NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|6320623|ref|NP_010703|]
View 

putative aminopeptidase [Saccharomyces cerevisiae S288C]

Protein Classification

M28 family metallopeptidase( domain architecture ID 10133839)

M28 family metallopeptidase is a zinc-dependent peptidase that may be an aminopeptidase or a carboxypeptidase with co-catalytic zinc ions; similar to leucine aminopeptidase that catalyzes the release of an N-terminal amino acid, preferentially leucine, but not glutamic or aspartic acids

CATH:  3.40.630.10
EC:  3.-.-.-
Gene Ontology:  GO:0008270|GO:0008237|GO:0006508
MEROPS:  M28
PubMed:  12773192|18429165|7674922|10493853

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 81-369 1.23e-166

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: 466.72  E-value: 1.23e-166
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623   81 EISNKEVVDDSIKNIDKGSMHKNLAKFTSFYTRYYKSDHGFESAEWLAATIANITKDIPQDTLTIEHFDHKeWKQYSIIV 160
Cdd:cd03879   1 PITHQATVNSLLPQLSKSNMQDTLESLTSFNNRYYKSQTGVESAEWLLDQVQAIIASSGRSGATVEQFTHS-FPQPSIIA 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  161 RVTGSTTPEDIIIIGSHQDSINLLLPSIMAAPGADDNGSGTVTNMEALRLYTENflkrGFRPNNTVEFHFYSAEEGGLLG 240
Cdd:cd03879  80 TIPGSEKSDEIVVIGAHQDSINGSNPSNGRAPGADDDGSGTVTILEALRVLLES----GFQPKNTIEFHWYAAEEGGLLG 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  241 SLDVFTAYAKQKKHVRAMLQQDMTGYVSDPEDEHVGIVTDYTTPALTDFIKLIINSYLSIPYRDTQCGYACSDHGSATRN 320
Cdd:cd03879 156 SQAIATQYKSEGKNVKAMLQLDMTGYVKPGSAEDIGLITDYTDSNLTQFLKQLIDEYLPIPYGDTKCGYACSDHASWTKA 235

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 6320623  321 GFPGSFVIESEFKKTNKYIHSTMDTLDR--LSLAHMAEHTKIVLGVIIELG 369
Cdd:cd03879 236 GYPAAFPFESAFEDYNPYIHTTNDTLDNsgLSFDHMLEFAKLALAFAVELG 286
 
Name Accession Description Interval E-value
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 81-369 1.23e-166

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: 466.72  E-value: 1.23e-166
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623   81 EISNKEVVDDSIKNIDKGSMHKNLAKFTSFYTRYYKSDHGFESAEWLAATIANITKDIPQDTLTIEHFDHKeWKQYSIIV 160
Cdd:cd03879   1 PITHQATVNSLLPQLSKSNMQDTLESLTSFNNRYYKSQTGVESAEWLLDQVQAIIASSGRSGATVEQFTHS-FPQPSIIA 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  161 RVTGSTTPEDIIIIGSHQDSINLLLPSIMAAPGADDNGSGTVTNMEALRLYTENflkrGFRPNNTVEFHFYSAEEGGLLG 240
Cdd:cd03879  80 TIPGSEKSDEIVVIGAHQDSINGSNPSNGRAPGADDDGSGTVTILEALRVLLES----GFQPKNTIEFHWYAAEEGGLLG 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  241 SLDVFTAYAKQKKHVRAMLQQDMTGYVSDPEDEHVGIVTDYTTPALTDFIKLIINSYLSIPYRDTQCGYACSDHGSATRN 320
Cdd:cd03879 156 SQAIATQYKSEGKNVKAMLQLDMTGYVKPGSAEDIGLITDYTDSNLTQFLKQLIDEYLPIPYGDTKCGYACSDHASWTKA 235

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 6320623  321 GFPGSFVIESEFKKTNKYIHSTMDTLDR--LSLAHMAEHTKIVLGVIIELG 369
Cdd:cd03879 236 GYPAAFPFESAFEDYNPYIHTTNDTLDNsgLSFDHMLEFAKLALAFAVELG 286
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 127-368 7.75e-50

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: 168.00  E-value: 7.75e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  127 LAATIANITKDIPQDTLTIEHFDHKEWKQYSIIVRVTGSTTPEDIIIIGSHQDSinllLPSImaAPGADDNGSGTVTNME 206
Cdd:COG2234  18 AAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPDEVVVLGAHYDS----VGSI--GPGADDNASGVAALLE 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  207 ALRLytenFLKRGFRPNNTVEFHFYSAEEGGLLGSldvfTAYAKQ----KKHVRAMLQQDMTGYVSDPEDehVGIVTDYT 282
Cdd:COG2234  92 LARA----LAALGPKPKRTIRFVAFGAEEQGLLGS----RYYAENlkapLEKIVAVLNLDMIGRGGPRNY--LYVDGDGG 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  283 TPALTDFIKLIINSY---LSIPYRDTQCGYACSDHGSATRNGFPGSFVIESEFKKtNKYIHSTMDTLDRLSLAHMAEHTK 359
Cdd:COG2234 162 SPELADLLEAAAKAYlpgLGVDPPEETGGYGRSDHAPFAKAGIPALFLFTGAEDY-HPDYHTPSDTLDKIDLDALAKVAQ 240


                ....*....
gi 6320623  360 IVLGVIIEL 368
Cdd:COG2234 241 LLAALVYEL 249
Peptidase_M28 pfam04389
Peptidase family M28;
158-365 1.10e-34

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 126.25  E-value: 1.10e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623    158 IIVRVTGSTTPEdIIIIGSHQDSINlllpsimAAPGADDNGSGTVTNMEALRlytenFLKRGFRPNNTVEFHFYSAEEGG 237
Cdd:pfam04389   2 VIAKLPGKAPDE-VVLLSAHYDSVG-------TGPGADDNASGVAALLELAR-----VLAAGQRPKRSVRFLFFDAEEAG 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623    238 LLGSldvfTAYAKQKKH---VRAMLQQDMTGYVSDPEDEHVGivtDYTTPALTDFIKLIINSYLSI---PYRDTQCGYAC 311
Cdd:pfam04389  69 LLGS----HHFAKSHPPlkkIRAVINLDMIGSGGPALLFQSG---PKGSSLLEKYLKAAAKPYGVTlaeDPFQERGGPGR 141

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 6320623    312 SDHGSATRNGFPGSFVIeseFKKTNKYIHSTMDTLDRLSLAHMAEHTKIVLGVI 365
Cdd:pfam04389 142 SDHAPFIKAGIPGLDLA---FTDFGYRYHTPADTIDNIDPGTLQRIGDLVLALV 192
 
Name Accession Description Interval E-value
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 81-369 1.23e-166

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: 466.72  E-value: 1.23e-166
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623   81 EISNKEVVDDSIKNIDKGSMHKNLAKFTSFYTRYYKSDHGFESAEWLAATIANITKDIPQDTLTIEHFDHKeWKQYSIIV 160
Cdd:cd03879   1 PITHQATVNSLLPQLSKSNMQDTLESLTSFNNRYYKSQTGVESAEWLLDQVQAIIASSGRSGATVEQFTHS-FPQPSIIA 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  161 RVTGSTTPEDIIIIGSHQDSINLLLPSIMAAPGADDNGSGTVTNMEALRLYTENflkrGFRPNNTVEFHFYSAEEGGLLG 240
Cdd:cd03879  80 TIPGSEKSDEIVVIGAHQDSINGSNPSNGRAPGADDDGSGTVTILEALRVLLES----GFQPKNTIEFHWYAAEEGGLLG 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  241 SLDVFTAYAKQKKHVRAMLQQDMTGYVSDPEDEHVGIVTDYTTPALTDFIKLIINSYLSIPYRDTQCGYACSDHGSATRN 320
Cdd:cd03879 156 SQAIATQYKSEGKNVKAMLQLDMTGYVKPGSAEDIGLITDYTDSNLTQFLKQLIDEYLPIPYGDTKCGYACSDHASWTKA 235

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 6320623  321 GFPGSFVIESEFKKTNKYIHSTMDTLDR--LSLAHMAEHTKIVLGVIIELG 369
Cdd:cd03879 236 GYPAAFPFESAFEDYNPYIHTTNDTLDNsgLSFDHMLEFAKLALAFAVELG 286
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 127-368 7.75e-50

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: 168.00  E-value: 7.75e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  127 LAATIANITKDIPQDTLTIEHFDHKEWKQYSIIVRVTGSTTPEDIIIIGSHQDSinllLPSImaAPGADDNGSGTVTNME 206
Cdd:COG2234  18 AAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPDEVVVLGAHYDS----VGSI--GPGADDNASGVAALLE 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  207 ALRLytenFLKRGFRPNNTVEFHFYSAEEGGLLGSldvfTAYAKQ----KKHVRAMLQQDMTGYVSDPEDehVGIVTDYT 282
Cdd:COG2234  92 LARA----LAALGPKPKRTIRFVAFGAEEQGLLGS----RYYAENlkapLEKIVAVLNLDMIGRGGPRNY--LYVDGDGG 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  283 TPALTDFIKLIINSY---LSIPYRDTQCGYACSDHGSATRNGFPGSFVIESEFKKtNKYIHSTMDTLDRLSLAHMAEHTK 359
Cdd:COG2234 162 SPELADLLEAAAKAYlpgLGVDPPEETGGYGRSDHAPFAKAGIPALFLFTGAEDY-HPDYHTPSDTLDKIDLDALAKVAQ 240


                ....*....
gi 6320623  360 IVLGVIIEL 368
Cdd:COG2234 241 LLAALVYEL 249
Peptidase_M28 pfam04389
Peptidase family M28;
158-365 1.10e-34

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 126.25  E-value: 1.10e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623    158 IIVRVTGSTTPEdIIIIGSHQDSINlllpsimAAPGADDNGSGTVTNMEALRlytenFLKRGFRPNNTVEFHFYSAEEGG 237
Cdd:pfam04389   2 VIAKLPGKAPDE-VVLLSAHYDSVG-------TGPGADDNASGVAALLELAR-----VLAAGQRPKRSVRFLFFDAEEAG 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623    238 LLGSldvfTAYAKQKKH---VRAMLQQDMTGYVSDPEDEHVGivtDYTTPALTDFIKLIINSYLSI---PYRDTQCGYAC 311
Cdd:pfam04389  69 LLGS----HHFAKSHPPlkkIRAVINLDMIGSGGPALLFQSG---PKGSSLLEKYLKAAAKPYGVTlaeDPFQERGGPGR 141

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 6320623    312 SDHGSATRNGFPGSFVIeseFKKTNKYIHSTMDTLDRLSLAHMAEHTKIVLGVI 365
Cdd:pfam04389 142 SDHAPFIKAGIPGLDLA---FTDFGYRYHTPADTIDNIDPGTLQRIGDLVLALV 192
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 155-368 6.23e-32

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: 6.23e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  155 QYSIIVRVTGSTTPEDIIIIGSHQDSINLllpsimaAPGADDNGSGTVTNMEALRLytenFLKRGFRPNNTVEFHFYSAE 234
Cdd:cd02690   1 GYNVIATIKGSDKPDEVILIGAHYDSVPL-------SPGANDNASGVAVLLELARV----LSKLQLKPKRSIRFAFWDAE 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  235 EGGLLGSLDVFTAYAKQKKHVRAMLQQDMTGYvsdPEDEHVGIVTDYTTPALTDFIKLIINSYLSIPY---RDTQCGYAC 311
Cdd:cd02690  70 ELGLLGSKYYAEQLLSSLKNIRAALNLDMIGG---AGPDLYLQTAPGNDALVEKLLRALAHELENVVYtvvYKEDGGTGG 146

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6320623  312 SDHGSATRNGFPGSFVIESEFKKtNKYIHSTMDTLDRLSLAHMAEHTKIVLGVIIEL 368
Cdd:cd02690 147 SDHRPFLARGIPAASLIQSESYN-FPYYHTTQDTLENIDKDTLKRAGDILASFLYRL 202
M28_like cd05640
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
 141-358 4.86e-21

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: 91.74  E-value: 4.86e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  141 DTLTIEHFDHKEWKQYSIIVRVTGSTTPEDIIIIGSHQDSinllLPSimaAPGADDNGSGTVTNMEALRLYTENflkrgf 220
Cdd:cd05640  38 YNVTSHFFSHQEGVYANLIADLPGSYSQDKLILIGAHYDT----VPG---SPGADDNASGVAALLELARLLATL------ 104

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  221 RPNNTVEFHFYSAEE-----GGLLGSldvfTAYAKQ----KKHVRAMLQQDMTGYV-SDPEDEHV-GIVTDYTTPALTDF 289
Cdd:cd05640 105 DPNHTLRFVAFDLEEypffaRGLMGS----HAYAEDllrpLTPIVGMLSLEMIGYYdPFPHSQAYpAGFELHFYPHMGDF 180

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  290 IKLIIN----SYLSIPYR------DTQC-------------GYACSDHGSATRNGFPGSFVIESEFKKtNKYIHSTMDTL 346
Cdd:cd05640 181 IAVVGRlrsrKLVRAFKRafrmlsDFPVeslnlpfngpgvpPFRRSDHSSFWDHGYPAIMVTDTAFYR-NPQYHLPCDTP 259

                       250
                ....*....|..
gi 6320623  347 DRLSLAHMAEHT 358
Cdd:cd05640 260 DTLNYKFLTRVT 271
M28_like cd03877
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
 156-368 4.13e-16

M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This subfamily is composed of uncharacterized proteins, many of which contain a protease-associated (PA) domain insert which may participate in substrate binding and/or promote conformational changes, influencing the stability and accessibility of the site to substrate. Some proteins in this subfamily are also associated with the PDZ domain, a widespread protein module that has been recruited to serve multiple functions during the course of evolution.


Pssm-ID: 349874 [Multi-domain]  Cd Length: 206  Bit Score: 76.13  E-value: 4.13e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  156 YSIIVRVTGSTTPEDIIIIGSHQDSINLLLP--SIMAAPGADDNGSGTVTNMEalrlytenfLKRGFR----PNNTVEFH 229
Cdd:cd03877   2 HNVVGVLEGSDLPDETIVIGAHYDHLGIGGGdsGDKIYNGADDNASGVAAVLE---------LARYFAkqktPKRSIVFA 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  230 FYSAEEGGLLGSldvfTAYAKQ----KKHVRAMLQQDMtgyVSDPEDEHVGIVTDYTTPALTDFIKlIINSYLSIPYRDT 305
Cdd:cd03877  73 AFTAEEKGLLGS----KYFAENpkfpLDKIVAMLNLDM---IGRLGRSKDVYLIGSGSSELENLLK-KANKAAGRVLSKD 144

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6320623  306 Q---CGYACSDHGSATRNGFPGSFVieseFKKTNKYIHSTMDTLDRLSLAHMAEHTKIVLGVIIEL 368
Cdd:cd03877 145 PlpeWGFFRSDHYPFAKAGVPALYF----FTGLHDDYHKPSDDYEKIDYEGMARVVNLIYQLLRGL 206
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
 143-356 4.78e-15

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: 75.81  E-value: 4.78e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  143 LTIEHFDHKEWKQYSIIVRVTGSTTPEDIIIIGSHQDSINLllpsimaAPGADDNGSGTVTNMEALRLytenFLKRGFRP 222
Cdd:cd03883 214 LKMEAKTYPDATSRNVIAEITGSKYPDEVVLVGGHLDSWDV-------GTGAMDDGGGVAISWEALKL----IKDLGLKP 282

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  223 NNTVEFHFYSAEEGGLLGSldvfTAYAKQ-----KKHVRAMlQQDMTGyvsdpeDEHVGIvtDYTTPALTDFIKLIINSY 297
Cdd:cd03883 283 KRTIRVVLWTGEEQGLVGA----KAYAEAhkdelENHVFAM-ESDIGT------FTPYGL--QFTGSDTARAIVKEVMKL 349

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6320623  298 LSiPYRDTQC---GYACSDHGSATRNGFPGSfvieSEFKKTNKYI---HSTMDTLDRLSLAHMAE 356
Cdd:cd03883 350 LS-PLGITQVlpkAGVGPDISFLKAAGVPGA----SLIQDNSDYFdyhHTAGDTMDVMDPKQLDQ 409
M28_SGAP_like cd03876
M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family ...
 168-351 7.47e-15

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: 74.26  E-value: 7.47e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  168 PEDIIIIGSHQDSINlllpsimAAPGADDNGSGTVTNME-ALRLyTEnflkrgFRPNNTVEFHFYSAEEGGLLGSldvfT 246
Cdd:cd03876  75 PNNVVMLGAHLDSVS-------AGPGINDNGSGSAALLEvALAL-AK------FKVKNAVRFAWWTAEEFGLLGS----K 136

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  247 AYAK-----QKKHVRAMLQQDMTG--------YVSDpedehvGIVTDYTTPALTDFIKLIINSYLS---IPYRDTQcGYA 310
Cdd:cd03876 137 FYVNnlsseERSKIRLYLNFDMIAspnygyfiYDGD------GSAFNLTGPPGSAEIERLFEAYFTslgLPSTPTE-FDG 209

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6320623  311 CSDHGSATRNGFP------GSFVIESE-----FKKTNK------YiHSTMDTLDRLSL 351
Cdd:cd03876 210 RSDYAPFIEAGIPagglftGAEGIKTEeqaalWGGTAGvaydpcY-HQACDTIDNINR 266
M28_like cd08015
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 156-349 1.02e-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: 72.63  E-value: 1.02e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  156 YSIIVRVTGSTTPEDIIIIGSHQDSINlllpsimAAPGADDNGSGTVTNMEALRLytenfLKR-GFRPNNTVEFHFYSAE 234
Cdd:cd08015   2 YNVIAEIPGSDKKDEVVILGAHLDSWH-------GATGATDNGAGTAVMMEAMRI-----LKAiGSKPKRTIRVALWGSE 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  235 EGGLLGSLDVFTAY---------AKQKKHVRAMLQQDM-TGYV---SDPEDEHVGivtDYTTPALTDFIKLIINSYlsip 301
Cdd:cd08015  70 EQGLHGSRAYVEKHfgdpptmqlQRDHKKISAYFNLDNgTGRIrgiYLQGNLAAY---PIFSAWLYPFHDLGATTV---- 142

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 6320623  302 yrdTQCGYACSDHGSATRNGFPGSFVIESEFKKTNKYIHSTMDTLDRL 349
Cdd:cd08015 143 ---IERNTGGTDHAAFDAVGIPAFQFIQDPWDYWTRTHHTNRDTYDRL 187
M28_like_PA cd05661
M28 Zn-peptidase containing a PA domain insert; Peptidase family M28 (also called ...
 165-350 2.49e-13

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: 69.14  E-value: 2.49e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  165 STTPEDIIIIGSHQDSInlllpsiMAAPGADDNGSGTVTNMEALRLYTEnflkrgFRPNNTVEFHFYSAEEGGLLGSlDV 244
Cdd:cd05661  72 NKNNNDIIIVTSHYDSV-------VKAPGANDNASGTAVTLELARVFKK------VKTDKELRFIAFGAEENGLLGS-KY 137

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  245 FTAYAKQK--KHVRAMLQQDMTGyVSDPEDEHVGIVTDYTTPALTDFIKLIINSYLSIPYRDTQCGyaCSDHGSATRNGF 322
Cdd:cd05661 138 YVASLSEDeiKRTIGVFNLDMVG-TSDAKAGDLYAYTIDGKPNLVTDSGAAASKRLSGVLPLVQQG--SSDHVPFHEAGI 214

                       170       180       190
                ....*....|....*....|....*....|
gi 6320623  323 PGSFVI--ESEFKKTNKYIHSTMDTLDRLS 350
Cdd:cd05661 215 PAALFIhmDPETEPVEPWYHTPNDTVENIS 244
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
 102-265 2.58e-13

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: 69.92  E-value: 2.58e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  102 KNLAKFTSFYTRYYKSDHGFESAEWLAATIANITKDIPQDTLTIEHFDHKE--------WKQYS-------IIVRVTGST 166
Cdd:cd03875  11 EDLQVLISIGPHPYGSHNNDKVRDYLLARVEEIKERANANGLEVEVQDDTGsgsfnflsSGMTLvyfevtnIVVRISGKN 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  167 TPEDI-IIIGSHQDSInlllpsiMAAPGADDNGSGTVTNMEALRLYTenflKRGFRPNNTVEFHFYSAEEGGLLGSlDVF 245
Cdd:cd03875  91 SNSLPaLLLNAHFDSV-------PTSPGATDDGMGVAVMLEVLRYLS----KSGHQPKRDIIFLFNGAEENGLLGA-HAF 158

                       170       180
                ....*....|....*....|
gi 6320623  246 TAYAKQKKHVRAMLQQDMTG 265
Cdd:cd03875 159 ITQHPWAKNVRAFINLEAAG 178
M28_like cd05642
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 106-265 2.71e-12

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: 67.13  E-value: 2.71e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  106 KFTSFYTRYYKSD-----HGFESA-EWLAATIANITKDiPQDTLTIEhfdhkeWKQY---------------SIIVRVTG 164
Cdd:cd05642  25 KLVSFGTRHTLSTqtdptRGIGAArDWIAEEFREYAAA-SGGRMTVE------VPSYvqgpasripfpvnisNVVATLKG 97

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  165 STTPEDIIIIGSHQDSINL-LLPSIMAAPGADDNGSGTVTNMEALRLYTENflkrgfRPNNTVEFHFYSAEEGGLLGSLD 243
Cdd:cd05642  98 SEDPDRVYVVSGHYDSRVSdVMDYESDAPGANDDASGVAVSMELARIFAKH------RPKATIVFTAVAGEEQGLYGSTF 171

                       170       180
                ....*....|....*....|..
gi 6320623  244 VFTAYAKQKKHVRAMLQQDMTG 265
Cdd:cd05642 172 LAQTYRNNSVNVEGMLNNDIVG 193
M28_like_PA_PDZ_associated cd05663
M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ ...
 172-368 5.72e-12

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: 65.17  E-value: 5.72e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  172 IIIGSHQDSI-----NLLLPS--IMAAPGADDNGSGTVTnMEALRLYTENFLKRGFRPNNTVeFHFYSAEEGGLLGSLDV 244
Cdd:cd05663  73 VVVGAHYDHLgyggeGSLARGdeSLIHNGADDNASGVAA-MLELAAKLVDSDTSLALSRNLV-FIAFSGEELGLLGSKHF 150

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  245 FTAYAKQKKHVRAMLQQDMTGYVSDPEDEHVGIVTDYTTPALTDF------IKLIINSylsipyrdtqCGYACSDHGSAT 318
Cdd:cd05663 151 VKNPPFPIKNTVYMINMDMVGRLRDNKLIVQGTGTSPGWEQLVQArnkatgFKLILDP----------TGYGPSDHTSFY 220

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 6320623  319 RNGFPgsfvIESEFKKTNKYIHSTMDTLDRLSLAHMAEHTKIVLGVIIEL 368
Cdd:cd05663 221 LDDVP----VLHFFTGAHSDYHRPSDDSDKLNYDGMADIADFAVRIISAL 266
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 92-241 2.63e-10

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: 60.71  E-value: 2.63e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623   92 IKNIDKGSMHKNLAKFTSFytryyksDH------GFESAEWlaatIANITKDIPQDTLTIEHFDHKEWkqySIIVRVTGS 165
Cdd:cd08022   5 LDEPDAENIREWLRYYTSG-------PHlagtegNLELAQW----TEDKWREFGLDDVELEEYDVPIW---NVIGTIRGS 70

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6320623  166 TTPEDIIIIGSHQDSinlllpsimAAPGADDNGSGTVTNMEALRLYTEnFLKRGFRPNNTVEFHFYSAEEGGLLGS 241
Cdd:cd08022  71 EEPDEYIILGNHRDA---------WVFGAGDPNSGTAVLLEVARALGT-LLKKGWRPRRTIIFASWDAEEYGLIGS 136
Zinc_peptidase_like cd03873
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ...
 158-360 9.77e-10

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: 57.82  E-value: 9.77e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  158 IIVRVTGSTTPEdIIIIGSHQDSI------NLLLPSI--------MAAPGADDNGSGTVTNMEALRLYTENflkrGFRPN 223
Cdd:cd03873   2 LIARLGGGEGGK-SVALGAHLDVVpagegdNRDPPFAedteeegrLYGRGALDDKGGVAAALEALKRLKEN----GFKPK 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  224 NTVEFHFYSAEEGGLLGSLDVFTAYAKQK-KHVRAMLQQDMTGYVSdpEDEHVGIVTDyttpaLTDFIKLIINSYLSIPY 302
Cdd:cd03873  77 GTIVVAFTADEEVGSGGGKGLLSKFLLAEdLKVDAAFVIDATAGPI--LQKGVVIRNP-----LVDALRKAAREVGGKPQ 149

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6320623  303 RDTQCGyACSDHGSATRNGFPGSFVIESefkkTNKYIHStmdTLDRLSLAHMAEHTKI 360
Cdd:cd03873 150 RASVIG-GGTDGRLFAELGIPGVTLGPP----GDKGAHS---PNEFLNLDDLEKATKV 199
M28_like_PA cd05660
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ...
 156-374 1.31e-09

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: 58.53  E-value: 1.31e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  156 YSIIVRVTGSTTPEDIIIIGSHQDSINLLLPSIMAA--PGADDNGSGTVTNMEALRLYTENFLkrgfRPNNTVEFHFYSA 233
Cdd:cd05660  60 HNVVAILPGSKLPDEYIVLSAHWDHLGIGPPIGGDEiyNGAVDNASGVAAVLELARVFAAQDQ----RPKRSIVFLAVTA 135

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  234 EEGGLLGSlDVFTAY--AKQKKHVrAMLQQDMTGyVSDPEDEHVGIVTDYTTpaLTDFIKLI---INSYLSIPYRDTQCG 308
Cdd:cd05660 136 EEKGLLGS-RYYAANpiFPLDKIV-ANLNIDMIG-RIGPTKDVLLIGSGSSE--LENILKEAakaVGRVVDYDPNPENGS 210

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6320623  309 YACSDHGSATRNG------FPGSFVIESEFKKTNKYI----HSTMDTL-DRLSLAHMAEHTKIVLGVIIELGSWSAW 374
Cdd:cd05660 211 FYRSDHYNFAKKGvpvlffFGGYDLGDGGKKLAKAYLhtdyHKPADDVtEKWDYEGAAEDTKLIYATAWELANSEER 287
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 156-349 5.36e-09

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


Pssm-ID: 349871 [Multi-domain]  Cd Length: 278  Bit Score: 56.54  E-value: 5.36e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  156 YSIIVRVTGSTTPEDIIIIGSHQDSinlllpsimAAPGADDNGSGTVTNMEALRLYTENFLKRGFRPNNTVEFHFYSAEE 235
Cdd:cd03874  58 TNVVGKIEGIEQPDRAIIIGAHRDS---------WGYGAGYPNSGTAVLLEIARLFQQLKKKFGWKPLRTIYFISWDGSE 128

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  236 GGLLGSldvfTAYAKQKKHVramLQQDMTGYVsdpeDEHVGIVTDY-----TTPALtdfIKLIINSYLSIPYRDTQCGYA 310
Cdd:cd03874 129 FGLAGS----TELGEDRKAS---LKDEVYAYI----NIDQLVIGNSeldvdAHPLL---QSLFRKASKKVKFPGNEDWWK 194

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 6320623  311 CSD---------HGSAT----RNGFPgSFVIESEFKKTNKY-IHSTMDTLDRL 349
Cdd:cd03874 195 HSPnakvsnlhqYGDWTpflnHLGIP-VAVFSFKNDRNASYpINSSYDTFEWL 246
M28_like cd05662
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
 158-287 6.06e-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: 53.24  E-value: 6.06e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  158 IIVRVTGSTTPEDIIIIGSHQDSINLLLPSIMaaPGADDNGSGtvtnMEALRLYTENFLKRgfRPNNTVEFHFYSAEEGG 237
Cdd:cd05662  65 VLAVIKGSEPPTKWRVVSAHYDHLGIRGGKIY--NGADDNASG----VAALLALAEYFKKH--PPKHNVIFAATDAEEPG 136

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 6320623  238 LLGSLDVFTAYAKQKKHVRAMLQQDMtgyVSDPEDEHVGIVTDYTTPALT 287
Cdd:cd05662 137 LRGSYAFVEALKVPRAQIELNINLDM---ISRPERNELYVEGASQFPQLT 183
M28_like cd05643
M28 Zn-peptidase-like; Peptidase family M28 (also called aminopeptidase Y family), ...
 158-365 1.07e-07

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: 52.79  E-value: 1.07e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  158 IIVRVTGSTTPEdiIIIGSHqdsinLLLPSimaaPGADDNGSGTVTNMEALRLYTENFLkrgFRPNNTVEFhFYSAEegg 237
Cdd:cd05643  74 LYAIIGKETPPE--IAFVAH-----LCHPK----PGANDNASGSALLLEVARVLAKLIL---NRPKRGICF-LWVPE--- 135

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  238 LLGSLDVFTAYAKQKKHVRAMLQQDMTGyvSDPEDEHVGIVTDYTTPALTDFIKLII---------NSYLSIPYRdTQCG 308
Cdd:cd05643 136 YTGTAAYFAQHPDRLKKIIAVINLDMVG--EDQTKTGSTLMLVPTPLSFPSYLNEELaqklsnftgSSLPAVRYG-KEPY 212

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6320623  309 YACSDHGSATRNGFPGSFVIESefkkTNKYIHSTMDTLDRLSLAHMAEHTKIVLGVI 365
Cdd:cd05643 213 EGGSDHDVFSDPGIPAVMFNTW----PDRYYHTSDDTPDKLDPETLKNVGAAVLLTA 265
Peptidase_M20 pfam01546
Peptidase family M20/M25/M40; This family includes a range of zinc metallopeptidases belonging ...
 189-259 1.17e-05

Peptidase family M20/M25/M40; This family includes a range of zinc metallopeptidases belonging to several families in the peptidase classification. Family M20 are Glutamate carboxypeptidases. Peptidase family M25 contains X-His dipeptidases.


Pssm-ID: 460247 [Multi-domain]  Cd Length: 315  Bit Score: 46.57  E-value: 1.17e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6320623    189 MAAPGADDNGSGTVTNMEALRLYTENFLKRGfrpnnTVEFHFYSAEEGGLLGSLDVFTAYAKQKKHVRAML 259
Cdd:pfam01546  27 LYGRGHDDMKGGLLAALEALRALKEEGLKKG-----TVKLLFQPDEEGGMGGARALIEDGLLEREKVDAVF 92
M20_18_42 cd18669
M20, M18 and M42 Zn-peptidases include aminopeptidases and carboxypeptidases; This family ...
 158-237 1.03e-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: 39.72  E-value: 1.03e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  158 IIVRVTGSTTPEDIIIIGSHQDSINLL--LPS------------IMAAPGADDNGSGTVTNMEALRLYTENflkrGFRPN 223
Cdd:cd18669   1 NVIARYGGGGGGKRVLLGAHIDVVPAGegDPRdppffvdtveegRLYGRGALDDKGGVAAALEALKLLKEN----GFKLK 76

                        90
                ....*....|....
gi 6320623  224 NTVEFHFYSAEEGG 237
Cdd:cd18669  77 GTVVVAFTPDEEVG 90
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
 141-349 1.14e-03

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: 40.44  E-value: 1.14e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  141 DTLTIEHFdhkewKQYSIIVRVTGSTTPEDIIIIGSHQDSInlllpsimaAPGADDNGSGTVTNMEALRLYTENFLKRGF 220
Cdd:cd09848  47 KVWTDEHY-----KIHNIFGVIKGFVEPDRYVVIGAQRDAW---------GPGAAKSGVGTALLLELARTFSDMVKNDGF 112

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  221 RPNNTVEFHFYSAEEGGLLGSLDVFTAYakqkkhvRAMLQQDMTGYVSdpEDEHV---GIVTDYTTPALTDFIKLIIN-- 295
Cdd:cd09848 113 KPRRSIVFASWSAGDFGSVGATEWLEGY-------LSSLHLKAFTYIS--LDGAVlgdDSFKASASPLLYTLIESTMKqv 183

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6320623  296 -----SYLSIpYRDTQCGYACS------DHGSATRNGFPGSFVIESEF---KKTNKYIHSTMDTLDRL 349
Cdd:cd09848 184 kspvhSGQSY-YETRSSWWASIveplglDSAAYPFLAFSGIPSVSFHFtedDEDYPFLGTKEDTKENL 250
ArgE COG0624
Acetylornithine deacetylase/Succinyl-diaminopimelate desuccinylase or related deacylase [Amino ...
 191-250 1.49e-03

Acetylornithine deacetylase/Succinyl-diaminopimelate desuccinylase or related deacylase [Amino acid transport and metabolism]; Acetylornithine deacetylase/Succinyl-diaminopimelate desuccinylase or related deacylase is part of the Pathway/BioSystem: Arginine biosynthesis


Pssm-ID: 440389 [Multi-domain]  Cd Length: 388  Bit Score: 40.25  E-value: 1.49e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320623  191 APGADDNGSGTVTNMEALRLytenFLKRGFRPNNTVEFHFYSAEEGGLLGSLDVFTAYAK 250
Cdd:COG0624 107 GRGAADMKGGLAAMLAALRA----LLAAGLRLPGNVTLLFTGDEEVGSPGARALVEELAE 162
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH