ....*....|....*....|...
gi 1072989427 462 FVQHVGVPAVDMlfGGGYPVYHS 484
Cdd:cd05683   325 IINGLGIPTVNL--GIGYENIHT 345
M20_18_42 cd18669
M20, M18 and M42 Zn-peptidases include aminopeptidases and carboxypeptidases; This family ...
 325-484 6.60e-03

M20, M18 and M42 Zn-peptidases include aminopeptidases and carboxypeptidases; This family corresponds to the MEROPS MH clan families M18, M20, and M42. The peptidase M20 family contains exopeptidases, including carboxypeptidases such as the glutamate carboxypeptidase from Pseudomonas, the thermostable carboxypeptidase Ss1 of broad specificity from archaea and yeast Gly-X carboxypeptidase, dipeptidases such as bacterial dipeptidase, peptidase V (PepV), a eukaryotic, non-specific dipeptidase, and two Xaa-His dipeptidases (carnosinases). This family also includes the bacterial aminopeptidase peptidase T (PepT) that acts only on tripeptide substrates and has therefore been termed a tripeptidase. These peptidases generally hydrolyze the late products of protein degradation so as to complete the conversion of proteins to free amino acids. Glutamate carboxypeptidase hydrolyzes folate analogs such as methotrexate, and therefore can be used to treat methotrexate toxicity. Peptidase families M18 and M42 contain metallo-aminopeptidases. M18 (aspartyl aminopeptidase, DAP) family cleaves only unblocked N-terminal acidic amino-acid residues and is highly selective for hydrolyzing aspartate or glutamate residues. 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: 349948 [Multi-domain]  Cd Length: 198  Bit Score: 38.57  E-value: 6.60e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 325 DAWTFGAVDPNSGTAVLLEIAQRldkLQKRGWKPRRTIILCNWDAEEYALIGSTEWVEENREMLASRAVAYLNVDCAVSG 404
Cdd:cd18669    45 RLYGRGALDDKGGVAAALEALKL---LKENGFKLKGTVVVAFTPDEEVGSGAGKGLLSKDALEEDLKVDYLFVGDATPAP 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072989427 405 PGFRVSATPQLdDLIKQAAKEVQDPDnttqtVYESWIgssnsdeigrlgGGGSDyASFVQHVGVPAVDMLFGGGYpVYHS 484
Cdd:cd18669   122 QKGVGIRTPLV-DALSEAARKVFGKP-----QHAEGT------------GGGTD-GRYLQELGIPGVTLGAGGGK-GAHS 181
 
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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