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Conserved domains on  [gi|18410120|ref|NP_567007|]
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Peptidase M28 family protein [Arabidopsis thaliana]

Protein Classification

M28 family metallopeptidase( domain architecture ID 11978097)

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

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 ...
 333-556 4.59e-123

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: 368.10  E-value: 4.59e-123
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 333 KINNVVVTIRGSEEADRYVILGNHRDAWTYGAVDPNSGTSALLDISRRFALLLKSGWRPRRTILLCSWDAEEFGMIGSTE 412
Cdd:cd08022  59 PIWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFASWDAEEYGLIGSTE 138

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 413 WIEENVLNLGASAVAYLNVDCAVQGSGFFAGATPQLDGLLVDVLKLVQDPDAVGLTVEE--TFKSQNNIIQRLsRVDSDF 490
Cdd:cd08022 139 WVEENADWLQERAVAYLNVDVAVSGSTLRAAGSPLLQNLLREAAKEVQDPDEGATLKYLpsWWDDTGGEIGNL-GSGSDY 217

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 491 SGFLHHAGIPSIDMYYGAD----YPVYHTAFDSYDWMIHNADPLFHRHVAMAGIWGLLGILLADEPLIPF 556
Cdd:cd08022 218 TPFLDHLGIASIDFGFSGGptdpYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVWGLLALRLADDPILPF 287
PA super family cl28883
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
 141-321 2.38e-57

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.


The actual alignment was detected with superfamily member cd02121:

Pssm-ID: 333703  Cd Length: 220  Bit Score: 194.05  E-value: 2.38e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 141 LEFDLNDVPGDSP-VVRPYHAYSPSGSAQGNVVFVNHGEERDYHALESIGVSVKGCVVLARKGENlGRGAIVKIAEAKGA 219
Cdd:cd02121  18 LIEDTVLEEPPSPdVVPPFHAYSASGNVTAELVYANYGSPEDFEYLEDLGIDVKGKIVIARYGGI-FRGLKVKNAQLAGA 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 220 LGVLIYAENDGGGFGG-----------------IERGTVM---RGIGDPVSPGWPGVVGGEKLSLDDelvTRRFPKIPSL 279
Cdd:cd02121  97 VGVIIYSDPADDGYITgengktypdgparppsgVQRGSVLfmsIGPGDPLTPGYPSKPGAERRDKEE---SKGLPKIPSL 173

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 18410120 280 PLSLRNAEIILASLGGARAPLEWRNSGRV-----GPGQRVGPGRMVI 321
Cdd:cd02121 174 PISYRDAQPLLKALGGPGAPSDWQGGLPVtyrlgFGGPSPGKVRVNL 220
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 580-701 2.87e-30

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: 114.99  E-value: 2.87e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120   580 VSVNPLSMAIQEFSLVAKEAADEAKKLKgKSYSKNDVAaaakRRELNDRLMLVERGFLDAEGIKGKEWFKHLVYGPAAEP 659
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWAKKWE-DIKEPDLLA----VRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWT 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 18410120   660 ESKLGFFPGIADAIAMNASEGiIEHEIWRVARAIQRASKALK 701
Cdd:pfam04253  76 GYAGATFPGIRDAIEAGDWEL-AQKQISIVAKAIQSAAETLK 116
 
Name Accession Description Interval E-value
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 333-556 4.59e-123

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: 368.10  E-value: 4.59e-123
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 333 KINNVVVTIRGSEEADRYVILGNHRDAWTYGAVDPNSGTSALLDISRRFALLLKSGWRPRRTILLCSWDAEEFGMIGSTE 412
Cdd:cd08022  59 PIWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFASWDAEEYGLIGSTE 138

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 413 WIEENVLNLGASAVAYLNVDCAVQGSGFFAGATPQLDGLLVDVLKLVQDPDAVGLTVEE--TFKSQNNIIQRLsRVDSDF 490
Cdd:cd08022 139 WVEENADWLQERAVAYLNVDVAVSGSTLRAAGSPLLQNLLREAAKEVQDPDEGATLKYLpsWWDDTGGEIGNL-GSGSDY 217

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 491 SGFLHHAGIPSIDMYYGAD----YPVYHTAFDSYDWMIHNADPLFHRHVAMAGIWGLLGILLADEPLIPF 556
Cdd:cd08022 218 TPFLDHLGIASIDFGFSGGptdpYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVWGLLALRLADDPILPF 287
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 141-321 2.38e-57

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: 194.05  E-value: 2.38e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 141 LEFDLNDVPGDSP-VVRPYHAYSPSGSAQGNVVFVNHGEERDYHALESIGVSVKGCVVLARKGENlGRGAIVKIAEAKGA 219
Cdd:cd02121  18 LIEDTVLEEPPSPdVVPPFHAYSASGNVTAELVYANYGSPEDFEYLEDLGIDVKGKIVIARYGGI-FRGLKVKNAQLAGA 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 220 LGVLIYAENDGGGFGG-----------------IERGTVM---RGIGDPVSPGWPGVVGGEKLSLDDelvTRRFPKIPSL 279
Cdd:cd02121  97 VGVIIYSDPADDGYITgengktypdgparppsgVQRGSVLfmsIGPGDPLTPGYPSKPGAERRDKEE---SKGLPKIPSL 173

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 18410120 280 PLSLRNAEIILASLGGARAPLEWRNSGRV-----GPGQRVGPGRMVI 321
Cdd:cd02121 174 PISYRDAQPLLKALGGPGAPSDWQGGLPVtyrlgFGGPSPGKVRVNL 220
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 289-553 2.84e-31

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: 122.93  E-value: 2.84e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 289 ILASLGGARAPLEWRNSGRVGPGQRVGPGRMVINMTFQGEMKMKKINNVVVTIRGSEEADRYVILGNHRDAW---TYGAV 365
Cdd:COG2234   1 ALAAAGGGGGTTAGAAAAAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPDEVVVLGAHYDSVgsiGPGAD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 366 DPNSGTSALLDISRRFAlllKSGWRPRRTILLCSWDAEEFGMIGSTEWIeENVLNLGASAVAYLNVDCAvqGSG-----F 440
Cdd:COG2234  81 DNASGVAALLELARALA---ALGPKPKRTIRFVAFGAEEQGLLGSRYYA-ENLKAPLEKIVAVLNLDMI--GRGgprnyL 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 441 FAGAT---PQLDGLLVDVLKLVQDPDAVGLTVEETFksqnniiqrlsRVDSDFSGFlHHAGIPSIDMYYGAD--YPVYHT 515
Cdd:COG2234 155 YVDGDggsPELADLLEAAAKAYLPGLGVDPPEETGG-----------YGRSDHAPF-AKAGIPALFLFTGAEdyHPDYHT 222

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 18410120 516 AFDSYDwmihNADPLFHRHVAMAgiWGLLGILLADEPL 553
Cdd:COG2234 223 PSDTLD----KIDLDALAKVAQL--LAALVYELANADE 254
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 580-701 2.87e-30

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: 114.99  E-value: 2.87e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120   580 VSVNPLSMAIQEFSLVAKEAADEAKKLKgKSYSKNDVAaaakRRELNDRLMLVERGFLDAEGIKGKEWFKHLVYGPAAEP 659
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWAKKWE-DIKEPDLLA----VRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWT 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 18410120   660 ESKLGFFPGIADAIAMNASEGiIEHEIWRVARAIQRASKALK 701
Cdd:pfam04253  76 GYAGATFPGIRDAIEAGDWEL-AQKQISIVAKAIQSAAETLK 116
Peptidase_M28 pfam04389
Peptidase family M28;
336-521 1.10e-27

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 110.45  E-value: 1.10e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120   336 NVVVTIRGSEEaDRYVILGNHRDAW--TYGAVDPNSGTSALLDISRrfalLLKSGWRPRRTILLCSWDAEEFGMIGSTEW 413
Cdd:pfam04389   1 NVIAKLPGKAP-DEVVLLSAHYDSVgtGPGADDNASGVAALLELAR----VLAAGQRPKRSVRFLFFDAEEAGLLGSHHF 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120   414 IEENvlNLGASAVAYLNVD-CAVQGSGFFAGATPQLDGLLVDVLKLVqdPDAVGLTVEETFKSQNNIiqrlsRVDSDFSG 492
Cdd:pfam04389  76 AKSH--PPLKKIRAVINLDmIGSGGPALLFQSGPKGSSLLEKYLKAA--AKPYGVTLAEDPFQERGG-----PGRSDHAP 146

                         170       180
                  ....*....|....*....|....*....
gi 18410120   493 FlHHAGIPSIDMYYGADYPVYHTAFDSYD 521
Cdd:pfam04389 147 F-IKAGIPGLDLAFTDFGYRYHTPADTID 174
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
 168-225 2.17e-03

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: 37.88  E-value: 2.17e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 18410120   168 QGNVVFVNHGEERDYHaleSIGVSVKGCVVLARKGENlGRGAIVKIAEAKGALGVLIY 225
Cdd:pfam02225   1 TGPLVLAPGCYAGDGI---PADFDVKGKIVLVRCTFG-FRAEKVRNAQAAGAAGVIIY 54
 
Name Accession Description Interval E-value
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 333-556 4.59e-123

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: 368.10  E-value: 4.59e-123
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 333 KINNVVVTIRGSEEADRYVILGNHRDAWTYGAVDPNSGTSALLDISRRFALLLKSGWRPRRTILLCSWDAEEFGMIGSTE 412
Cdd:cd08022  59 PIWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFASWDAEEYGLIGSTE 138

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 413 WIEENVLNLGASAVAYLNVDCAVQGSGFFAGATPQLDGLLVDVLKLVQDPDAVGLTVEE--TFKSQNNIIQRLsRVDSDF 490
Cdd:cd08022 139 WVEENADWLQERAVAYLNVDVAVSGSTLRAAGSPLLQNLLREAAKEVQDPDEGATLKYLpsWWDDTGGEIGNL-GSGSDY 217

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 491 SGFLHHAGIPSIDMYYGAD----YPVYHTAFDSYDWMIHNADPLFHRHVAMAGIWGLLGILLADEPLIPF 556
Cdd:cd08022 218 TPFLDHLGIASIDFGFSGGptdpYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVWGLLALRLADDPILPF 287
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 332-555 1.74e-64

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: 215.24  E-value: 1.74e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 332 KKINNVVVTIRGSEEADRYVILGNHRDAWTYGAVDPNSGTSALLDISRRF-ALLLKSGWRPRRTILLCSWDAEEFGMIGS 410
Cdd:cd03874  55 SPITNVVGKIEGIEQPDRAIIIGAHRDSWGYGAGYPNSGTAVLLEIARLFqQLKKKFGWKPLRTIYFISWDGSEFGLAGS 134

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 411 TEWIEENVLNLGASAVAYLNVDCAVQG-SGFFAGATPQLDGLLVDVLKLVQDPDAVGLTVEETFKSQNNIIQrlsrvDSD 489
Cdd:cd03874 135 TELGEDRKASLKDEVYAYINIDQLVIGnSELDVDAHPLLQSLFRKASKKVKFPGNEDWWKHSPNAKVSNLHQ-----YGD 209

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18410120 490 FSGFLHHAGIPSIDMYYGAD---YPVYHTAFDSYDWMIHNADPLFHRHVAMAGIWGLLGILLADEPLIP 555
Cdd:cd03874 210 WTPFLNHLGIPVAVFSFKNDrnaSYPINSSYDTFEWLEKFLDPDFELHSTLAEFVGLLVLSLAEDPLLP 278
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 141-321 2.38e-57

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: 194.05  E-value: 2.38e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 141 LEFDLNDVPGDSP-VVRPYHAYSPSGSAQGNVVFVNHGEERDYHALESIGVSVKGCVVLARKGENlGRGAIVKIAEAKGA 219
Cdd:cd02121  18 LIEDTVLEEPPSPdVVPPFHAYSASGNVTAELVYANYGSPEDFEYLEDLGIDVKGKIVIARYGGI-FRGLKVKNAQLAGA 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 220 LGVLIYAENDGGGFGG-----------------IERGTVM---RGIGDPVSPGWPGVVGGEKLSLDDelvTRRFPKIPSL 279
Cdd:cd02121  97 VGVIIYSDPADDGYITgengktypdgparppsgVQRGSVLfmsIGPGDPLTPGYPSKPGAERRDKEE---SKGLPKIPSL 173

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 18410120 280 PLSLRNAEIILASLGGARAPLEWRNSGRV-----GPGQRVGPGRMVI 321
Cdd:cd02121 174 PISYRDAQPLLKALGGPGAPSDWQGGLPVtyrlgFGGPSPGKVRVNL 220
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
 333-557 1.18e-49

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: 175.26  E-value: 1.18e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 333 KINNVVVTIRGSEEADRYVILGNHRDAWTYGAVDPNSGTSALLDISRRFA-LLLKSGWRPRRTILLCSWDAEEFGMIGST 411
Cdd:cd09848  55 KIHNIFGVIKGFVEPDRYVVIGAQRDAWGPGAAKSGVGTALLLELARTFSdMVKNDGFKPRRSIVFASWSAGDFGSVGAT 134

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 412 EWIEENVLNLGASAVAYLNVDCAVQG-SGFFAGATPQLDGLLVDVLKLVQDPDAVGLTVEETFKS-QNNIIQRLSrVDSD 489
Cdd:cd09848 135 EWLEGYLSSLHLKAFTYISLDGAVLGdDSFKASASPLLYTLIESTMKQVKSPVHSGQSYYETRSSwWASIVEPLG-LDSA 213

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18410120 490 FSGFLHHAGIPSIDMYYGAD---YPVYHTAFDSYDWmIHNADPLFHRHVAMAG--IWGLLGILLADEPLIPFD 557
Cdd:cd09848 214 AYPFLAFSGIPSVSFHFTEDdedYPFLGTKEDTKEN-LDKFTNGELWEVAAAAaeVAGQMALRLVHDHLLPLD 285
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 289-553 2.84e-31

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: 122.93  E-value: 2.84e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 289 ILASLGGARAPLEWRNSGRVGPGQRVGPGRMVINMTFQGEMKMKKINNVVVTIRGSEEADRYVILGNHRDAW---TYGAV 365
Cdd:COG2234   1 ALAAAGGGGGTTAGAAAAAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPDEVVVLGAHYDSVgsiGPGAD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 366 DPNSGTSALLDISRRFAlllKSGWRPRRTILLCSWDAEEFGMIGSTEWIeENVLNLGASAVAYLNVDCAvqGSG-----F 440
Cdd:COG2234  81 DNASGVAALLELARALA---ALGPKPKRTIRFVAFGAEEQGLLGSRYYA-ENLKAPLEKIVAVLNLDMI--GRGgprnyL 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 441 FAGAT---PQLDGLLVDVLKLVQDPDAVGLTVEETFksqnniiqrlsRVDSDFSGFlHHAGIPSIDMYYGAD--YPVYHT 515
Cdd:COG2234 155 YVDGDggsPELADLLEAAAKAYLPGLGVDPPEETGG-----------YGRSDHAPF-AKAGIPALFLFTGAEdyHPDYHT 222

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 18410120 516 AFDSYDwmihNADPLFHRHVAMAgiWGLLGILLADEPL 553
Cdd:COG2234 223 PSDTLD----KIDLDALAKVAQL--LAALVYELANADE 254
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 580-701 2.87e-30

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: 114.99  E-value: 2.87e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120   580 VSVNPLSMAIQEFSLVAKEAADEAKKLKgKSYSKNDVAaaakRRELNDRLMLVERGFLDAEGIKGKEWFKHLVYGPAAEP 659
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWAKKWE-DIKEPDLLA----VRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWT 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 18410120   660 ESKLGFFPGIADAIAMNASEGiIEHEIWRVARAIQRASKALK 701
Cdd:pfam04253  76 GYAGATFPGIRDAIEAGDWEL-AQKQISIVAKAIQSAAETLK 116
Peptidase_M28 pfam04389
Peptidase family M28;
336-521 1.10e-27

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 110.45  E-value: 1.10e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120   336 NVVVTIRGSEEaDRYVILGNHRDAW--TYGAVDPNSGTSALLDISRrfalLLKSGWRPRRTILLCSWDAEEFGMIGSTEW 413
Cdd:pfam04389   1 NVIAKLPGKAP-DEVVLLSAHYDSVgtGPGADDNASGVAALLELAR----VLAAGQRPKRSVRFLFFDAEEAGLLGSHHF 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120   414 IEENvlNLGASAVAYLNVD-CAVQGSGFFAGATPQLDGLLVDVLKLVqdPDAVGLTVEETFKSQNNIiqrlsRVDSDFSG 492
Cdd:pfam04389  76 AKSH--PPLKKIRAVINLDmIGSGGPALLFQSGPKGSSLLEKYLKAA--AKPYGVTLAEDPFQERGG-----PGRSDHAP 146

                         170       180
                  ....*....|....*....|....*....
gi 18410120   493 FlHHAGIPSIDMYYGADYPVYHTAFDSYD 521
Cdd:pfam04389 147 F-IKAGIPGLDLAFTDFGYRYHTPADTID 174
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 334-521 4.42e-23

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: 97.41  E-value: 4.42e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 334 INNVVVTIRGSEEADRYVILGNHRDAW--TYGAVDPNSGTSALLDISRrfaLLLKSGWRPRRTILLCSWDAEEFGMIGST 411
Cdd:cd02690   1 GYNVIATIKGSDKPDEVILIGAHYDSVplSPGANDNASGVAVLLELAR---VLSKLQLKPKRSIRFAFWDAEELGLLGSK 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 412 EWIEENvLNLGASAVAYLNVDCAVQGSGFFAGATPQLDGLLVDvlKLVqdpDAVGLTVEETFKSQNNIIQRLSRvDSDFS 491
Cdd:cd02690  78 YYAEQL-LSSLKNIRAALNLDMIGGAGPDLYLQTAPGNDALVE--KLL---RALAHELENVVYTVVYKEDGGTG-GSDHR 150

                       170       180       190
                ....*....|....*....|....*....|..
gi 18410120 492 GFlHHAGIPSIDM--YYGADYPVYHTAFDSYD 521
Cdd:cd02690 151 PF-LARGIPAASLiqSESYNFPYYHTTQDTLE 181
PA_TfR cd02128
PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This ...
 157-311 2.19e-21

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: 92.08  E-value: 2.19e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 157 PYHAYSPSGSAQGNVVFVNHGEERDYHALESIGVSVKGCVVLARkgenLGRGAI---VKIAEAKGALGVLIY---AENDG 230
Cdd:cd02128  19 GYVAYSAAGTVTGKLVYANYGRKKDFEDLQSVGVSVNGSVVLVR----AGKISFaekVANAEKLGAVGVLIYpdpADFPI 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 231 GGFGGIERGTVMRGIGDPVSPGWPGVvggeKLSLDDELVTRRFPKIPSLPLSLRNAEIILASLGGARAPLEWRNSG---R 307
Cdd:cd02128  95 DPSETALFGHVHLGTGDPYTPGFPSF----NHTQFPPSQSSGLPNIPAQTISAAAAAKLLSKMGGPVCPSGWKGGDstcR 170


                ....
gi 18410120 308 VGPG 311
Cdd:cd02128 171 LGTS 174
M28_like cd03877
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
 336-521 5.87e-14

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: 71.12  E-value: 5.87e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 336 NVVVTIRGSEEADRYVILGNHRDAWTY-----------GAVDPNSGTSALLDISRRFAlllkSGWRPRRTILLCSWDAEE 404
Cdd:cd03877   3 NVVGVLEGSDLPDETIVIGAHYDHLGIgggdsgdkiynGADDNASGVAAVLELARYFA----KQKTPKRSIVFAAFTAEE 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 405 FGMIGSTEWIeENVLNLGASAVAYLNVDC--------AVQGSGFFAgatPQLDGLLVDVLKlvqdpdAVGLTVeetFKSQ 476
Cdd:cd03877  79 KGLLGSKYFA-ENPKFPLDKIVAMLNLDMigrlgrskDVYLIGSGS---SELENLLKKANK------AAGRVL---SKDP 145

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 18410120 477 NniiQRLSRVDSDFSGFlHHAGIPSIDMYYGaDYPVYHTAFDSYD 521
Cdd:cd03877 146 L---PEWGFFRSDHYPF-AKAGVPALYFFTG-LHDDYHKPSDDYE 185
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
 333-521 7.44e-14

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: 73.01  E-value: 7.44e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 333 KINNVVVTIRGSE-EADRYVILGNHRDAW--TYGAVDPNSGTSALLDISRRFAlllKSGWRPRRTILLCSWDAEEFGMIG 409
Cdd:cd03875  78 EVTNIVVRISGKNsNSLPALLLNAHFDSVptSPGATDDGMGVAVMLEVLRYLS---KSGHQPKRDIIFLFNGAEENGLLG 154

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 410 STEWIEENVLnlgASAV-AYLNVDCAvqGSG-----FFAGatpqlDGLLVDVLKLVqDPDAVGLTV-EETFKSqnniiqR 482
Cdd:cd03875 155 AHAFITQHPW---AKNVrAFINLEAA--GAGgrailFQTG-----PPWLVEAYYSA-AKHPFASVIaQDVFQS------G 217

                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 18410120 483 LSRVDSDFSGFLHHAGIPSIDM-YYGADYpVYHTAFDSYD 521
Cdd:cd03875 218 LIPSDTDYRVFRDYGGLPGLDIaFYKNRY-VYHTKYDTAD 256
M28_like cd08015
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 336-524 8.27e-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: 349937 [Multi-domain]  Cd Length: 218  Bit Score: 71.09  E-value: 8.27e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 336 NVVVTIRGSEEADRYVILGNHRDAW--TYGAVDPNSGTSALLDISRrfaLLLKSGWRPRRTILLCSWDAEEFGMIGSTEW 413
Cdd:cd08015   3 NVIAEIPGSDKKDEVVILGAHLDSWhgATGATDNGAGTAVMMEAMR---ILKAIGSKPKRTIRVALWGSEEQGLHGSRAY 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 414 IE-------ENVLNLGASAV-AYLNVDcavQGSGFFAGATPQLDGLLVDVLK--LVQDPDAVGLTVEETfksqnniiqrl 483
Cdd:cd08015  80 VEkhfgdppTMQLQRDHKKIsAYFNLD---NGTGRIRGIYLQGNLAAYPIFSawLYPFHDLGATTVIER----------- 145

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 18410120 484 srvdsDFSGFLHHA----GIPSIDMYY-GADYP--VYHTAFDSYDWMI 524
Cdd:cd08015 146 -----NTGGTDHAAfdavGIPAFQFIQdPWDYWtrTHHTNRDTYDRLI 188
M28_like_PA_PDZ_associated cd05663
M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ ...
 325-521 3.10e-13

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: 70.56  E-value: 3.10e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 325 FQG-EMKMKKINNVVVTI-RGSEEADRYVILGNHRDAWTYG----------------AVDPNSGTSALLDISRRFALLLK 386
Cdd:cd05663  45 FQPfEFTTGTGRNVIGVLpGKGDVADETVVVGAHYDHLGYGgegslargdeslihngADDNASGVAAMLELAAKLVDSDT 124

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 387 SGWRPRRtILLCSWDAEEFGMIGSTEWIeENVLNLGASAVAYLNVD---------CAVQGSGFFAGATPQLDGLLVDV-L 456
Cdd:cd05663 125 SLALSRN-LVFIAFSGEELGLLGSKHFV-KNPPFPIKNTVYMINMDmvgrlrdnkLIVQGTGTSPGWEQLVQARNKATgF 202

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18410120 457 KLVQDPDAVGltveetfksqnniiqrlsrvDSDFSGFlHHAGIPSIDMYYGAdYPVYHTAFDSYD 521
Cdd:cd05663 203 KLILDPTGYG--------------------PSDHTSF-YLDDVPVLHFFTGA-HSDYHRPSDDSD 245
M28_like_PA cd05660
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ...
 336-509 3.55e-13

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: 70.47  E-value: 3.55e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 336 NVVVTIRGSEEADRYVILGNHRDAW----------TY-GAVDPNSGTSALLDISRRFAlllKSGWRPRRTILLCSWDAEE 404
Cdd:cd05660  61 NVVAILPGSKLPDEYIVLSAHWDHLgigppiggdeIYnGAVDNASGVAAVLELARVFA---AQDQRPKRSIVFLAVTAEE 137

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 405 FGMIGSTEWIE------EN---VLNLGASAVAYLNVDCAVQGSGffagaTPQLDGLLVDVLKlvqdpdAVGLTVEETFKS 475
Cdd:cd05660 138 KGLLGSRYYAAnpifplDKivaNLNIDMIGRIGPTKDVLLIGSG-----SSELENILKEAAK------AVGRVVDYDPNP 206

                       170       180       190
                ....*....|....*....|....*....|....
gi 18410120 476 QNNIIQRlsrvdSDFSGFLhHAGIPSIDMYYGAD 509
Cdd:cd05660 207 ENGSFYR-----SDHYNFA-KKGVPVLFFFGGYD 234
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 335-454 6.81e-11

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: 63.80  E-value: 6.81e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 335 NNVVVTIRGSEEADRYVILGNHRDAWTY---------GAVDPNSGTSALLDISRrfaLLLKSGWRPRRTILLCSWDAEEF 405
Cdd:cd03879  75 PSIIATIPGSEKSDEIVVIGAHQDSINGsnpsngrapGADDDGSGTVTILEALR---VLLESGFQPKNTIEFHWYAAEEG 151

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 18410120 406 GMIGSTEwIEENVLNLGASAVAYLNVDCAvqgsGFFAGATPQLDGLLVD 454
Cdd:cd03879 152 GLLGSQA-IATQYKSEGKNVKAMLQLDMT----GYVKPGSAEDIGLITD 195
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
 191-410 1.74e-10

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: 63.48  E-value: 1.74e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 191 SVKG-CVVLARKGENLG-----RGAIVKIAEAKGALGVLIyaendgggfggiergtvmRGIGdPVSPGWP--GVVGGEKl 262
Cdd:cd03883 123 EVKGkIVVYNQPFKGYGetvkyRGQGAVEAAKYGAVAVLI------------------RSIT-PFSIYSPhtGIMRYQD- 182

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 263 slddelvtrRFPKIPSLPLSLRNAEIILASlggaraplewrnsgrvgpgQRVGPgRMVINMTFQGEMkMKKIN--NVVVT 340
Cdd:cd03883 183 ---------GVTKIPAAAITVEDAEMLSRM-------------------AARGQ-KIVIELKMEAKT-YPDATsrNVIAE 232

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18410120 341 IRGSEEADRYVILGNHRDAWTY--GAVDPNSG----TSALldisrrfALLLKSGWRPRRTILLCSWDAEEFGMIGS 410
Cdd:cd03883 233 ITGSKYPDEVVLVGGHLDSWDVgtGAMDDGGGvaisWEAL-------KLIKDLGLKPKRTIRVVLWTGEEQGLVGA 301
M28_like cd05662
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
 323-521 3.16e-10

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: 61.33  E-value: 3.16e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 323 MTFQGEMKMKKINNVVVTIRGSEEADRYVILGNHRD------AWTY-GAVDPNSGTSALLdisrRFALLLKSGwRPRRTI 395
Cdd:cd05662  51 FSYTKRFSTRQGVNVLAVIKGSEPPTKWRVVSAHYDhlgirgGKIYnGADDNASGVAALL----ALAEYFKKH-PPKHNV 125

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 396 LLCSWDAEEFGMIGSTEWIEENVLNLGASAVAyLNVDCA---------VQGSGFFAGATPQLDGL--LVDVLKLVQDPDA 464
Cdd:cd05662 126 IFAATDAEEPGLRGSYAFVEALKVPRAQIELN-INLDMIsrpernelyVEGASQFPQLTSILENVkgTCIKALHPKDTDG 204

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18410120 465 VGLTVEETFKsqnniiqrlsrvdSDFSGFlHHAGIPSIdmYYGA-DYPVYHTAFDSYD 521
Cdd:cd05662 205 SIGSIDWTRA-------------SDHYPF-HKAKIPWL--YFGVeDHPDYHKPTDDFE 246
M28_like cd05642
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 310-432 1.58e-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: 54.04  E-value: 1.58e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 310 PGQRVGPGRMVINMTfqgemkmkKINNVVVTIRGSEEADRYVILGNHRDAWTY----------GAVDPNSGTSALLDISR 379
Cdd:cd05642  72 PSYVQGPASRIPFPV--------NISNVVATLKGSEDPDRVYVVSGHYDSRVSdvmdyesdapGANDDASGVAVSMELAR 143

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 18410120 380 RFAlllksGWRPRRTILLCSWDAEEFGMIGSTeWIEENVLNLGASAVAYLNVD 432
Cdd:cd05642 144 IFA-----KHRPKATIVFTAVAGEEQGLYGST-FLAQTYRNNSVNVEGMLNND 190
M28_SGAP_like cd03876
M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family ...
 335-521 2.60e-05

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: 46.52  E-value: 2.60e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 335 NNVVVTIRGSEeADRYVILGNHRDAWTYGA--VDPNSGTSALLDIsrrfALLLkSGWRPRRTILLCSWDAEEFGMIGSTE 412
Cdd:cd03876  64 YNVIAETKGGD-PNNVVMLGAHLDSVSAGPgiNDNGSGSAALLEV----ALAL-AKFKVKNAVRFAWWTAEEFGLLGSKF 137

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 413 WIEenvlNLGASAV----AYLNVDcaVQGSGFFA-------GATPQLDGllvdvlklVQDPDAVGLTVEETFKSQNniiq 481
Cdd:cd03876 138 YVN----NLSSEERskirLYLNFD--MIASPNYGyfiydgdGSAFNLTG--------PPGSAEIERLFEAYFTSLG---- 199

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18410120 482 rLSRVDSDFSG------FLhHAGIPSIDMYYGADY-------------------PVYHTAFDSYD 521
Cdd:cd03876 200 -LPSTPTEFDGrsdyapFI-EAGIPAGGLFTGAEGikteeqaalwggtagvaydPCYHQACDTID 262
M28_like cd05640
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
 336-416 1.15e-04

M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions.


Pssm-ID: 349893 [Multi-domain]  Cd Length: 281  Bit Score: 44.75  E-value: 1.15e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 336 NVVVTIRGSEEADRYVILGNHRDAW--TYGAVDPNSGTSALLDISRRFALLlksgwRPRRTILLCSWDAEEF-----GMI 408
Cdd:cd05640  54 NLIADLPGSYSQDKLILIGAHYDTVpgSPGADDNASGVAALLELARLLATL-----DPNHTLRFVAFDLEEYpffarGLM 128


                ....*...
gi 18410120 409 GSTEWIEE 416
Cdd:cd05640 129 GSHAYAED 136
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
 157-295 5.62e-04

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: 40.58  E-value: 5.62e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 157 PYHAYSPSGSAQ-GNVVFVNHGEERDyhalesIGVSVKGCVVLARKGENLgRGAIVKIAEAKGALGVLIYaendgggfgg 235
Cdd:cd00538  15 LFNPPSSPVGVVaGPLVGCGYGTTDD------SGADVKGKIVLVRRGGCS-FSEKVKNAQKAGAKAVIIY---------- 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 236 iergtvmrgiGDPVSPGWPGVVGGEKLSLddelvtrrfPKIPSLPLSLRNAEIILASLGG 295
Cdd:cd00538  78 ----------NNGDDPGPQMGSVGLESTD---------PSIPTVGISYADGEALLSLLEA 118
PA_C5a_like cd02133
PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a ...
 171-225 5.94e-04

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: 40.73  E-value: 5.94e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18410120 171 VVFVNHGEERDYhalesIGVSVKGCVVLARKGENlgrgAIV-KIAEAK--GALGVLIY 225
Cdd:cd02133  30 LVDAGLGTPEDF-----EGKDVKGKIALIQRGEI----TFVeKIANAKaaGAVGVIIY 78
PA_ScAPY_like cd02130
PA_ScAPY_like: Protease-associated domain containing proteins like Saccharomyces cerevisiae ...
 148-225 1.26e-03

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: 39.16  E-value: 1.26e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 148 VPGDSPVVRPYHaYSPSGSAQGNVVFV-NHG-EERDYhalesiGVSVKGCVVLARKGEnLGRGAIVKIAEAKGALGVLIY 225
Cdd:cd02130   4 ANGEAIPTTAFT-YSPAGEVTGPLVVVpNLGcDAADY------PASVAGNIALIERGE-CPFGDKSALAGAAGAAAAIIY 75
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
 168-225 2.17e-03

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: 37.88  E-value: 2.17e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 18410120   168 QGNVVFVNHGEERDYHaleSIGVSVKGCVVLARKGENlGRGAIVKIAEAKGALGVLIY 225
Cdd:pfam02225   1 TGPLVLAPGCYAGDGI---PADFDVKGKIVLVRCTFG-FRAEKVRNAQAAGAAGVIIY 54
M20_yscS_like cd05675
M20 Peptidase, carboxypeptidase yscS-like; Peptidase M20 family, yscS (GlyX-carboxypeptidase, ...
 336-417 8.90e-03

M20 Peptidase, carboxypeptidase yscS-like; Peptidase M20 family, yscS (GlyX-carboxypeptidase, CPS1, carboxypeptidase S, carboxypeptidase a, carboxypeptidase yscS, glycine carboxypeptidase)-like subfamily. This group contains proteins that have been uncharacterized to date with similarity to vacuolar proteins involved in nitrogen metabolism which are essential for use of certain peptides that are sole nitrogen sources. YscS releases a C-terminal amino acid from a peptide that has glycine as the penultimate residue. It is synthesized as one polypeptide chain precursor which yields two active precursor molecules after carbohydrate modification in the secretory pathway. The proteolytically unprocessed forms are associated with the membrane, whereas the mature forms of the enzyme are soluble. Enzymes in this subfamily may also cleave intracellularly generated peptides in order to recycle amino acids for protein synthesis.


Pssm-ID: 349924 [Multi-domain]  Cd Length: 431  Bit Score: 39.27  E-value: 8.90e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18410120 336 NVVVTIRGSEEADRYVILGNH--------------------RDAWTY--GAVDPNSGTSALLDISRRFAlllKSGWRPRR 393
Cdd:cd05675  53 NLVARIGGTDPSAGPLLLLGHidvvpadasdwsvdpfsgeiKDGYVYgrGAVDMKNMAAMMLAVLRHYK---REGFKPKR 129

                        90       100
                ....*....|....*....|....
gi 18410120 394 TILLCSWDAEEFGMIGSTEWIEEN 417
Cdd:cd05675 130 DLVFAFVADEEAGGENGAKWLVDN 153
 
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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