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Conserved domains on  [gi|7706387|ref|NP_057218|]
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carboxypeptidase Q preproprotein [Homo sapiens]

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 ...
 42-449 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: 740.66  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387   42 SCGDVAKAIINLAVYGKAQnRSYERLALLVDTVGPRLSGSKNLEKAIQIMYQNLQQDGLEKVHLEPVRIPHWERGEESAV 121
Cdd:cd03883   1 SYKKVAKQIIQTALNGSLK-QAYDRLAYLVDTFGPRLSGSENLEKAIDWLYAKLQNDGFDKVHEEPVEVPHWVRGEESAT 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  122 MLEPRIHKIAILGLGSSIGTPPEGITAEVLVVTSFDELQRRASEARGKIVVYNQPYINYSRTVQYRTQGAVEAAKVGALA 201
Cdd:cd03883  80 LLEPRPQKLAILGLGGSVGTPVEGIEAEVVVVFSFEELQAKADEVKGKIVVYNQPFKGYGETVKYRGQGAVEAAKYGAVA 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  202 SLIRSVASFSIYSPHTGIQEYQDGVPKIPTACITVEDAEMMSRMASHGIKIVIQLKMGAKTYPDTDSFNTVAEITGSKYP 281
Cdd:cd03883 160 VLIRSITPFSIYSPHTGIMRYQDGVTKIPAAAITVEDAEMLSRMAARGQKIVIELKMEAKTYPDATSRNVIAEITGSKYP 239

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  282 EQVVLVSGHLDSWDVGQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGAFQYYQLHKVNISNYSLVM 361
Cdd:cd03883 240 DEVVLVGGHLDSWDVGTGAMDDGGGVAISWEALKLIKDLGLKPKRTIRVVLWTGEEQGLVGAKAYAEAHKDELENHVFAM 319

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  362 ESDAGTFLPTGLQFTGSEKARAIMEEVMSLLQPLNITQVLSH-GEGTDINFWIQAGVPGASLLDDLYKYFFFHHSHGDTM 440
Cdd:cd03883 320 ESDIGTFTPYGLQFTGSDTARAIVKEVMKLLSPLGITQVLPKaGVGPDISFLKAAGVPGASLIQDNSDYFDYHHTAGDTM 399


                ....*....
gi 7706387  441 TVMDPKQMN 449
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 ...
 42-449 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: 740.66  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387   42 SCGDVAKAIINLAVYGKAQnRSYERLALLVDTVGPRLSGSKNLEKAIQIMYQNLQQDGLEKVHLEPVRIPHWERGEESAV 121
Cdd:cd03883   1 SYKKVAKQIIQTALNGSLK-QAYDRLAYLVDTFGPRLSGSENLEKAIDWLYAKLQNDGFDKVHEEPVEVPHWVRGEESAT 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  122 MLEPRIHKIAILGLGSSIGTPPEGITAEVLVVTSFDELQRRASEARGKIVVYNQPYINYSRTVQYRTQGAVEAAKVGALA 201
Cdd:cd03883  80 LLEPRPQKLAILGLGGSVGTPVEGIEAEVVVVFSFEELQAKADEVKGKIVVYNQPFKGYGETVKYRGQGAVEAAKYGAVA 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  202 SLIRSVASFSIYSPHTGIQEYQDGVPKIPTACITVEDAEMMSRMASHGIKIVIQLKMGAKTYPDTDSFNTVAEITGSKYP 281
Cdd:cd03883 160 VLIRSITPFSIYSPHTGIMRYQDGVTKIPAAAITVEDAEMLSRMAARGQKIVIELKMEAKTYPDATSRNVIAEITGSKYP 239

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  282 EQVVLVSGHLDSWDVGQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGAFQYYQLHKVNISNYSLVM 361
Cdd:cd03883 240 DEVVLVGGHLDSWDVGTGAMDDGGGVAISWEALKLIKDLGLKPKRTIRVVLWTGEEQGLVGAKAYAEAHKDELENHVFAM 319

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  362 ESDAGTFLPTGLQFTGSEKARAIMEEVMSLLQPLNITQVLSH-GEGTDINFWIQAGVPGASLLDDLYKYFFFHHSHGDTM 440
Cdd:cd03883 320 ESDIGTFTPYGLQFTGSDTARAIVKEVMKLLSPLGITQVLPKaGVGPDISFLKAAGVPGASLIQDNSDYFDYHHTAGDTM 399


                ....*....
gi 7706387  441 TVMDPKQMN 449
Cdd:cd03883 400 DVMDPKQLD 408
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 235-448 3.14e-36

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: 134.49  E-value: 3.14e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  235 TVEDAEMMSRMASHGIKIVIQLKMGAKTYPDTDSFNTVAEITGSKYPEQVVLVSGHLDSWD-VGQGAMDDGGGAFISWEA 313
Cdd:COG2234  13 AGAAAAAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPDEVVVLGAHYDSVGsIGPGADDNASGVAALLEL 92

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  314 LSLIKDLGLRPKRTLRLVLWTAEEQGGVGAFQYYQLHKVNISNYSLVMESDA-GTFLPT-GLQFTG---SEKARAIMEEV 388
Cdd:COG2234  93 ARALAALGPKPKRTIRFVAFGAEEQGLLGSRYYAENLKAPLEKIVAVLNLDMiGRGGPRnYLYVDGdggSPELADLLEAA 172

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 7706387  389 M-SLLQPLNITQVLS--HGEGTDINFWIQAGVPGASLLDDLYKYFFFHHSHGDTMTVMDPKQM 448
Cdd:COG2234 173 AkAYLPGLGVDPPEEtgGYGRSDHAPFAKAGIPALFLFTGAEDYHPDYHTPSDTLDKIDLDAL 235
Peptidase_M28 pfam04389
Peptidase family M28;
270-446 9.84e-27

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 106.60  E-value: 9.84e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387    270 NTVAEITGSKYPEqVVLVSGHLDSWDVGQGAMDDGGGAFISWEALSLIKDlGLRPKRTLRLVLWTAEEQGGVGAfQYYQL 349
Cdd:pfam04389   1 NVIAKLPGKAPDE-VVLLSAHYDSVGTGPGADDNASGVAALLELARVLAA-GQRPKRSVRFLFFDAEEAGLLGS-HHFAK 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387    350 HKVNISNYSLVMESDAGTFLPTGLQF-TGSEKARAIMEEVMSLLQPLNIT---QVLSHGEG---TDINFWIQAGVPGASL 422
Cdd:pfam04389  78 SHPPLKKIRAVINLDMIGSGGPALLFqSGPKGSSLLEKYLKAAAKPYGVTlaeDPFQERGGpgrSDHAPFIKAGIPGLDL 157

                         170       180
                  ....*....|....*....|....
gi 7706387    423 LDDLYKYFFfhHSHGDTMTVMDPK 446
Cdd:pfam04389 158 AFTDFGYRY--HTPADTIDNIDPG 179
PRK06156 PRK06156
dipeptidase;
281-354 3.61e-04

dipeptidase;


Pssm-ID: 235720 [Multi-domain]  Cd Length: 520  Bit Score: 43.03  E-value: 3.61e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387   281 PEQVVLVSGHLDSWDV--------GQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGA---FQYYQL 349
Cdd:PRK06156 125 PELWVLDGTRLDPFKVtlvgdrlyGRGTEDDKGAIVTALYAMKAIKDSGLPLARRIELLVYTTEETDGDPLkyyLERYTP 204


                 ....*
gi 7706387   350 HKVNI 354
Cdd:PRK06156 205 PDYNI 209
 
Name Accession Description Interval E-value
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
 42-449 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: 740.66  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387   42 SCGDVAKAIINLAVYGKAQnRSYERLALLVDTVGPRLSGSKNLEKAIQIMYQNLQQDGLEKVHLEPVRIPHWERGEESAV 121
Cdd:cd03883   1 SYKKVAKQIIQTALNGSLK-QAYDRLAYLVDTFGPRLSGSENLEKAIDWLYAKLQNDGFDKVHEEPVEVPHWVRGEESAT 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  122 MLEPRIHKIAILGLGSSIGTPPEGITAEVLVVTSFDELQRRASEARGKIVVYNQPYINYSRTVQYRTQGAVEAAKVGALA 201
Cdd:cd03883  80 LLEPRPQKLAILGLGGSVGTPVEGIEAEVVVVFSFEELQAKADEVKGKIVVYNQPFKGYGETVKYRGQGAVEAAKYGAVA 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  202 SLIRSVASFSIYSPHTGIQEYQDGVPKIPTACITVEDAEMMSRMASHGIKIVIQLKMGAKTYPDTDSFNTVAEITGSKYP 281
Cdd:cd03883 160 VLIRSITPFSIYSPHTGIMRYQDGVTKIPAAAITVEDAEMLSRMAARGQKIVIELKMEAKTYPDATSRNVIAEITGSKYP 239

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  282 EQVVLVSGHLDSWDVGQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGAFQYYQLHKVNISNYSLVM 361
Cdd:cd03883 240 DEVVLVGGHLDSWDVGTGAMDDGGGVAISWEALKLIKDLGLKPKRTIRVVLWTGEEQGLVGAKAYAEAHKDELENHVFAM 319

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  362 ESDAGTFLPTGLQFTGSEKARAIMEEVMSLLQPLNITQVLSH-GEGTDINFWIQAGVPGASLLDDLYKYFFFHHSHGDTM 440
Cdd:cd03883 320 ESDIGTFTPYGLQFTGSDTARAIVKEVMKLLSPLGITQVLPKaGVGPDISFLKAAGVPGASLIQDNSDYFDYHHTAGDTM 399


                ....*....
gi 7706387  441 TVMDPKQMN 449
Cdd:cd03883 400 DVMDPKQLD 408
PA_M28_2 cd04815
PA_M28_2: Protease-associated (PA) domain, peptidase family M28, subfamily-2. A subfamily of ...
 130-256 2.13e-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: 209.41  E-value: 2.13e-66
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  130 IAILGLGSSIGTPPEGITAEVLVVTSFDELQRR-ASEARGKIVVYNQPYI------NYSRTVQYRTQGAVEAAKVGALAS 202
Cdd:cd04815   1 LAILALGGSVATPPEGITAEVVVVKSFDELKAApAGAVKGKIVFFNQPMVrtqtgsGYGPTVAYRRRGAVEAAKKGAVAV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 7706387  203 LIRSVASFSIYSPHTGIQEYQDGVPKIPTACITVEDAEMMSRMASHGIKIVIQL 256
Cdd:cd04815  81 LIRSIGTDSHRSPHTGMMSYDDGVPKIPAAAISVEDADMLERLAARGKPIRVNL 134
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 235-448 3.14e-36

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: 134.49  E-value: 3.14e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  235 TVEDAEMMSRMASHGIKIVIQLKMGAKTYPDTDSFNTVAEITGSKYPEQVVLVSGHLDSWD-VGQGAMDDGGGAFISWEA 313
Cdd:COG2234  13 AGAAAAAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPDEVVVLGAHYDSVGsIGPGADDNASGVAALLEL 92

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  314 LSLIKDLGLRPKRTLRLVLWTAEEQGGVGAFQYYQLHKVNISNYSLVMESDA-GTFLPT-GLQFTG---SEKARAIMEEV 388
Cdd:COG2234  93 ARALAALGPKPKRTIRFVAFGAEEQGLLGSRYYAENLKAPLEKIVAVLNLDMiGRGGPRnYLYVDGdggSPELADLLEAA 172

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 7706387  389 M-SLLQPLNITQVLS--HGEGTDINFWIQAGVPGASLLDDLYKYFFFHHSHGDTMTVMDPKQM 448
Cdd:COG2234 173 AkAYLPGLGVDPPEEtgGYGRSDHAPFAKAGIPALFLFTGAEDYHPDYHTPSDTLDKIDLDAL 235
M28_like cd08015
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 268-471 4.81e-30

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: 116.54  E-value: 4.81e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  268 SFNTVAEITGSKYPEQVVLVSGHLDSWDVGQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGAFQYY 347
Cdd:cd08015   1 TYNVIAEIPGSDKKDEVVILGAHLDSWHGATGATDNGAGTAVMMEAMRILKAIGSKPKRTIRVALWGSEEQGLHGSRAYV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  348 QLH---------KVNISNYSLVMESDAGTFLPTGLQFTGSEKARAIMEEVMSLLQPLNITQVLSHGEG-TDINFWIQAGV 417
Cdd:cd08015  81 EKHfgdpptmqlQRDHKKISAYFNLDNGTGRIRGIYLQGNLAAYPIFSAWLYPFHDLGATTVIERNTGgTDHAAFDAVGI 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 7706387  418 PGASLLDDLYKYF-FFHHSHGDTMTVMDPKQMNVAAAVWAVVSYVVADMEEMLPR 471
Cdd:cd08015 161 PAFQFIQDPWDYWtRTHHTNRDTYDRLIPEDLKQAAIITASFAYHASSREKIVPR 215
Peptidase_M28 pfam04389
Peptidase family M28;
270-446 9.84e-27

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 106.60  E-value: 9.84e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387    270 NTVAEITGSKYPEqVVLVSGHLDSWDVGQGAMDDGGGAFISWEALSLIKDlGLRPKRTLRLVLWTAEEQGGVGAfQYYQL 349
Cdd:pfam04389   1 NVIAKLPGKAPDE-VVLLSAHYDSVGTGPGADDNASGVAALLELARVLAA-GQRPKRSVRFLFFDAEEAGLLGS-HHFAK 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387    350 HKVNISNYSLVMESDAGTFLPTGLQF-TGSEKARAIMEEVMSLLQPLNIT---QVLSHGEG---TDINFWIQAGVPGASL 422
Cdd:pfam04389  78 SHPPLKKIRAVINLDMIGSGGPALLFqSGPKGSSLLEKYLKAAAKPYGVTlaeDPFQERGGpgrSDHAPFIKAGIPGLDL 157

                         170       180
                  ....*....|....*....|....
gi 7706387    423 LDDLYKYFFfhHSHGDTMTVMDPK 446
Cdd:pfam04389 158 AFTDFGYRY--HTPADTIDNIDPG 179
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 270-439 1.88e-24

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: 100.50  E-value: 1.88e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  270 NTVAEITGSKYPEQVVLVSGHLDSWDVGQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGAFQYYQL 349
Cdd:cd02690   3 NVIATIKGSDKPDEVILIGAHYDSVPLSPGANDNASGVAVLLELARVLSKLQLKPKRSIRFAFWDAEELGLLGSKYYAEQ 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  350 HKVNISNYSLVMESDAGTFLPTGLQFTGSEKARAIMEE----VMSLLQPLNITQVLSHGEGT---D-INFWIqAGVPGAS 421
Cdd:cd02690  83 LLSSLKNIRAALNLDMIGGAGPDLYLQTAPGNDALVEKllraLAHELENVVYTVVYKEDGGTggsDhRPFLA-RGIPAAS 161

                       170
                ....*....|....*...
gi 7706387  422 LLDDLYKYFFFHHSHGDT 439
Cdd:cd02690 162 LIQSESYNFPYYHTTQDT 179
M28_like_PA cd05660
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ...
 260-350 3.00e-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: 63.92  E-value: 3.00e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  260 AKTYPDTDSFNTVAEITGSKYPEQVVLVSGHLDSWDVGQ---------GAMDDGGGAFISWEALSLIKDLGLRPKRTLRL 330
Cdd:cd05660  51 VSKIEYSTSHNVVAILPGSKLPDEYIVLSAHWDHLGIGPpiggdeiynGAVDNASGVAAVLELARVFAAQDQRPKRSIVF 130

                        90       100
                ....*....|....*....|
gi 7706387  331 VLWTAEEQGGVGAfQYYQLH 350
Cdd:cd05660 131 LAVTAEEKGLLGS-RYYAAN 149
Zinc_peptidase_like cd03873
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ...
 270-442 8.80e-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: 58.21  E-value: 8.80e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  270 NTVAEITGSKYPEqVVLVSGHLDS--------WD-------------VGQGAMDDGGGAFISWEALSLIKDLGLRPKRTL 328
Cdd:cd03873   1 NLIARLGGGEGGK-SVALGAHLDVvpagegdnRDppfaedteeegrlYGRGALDDKGGVAAALEALKRLKENGFKPKGTI 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  329 RLVLWTAEEQGGVGAFQY---YQLHKVNISNYSLVMESDAGTFLPTG--LQFTGSEKARAIMEEVmsLLQPLNITQVlsh 403
Cdd:cd03873  80 VVAFTADEEVGSGGGKGLlskFLLAEDLKVDAAFVIDATAGPILQKGvvIRNPLVDALRKAAREV--GGKPQRASVI--- 154

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 7706387  404 GEGTDINFWIQAGVPGASLLDDLYKYFffhHSHGDTMTV 442
Cdd:cd03873 155 GGGTDGRLFAELGIPGVTLGPPGDKGA---HSPNEFLNL 190
M28_SGAP_like cd03876
M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family ...
 268-418 6.46e-09

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


Pssm-ID: 349873 [Multi-domain]  Cd Length: 289  Bit Score: 56.92  E-value: 6.46e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  268 SFNTVAEITGSKyPEQVVLVSGHLDSWDVGQGAMDDGGGAFISWE-ALSLIKdlgLRPKRTLRLVLWTAEEQGGVGAfQY 346
Cdd:cd03876  63 TYNVIAETKGGD-PNNVVMLGAHLDSVSAGPGINDNGSGSAALLEvALALAK---FKVKNAVRFAWWTAEEFGLLGS-KF 137

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  347 Y-------QLHKVNI---------SNYSL-VMESDAGTFLPTGLQftGSEKARAIMEEVMSLlqpLNITQVLSHGEG-TD 408
Cdd:cd03876 138 YvnnlsseERSKIRLylnfdmiasPNYGYfIYDGDGSAFNLTGPP--GSAEIERLFEAYFTS---LGLPSTPTEFDGrSD 212

                       170
                ....*....|
gi 7706387  409 INFWIQAGVP 418
Cdd:cd03876 213 YAPFIEAGIP 222
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 269-354 8.29e-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: 53.40  E-value: 8.29e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  269 FNTVAEITGSKYPEQVVLVSGHLDS---WDVGQ----GAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGV 341
Cdd:cd03879  75 PSIIATIPGSEKSDEIVVIGAHQDSingSNPSNgrapGADDDGSGTVTILEALRVLLESGFQPKNTIEFHWYAAEEGGLL 154

                        90
                ....*....|....*.
gi 7706387  342 GA---FQYYQLHKVNI 354
Cdd:cd03879 155 GSqaiATQYKSEGKNV 170
ArgE COG0624
Acetylornithine deacetylase/Succinyl-diaminopimelate desuccinylase or related deacylase [Amino ...
 228-343 2.07e-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: 52.97  E-value: 2.07e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  228 KIPTacITVEDAEMM----SRMASHGIKIVIQlkmgaktYPDTDSFNTVAEITGSKyPEQVVLVSGHLD--------SWD 295
Cdd:COG0624  23 RIPS--VSGEEAAAAellaELLEALGFEVERL-------EVPPGRPNLVARRPGDG-GGPTLLLYGHLDvvppgdleLWT 92

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 7706387  296 V-------------GQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGA 343
Cdd:COG0624  93 SdpfeptiedgrlyGRGAADMKGGLAAMLAALRALLAAGLRLPGNVTLLFTGDEEVGSPGA 153
M28_like cd03877
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
 268-347 3.38e-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: 50.70  E-value: 3.38e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  268 SFNTVAEITGSKYPEQVVLVSGHLD---------SWDVGQGAMDDGGG-AFIsweaLSLIKDL--GLRPKRTLRLVLWTA 335
Cdd:cd03877   1 GHNVVGVLEGSDLPDETIVIGAHYDhlgigggdsGDKIYNGADDNASGvAAV----LELARYFakQKTPKRSIVFAAFTA 76

                        90
                ....*....|..
gi 7706387  336 EEQGGVGAfQYY 347
Cdd:cd03877  77 EEKGLLGS-KYF 87
M20_18_42 cd18669
M20, M18 and M42 Zn-peptidases include aminopeptidases and carboxypeptidases; This family ...
 289-434 5.44e-07

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: 50.12  E-value: 5.44e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  289 GHLDSWDVGQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGAfqYYQLHKV-----NISNYSLVMES 363
Cdd:cd18669  40 TVEEGRLYGRGALDDKGGVAAALEALKLLKENGFKLKGTVVVAFTPDEEVGSGAG--KGLLSKDaleedLKVDYLFVGDA 117

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 7706387  364 DAGTFLPTGLQFTGSEKARAIMEEVMSLLQPLNITqvlshGEGTDINFWIQAGVPGASLLddLYKYFFFHH 434
Cdd:cd18669 118 TPAPQKGVGIRTPLVDALSEAARKVFGKPQHAEGT-----GGGTDGRYLQELGIPGVTLG--AGGGKGAHS 181
M20_PepV cd03888
M20 Peptidase Xaa-His dipeptidase (PepV) degrades hydrophobic dipeptides; Peptidase M20 family, ...
 257-352 7.66e-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: 51.48  E-value: 7.66e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  257 KMGAKTYpDTDSFNTVAEItGSKypEQVVLVSGHLD------SWDV-------------GQGAMDDGGGAFISWEALSLI 317
Cdd:cd03888  50 RLGFKTK-NIDNYAGYAEY-GEG--EEVLGILGHLDvvpageGWTTdpfkpvikdgklyGRGTIDDKGPTIAALYALKIL 125

                        90       100       110
                ....*....|....*....|....*....|....*
gi 7706387  318 KDLGLRPKRTLRLVLWTAEEQGGVGAFQYYQLHKV 352
Cdd:cd03888 126 KDLGLPLKKKIRLIFGTDEETGWKCIEHYFEHEEY 160
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 268-342 1.34e-06

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: 49.92  E-value: 1.34e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7706387  268 SFNTVAEITGSKYPEQVVLVSGHLDSWdvGQGAMDDGGGAFISWE---ALSLIKDLGLRPKRTLRLVLWTAEEQGGVG 342
Cdd:cd08022  60 IWNVIGTIRGSEEPDEYIILGNHRDAW--VFGAGDPNSGTAVLLEvarALGTLLKKGWRPRRTIIFASWDAEEYGLIG 135
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
 262-368 1.74e-06

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: 49.68  E-value: 1.74e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  262 TYPDTDSF----NTVAEITGSKYPEQVVLVSGHLDSWdvGQGAMDDGGGAFISWEALS----LIKDLGLRPKRTLRLVLW 333
Cdd:cd09848  46 MKVWTDEHykihNIFGVIKGFVEPDRYVVIGAQRDAW--GPGAAKSGVGTALLLELARtfsdMVKNDGFKPRRSIVFASW 123

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 7706387  334 TAEEQGGVGA---FQYY--QLHKVNISNYSL-VMESDAGTF 368
Cdd:cd09848 124 SAGDFGSVGAtewLEGYlsSLHLKAFTYISLdGAVLGDDSF 164
M28_like cd05642
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 270-354 6.85e-06

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: 47.87  E-value: 6.85e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  270 NTVAEITGSKYPEQVVLVSGHLDS--WDV------GQGAMDDGGGAFISWEALSLIKDlgLRPKRTLRLVLWTAEEQGGV 341
Cdd:cd05642  90 NVVATLKGSEDPDRVYVVSGHYDSrvSDVmdyesdAPGANDDASGVAVSMELARIFAK--HRPKATIVFTAVAGEEQGLY 167

                        90
                ....*....|....*.
gi 7706387  342 GA---FQYYQLHKVNI 354
Cdd:cd05642 168 GStflAQTYRNNSVNV 183
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 268-346 7.20e-06

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: 47.68  E-value: 7.20e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  268 SFNTVAEITGSKYPEQVVLVSGHLDSWDVGqgAMDDGGGAFISWEAL----SLIKDLGLRPKRTLRLVLWTAEEQGGVGA 343
Cdd:cd03874  57 ITNVVGKIEGIEQPDRAIIIGAHRDSWGYG--AGYPNSGTAVLLEIArlfqQLKKKFGWKPLRTIYFISWDGSEFGLAGS 134


                ...
gi 7706387  344 FQY 346
Cdd:cd03874 135 TEL 137
M20_yscS_like cd05675
M20 Peptidase, carboxypeptidase yscS-like; Peptidase M20 family, yscS (GlyX-carboxypeptidase, ...
 241-340 1.13e-05

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: 47.74  E-value: 1.13e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  241 MMSRMASHGIKIVIQLKMGA--KTypdtdsfNTVAEITGSKYPEQVVLVSGHLD-------SWDV-------------GQ 298
Cdd:cd05675  29 LAARLAEAGIQTEIFVVESHpgRA-------NLVARIGGTDPSAGPLLLLGHIDvvpadasDWSVdpfsgeikdgyvyGR 101

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 7706387  299 GAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGG 340
Cdd:cd05675 102 GAVDMKNMAAMMLAVLRHYKREGFKPKRDLVFAFVADEEAGG 143
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
 147-240 5.84e-05

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: 41.73  E-value: 5.84e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387    147 TAEVLVVTSFDELQRRASEA--RGKIVVynqpyINYSRTVqyRTQGAVEAAKVGALASLIRSVASFSIYSPHTGIQEYQD 224
Cdd:pfam02225   1 TGPLVLAPGCYAGDGIPADFdvKGKIVL-----VRCTFGF--RAEKVRNAQAAGAAGVIIYNNVEGLGGPPGAGGNELYP 73

                          90
                  ....*....|....*.
gi 7706387    225 GVPKIPTACITVEDAE 240
Cdd:pfam02225  74 DGIYIPAVGVSRADGE 89
M20_ArgE_DapE-like cd05650
M20 Peptidases with similarity to acetylornithine deacetylases and succinyl-diaminopimelate ...
 270-380 8.00e-05

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: 44.76  E-value: 8.00e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  270 NTVAEITGSKypEQVVLVSGHLDS-------------WDV--------GQGAMDDGGGAFISWEALSLIKDLGLRPKRTL 328
Cdd:cd05650  59 NIVAKIPGGN--DKTLWIISHLDTvppgdlslwetdpWEPvvkdgkiyGRGVEDNQQGIVSSLLALKAIIKNGITPKYNF 136

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 7706387  329 RLVLWTAEEQGGVGAFQYYqLHKVNI-SNYSLVMESDAGTflPTGLQFTGSEK 380
Cdd:cd05650 137 GLLFVADEEDGSEYGIQYL-LNKFDLfKKDDLIIVPDFGT--EDGEFIEIAEK 186
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
 270-343 3.47e-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: 42.57  E-value: 3.47e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7706387  270 NTVAEITGSKYPEQ-VVLVSGHLDSWDVGQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGA 343
Cdd:cd03875  81 NIVVRISGKNSNSLpALLLNAHFDSVPTSPGATDDGMGVAVMLEVLRYLSKSGHQPKRDIIFLFNGAEENGLLGA 155
PRK06156 PRK06156
dipeptidase;
281-354 3.61e-04

dipeptidase;


Pssm-ID: 235720 [Multi-domain]  Cd Length: 520  Bit Score: 43.03  E-value: 3.61e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387   281 PEQVVLVSGHLDSWDV--------GQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGA---FQYYQL 349
Cdd:PRK06156 125 PELWVLDGTRLDPFKVtlvgdrlyGRGTEDDKGAIVTALYAMKAIKDSGLPLARRIELLVYTTEETDGDPLkyyLERYTP 204


                 ....*
gi 7706387   350 HKVNI 354
Cdd:PRK06156 205 PDYNI 209
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
 168-256 1.02e-03

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


Pssm-ID: 238300 [Multi-domain]  Cd Length: 126  Bit Score: 39.04  E-value: 1.02e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  168 GKIVVYnqpyinySRTVQYRTQGAVEAAKVGALASLIRS-VASFSIYSPHTGIQeyqDGVPKIPTACITVEDAEMMSRMA 246
Cdd:cd00538  47 GKIVLV-------RRGGCSFSEKVKNAQKAGAKAVIIYNnGDDPGPQMGSVGLE---STDPSIPTVGISYADGEALLSLL 116

                        90
                ....*....|
gi 7706387  247 SHGIKIVIQL 256
Cdd:cd00538 117 EAGKTVTVDL 126
M28_like cd05640
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
 270-337 1.05e-03

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: 40.89  E-value: 1.05e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7706387  270 NTVAEITGSKYPEQVVLVSGHLDSWDVGQGAMDDGGGAFISWEALSLIKdlGLRPKRTLRLVLWTAEE 337
Cdd:cd05640  54 NLIADLPGSYSQDKLILIGAHYDTVPGSPGADDNASGVAALLELARLLA--TLDPNHTLRFVAFDLEE 119
Peptidase_M20 pfam01546
Peptidase family M20/M25/M40; This family includes a range of zinc metallopeptidases belonging ...
 286-343 1.87e-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: 40.41  E-value: 1.87e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7706387    286 LVSGHLD------SWDV-----------GQGAMDDGGGAFISWEALSLIKDLGLRPkRTLRLVLWTAEEQGGVGA 343
Cdd:pfam01546   1 LLRGHMDvvpdeeTWGWpfkstedgklyGRGHDDMKGGLLAALEALRALKEEGLKK-GTVKLLFQPDEEGGMGGA 74
M20_CPDG2 cd03885
M20 Peptidase Glutamate carboxypeptidase, a periplasmic enzyme; Peptidase M20 family, ...
 272-343 2.68e-03

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: 39.88  E-value: 2.68e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  272 VAEITGSKYPEqvVLVSGHLDS-----------------WDVGQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWT 334
Cdd:cd03885  52 IATFKGTGGKR--VLLIGHMDTvfpegtlafrpftvdgdRAYGPGVADMKGGLVVILHALKALKAAGGRDYLPITVLLNS 129


                ....*....
gi 7706387  335 AEEQGGVGA 343
Cdd:cd03885 130 DEEIGSPGS 138
PRK08588 PRK08588
succinyl-diaminopimelate desuccinylase; Reviewed
 246-350 6.85e-03

succinyl-diaminopimelate desuccinylase; Reviewed


Pssm-ID: 181490 [Multi-domain]  Cd Length: 377  Bit Score: 38.71  E-value: 6.85e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387   246 ASHGI--KIViqlkmgakTYPDTDSfNTVAEItGSKYPeqVVLVSGHLD--------SWDV-------------GQGAMD 302
Cdd:PRK08588  33 AKHGIesKIV--------KVNDGRA-NLVAEI-GSGSP--VLALSGHMDvvaagdvdKWTYdpfeltekdgklyGRGATD 100

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 7706387   303 DGGGafISWEALSLI--KDLGLRPKRTLRLVLWTAEEQGGVGAFQYYQLH 350
Cdd:PRK08588 101 MKSG--LAALVIAMIelKEQGQLLNGTIRLLATAGEEVGELGAKQLTEKG 148
M20_Dipept_like cd03893
M20 Dipeptidases; Peptidase M20 family, dipeptidase-like subfamily. This group contains a ...
 285-351 8.04e-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: 38.46  E-value: 8.04e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7706387  285 VLVSGHLD--------SWDV-------------GQGAMDDGGGAFISWEALSLIKDLGLRPKRTLRLVLWTAEEQGGVGA 343
Cdd:cd03893  66 VLLYGHYDvqpagdedGWDSdpfelterdgrlyGRGAADDKGPILAHLAALRALMQQGGDLPVNVKFIIEGEEESGSPSL 145


                ....*...
gi 7706387  344 FQYYQLHK 351
Cdd:cd03893 146 DQLVEAHR 153
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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