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Conserved domains on  [gi|148232950|ref|NP_061225|]
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carboxypeptidase Q precursor [Mus musculus]

Protein Classification

M28 family metallopeptidase( domain architecture ID 10133863)

M28 family metallopeptidase similar to vertebrate carboxypeptidase Q, which catalyzes the hydrolysis of dipeptides with unsubstituted terminals into amino acids

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
 40-447 0e+00

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: 729.11  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950  40 NYEDVAKAIINLAVYGKYQnRSYERLGLLVDTVGPRLSGSKNLEKAIQIMYQNLQQDGLENVHLEQVRIPHWERGEESAV 119
Cdd:cd03883    1 SYKKVAKQIIQTALNGSLK-QAYDRLAYLVDTFGPRLSGSENLEKAIDWLYAKLQNDGFDKVHEEPVEVPHWVRGEESAT 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 120 MLEPRIHKMAILGLGSSIGTPPGGITAEVLVVASFDELQRRASEARGKIIVYNQPYTGYEKTVQYRVQGAVEAAKVGAVA 199
Cdd:cd03883   80 LLEPRPQKLAILGLGGSVGTPVEGIEAEVVVVFSFEELQAKADEVKGKIVVYNQPFKGYGETVKYRGQGAVEAAKYGAVA 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 200 SLIQSVASFSIYSPHTGIQKYQDGVPKIPTACITVEDAEMMSRMASRGNKIVIHLEMGAKTYPDTDSFNTVAEITGSMYP 279
Cdd:cd03883  160 VLIRSITPFSIYSPHTGIMRYQDGVTKIPAAAITVEDAEMLSRMAARGQKIVIELKMEAKTYPDATSRNVIAEITGSKYP 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 280 EEVVLVSGHLDSWDVGQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQYYELHKANISKYSLVM 359
Cdd:cd03883  240 DEVVLVGGHLDSWDVGTGAMDDGGGVAISWEALKLIKDLGLKPKRTIRVVLWTGEEQGLVGAKAYAEAHKDELENHVFAM 319

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 360 EADSGTFLPTGLQFTGSDKARAIMKEVMNLLQPLNVTKVFSN-GEGTDINFWIQAGVPGASLRDDLYKYFFFHHSHGDTM 438
Cdd:cd03883  320 ESDIGTFTPYGLQFTGSDTARAIVKEVMKLLSPLGITQVLPKaGVGPDISFLKAAGVPGASLIQDNSDYFDYHHTAGDTM 399


                 ....*....
gi 148232950 439 TVMDPKQMN 447
Cdd:cd03883  400 DVMDPKQLD 408
 
Name Accession Description Interval E-value
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
 40-447 0e+00

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: 729.11  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950  40 NYEDVAKAIINLAVYGKYQnRSYERLGLLVDTVGPRLSGSKNLEKAIQIMYQNLQQDGLENVHLEQVRIPHWERGEESAV 119
Cdd:cd03883    1 SYKKVAKQIIQTALNGSLK-QAYDRLAYLVDTFGPRLSGSENLEKAIDWLYAKLQNDGFDKVHEEPVEVPHWVRGEESAT 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 120 MLEPRIHKMAILGLGSSIGTPPGGITAEVLVVASFDELQRRASEARGKIIVYNQPYTGYEKTVQYRVQGAVEAAKVGAVA 199
Cdd:cd03883   80 LLEPRPQKLAILGLGGSVGTPVEGIEAEVVVVFSFEELQAKADEVKGKIVVYNQPFKGYGETVKYRGQGAVEAAKYGAVA 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 200 SLIQSVASFSIYSPHTGIQKYQDGVPKIPTACITVEDAEMMSRMASRGNKIVIHLEMGAKTYPDTDSFNTVAEITGSMYP 279
Cdd:cd03883  160 VLIRSITPFSIYSPHTGIMRYQDGVTKIPAAAITVEDAEMLSRMAARGQKIVIELKMEAKTYPDATSRNVIAEITGSKYP 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 280 EEVVLVSGHLDSWDVGQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQYYELHKANISKYSLVM 359
Cdd:cd03883  240 DEVVLVGGHLDSWDVGTGAMDDGGGVAISWEALKLIKDLGLKPKRTIRVVLWTGEEQGLVGAKAYAEAHKDELENHVFAM 319

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 360 EADSGTFLPTGLQFTGSDKARAIMKEVMNLLQPLNVTKVFSN-GEGTDINFWIQAGVPGASLRDDLYKYFFFHHSHGDTM 438
Cdd:cd03883  320 ESDIGTFTPYGLQFTGSDTARAIVKEVMKLLSPLGITQVLPKaGVGPDISFLKAAGVPGASLIQDNSDYFDYHHTAGDTM 399


                 ....*....
gi 148232950 439 TVMDPKQMN 447
Cdd:cd03883  400 DVMDPKQLD 408
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 233-446 1.03e-35

Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein turnover, chaperones, Amino acid transport and metabolism];


Pssm-ID: 441835 [Multi-domain]  Cd Length: 257  Bit Score: 132.95  E-value: 1.03e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 233 TVEDAEMMSRMASRGNKIVIHLEMGAKTYPDTDSFNTVAEITGSMYPEEVVLVSGHLDSWD-VGQGALDDGGGAFISWEA 311
Cdd:COG2234   13 AGAAAAAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPDEVVVLGAHYDSVGsIGPGADDNASGVAALLEL 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 312 LSLVKDLGLRPKRTLRLVLWTAEEQGGIGaSQYY-ELHKANISKYSLVMEADS-GTFLPT-GLQFTG---SDKARAIMKE 385
Cdd:COG2234   93 ARALAALGPKPKRTIRFVAFGAEEQGLLG-SRYYaENLKAPLEKIVAVLNLDMiGRGGPRnYLYVDGdggSPELADLLEA 171

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 148232950 386 VM-NLLQPLNVTKVFSNGE--GTDINFWIQAGVPGASLRDDLYKYFFFHHSHGDTMTVMDPKQM 446
Cdd:COG2234  172 AAkAYLPGLGVDPPEETGGygRSDHAPFAKAGIPALFLFTGAEDYHPDYHTPSDTLDKIDLDAL 235
Peptidase_M28 pfam04389
Peptidase family M28;
268-444 2.35e-27

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 108.14  E-value: 2.35e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950  268 NTVAEITGSMyPEEVVLVSGHLDSWDVGQGALDDGGGAFISWEALSLVKDlGLRPKRTLRLVLWTAEEQGGIGASQYYEL 347
Cdd:pfam04389   1 NVIAKLPGKA-PDEVVLLSAHYDSVGTGPGADDNASGVAALLELARVLAA-GQRPKRSVRFLFFDAEEAGLLGSHHFAKS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950  348 HKANiSKYSLVMEADSGTFLPTGLQF-TGSDKARAIMKEVMNLLQPLNVTK---VFSNGEG---TDINFWIQAGVPGASL 420
Cdd:pfam04389  79 HPPL-KKIRAVINLDMIGSGGPALLFqSGPKGSSLLEKYLKAAAKPYGVTLaedPFQERGGpgrSDHAPFIKAGIPGLDL 157

                         170       180
                  ....*....|....*....|....
gi 148232950  421 RDDLYKYFFfhHSHGDTMTVMDPK 444
Cdd:pfam04389 158 AFTDFGYRY--HTPADTIDNIDPG 179
PRK06156 PRK06156
dipeptidase;
279-369 6.89e-05

dipeptidase;


Pssm-ID: 235720 [Multi-domain]  Cd Length: 520  Bit Score: 45.35  E-value: 6.89e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 279 PEEVVLVSGHLDSWDV--------GQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQY---YEL 347
Cdd:PRK06156 125 PELWVLDGTRLDPFKVtlvgdrlyGRGTEDDKGAIVTALYAMKAIKDSGLPLARRIELLVYTTEETDGDPLKYYlerYTP 204

                         90       100
                 ....*....|....*....|....*.
gi 148232950 348 HKANI---SKYSLVM-EADSGTFLPT 369
Cdd:PRK06156 205 PDYNItldAEYPVVTaEKGWGTIMAT 230
 
Name Accession Description Interval E-value
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
 40-447 0e+00

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: 729.11  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950  40 NYEDVAKAIINLAVYGKYQnRSYERLGLLVDTVGPRLSGSKNLEKAIQIMYQNLQQDGLENVHLEQVRIPHWERGEESAV 119
Cdd:cd03883    1 SYKKVAKQIIQTALNGSLK-QAYDRLAYLVDTFGPRLSGSENLEKAIDWLYAKLQNDGFDKVHEEPVEVPHWVRGEESAT 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 120 MLEPRIHKMAILGLGSSIGTPPGGITAEVLVVASFDELQRRASEARGKIIVYNQPYTGYEKTVQYRVQGAVEAAKVGAVA 199
Cdd:cd03883   80 LLEPRPQKLAILGLGGSVGTPVEGIEAEVVVVFSFEELQAKADEVKGKIVVYNQPFKGYGETVKYRGQGAVEAAKYGAVA 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 200 SLIQSVASFSIYSPHTGIQKYQDGVPKIPTACITVEDAEMMSRMASRGNKIVIHLEMGAKTYPDTDSFNTVAEITGSMYP 279
Cdd:cd03883  160 VLIRSITPFSIYSPHTGIMRYQDGVTKIPAAAITVEDAEMLSRMAARGQKIVIELKMEAKTYPDATSRNVIAEITGSKYP 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 280 EEVVLVSGHLDSWDVGQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQYYELHKANISKYSLVM 359
Cdd:cd03883  240 DEVVLVGGHLDSWDVGTGAMDDGGGVAISWEALKLIKDLGLKPKRTIRVVLWTGEEQGLVGAKAYAEAHKDELENHVFAM 319

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 360 EADSGTFLPTGLQFTGSDKARAIMKEVMNLLQPLNVTKVFSN-GEGTDINFWIQAGVPGASLRDDLYKYFFFHHSHGDTM 438
Cdd:cd03883  320 ESDIGTFTPYGLQFTGSDTARAIVKEVMKLLSPLGITQVLPKaGVGPDISFLKAAGVPGASLIQDNSDYFDYHHTAGDTM 399


                 ....*....
gi 148232950 439 TVMDPKQMN 447
Cdd:cd03883  400 DVMDPKQLD 408
PA_M28_2 cd04815
PA_M28_2: Protease-associated (PA) domain, peptidase family M28, subfamily-2. A subfamily of ...
 128-254 3.15e-66

PA_M28_2: Protease-associated (PA) domain, peptidase family M28, subfamily-2. A subfamily of PA-domain containing proteins belonging to the peptidase family M28. Family M28 contains aminopeptidases and carboxypeptidases, and has co-catalytic zinc ions. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. Proteins into which the PA domain is inserted include the following members of the peptidase family M28: i) prostate-specific membrane antigen (PSMA), ii) yeast aminopeptidase Y, and ii) human TfR (transferrin receptor)1 and human TfR2. The proteins listed above belong to other subfamilies; relatively little is known about proteins in this subfamily.


Pssm-ID: 240119  Cd Length: 134  Bit Score: 209.02  E-value: 3.15e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 128 MAILGLGSSIGTPPGGITAEVLVVASFDELQRR-ASEARGKIIVYNQPYT------GYEKTVQYRVQGAVEAAKVGAVAS 200
Cdd:cd04815    1 LAILALGGSVATPPEGITAEVVVVKSFDELKAApAGAVKGKIVFFNQPMVrtqtgsGYGPTVAYRRRGAVEAAKKGAVAV 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 148232950 201 LIQSVASFSIYSPHTGIQKYQDGVPKIPTACITVEDAEMMSRMASRGNKIVIHL 254
Cdd:cd04815   81 LIRSIGTDSHRSPHTGMMSYDDGVPKIPAAAISVEDADMLERLAARGKPIRVNL 134
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 233-446 1.03e-35

Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein turnover, chaperones, Amino acid transport and metabolism];


Pssm-ID: 441835 [Multi-domain]  Cd Length: 257  Bit Score: 132.95  E-value: 1.03e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 233 TVEDAEMMSRMASRGNKIVIHLEMGAKTYPDTDSFNTVAEITGSMYPEEVVLVSGHLDSWD-VGQGALDDGGGAFISWEA 311
Cdd:COG2234   13 AGAAAAAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPDEVVVLGAHYDSVGsIGPGADDNASGVAALLEL 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 312 LSLVKDLGLRPKRTLRLVLWTAEEQGGIGaSQYY-ELHKANISKYSLVMEADS-GTFLPT-GLQFTG---SDKARAIMKE 385
Cdd:COG2234   93 ARALAALGPKPKRTIRFVAFGAEEQGLLG-SRYYaENLKAPLEKIVAVLNLDMiGRGGPRnYLYVDGdggSPELADLLEA 171

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 148232950 386 VM-NLLQPLNVTKVFSNGE--GTDINFWIQAGVPGASLRDDLYKYFFFHHSHGDTMTVMDPKQM 446
Cdd:COG2234  172 AAkAYLPGLGVDPPEETGGygRSDHAPFAKAGIPALFLFTGAEDYHPDYHTPSDTLDKIDLDAL 235
M28_like cd08015
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 266-437 4.11e-33

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: 124.63  E-value: 4.11e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 266 SFNTVAEITGSMYPEEVVLVSGHLDSWDVGQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQYY 345
Cdd:cd08015    1 TYNVIAEIPGSDKKDEVVILGAHLDSWHGATGATDNGAGTAVMMEAMRILKAIGSKPKRTIRVALWGSEEQGLHGSRAYV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 346 ELHKAN---------ISKYSLVMEADSGTFLPTGLQFTGSDKARAIMKEVMNLLQPLNVTKVF-SNGEGTDINFWIQAGV 415
Cdd:cd08015   81 EKHFGDpptmqlqrdHKKISAYFNLDNGTGRIRGIYLQGNLAAYPIFSAWLYPFHDLGATTVIeRNTGGTDHAAFDAVGI 160

                        170       180
                 ....*....|....*....|...
gi 148232950 416 PGASLRDDLYKYF-FFHHSHGDT 437
Cdd:cd08015  161 PAFQFIQDPWDYWtRTHHTNRDT 183
Peptidase_M28 pfam04389
Peptidase family M28;
268-444 2.35e-27

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 108.14  E-value: 2.35e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950  268 NTVAEITGSMyPEEVVLVSGHLDSWDVGQGALDDGGGAFISWEALSLVKDlGLRPKRTLRLVLWTAEEQGGIGASQYYEL 347
Cdd:pfam04389   1 NVIAKLPGKA-PDEVVLLSAHYDSVGTGPGADDNASGVAALLELARVLAA-GQRPKRSVRFLFFDAEEAGLLGSHHFAKS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950  348 HKANiSKYSLVMEADSGTFLPTGLQF-TGSDKARAIMKEVMNLLQPLNVTK---VFSNGEG---TDINFWIQAGVPGASL 420
Cdd:pfam04389  79 HPPL-KKIRAVINLDMIGSGGPALLFqSGPKGSSLLEKYLKAAAKPYGVTLaedPFQERGGpgrSDHAPFIKAGIPGLDL 157

                         170       180
                  ....*....|....*....|....
gi 148232950  421 RDDLYKYFFfhHSHGDTMTVMDPK 444
Cdd:pfam04389 158 AFTDFGYRY--HTPADTIDNIDPG 179
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 268-437 5.48e-27

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: 107.43  E-value: 5.48e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 268 NTVAEITGSMYPEEVVLVSGHLDSWDVGQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQYYEL 347
Cdd:cd02690    3 NVIATIKGSDKPDEVILIGAHYDSVPLSPGANDNASGVAVLLELARVLSKLQLKPKRSIRFAFWDAEELGLLGSKYYAEQ 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 348 HKANISKYSLVMEADSGTFLPTGLQFTGSDKARAIM----KEVMNLLQPLNVTKVFSNGEGT---D-INFWIqAGVPGAS 419
Cdd:cd02690   83 LLSSLKNIRAALNLDMIGGAGPDLYLQTAPGNDALVekllRALAHELENVVYTVVYKEDGGTggsDhRPFLA-RGIPAAS 161

                        170
                 ....*....|....*...
gi 148232950 420 LRDDLYKYFFFHHSHGDT 437
Cdd:cd02690  162 LIQSESYNFPYYHTTQDT 179
M28_like_PA cd05660
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ...
 258-348 8.98e-11

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: 62.76  E-value: 8.98e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 258 AKTYPDTDSFNTVAEITGSMYPEEVVLVSGHLDSWDVGQ---------GALDDGGGAFISWEALSLVKDLGLRPKRTLRL 328
Cdd:cd05660   51 VSKIEYSTSHNVVAILPGSKLPDEYIVLSAHWDHLGIGPpiggdeiynGAVDNASGVAAVLELARVFAAQDQRPKRSIVF 130

                         90       100
                 ....*....|....*....|
gi 148232950 329 VLWTAEEQGGIGaSQYYELH 348
Cdd:cd05660  131 LAVTAEEKGLLG-SRYYAAN 149
Zinc_peptidase_like cd03873
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ...
 268-420 3.40e-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: 59.36  E-value: 3.40e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 268 NTVAEITGSMyPEEVVLVSGHLDS--------WD-------------VGQGALDDGGGAFISWEALSLVKDLGLRPKRTL 326
Cdd:cd03873    1 NLIARLGGGE-GGKSVALGAHLDVvpagegdnRDppfaedteeegrlYGRGALDDKGGVAAALEALKRLKENGFKPKGTI 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 327 RLVLWTAEEQGGIGASQY---YELHKANISKYSLV--MEADSGTFLPTGLQFTGSDKARAIMKEVMNLLQPLNVTkvfsn 401
Cdd:cd03873   80 VVAFTADEEVGSGGGKGLlskFLLAEDLKVDAAFVidATAGPILQKGVVIRNPLVDALRKAAREVGGKPQRASVI----- 154

                        170
                 ....*....|....*....
gi 148232950 402 GEGTDINFWIQAGVPGASL 420
Cdd:cd03873  155 GGGTDGRLFAELGIPGVTL 173
M28_SGAP_like cd03876
M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family ...
 266-416 1.02e-08

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: 56.54  E-value: 1.02e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 266 SFNTVAEITGSMyPEEVVLVSGHLDSWDVGQGALDDGGGAFISWE-ALSLVKdlgLRPKRTLRLVLWTAEEQGGIGaSQY 344
Cdd:cd03876   63 TYNVIAETKGGD-PNNVVMLGAHLDSVSAGPGINDNGSGSAALLEvALALAK---FKVKNAVRFAWWTAEEFGLLG-SKF 137

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 345 Y--ELHKANISKYSL---------------VMEADSGTFLPTGLQftGSDKARAIMKEVMNLLQpLNVTKVFSNGEGTDI 407
Cdd:cd03876  138 YvnNLSSEERSKIRLylnfdmiaspnygyfIYDGDGSAFNLTGPP--GSAEIERLFEAYFTSLG-LPSTPTEFDGRSDYA 214


                 ....*....
gi 148232950 408 NFWiQAGVP 416
Cdd:cd03876  215 PFI-EAGIP 222
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 266-391 1.74e-08

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: 55.70  E-value: 1.74e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 266 SFNTVAEITGSMYPEEVVLVSGHLDSWdvGQGALDDGGGAFISWE---AL-SLVKDlGLRPKRTLRLVLWTAEEQGGIGA 341
Cdd:cd08022   60 IWNVIGTIRGSEEPDEYIILGNHRDAW--VFGAGDPNSGTAVLLEvarALgTLLKK-GWRPRRTIIFASWDAEEYGLIGS 136

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 148232950 342 SQYYELHkANISKYSLVM--EADSGTFLPTgLQFTGSDKARAIMKEVMNLLQ 391
Cdd:cd08022  137 TEWVEEN-ADWLQERAVAylNVDVAVSGST-LRAAGSPLLQNLLREAAKEVQ 186
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 267-344 3.15e-08

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: 54.94  E-value: 3.15e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 267 FNTVAEITGSMYPEEVVLVSGHLDS---WDVGQ----GALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGI 339
Cdd:cd03879   75 PSIIATIPGSEKSDEIVVIGAHQDSingSNPSNgrapGADDDGSGTVTILEALRVLLESGFQPKNTIEFHWYAAEEGGLL 154


                 ....*....
gi 148232950 340 G----ASQY 344
Cdd:cd03879  155 GsqaiATQY 163
M20_18_42 cd18669
M20, M18 and M42 Zn-peptidases include aminopeptidases and carboxypeptidases; This family ...
 287-417 4.88e-08

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: 53.21  E-value: 4.88e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 287 GHLDSWDVGQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQY---YELHKANISKYSLVMEADS 363
Cdd:cd18669   40 TVEEGRLYGRGALDDKGGVAAALEALKLLKENGFKLKGTVVVAFTPDEEVGSGAGKGLlskDALEEDLKVDYLFVGDATP 119

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 148232950 364 GTFLPTGLQFTGSDKARAIMKEVMNLLQPLNVTkvfsnGEGTDINFWIQAGVPG 417
Cdd:cd18669  120 APQKGVGIRTPLVDALSEAARKVFGKPQHAEGT-----GGGTDGRYLQELGIPG 168
M20_PepV cd03888
M20 Peptidase Xaa-His dipeptidase (PepV) degrades hydrophobic dipeptides; Peptidase M20 family, ...
 280-350 1.58e-07

M20 Peptidase Xaa-His dipeptidase (PepV) degrades hydrophobic dipeptides; Peptidase M20 family, Peptidase V (Xaa-His dipeptidase; PepV g.p. (Lactobacillus lactis); X-His dipeptidase; beta-Ala-His dipeptidase; carnosinase) subfamily. The PepV group of proteins is widely distributed in lactic acid bacteria. PepV, along with PepT, functions at the end of the proteolytic processing system. PepV is a monomeric metalloenzyme that preferentially degrades hydrophobic dipeptides. The Streptococcus gordonii PepV gene is homologous to the PepV gene family from Lactobacillus and Lactococcus spp. PepV recognizes and fixes the dipeptide backbone, while the side chains are not specifically probed and can vary, rendering it a nonspecific dipeptidase. It has been shown that Lactococcus lactis subspecies lactis (L9) PepV does not hydrolyze dipeptides containing Pro or D-amino acids at the C-terminus, while PepV from Lactobaccilus has been shown to have L-carnosine hydrolyzing activity. The mammalian PepV also acts on anserine and homocarnosine (but not on homoanserine), and to a lesser extent on some other aminoacyl-L-histidine dipeptides. Also included is the Staphylococcus aureus metallopeptidase, Sapep, a Mn(2+)-dependent dipeptidase where large interdomain movements could potentially regulate the activity of this enzyme.


Pssm-ID: 349884 [Multi-domain]  Cd Length: 449  Bit Score: 53.40  E-value: 1.58e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 280 EEVVLVSGHLD------SWDV-------------GQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIG 340
Cdd:cd03888   71 EEVLGILGHLDvvpageGWTTdpfkpvikdgklyGRGTIDDKGPTIAALYALKILKDLGLPLKKKIRLIFGTDEETGWKC 150

                         90
                 ....*....|
gi 148232950 341 ASQYYELHKA 350
Cdd:cd03888  151 IEHYFEHEEY 160
M28_like cd03877
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
 266-345 1.88e-07

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


Pssm-ID: 349874 [Multi-domain]  Cd Length: 206  Bit Score: 51.47  E-value: 1.88e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 266 SFNTVAEITGSMYPEEVVLVSGHLD---------SWDVGQGALDDGGG-AFIsweaLSLVKDL--GLRPKRTLRLVLWTA 333
Cdd:cd03877    1 GHNVVGVLEGSDLPDETIVIGAHYDhlgigggdsGDKIYNGADDNASGvAAV----LELARYFakQKTPKRSIVFAAFTA 76

                         90
                 ....*....|..
gi 148232950 334 EEQGGIGaSQYY 345
Cdd:cd03877   77 EEKGLLG-SKYF 87
ArgE COG0624
Acetylornithine deacetylase/Succinyl-diaminopimelate desuccinylase or related deacylase [Amino ...
 226-360 2.44e-07

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: 52.58  E-value: 2.44e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 226 KIPTacITVEDAEMMSRMASRgnkivihLE-MGAKT---YPDTDSFNTVAEITGSMyPEEVVLVSGHLD--------SWD 293
Cdd:COG0624   23 RIPS--VSGEEAAAAELLAEL-------LEaLGFEVerlEVPPGRPNLVARRPGDG-GGPTLLLYGHLDvvppgdleLWT 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 294 V-------------GQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQYYELHKANI-SKYSLVM 359
Cdd:COG0624   93 SdpfeptiedgrlyGRGAADMKGGLAAMLAALRALLAAGLRLPGNVTLLFTGDEEVGSPGARALVEELAEGLkADAAIVG 172


                 .
gi 148232950 360 E 360
Cdd:COG0624  173 E 173
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
 241-363 2.83e-07

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: 51.99  E-value: 2.83e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 241 SRMASRGNKIVIHLEMGAKTYPDTDSF----NTVAEITGSMYPEEVVLVSGHLDSWdvGQGALDDGGGAFISWEALS--- 313
Cdd:cd09848   27 SGDENLANYIMNEFKNLKLMKVWTDEHykihNIFGVIKGFVEPDRYVVIGAQRDAW--GPGAAKSGVGTALLLELARtfs 104

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 148232950 314 -LVKDLGLRPKRTLRLVLWTAEEQGGIGASQYYE-----LHKANISKYSL---VMEADS 363
Cdd:cd09848  105 dMVKNDGFKPRRSIVFASWSAGDFGSVGATEWLEgylssLHLKAFTYISLdgaVLGDDS 163
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 266-354 8.63e-07

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: 50.37  E-value: 8.63e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 266 SFNTVAEITGSMYPEEVVLVSGHLDSWDVGqgALDDGGGAFISWEAL----SLVKDLGLRPKRTLRLVLWTAEEQGGIGA 341
Cdd:cd03874   57 ITNVVGKIEGIEQPDRAIIIGAHRDSWGYG--AGYPNSGTAVLLEIArlfqQLKKKFGWKPLRTIYFISWDGSEFGLAGS 134

                         90
                 ....*....|...
gi 148232950 342 SQYYELHKANISK 354
Cdd:cd03874  135 TELGEDRKASLKD 147
M20_yscS_like cd05675
M20 Peptidase, carboxypeptidase yscS-like; Peptidase M20 family, yscS (GlyX-carboxypeptidase, ...
 239-349 1.80e-06

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: 50.05  E-value: 1.80e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 239 MMSRMASRGNKIVIHLEMGA--KTypdtdsfNTVAEITGSMYPEEVVLVSGHLD-------SWDV-------------GQ 296
Cdd:cd05675   29 LAARLAEAGIQTEIFVVESHpgRA-------NLVARIGGTDPSAGPLLLLGHIDvvpadasDWSVdpfsgeikdgyvyGR 101

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 148232950 297 GALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGI-GASQYYELHK 349
Cdd:cd05675  102 GAVDMKNMAAMMLAVLRHYKREGFKPKRDLVFAFVADEEAGGEnGAKWLVDNHP 155
M28_like cd05642
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 268-352 4.60e-05

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: 45.56  E-value: 4.60e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 268 NTVAEITGSMYPEEVVLVSGHLDS--WDV------GQGALDDGGGAFISWEALSLVKDlgLRPKRTLRLVLWTAEEQGGI 339
Cdd:cd05642   90 NVVATLKGSEDPDRVYVVSGHYDSrvSDVmdyesdAPGANDDASGVAVSMELARIFAK--HRPKATIVFTAVAGEEQGLY 167

                         90
                 ....*....|....*.
gi 148232950 340 GA---SQYYELHKANI 352
Cdd:cd05642  168 GStflAQTYRNNSVNV 183
PRK06156 PRK06156
dipeptidase;
279-369 6.89e-05

dipeptidase;


Pssm-ID: 235720 [Multi-domain]  Cd Length: 520  Bit Score: 45.35  E-value: 6.89e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 279 PEEVVLVSGHLDSWDV--------GQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQY---YEL 347
Cdd:PRK06156 125 PELWVLDGTRLDPFKVtlvgdrlyGRGTEDDKGAIVTALYAMKAIKDSGLPLARRIELLVYTTEETDGDPLKYYlerYTP 204

                         90       100
                 ....*....|....*....|....*.
gi 148232950 348 HKANI---SKYSLVM-EADSGTFLPT 369
Cdd:PRK06156 205 PDYNItldAEYPVVTaEKGWGTIMAT 230
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
 268-361 2.23e-04

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: 42.96  E-value: 2.23e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 268 NTVAEITGSMYPEE-VVLVSGHLDSWDVGQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQYYE 346
Cdd:cd03875   81 NIVVRISGKNSNSLpALLLNAHFDSVPTSPGATDDGMGVAVMLEVLRYLSKSGHQPKRDIIFLFNGAEENGLLGAHAFIT 160

                         90
                 ....*....|....*.
gi 148232950 347 LHK-ANISKYSLVMEA 361
Cdd:cd03875  161 QHPwAKNVRAFINLEA 176
M20_CPDG2 cd03885
M20 Peptidase Glutamate carboxypeptidase, a periplasmic enzyme; Peptidase M20 family, ...
 270-361 2.32e-04

M20 Peptidase Glutamate carboxypeptidase, a periplasmic enzyme; Peptidase M20 family, Glutamate carboxypeptidase (carboxypeptidase G; carboxypeptidase G1; carboxypeptidase G2; CPDG2; CPG2; Folate hydrolase G2; Pteroylmonoglutamic acid hydrolase G2; Glucarpidase; E.C. 3.4.17.11) subfamily. CPDG2 is a periplasmic enzyme that is synthesized with a signal peptide. It is a dimeric zinc-dependent exopeptidase, with two domains, a catalytic domain, which provides the ligands for the two zinc ions in the active site, and a dimerization domain. CPDG2 cleaves the C-terminal glutamate moiety from a wide range of N-acyl groups, including peptidyl, aminoacyl, benzoyl, benzyloxycarbonyl, folyl, and pteroyl groups to release benzoic acid, phenol, and aniline mustards. It is used clinically to treat methotrexate toxicity by hydrolyzing it to inactive and non-toxic metabolites. It is also proposed for use in antibody-directed enzyme prodrug therapy; for example, glutamate can be cleaved from glutamated benzoyl nitrogen mustards, producing nitrogen mustards with effective cytotoxicity against tumor cells.


Pssm-ID: 349881 [Multi-domain]  Cd Length: 362  Bit Score: 43.35  E-value: 2.32e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 270 VAEITGSmyPEEVVLVSGHLDS-----------------WDVGQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWT 332
Cdd:cd03885   52 IATFKGT--GGKRVLLIGHMDTvfpegtlafrpftvdgdRAYGPGVADMKGGLVVILHALKALKAAGGRDYLPITVLLNS 129

                         90       100
                 ....*....|....*....|....*....
gi 148232950 333 AEEQGGIGASQYYElHKANISKYSLVMEA 361
Cdd:cd03885  130 DEEIGSPGSRELIE-EEAKGADYVLVFEP 157
M20_ArgE_DapE-like cd05650
M20 Peptidases with similarity to acetylornithine deacetylases and succinyl-diaminopimelate ...
 268-370 4.28e-04

M20 Peptidases with similarity to acetylornithine deacetylases and succinyl-diaminopimelate desuccinylases; Peptidase M20 family, uncharacterized protein subfamily with similarity to acetylornithine deacetylase/succinyl-diaminopimelate desuccinylase (ArgE/DapE) subfamily. ArgE/DapE enzymes catalyze analogous reactions and share a common activator, the metal ion (usually Co2+ or Zn2+). ArgE catalyzes a broad range of substrates, including N-acetylornithine, alpha-N-acetylmethionine and alpha-N-formylmethionine, while DapE catalyzes the hydrolysis of N-succinyl-L,L-diaminopimelate (L,L-SDAP) to L,L-diaminopimelate and succinate. Proteins in this subfamily are mostly bacterial and archaeal, and have been inferred by homology as being related to both ArgE and DapE.


Pssm-ID: 349901 [Multi-domain]  Cd Length: 389  Bit Score: 42.45  E-value: 4.28e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 268 NTVAEITGSMypEEVVLVSGHLDS-------------WDV--------GQGALDDGGGAFISWEALSLVKDLGLRPKRTL 326
Cdd:cd05650   59 NIVAKIPGGN--DKTLWIISHLDTvppgdlslwetdpWEPvvkdgkiyGRGVEDNQQGIVSSLLALKAIIKNGITPKYNF 136

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 148232950 327 RLVLWTAEEQGgigaSQY---YELHKANI-SKYSLVMEADSGTflPTG 370
Cdd:cd05650  137 GLLFVADEEDG----SEYgiqYLLNKFDLfKKDDLIIVPDFGT--EDG 178
M20_Dipept_like cd03893
M20 Dipeptidases; Peptidase M20 family, dipeptidase-like subfamily. This group contains a ...
 283-364 1.34e-03

M20 Dipeptidases; Peptidase M20 family, dipeptidase-like subfamily. This group contains a large variety of enzymes, including cytosolic nonspecific dipeptidase (CNDP), Xaa-methyl-His dipeptidase (anserinase), canosinase, DUG2 type proteins, as well as many proteins inferred by homology to be dipeptidases. These enzymes have been shown to act on a wide range of dipeptides, but not larger peptides. For example, anserinase mainly catalyzes the hydrolysis of N-alpha-acetylhistidine while carnosinase degrades beta-alanyl-L-histidine. Substrates of CNDP are varied and not limited to Xaa-His dipeptides. DUG2 proteins contain a metallopeptidase domain and a large N-terminal WD40 repeat region, and are involved in the alternative pathway of glutathione degradation.


Pssm-ID: 349888 [Multi-domain]  Cd Length: 426  Bit Score: 41.16  E-value: 1.34e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 283 VLVSGHLD--------SWDV-------------GQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGA 341
Cdd:cd03893   66 VLLYGHYDvqpagdedGWDSdpfelterdgrlyGRGAADDKGPILAHLAALRALMQQGGDLPVNVKFIIEGEEESGSPSL 145

                         90       100
                 ....*....|....*....|...
gi 148232950 342 SQYYELHKaNISKYSLVMEADSG 364
Cdd:cd03893  146 DQLVEAHR-DLLAADAIVISDST 167
M20_dipept_dapE cd05682
uncharacterized M20 dipeptidase; Peptidase M20 family, unknown dipeptidase-like subfamily ...
 272-364 1.83e-03

uncharacterized M20 dipeptidase; Peptidase M20 family, unknown dipeptidase-like subfamily (inferred by homology to be dipeptidases). M20 dipeptidases include a large variety of bacterial enzymes including cytosolic nonspecific dipeptidase (CNDP), Xaa-methyl-His dipeptidase (anserinase),and canosinase. These dipeptidases have been shown to act on a wide range of dipeptides, but not larger peptides. For example, anserinase mainly catalyzes the hydrolysis of N-alpha-acetylhistidine while carnosinase degrades beta-alanyl-L-histidine. This family includes dapE (Lpg0809) from Legionella pneumophila.


Pssm-ID: 349931 [Multi-domain]  Cd Length: 451  Bit Score: 40.78  E-value: 1.83e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 272 EITGSMYPEEVVLVSGHLDS------WD---------------VGQGALDDGGGAFISWEALSLVKDLGLrPKRTLRLVL 330
Cdd:cd05682   65 EIPGTEQDDDTVLLYGHMDKqppftgWDeglgptkpvirgdklYGRGGADDGYAIFASLTAIKALQEQGI-PHPRCVVLI 143

                         90       100       110
                 ....*....|....*....|....*....|....
gi 148232950 331 WTAEEQGGIGASQYYELHKANISKYSLVMEADSG 364
Cdd:cd05682  144 EACEESGSADLPFYLDKLKERIGNVDLVVCLDSG 177
Peptidase_M20 pfam01546
Peptidase family M20/M25/M40; This family includes a range of zinc metallopeptidases belonging ...
 284-384 2.73e-03

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: 39.64  E-value: 2.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950  284 LVSGHLD------SWDV-----------GQGALDDGGGAFISWEALSLVKDLGLRPkRTLRLVLWTAEEQGGIGASQYYE 346
Cdd:pfam01546   1 LLRGHMDvvpdeeTWGWpfkstedgklyGRGHDDMKGGLLAALEALRALKEEGLKK-GTVKLLFQPDEEGGMGGARALIE 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 148232950  347 LHKANISKYSLVMEADSGTflPTGLQFTGSDKARAIMK 384
Cdd:pfam01546  80 DGLLEREKVDAVFGLHIGE--PTLLEGGIAIGVVTGHR 115
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
 145-238 3.77e-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: 36.72  E-value: 3.77e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950  145 TAEVLVVASFDELQRRASEA--RGKIIVYnqpytgyEKTVQYRVQGAVEAAKVGAVASLIQSVASFSIYSPHTGIQKYQD 222
Cdd:pfam02225   1 TGPLVLAPGCYAGDGIPADFdvKGKIVLV-------RCTFGFRAEKVRNAQAAGAAGVIIYNNVEGLGGPPGAGGNELYP 73

                          90
                  ....*....|....*.
gi 148232950  223 GVPKIPTACITVEDAE 238
Cdd:pfam02225  74 DGIYIPAVGVSRADGE 89
PRK08588 PRK08588
succinyl-diaminopimelate desuccinylase; Reviewed
 268-351 6.40e-03

succinyl-diaminopimelate desuccinylase; Reviewed


Pssm-ID: 181490 [Multi-domain]  Cd Length: 377  Bit Score: 38.71  E-value: 6.40e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148232950 268 NTVAEItGSMYPeeVVLVSGHLD--------SWDV-------------GQGALDDGGGafISWEALSLV--KDLGLRPKR 324
Cdd:PRK08588  50 NLVAEI-GSGSP--VLALSGHMDvvaagdvdKWTYdpfeltekdgklyGRGATDMKSG--LAALVIAMIelKEQGQLLNG 124

                         90       100
                 ....*....|....*....|....*..
gi 148232950 325 TLRLVLWTAEEQGGIGASQYYELHKAN 351
Cdd:PRK08588 125 TIRLLATAGEEVGELGAKQLTEKGYAD 151
PRK08262 PRK08262
M20 family peptidase;
295-350 8.83e-03

M20 family peptidase;


Pssm-ID: 236208 [Multi-domain]  Cd Length: 486  Bit Score: 38.39  E-value: 8.83e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 148232950 295 GQGALDDGGGAFISWEALSLVKDLGLRPKRTLRLVLWTAEEQGGIGASQYYELHKA 350
Cdd:PRK08262 149 GRGALDDKGSLVAILEAAEALLAQGFQPRRTIYLAFGHDEEVGGLGARAIAELLKE 204
 
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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