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Conserved domains on  [gi|530386343|ref|XP_005250610|]
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PREDICTED: transferrin receptor protein 2 isoform X1 [Homo sapiens]

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List of domain hits

Name Accession Description Interval E-value
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
409-642 9.03e-138

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: 193572 [Multi-domain]  Cd Length: 285  Bit Score: 412.18  E-value: 9.03e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 409 PINNIFGCIEGRSEPDHYVVIGAQRDAWGPGAAKSAVGTAILLELVRTFSSMVSN-GFRPRRSLLFISWDGGDFGSVGST 487
Cdd:cd09848   54 KIHNIFGVIKGFVEPDRYVVIGAQRDAWGPGAAKSGVGTALLLELARTFSDMVKNdGFKPRRSILFASWSAGDFGSVGAT 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 488 EWLEGYLSVLHLKAVVYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPNHSGQTLYEqvvFTNPSWDAEVIRPLPM 567
Cdd:cd09848  134 EWLEGYLSSLHLKAFTYISLDGAVLGDDSFKASASPLLYTLLESTMKQVKSPVHSGQSYYE---FTRSSWWASIVEPLGL 210
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530386343 568 DSSAYSFTAFVGVPAVEFSFMEDDQAYPFLHTKEDTYENLHKVLQGRLPAVAQAVAQLAGQLLIRLSHDRLLPLD 642
Cdd:cd09848  211 DNAAYPFLAFSGIPSVSFHFTEDDEDYPYLGTKLDTKENLDKVTNGRLNAVARAAAEVAGQMALRLVHDHLLNLD 285
PA_TfR cd02128
PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This ...
211-401 1.56e-99

PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This group contains various PA domain-containing proteins similar to human TfR1 and TfR2. TfR1 and TfR2 are type II membrane proteins, belonging to the peptidase M28 family. TfR1 is homodimeric, widely expressed, and a key player in the uptake of iron-loaded transferrin (Tf) into cells. The TfR1 homodimer binds two molecules of Tf and this complex is internalized. In addition to its role in iron uptake, TfR1 may participate in cell growth and proliferation. TfR2 also binds Tf but with a significantly lower affinity than does TfR1. TfR2 is expressed chiefly in hepatocytes, hematopoietic cells, and duodenal crypt cells; its expression overlaps with that of hereditary hemochromatosis protein (HFE). TfR2 is involved in iron homeostasis. HFE and TfR2 interact in cells. By one model for serum iron sensing, at low or basal iron concentrations, HFE and TFR1 form a complex at the plasma membrane; at increased Tf, Tf competes with HFE for binding of TfR1, resulting in HFE disassociating from TfR1 and associating with TfR2 . The TfR1-TfR2 association might initiate a signal cascade leading to the induction of hepcidin (a small peptide hormone that controls systemic iron levels). Human mutations in TfR2 are associated with a form of hemochromatosis (HFE3). The significance of the PA domain to TfRs has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


:

Pssm-ID: 239043  Cd Length: 183  Bit Score: 308.56  E-value: 1.56e-99
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 211 LHWVDEAGkvGEQLPLEDPDVYCPYSAIGNVTGELVYAHYGRPEDLQDLRARGVDPVGRLLLVRVGVISFAQKVTNAQDF 290
Cdd:cd02128    1 SVIIGDAG--RLNELVENPGGYVAYSAAGTVTGKLVYANYGRKKDFEDLQSVGVSVNGSVVLVRAGKISFAEKVANAEKL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 291 GAQGVLIYPEPADFSQDPpkpslsSQQAVYGHVHLGTGDPYTPGFPSFNQTQFPPVASSGLPSIPAQPISADIASRLLRK 370
Cdd:cd02128   79 GAVGVLIYPDPADFPIDP------SETALFGHVHLGTGDPYTPGFPSFNHTQFPPSQSSGLPNIPAQTISAAAAAKLLSK 152
                        170       180       190
                 ....*....|....*....|....*....|...
gi 530386343 371 LKGPVAPQEWQGSllGSPYHLGP--GPRLRLVV 401
Cdd:cd02128  153 MGGPVCPSGWKGG--DSTCRLGTssSKNVKLTV 183
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
668-793 1.73e-32

Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the transferrin receptor as shown in its crystal structure.


:

Pssm-ID: 202944  Cd Length: 122  Bit Score: 122.76  E-value: 1.73e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343  668 GLTLQWVYSARGDYIRAAEKLRQEIYSSE--ERDERLTRMYNVRIMRVEFYFLSQYVSPADSPFRHIFMGRG------DH 739
Cdd:pfam04253   1 GLSLDPLFSAVKKFKKAAKELESWIKNWDnfEPNPLAVRRWNDRLMRVERAFLNPYGLPGRPFYRHVIFGPSlwngydGW 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530386343  740 TLGALLDHLRLLRSNSSgtpgatsstgfqESRFRRQLALLTWTLQGAANALSGD 793
Cdd:pfam04253  81 TFPGIRDALFDANNSGD------------WDEAQRQLSLVAWALQGAANTLSEV 122
 
Name Accession Description Interval E-value
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
409-642 9.03e-138

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: 193572 [Multi-domain]  Cd Length: 285  Bit Score: 412.18  E-value: 9.03e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 409 PINNIFGCIEGRSEPDHYVVIGAQRDAWGPGAAKSAVGTAILLELVRTFSSMVSN-GFRPRRSLLFISWDGGDFGSVGST 487
Cdd:cd09848   54 KIHNIFGVIKGFVEPDRYVVIGAQRDAWGPGAAKSGVGTALLLELARTFSDMVKNdGFKPRRSILFASWSAGDFGSVGAT 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 488 EWLEGYLSVLHLKAVVYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPNHSGQTLYEqvvFTNPSWDAEVIRPLPM 567
Cdd:cd09848  134 EWLEGYLSSLHLKAFTYISLDGAVLGDDSFKASASPLLYTLLESTMKQVKSPVHSGQSYYE---FTRSSWWASIVEPLGL 210
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530386343 568 DSSAYSFTAFVGVPAVEFSFMEDDQAYPFLHTKEDTYENLHKVLQGRLPAVAQAVAQLAGQLLIRLSHDRLLPLD 642
Cdd:cd09848  211 DNAAYPFLAFSGIPSVSFHFTEDDEDYPYLGTKLDTKENLDKVTNGRLNAVARAAAEVAGQMALRLVHDHLLNLD 285
PA_TfR cd02128
PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This ...
211-401 1.56e-99

PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This group contains various PA domain-containing proteins similar to human TfR1 and TfR2. TfR1 and TfR2 are type II membrane proteins, belonging to the peptidase M28 family. TfR1 is homodimeric, widely expressed, and a key player in the uptake of iron-loaded transferrin (Tf) into cells. The TfR1 homodimer binds two molecules of Tf and this complex is internalized. In addition to its role in iron uptake, TfR1 may participate in cell growth and proliferation. TfR2 also binds Tf but with a significantly lower affinity than does TfR1. TfR2 is expressed chiefly in hepatocytes, hematopoietic cells, and duodenal crypt cells; its expression overlaps with that of hereditary hemochromatosis protein (HFE). TfR2 is involved in iron homeostasis. HFE and TfR2 interact in cells. By one model for serum iron sensing, at low or basal iron concentrations, HFE and TFR1 form a complex at the plasma membrane; at increased Tf, Tf competes with HFE for binding of TfR1, resulting in HFE disassociating from TfR1 and associating with TfR2 . The TfR1-TfR2 association might initiate a signal cascade leading to the induction of hepcidin (a small peptide hormone that controls systemic iron levels). Human mutations in TfR2 are associated with a form of hemochromatosis (HFE3). The significance of the PA domain to TfRs has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239043  Cd Length: 183  Bit Score: 308.56  E-value: 1.56e-99
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 211 LHWVDEAGkvGEQLPLEDPDVYCPYSAIGNVTGELVYAHYGRPEDLQDLRARGVDPVGRLLLVRVGVISFAQKVTNAQDF 290
Cdd:cd02128    1 SVIIGDAG--RLNELVENPGGYVAYSAAGTVTGKLVYANYGRKKDFEDLQSVGVSVNGSVVLVRAGKISFAEKVANAEKL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 291 GAQGVLIYPEPADFSQDPpkpslsSQQAVYGHVHLGTGDPYTPGFPSFNQTQFPPVASSGLPSIPAQPISADIASRLLRK 370
Cdd:cd02128   79 GAVGVLIYPDPADFPIDP------SETALFGHVHLGTGDPYTPGFPSFNHTQFPPSQSSGLPNIPAQTISAAAAAKLLSK 152
                        170       180       190
                 ....*....|....*....|....*....|...
gi 530386343 371 LKGPVAPQEWQGSllGSPYHLGP--GPRLRLVV 401
Cdd:cd02128  153 MGGPVCPSGWKGG--DSTCRLGTssSKNVKLTV 183
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
668-793 1.73e-32

Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the transferrin receptor as shown in its crystal structure.


Pssm-ID: 202944  Cd Length: 122  Bit Score: 122.76  E-value: 1.73e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343  668 GLTLQWVYSARGDYIRAAEKLRQEIYSSE--ERDERLTRMYNVRIMRVEFYFLSQYVSPADSPFRHIFMGRG------DH 739
Cdd:pfam04253   1 GLSLDPLFSAVKKFKKAAKELESWIKNWDnfEPNPLAVRRWNDRLMRVERAFLNPYGLPGRPFYRHVIFGPSlwngydGW 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530386343  740 TLGALLDHLRLLRSNSSgtpgatsstgfqESRFRRQLALLTWTLQGAANALSGD 793
Cdd:pfam04253  81 TFPGIRDALFDANNSGD------------WDEAQRQLSLVAWALQGAANTLSEV 122
Peptidase_M28 pfam04389
Peptidase family M28;
425-609 1.79e-18

Peptidase family M28;


Pssm-ID: 252561  Cd Length: 173  Bit Score: 84.27  E-value: 1.79e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343  425 HYVVIGAQRD--AWGPGAAKSAVGTAILLELVRTFSSMvsnGFRPRRSLLFISWDGGDFGSVGSTEWLEGYLSVLHlKAV 502
Cdd:pfam04389   1 EVVLLGAHYDsvPIGPGATDNASGVAALLELARVLAAQ---GPQPKRSVVFLFFDAEEDGLLGSRAFAELPHPPLK-KIR 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343  503 VYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPnhSGQTLYEQVVFTNPSwdaevirplPMDSSAYSFTAfVGVPA 582
Cdd:pfam04389  77 AVINLDMIGSGGPAVLFQDGDKLPSLLEAYARKAAKP--YGTTLGLDPFPEGGG---------DGRSDHAPFLG-AGVPG 144
                         170       180
                  ....*....|....*....|....*..
gi 530386343  583 VEFSFmeDDQAYPFLHTKEDTYENLHK 609
Cdd:pfam04389 145 LDFAA--GPNFPPVYHTPCDTLDNIDP 169
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
236-298 4.99e-09

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 and members of the RZF family. 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: 251168  Cd Length: 92  Bit Score: 54.49  E-value: 4.99e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530386343  236 SAIGNVTGELVYAHYGRPEDL-QDLRARGVDPVGRLLLVRVGVISFAQKVTNAQDFGAQGVLIY 298
Cdd:pfam02225   1 SPGGTVTGPLVYVGNGDDEGAcCPSDLAPSDVKGKIVLVRRGGCSFVEKAENAQRAGAKGVIII 64
Iap COG2234
Predicted aminopeptidases [General function prediction only]
382-603 9.79e-10

Predicted aminopeptidases [General function prediction only]


Pssm-ID: 225143 [Multi-domain]  Cd Length: 435  Bit Score: 60.31  E-value: 9.79e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 382 GSLLGSPYHLGPGPRLRLVVNNHRTStpiNNIFGCIEGRSEPDHYVVIGAQRDAW--GPGAAKSAVGTAILLELVRTFSs 459
Cdd:COG2234  169 GNRLIFYKQAGGGLTSKNVAATISGS---SQIIEAIIGTAHSDSLGLLGAHIDSVptGPGADDNASGVAALLELARVLK- 244
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 460 mvsnGFRPRRSLLFISWDGGDFGSVGSTEWLEGYLSVLHLKAVVYVSLDNAVLGDdkfHAKTSPLLTSLIESVLkqvDSP 539
Cdd:COG2234  245 ----GNPPKRTVRFVAFGAEESGLLGSEAYVKRLSKDLDKKIALVINLDMLGSPN---PTPTLILYGNGLERVP---PGL 314
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530386343 540 NHSGQTLYEQVVFtnpswdAEVIRPLPMdSSAYSFTaFVGVPAVEFSFMED--DQAYPFLHTKEDT 603
Cdd:COG2234  315 RAVAALIGRPVDP------STVQDFDPR-SDHYPFT-EAGIPSLFLFSGAPggVEAVAWGHTAADT 372
 
Name Accession Description Interval E-value
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
409-642 9.03e-138

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: 193572 [Multi-domain]  Cd Length: 285  Bit Score: 412.18  E-value: 9.03e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 409 PINNIFGCIEGRSEPDHYVVIGAQRDAWGPGAAKSAVGTAILLELVRTFSSMVSN-GFRPRRSLLFISWDGGDFGSVGST 487
Cdd:cd09848   54 KIHNIFGVIKGFVEPDRYVVIGAQRDAWGPGAAKSGVGTALLLELARTFSDMVKNdGFKPRRSILFASWSAGDFGSVGAT 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 488 EWLEGYLSVLHLKAVVYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPNHSGQTLYEqvvFTNPSWDAEVIRPLPM 567
Cdd:cd09848  134 EWLEGYLSSLHLKAFTYISLDGAVLGDDSFKASASPLLYTLLESTMKQVKSPVHSGQSYYE---FTRSSWWASIVEPLGL 210
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530386343 568 DSSAYSFTAFVGVPAVEFSFMEDDQAYPFLHTKEDTYENLHKVLQGRLPAVAQAVAQLAGQLLIRLSHDRLLPLD 642
Cdd:cd09848  211 DNAAYPFLAFSGIPSVSFHFTEDDEDYPYLGTKLDTKENLDKVTNGRLNAVARAAAEVAGQMALRLVHDHLLNLD 285
PA_TfR cd02128
PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This ...
211-401 1.56e-99

PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This group contains various PA domain-containing proteins similar to human TfR1 and TfR2. TfR1 and TfR2 are type II membrane proteins, belonging to the peptidase M28 family. TfR1 is homodimeric, widely expressed, and a key player in the uptake of iron-loaded transferrin (Tf) into cells. The TfR1 homodimer binds two molecules of Tf and this complex is internalized. In addition to its role in iron uptake, TfR1 may participate in cell growth and proliferation. TfR2 also binds Tf but with a significantly lower affinity than does TfR1. TfR2 is expressed chiefly in hepatocytes, hematopoietic cells, and duodenal crypt cells; its expression overlaps with that of hereditary hemochromatosis protein (HFE). TfR2 is involved in iron homeostasis. HFE and TfR2 interact in cells. By one model for serum iron sensing, at low or basal iron concentrations, HFE and TFR1 form a complex at the plasma membrane; at increased Tf, Tf competes with HFE for binding of TfR1, resulting in HFE disassociating from TfR1 and associating with TfR2 . The TfR1-TfR2 association might initiate a signal cascade leading to the induction of hepcidin (a small peptide hormone that controls systemic iron levels). Human mutations in TfR2 are associated with a form of hemochromatosis (HFE3). The significance of the PA domain to TfRs has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239043  Cd Length: 183  Bit Score: 308.56  E-value: 1.56e-99
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 211 LHWVDEAGkvGEQLPLEDPDVYCPYSAIGNVTGELVYAHYGRPEDLQDLRARGVDPVGRLLLVRVGVISFAQKVTNAQDF 290
Cdd:cd02128    1 SVIIGDAG--RLNELVENPGGYVAYSAAGTVTGKLVYANYGRKKDFEDLQSVGVSVNGSVVLVRAGKISFAEKVANAEKL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 291 GAQGVLIYPEPADFSQDPpkpslsSQQAVYGHVHLGTGDPYTPGFPSFNQTQFPPVASSGLPSIPAQPISADIASRLLRK 370
Cdd:cd02128   79 GAVGVLIYPDPADFPIDP------SETALFGHVHLGTGDPYTPGFPSFNHTQFPPSQSSGLPNIPAQTISAAAAAKLLSK 152
                        170       180       190
                 ....*....|....*....|....*....|...
gi 530386343 371 LKGPVAPQEWQGSllGSPYHLGP--GPRLRLVV 401
Cdd:cd02128  153 MGGPVCPSGWKGG--DSTCRLGTssSKNVKLTV 183
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
409-640 1.94e-66

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 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: 193496  Cd Length: 279  Bit Score: 223.27  E-value: 1.94e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 409 PINNIFGCIEGRSEPDHYVVIGAQRDAWGPGAAKSAVGTAILLELVRTFSSMVSNGFRPRRSLLFISWDGGDFGSVGSTE 488
Cdd:cd03874   56 PIWNVVGKIEGIEQNDKAIIIGAHRDSWCFGAADPNSGTAVLLEIARLFGKLVYKGWKPLRTIKFISWDGSEYNLAGSTE 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 489 WLEGYLSVLHLKAVVYVSLDNAVLGdDKFHAKTSPLLTSLIESVLKQVDSPNHsGQTLYEQVVFTNPSwdaevIRPLPMD 568
Cdd:cd03874  136 LVEDNKDSLRDEAYAYINLDQAVSG-SEFRVDAHPLLKSLLLRALKRVKFPDE-NATLKWWWDDKNAK-----VDNLGLG 208
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530386343 569 SSAYSFTAFVGVPAVEFSFMEDDQAYPFLHTKEDTYENLHKVLQGRLpAVAQAVAQLAGQLLIRLSHDRLLP 640
Cdd:cd03874  209 SDYTPFQNHLGIPSIDISFTGDRNAIYPINSCYDTFEWLEKFGDPDF-ELHGTLAQVLGLLILELADDPLLP 279
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
409-641 2.47e-50

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 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. This gene likely arose from a duplication event of a nearby chromosomal region. Alternative splicing gives rise to multiple transcript variants.


Pssm-ID: 193568  Cd Length: 286  Bit Score: 178.17  E-value: 2.47e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 409 PINNIFGCIEGRSEPDHYVVIGAQRDAWGPGAAKSAVGTAILLELVRTFSSMVSNGFRPRRSLLFISWDGGDFGSVGSTE 488
Cdd:cd08022   57 PIYNVIGTIRGSEEPDEYVILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWKPRRTIIFASWDAEEYGLIGSTE 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 489 WLEGYLSVLHLKAVVYVSLDNAVLGdDKFHAKTSPLLTSLIESVLKQVDSPNHSGQTLYEQVVFTNPSWDaeVIRPLPMD 568
Cdd:cd08022  137 WVEENAPWLKERAVAYLNVDVAVSG-STLRASASPLLHKLIREAAKKVPDPDKGGSSQYLYDSWEKSTDP--RIGNLGSG 213
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 569 SSAYSFTAFVGVPAVEFSFM-EDDQAYPFLHTKEDTYE----------NLHKVLqGRLpavaqavaqlAGQLLIRLSHDR 637
Cdd:cd08022  214 SDYTVFLQHLGIPSLDLGYGgGPTDPYPVYHSNYDSFYwmenfgdpgfKYHLAM-AKL----------WGLLALRLADSE 282

                 ....
gi 530386343 638 LLPL 641
Cdd:cd08022  283 VLPF 286
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
203-394 8.21e-41

PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to the peptidase M28 family. GCPII is also known N-acetylated-alpha-linked acidic dipeptidase (NAALDase1), folate hydrolase or prostate-specific membrane antigen (PSMA). GCPII is found in various human tissues including prostate, small intestine, and the central nervous system. In the brain, GCPII is known as NAALDase1, it functions as a NAALDase hydrolyzing the neuropeptide N-acetyl-L-aspartyl-L-glutamate (alpha-NAAG), to release free glutamate. In the small intestine, GCPII releases the terminal glutamate from poly-gamma-glutamated folates. GCPII (PSMA) is a useful cancer marker; its expression is markedly increased in prostate cancer and in tumor-associated neovasculature. GCPIII hydrolyzes alpha-NAAG with a lower efficiency than does GCPII; NAALADase L is not able to hydrolyze alpha-NAAG. The GCPII PA domain (referred to as the apical domain) participates in substrate binding and may act as a protein-protein interaction domain.


Pssm-ID: 239036  Cd Length: 220  Bit Score: 149.75  E-value: 8.21e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 203 PDPAHPNTLHWVDEAGKVGEQLPLEDPDV------YCPYSAIGNVTGELVYAHYGRPEDLQDLRARGVDPVGRLLLVRVG 276
Cdd:cd02121    1 PVKRSLILTKPDGATGKLIEDTVLEEPPSpdvvppFHAYSASGNVTAELVYANYGSPEDFEYLEDLGIDVKGKIVIARYG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 277 VISFAQKVTNAQDFGAQGVLIYPEPAD-----------FSQDPPKPSLSSQQAVYGHVHLGTGDPYTPGFPSF-NQTQFP 344
Cdd:cd02121   81 GIFRGLKVKNAQLAGAVGVIIYSDPADdgyitgengktYPDGPARPPSGVQRGSVLFMSIGPGDPLTPGYPSKpGAERRD 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 530386343 345 PVASSGLPSIPAQPISADIASRLLRKLKGPVAPQEWQGSlLGSPYHLGPG 394
Cdd:cd02121  161 KEESKGLPKIPSLPISYRDAQPLLKALGGPGAPSDWQGG-LPVTYRLGFG 209
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
668-793 1.73e-32

Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the transferrin receptor as shown in its crystal structure.


Pssm-ID: 202944  Cd Length: 122  Bit Score: 122.76  E-value: 1.73e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343  668 GLTLQWVYSARGDYIRAAEKLRQEIYSSE--ERDERLTRMYNVRIMRVEFYFLSQYVSPADSPFRHIFMGRG------DH 739
Cdd:pfam04253   1 GLSLDPLFSAVKKFKKAAKELESWIKNWDnfEPNPLAVRRWNDRLMRVERAFLNPYGLPGRPFYRHVIFGPSlwngydGW 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530386343  740 TLGALLDHLRLLRSNSSgtpgatsstgfqESRFRRQLALLTWTLQGAANALSGD 793
Cdd:pfam04253  81 TFPGIRDALFDANNSGD------------WDEAQRQLSLVAWALQGAANTLSEV 122
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
401-607 9.23e-29

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 the 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: 193493  Cd Length: 252  Bit Score: 115.98  E-value: 9.23e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 401 VNNHRTSTPINNIFGCIEGrSEPDHYVVIGAQRDAWG--PGAAKSAVGTAILLELVRTFSSMvsngfRPRRSLLFISWDG 478
Cdd:cd02690   48 VRKSLENVTSYNVIAVLKG-KNSDKVIVIGAHYDSWGtaPGADDNASGVAVLLELARVLSKL-----PLDRTIRFVFFGA 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 479 GDFGSVGSTEWLEGYLSVLHLKAVVYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPNHSGQTlyeqvvftnpswd 558
Cdd:cd02690  122 EEVGLLGSKYYAEDLSSYELENIVAVINLDMVGGGGDPLYVHAAPGNDDLLLKLARALGHKLGTGDP------------- 188
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 530386343 559 aeVIRPLPMDSSAYSFtAFVGVPAVEFSFMEDDqAYPFLHTKEDTYENL 607
Cdd:cd02690  189 --VVSPGGPGSDHEPF-AEAGIPAVTLESTNGD-GGPWYHTPADTLDNI 233
Peptidase_M28 pfam04389
Peptidase family M28;
425-609 1.79e-18

Peptidase family M28;


Pssm-ID: 252561  Cd Length: 173  Bit Score: 84.27  E-value: 1.79e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343  425 HYVVIGAQRD--AWGPGAAKSAVGTAILLELVRTFSSMvsnGFRPRRSLLFISWDGGDFGSVGSTEWLEGYLSVLHlKAV 502
Cdd:pfam04389   1 EVVLLGAHYDsvPIGPGATDNASGVAALLELARVLAAQ---GPQPKRSVVFLFFDAEEDGLLGSRAFAELPHPPLK-KIR 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343  503 VYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPnhSGQTLYEQVVFTNPSwdaevirplPMDSSAYSFTAfVGVPA 582
Cdd:pfam04389  77 AVINLDMIGSGGPAVLFQDGDKLPSLLEAYARKAAKP--YGTTLGLDPFPEGGG---------DGRSDHAPFLG-AGVPG 144
                         170       180
                  ....*....|....*....|....*..
gi 530386343  583 VEFSFmeDDQAYPFLHTKEDTYENLHK 609
Cdd:pfam04389 145 LDFAA--GPNFPPVYHTPCDTLDNIDP 169
M28_like_PA cd03877
M28 Zn-Peptidases containing a PA domain insert; Peptidase family M28 (also called ...
404-608 7.01e-16

M28 Zn-Peptidases containing a PA domain insert; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This subfamily is composed of uncharacterized proteins, 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: 193499  Cd Length: 254  Bit Score: 77.27  E-value: 7.01e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 404 HRTSTPINNIFGCIEGRSEPDHYVVIGAQRDAWG--------PGAAKSAVGTAILLELVRTFSsmvSNGfRPRRSLLFIS 475
Cdd:cd03877   45 QPFPLVSYNVIGIIEGKDLKDEAVVISAHYDHLGedgngeiyNGADDNASGTAAVLELARALA---KAG-TPKRSIIFLA 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 476 WDGGDFGSVGStEWLEGYLSVLHLKAVVYVSLDNAVLGDDK-----FHAKTSPLLTSLIESVLKQvdspnhsgqtlyeqv 550
Cdd:cd03877  121 FTGEEKGLLGS-KYFVKHPLVPLANIVANLNIDMIGRGDDGgpiylIGSDLSSELDDLIKEVNKA--------------- 184
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 530386343 551 vFTNPSWDAEVIRPLPMDSSAYSFTAFvGVPAVEFSFMEDDqAYpflHTKEDTYENLH 608
Cdd:cd03877  185 -CSNDKLDPNREAQFFYRSDHYPFAKK-GIPAIFFFTGLHD-DY---HRPTDTIEKID 236
PA_hNAALADL2_like cd02131
PA_hNAALADL2_like: Protease-associated domain containing proteins like human N-acetylated ...
232-368 1.25e-13

PA_hNAALADL2_like: Protease-associated domain containing proteins like human N-acetylated alpha-linked acidic dipeptidase-like 2 protein (hNAALADL2). This group contains various PA domain-containing proteins similar to hNAALADL2. The function of hNAALADL2 is unknown. This gene has been mapped to a chromosomal region associated with Cornelia de Lange syndrome. The significance of the PA domain to hNAALADL2 has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239046  Cd Length: 153  Bit Score: 69.19  E-value: 1.25e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 232 YCPYSAIGNVTGELVYAHYGRPEDLQDLRaRGVDPVGRLLLVRVGVISFAQKVTNAQDFGAQGVLIYPEPADFsqdpPKP 311
Cdd:cd02131    6 YAAYSAKGTLQAEVVDVQYGSVEDLRRIR-DNMNVTNQIALLKLGQAPLLYKLSLLEEAGFGGVLLYVDPCDL----PKT 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 530386343 312 SLSSQQAVYGHVHLGtGDPYTPGFPSFNQTQFPpvASSGLPSIPAQPISADIASRLL 368
Cdd:cd02131   81 RHTWHQAFMVSLNPG-GDPSTPGYPSADQSCRQ--CRGNLTSLLVQPISAYLAKKLL 134
M28_like_4 cd08015
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
412-607 1.61e-13

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


Pssm-ID: 193563 [Multi-domain]  Cd Length: 275  Bit Score: 70.50  E-value: 1.61e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 412 NIFGCIEGRSEPDHYVVIGAQRDAW--GPGAAKSAVGTAILLELVRTFSSMvsnGFRPRRSLLFISWDGGDFGSVGSTEW 489
Cdd:cd08015   60 NVVAEIPGTDKKDEYVMIGGHFDSWhgATGATDNAAGSAVMMEAMRILKAL---GLKPKRTIRVALWGGEEQGLLGSRAY 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 490 LEGYL--------SVLHLKAVVYVSLDNavlGDDKF-------HAKTSPLLtsliESVLKQVDSpnhsgqtLYEQVVFTN 554
Cdd:cd08015  137 VEQHFadpptmkpKPEHEKLSAYFNLDN---GTGKIrgiylqgNAAARPVF----EEWLAPFRD-------LGVTTVTGR 202
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 530386343 555 PSWdaevirplPMDSSaySFTAfVGVPAveFSFMEDDQAY--PFLHTKEDTYENL 607
Cdd:cd08015  203 NTG--------GTDHL--SFDA-VGLPG--FQFIQDPLDYytRTHHSNMDTYDHI 244
M28_like_PA_PDZ_associated cd05663
M28 Zn-Peptidases containing a PA domain insert and associated with a PDZ domain; Peptidase ...
409-537 4.24e-12

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


Pssm-ID: 193539 [Multi-domain]  Cd Length: 260  Bit Score: 65.70  E-value: 4.24e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 409 PINNIFGCIEGRSEP-DHYVVIGAQRDAWG---------------PGAAKSAVGTAILLELVRTFSSmvsNGFRPRRSLL 472
Cdd:cd05663   51 TGRNVIGVLPGKDPLaDETVVIGAHYDHLGyggggslapgegkihNGADDNASGTAALLELARYLAA---NKEKLQRNIL 127
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 473 FISWDGGDFGSVGSTEWLEGYLSVLHlKAVVYVSLDnAV--LGDDK---FHAKTSPLLTSLIESVLKQVD 537
Cdd:cd05663  128 FIAFSGEELGLLGSKHFVENPTFPLD-KVVAMLNLD-MVgrLRDNKltvSGTGTSPEWPPLLDELNEASG 195
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
234-373 1.49e-09

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  Cd Length: 126  Bit Score: 56.76  E-value: 1.49e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 234 PYSAIGNVTGELVYAHYGRPEDlqdlraRGVDPVGRLLLVRVGVISFAQKVTNAQDFGAQGVLIYpepadfsqdppkpsl 313
Cdd:cd00538   19 PSSPVGVVAGPLVGCGYGTTDD------SGADVKGKIVLVRRGGCSFSEKVKNAQKAGAKAVIIY--------------- 77
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 314 ssqqavyghvhlgtGDPYTPGFPSFNqtqfpPVASSGLPSIPAQPISADIASRLLRKLKG 373
Cdd:cd00538   78 --------------NNGDDPGPQMGS-----VGLESTDPSIPTVGISYADGEALLSLLEA 118
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
236-298 4.99e-09

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 and members of the RZF family. 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: 251168  Cd Length: 92  Bit Score: 54.49  E-value: 4.99e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530386343  236 SAIGNVTGELVYAHYGRPEDL-QDLRARGVDPVGRLLLVRVGVISFAQKVTNAQDFGAQGVLIY 298
Cdd:pfam02225   1 SPGGTVTGPLVYVGNGDDEGAcCPSDLAPSDVKGKIVLVRRGGCSFVEKAENAQRAGAKGVIII 64
PA_C5a_like cd02133
PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a ...
240-298 5.80e-09

PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a peptidase. This group contains various PA domain-containing proteins similar to S. pyogenes C5a, including, i) Vpr, a minor extracellular serine protease from Bacillus subtilis, ii) a large molecular mass collagenolytic protease from Geobacillus collagenovorans MO-1, and iii) PrtS, a cell envelope protease from Streptococcus thermophilus CNRZ 385. Proteins in this group belong to the peptidase S8 family. C5a peptidase is a cell surface serine protease which specifically inactivates C5a [a chemotactic peptide, which attracts polymorphonuclear leukocytes (PMNs)], by cleaving it to release a 7-residue carboxy-terminal fragment which contains the PMN binding site. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239048  Cd Length: 143  Bit Score: 54.99  E-value: 5.80e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 530386343 240 NVTGELVYAHYGRPEDLqdlraRGVDPVGRLLLVRVGVISFAQKVTNAQDFGAQGVLIY 298
Cdd:cd02133   25 GKTYELVDAGLGTPEDF-----EGKDVKGKIALIQRGEITFVEKIANAKAAGAVGVIIY 78
M28_like_PA_1 cd05660
M28 Zn-Peptidases containing a PA domain insert; Peptidase family M28 (also called ...
411-486 4.17e-08

M28 Zn-Peptidases containing a PA domain insert; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This subfamily is composed of uncharacterized proteins containing a protease-associated (PA) domain insert which may participate in substrate binding and/or promote conformational changes, influencing the stability and accessibility of the site to substrate.


Pssm-ID: 193536 [Multi-domain]  Cd Length: 306  Bit Score: 54.50  E-value: 4.17e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 411 NNIFGCIEGRSEPDHYVVIGAQRDAWGP------------GAAKSAVGTAILLELVRTFssmvSNGFRPRRSLLFISWDG 478
Cdd:cd05660   64 HNVVARLPGSKRPDEYVLYSAHWDHLGIgapdatgdtiynGAVDNASGTAALLELARAF----AAGPQPERSVVFLAVTA 139

                 ....*...
gi 530386343 479 GDFGSVGS 486
Cdd:cd05660  140 EEQGLLGS 147
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
408-485 8.47e-07

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. However, PGCP has not been linked to any type of cancer. It provides an attractive target for serological analysis in hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) patients.


Pssm-ID: 193504 [Multi-domain]  Cd Length: 276  Bit Score: 49.88  E-value: 8.47e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 408 TPINNIFGCIEGRSEPDHYVVIGAQRDAW--GPGAAKSAVGTAILLELVRTFSSMvsnGFRPRRSLLFISWDGGDFGSVG 485
Cdd:cd03883   75 APSGNVIAEIKGSEYPEEIVLVGGHLDSWdvGTGAIDDGAGVAISMEAAKLIKDL---GLRPKRTIRVVLWTAEENGLRG 151
M28_nicalin_like cd03882
M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin ...
427-538 1.56e-06

M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin (nicastrin-like protein) subfamily. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated gamma-secretase, and forms a complex with Nomo (nodal modulator) pM5. Similar to Nicastrin, Nicalin lacks the amino-acid conservation required for catalytically active aminopeptidases. Functional studies in zebrafish embryos and cultured human cells reveal that nicalin and Nomo collaborate to antagonize the Nodal/TGFbeta signaling pathway. Thus, nicastrin and nicalin are both associated with protein complexes involved in cell fate decisions during early embryonic development.


Pssm-ID: 193503  Cd Length: 290  Bit Score: 49.31  E-value: 1.56e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 427 VVIGAQRDAWG------PGAAKSAVGTAILLELVRTFSSMVSN-GFRPRRSLLFISWDGGDFGSVGSTEWLEGYLsVLHL 499
Cdd:cd03882   88 IVIVAHYDSFGvapalsSGADSNGSGVAALLELARLFSRLYSNpRTHPKYNLLFLLTGGGKFNYQGTKHWLESNL-DRLL 166
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 530386343 500 KAVVYV-SLDNAVLGDDKF-HAKTSPLLTSLIESVLKQVDS 538
Cdd:cd03882  167 DNVEFVlCLDSIGSKDSLYlHVSKPPKEGTPAFQFFEELES 207
PA_subtilisin_1 cd04818
PA_subtilisin_1: Protease-associated domain containing subtilisin-like proteases, subgroup 1. ...
237-318 6.43e-06

PA_subtilisin_1: Protease-associated domain containing subtilisin-like proteases, subgroup 1. A subgroup of PA domain-containing subtilisin-like 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 subtilisin-like proteases: i) melon cucumisin, ii) Arabidopsis thaliana Ara12, iii) Alnus glutinosa ag12, iv) members of the tomato P69 family, and v) tomato LeSBT2. However, these proteins belong to other subtilisin-like subgroups. Relatively little is known about proteins in this subgroup.


Pssm-ID: 240122  Cd Length: 118  Bit Score: 45.40  E-value: 6.43e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 237 AIGNVTGELVYAHYGRPEDLQ--DLRARGVDPVGRLLLVRVGVISFAQKVTNAQDFGAQGVLIY-----PEPADFSQDPP 309
Cdd:cd04818    8 ALTNVTADVVLAGAAPASNTDgcTAFTNAAAFAGKIALIDRGTCNFTVKVLNAQNAGAIAVIVAnnvagGAPITMGGDDP 87
                         90
                 ....*....|..
gi 530386343 310 K---PSLSSQQA 318
Cdd:cd04818   88 DitiPAVMISQA 99
M28_like_PA_2 cd05661
M28 Zn-Peptidases containing a PA domain insert; Peptidase family M28 (also called ...
412-487 1.26e-05

M28 Zn-Peptidases containing a PA domain insert; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This subfamily is composed of uncharacterized proteins containing a protease-associated (PA) domain insert which may participate in substrate binding and/or promote conformational changes, influencing the stability and accessibility of the site to substrate.


Pssm-ID: 193537 [Multi-domain]  Cd Length: 305  Bit Score: 46.48  E-value: 1.26e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 412 NIFGCIEGrSEP---DHYVVIGAQRDAWG-----------PGAAKSAVGTAILLELVRTFSSMvsnGFRPRRSLLFISWD 477
Cdd:cd05661   68 NVVGVLPG-SDPalkDEYVVLSAHLDHIGigepvggdniyNGAMDNASGVATLLEVARAFAES---EERPKRSILFLAVT 143
                         90
                 ....*....|
gi 530386343 478 GGDFGSVGST 487
Cdd:cd05661  144 AEEKGLLGSR 153
PA_PoS1_like cd02124
PA_PoS1_like: Protease-associated (PA) domain PoS1-like. This group includes various PA ...
253-319 3.07e-05

PA_PoS1_like: Protease-associated (PA) domain PoS1-like. This group includes various PA domain-containing proteins similar to Pleurotus ostreatus (Po)S1. PoSl, the main extracellular protease in P. ostreatus is a subtilisin-like serine protease belonging to the peptidase S8 family. Ca2+ and Mn2+ both stimulate the protease activity of (Po)S1. Ca2+ protects PoS1 from autolysis. PoS1 is a monomeric glycoprotein, which may play a role in the regulation of laccases in lignin formation. (Po)S1 participates in the degradation of POXA1b, and in the activation of POXA3, (POXA1b and POXA3 are laccase isoenzymes), but its effect may be indirect. The significance of the PA domain to PoS1 has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239039  Cd Length: 129  Bit Score: 43.09  E-value: 3.07e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530386343 253 PEDLQDLRargvdpvGRLLLVRVGVISFAQKVTNAQDFGAQGVLIYPEPADFSQDPPKPSLSSQQAV 319
Cdd:cd02124   48 PDDTPDLS-------GYIVLVRRGTCTFATKAANAAAKGAKYVLIYNNGSGPTDQVGSDADSIIAAV 107
PA_2 cd04819
PA_2: Protease-associated (PA) domain subgroup 2. A subgroup of PA-domain containing proteins. ...
234-298 3.47e-05

PA_2: Protease-associated (PA) domain subgroup 2. A subgroup of PA-domain containing proteins. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. Proteins in this group contain a C-terminal RING-finger domain. Proteins into which the PA domain is inserted include the following: i) various signal peptide peptidases: such as hSPPL2a and 2b, ii) various E3 ubiquitin ligases similar to human GRAIL (gene related to anergy in lymphocytes) protein, iii) various proteins containing a RING finger motif such as Arabidopsis ReMembR-H2 protein, iv) EDEM3 (ER-degradation-enhancing mannosidase-like 3 protein), v) various plant vacuolar sorting receptors such as Pisum sativum BP-80, vi) prostate-specific membrane antigen (PSMA), vii) yeast aminopeptidase Y viii) Vibrio metschnikovii VapT, a sodium dodecyl sulfate (SDS) resistant extracellular alkaline serine protease, ix) various subtilisin-like proteases such as Cucumisin from the juice of melon fruits, and x) human TfR (transferrin receptor) 1 and human TfR2. The proteins listed above belong to other subgroups; relatively little is known about proteins in this subgroup.


Pssm-ID: 240123  Cd Length: 127  Bit Score: 43.15  E-value: 3.47e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530386343 234 PYSAIGNVTGELVYAHYGRPEDLQdlrarGVDPVGRLLLVRVGV--ISFAQKVTNAQDFGAQGVLIY 298
Cdd:cd04819   16 PRSPSGEAKGEPVDAGYGLPKDFD-----GLDLEGKIAVVKRDDpdVDRKEKYAKAVAAGAAAFVVV 77
PA_ScAPY_like cd02130
PA_ScAPY_like: Protease-associated domain containing proteins like Saccharomyces cerevisiae ...
234-298 4.02e-05

PA_ScAPY_like: Protease-associated domain containing proteins like Saccharomyces cerevisiae aminopeptidase Y (ScAPY). This group contains various PA domain-containing proteins similar to the S. cerevisiae APY, including Trichophyton rubrum leucine aminopeptidase 1(LAP1). Proteins in this group belong to the peptidase M28 family. ScAPY hydrolyzes amino acid-4-methylcoumaryl-7-amides (MCAs). ScAPY more rapidly hydrolyzes dipeptidyl-MCAs. Hydrolysis of amino acid-MCAs or dipeptides is stimulated by Co2+ while the hydrolysis of dipeptidyl-MCAs, tripeptides, and longer peptides is inhibited by Co2+. ScAPY is vacuolar and is activated by proteolytic processing. LAP1 is a secreted leucine aminopeptidase. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 239045  Cd Length: 122  Bit Score: 43.02  E-value: 4.02e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530386343 234 PYSAIGNVTGELVY--------AHYgrPEDLQdlrargvdpvGRLLLVRVGVISFAQKVTNAQDFGAQGVLIY 298
Cdd:cd02130   15 TYSPAGEVTGPLVVvpnlgcdaADY--PASVA----------GNIALIERGECPFGDKSALAGAAGAAAAIIY 75
M28_AAP cd03879
M28 Zn-Peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
403-486 4.10e-05

M28 Zn-Peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; Aeromonas (Vibrio) proteolytica aminopeptidase (AAP; leucine aminopeptidase from Vibrio proteolyticus; Bacterial leucyl aminopeptidase; E.C. 3.4.11.10) subfamily. AAP is a small (32kDa), heat stable leucine aminopeptidase and is active as a monomer. Similar forms of the enzyme have been isolated from Escherichia coli and Staphylococcus thermophilus. Leucine aminopeptidases, in general, play important roles in many biological processes such as protein catabolism, hormone degradation, regulation of migration and cell proliferation, as well as HIV infection and proliferation. AAP is a broad-specificity enzyme, utilizing two zinc(II) ions in its active site to remove N-terminal amino acids, with preference for large hydrophobic amino acids in the P1 position of the substrate, Leu being the most efficiently cleaved. It can accommodate all residues, except Pro, Asp and Glu in the P1' position.


Pssm-ID: 193500 [Multi-domain]  Cd Length: 285  Bit Score: 44.87  E-value: 4.10e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 403 NHrTSTPINNIFGCIEGRSEPDHYVVIGAQRD----AWG-----PGAAKSAVGTAILLELVRTfssMVSNGFRPRRSLLF 473
Cdd:cd03879   68 NH-SGWPQPSIIVTIPGSEKSDETVVVGAHLDsingSNPsngraPGADDDGSGIATILEALRV---LLESGFQPKRTIEF 143
                         90
                 ....*....|...
gi 530386343 474 ISWDGGDFGSVGS 486
Cdd:cd03879  144 HWYAAEEVGLLGS 156
M28_like_5 cd08021
M28 Zn-Peptidase IAP aminopeptidase may contain PA domain insert; Peptidase family M28 (also ...
412-607 6.16e-05

M28 Zn-Peptidase IAP aminopeptidase may contain 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 that do not contain a protease-associated (PA) domain.


Pssm-ID: 193567 [Multi-domain]  Cd Length: 277  Bit Score: 44.17  E-value: 6.16e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 412 NIFGCIEGRSE--PDHYVVIGAQRDAWG-----------PGAAKSAVGTAILLELVRTFSSMVSNgfrpRRSLLFISWDG 478
Cdd:cd08021   55 NVVGVLEGKDPklKNEYVVIGAHYDHIGilkavngdsiaNGANDNASGTTAVLELAKYFAKLKNN----KRTLIFAAFSA 130
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 479 GDFGSVGSTewlegYLSVlHLKA---VVYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPNHSGQTLyeqVVFTNP 555
Cdd:cd08021  131 EEKGLLGSK-----HLAK-KLKAqniDVYAMFNIEMIGVPMKFGDYTAYITGYEKSNLAEILNKYAGGSKF---VGFLDP 201
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 530386343 556 swdaEVIRPLPMDSSAYSFTAFVGVPAVEFSFMEDDQaYPFLHTKEDTYENL 607
Cdd:cd08021  202 ----APEQNLFYRSDNYPFAREFGVPAHTFSTFDFTN-FDYYHQVSDEVETL 248
M28_like_2 cd05662
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
412-608 6.41e-05

M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. This subfamily is composed of uncharacterized proteins that do not contain a protease-associated (PA) domain.


Pssm-ID: 193538  Cd Length: 267  Bit Score: 44.15  E-value: 6.41e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 412 NIFGCIEGRSEPDHYVVIGAQRDAWG-------PGAAKSAVGTAILLELVRTFSSMvsngfRPRRSLLFISWDGGDFGSV 484
Cdd:cd05662   64 NVIGLIPGTKPSNRWIVITAHYDHLGvrggkiyNGADDNASGVAALLALAEYFKKQ-----PPKHNLIFAATDAEEPGLY 138
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 485 GSTEWLEGyLSVLHLKAVVYVSLD-------NA--VLGDDKFhaktsPLLTSLIE------SVLKQvDSPNHSGQtlyeQ 549
Cdd:cd05662  139 GAKAFVEA-LPVPLSQIELNINLDmigrpdrNElyAEGTYHF-----PELKPILEqvaklaIVLGH-DHPDPDGG----A 207
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 530386343 550 VVFTNPSwdaevirplpmDSsaYSFTAfVGVPAVEFSfMEDDQAYpflHTKEDTYENLH 608
Cdd:cd05662  208 IDWTRAS-----------DH--YAFHK-AGIPFLYFG-VEDHPDY---HTPTDTFEKID 248
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
410-473 3.39e-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 cluster 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: 193497 [Multi-domain]  Cd Length: 307  Bit Score: 42.19  E-value: 3.39e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530386343 410 INNIFGCIEGR-SEPDHYVVIGAQRDAW--GPGAAKSAVGTAILLELVRTFSsmvSNGFRPRRSLLF 473
Cdd:cd03875   78 GTNIVVRISGKnNGSEGALLLNAHYDSVptSPGASDDGSGVAVMLEVLRALA---KSGEPPKRDVIF 141
PA_SaNapH_like cd04816
PA_SaNapH_like: Protease-associated domain containing proteins like Streptomyces anulatus ...
239-298 6.33e-04

PA_SaNapH_like: Protease-associated domain containing proteins like Streptomyces anulatus N-acetylpuromycin N-acetylhydrolase (SaNapH).This group contains various PA domain-containing proteins similar SaNapH. Proteins in this group belong to the peptidase M28 family. NapH is a terminal enzyme in the puromycin biosynthetic pathway; NapH hydrolyzes N-acetylpuromycin to the active antibiotic. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.


Pssm-ID: 240120  Cd Length: 122  Bit Score: 39.23  E-value: 6.33e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530386343 239 GNVTGELVYAhygRPEDLQDLRA---RGVDPVGRLLLVRVGVISFAQKVTNAQDFGAQGVLIY 298
Cdd:cd04816   15 GGVTAPLVPL---DPERPAGCDAsdyDGLDVKGAIVLVDRGGCPFADKQKVAAARGAVAVIVV 74
M28_like_1 cd05640
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
368-477 1.67e-03

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


Pssm-ID: 193519  Cd Length: 279  Bit Score: 39.89  E-value: 1.67e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 368 LRKLKGPVAPQEWQgsLLGSPYHlgpgprlrlvvnnhrtstpinNIFGCIEGRSEPDHYVVIGAQRDAWG--PGAAKSAV 445
Cdd:cd05640   34 LRAAGGPVERQLYP--VNGKSYR---------------------NLIAERPGTDPPGPRILVGAHYDTVPgsPGADDNAS 90
                         90       100       110
                 ....*....|....*....|....*....|..
gi 530386343 446 GTAILLELVRTFSSMvsngfRPRRSLLFISWD 477
Cdd:cd05640   91 GVAVLLELARLLAAL-----PPARTLRLVAFD 117
M28_AAP_like cd05642
M28 Zn-Peptidase Aeromonas (Vibrio) proteolytica aminopeptidase (AAP)-like; Peptidase M28 ...
408-483 2.58e-03

M28 Zn-Peptidase Aeromonas (Vibrio) proteolytica aminopeptidase (AAP)-like; Peptidase M28 family; Aeromonas (Vibrio) proteolytica aminopeptidase-like (AAP-like; leucine aminopeptidase from Vibrio proteolyticus; Bacterial leucyl aminopeptidase) subfamily. This group includes uncharacterized proteins with predicted aminopeptidase activity. 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. While it can accommodate all residues except Pro, Asp and Glu in the P1' position, it prefers large hydrophobic amino acids in the P1 position of the substrate, with Leu being the most efficiently cleaved.


Pssm-ID: 193520 [Multi-domain]  Cd Length: 348  Bit Score: 39.55  E-value: 2.58e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 408 TPINNIFGCIEGRSEPDHYVVIG------------AQRDAwgPGAAKSAVGTAILLELVRTFSSMvsngfRPRRSLLFIS 475
Cdd:cd05642   87 VEIVNVVAILKGTDDPNRVVIVSghydsrvsdvmdYTSDA--PGANDDASGVAVVIEAARVLSKR-----RFPATIVFVA 159
                         90
                 ....*....|.
gi 530386343 476 WDG---GDFGS 483
Cdd:cd05642  160 LAGeeqGLFGS 170
Zinc_peptidase_like cd03873
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ...
391-611 3.70e-03

Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and signaling pathways throughout all kingdoms of life. This family corresponds to several clans in the MEROPS database, including the MH clan, 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 eukaryotic, non-specific 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 carbxypeptidase II and plasma glutamate carboxypeptidase hydrolyze dipeptides. Peptidase families M18 and M42 contain metalloaminopeptidases. M18 is widely distributed in bacteria and eukaryotes. However, only yeast aminopeptidase I and mammalian aspartyl aminopeptidase have been characterized in detail. Some of M42 (also known as glutamyl aminopeptidase) enzymes exhibit aminopeptidase specificity while others also have acylaminoacylpeptidase activity (i.e. hydrolysis of acylated N-terminal residues).


Pssm-ID: 193495  Cd Length: 237  Bit Score: 38.56  E-value: 3.70e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 391 LGPGPRLRLVVNNHRTSTPINNifgciEGRSEPDHYVVIGAQRDAWGPGAAKSAVGTAILLELVRTFssmVSNGFRPRRS 470
Cdd:cd03873   46 YGGGEKPPVLLMAHIDVVPAGD-----TWWWEFPFAVDTLKDGRLYGRGAADDKGSVAALLEALRDL---KENGFKPKGT 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 471 LLFISWDGGDFGSVGSTEWLEGYLSVlHLKAVVYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPNHsgqtlyeqv 550
Cdd:cd03873  118 IIFAFTADEEAGGSAGAGLALWLLEE-GLKVDYLFVLDGGPAPPQQGVVIRTPFVDALLAAAEDVGGKPVP--------- 187
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530386343 551 vftnpswdaevirplPMDSSAYS---FTAFVGVPAVEFSFMEDdqayPFLHTK-----EDTYENLHKVL 611
Cdd:cd03873  188 ---------------AISIGGGTdgrYFAELGIPGVTLGPPGT----ANYHSPnetvsLESLEKAIKVL 237
Iap COG2234
Predicted aminopeptidases [General function prediction only]
382-603 9.79e-10

Predicted aminopeptidases [General function prediction only]


Pssm-ID: 225143 [Multi-domain]  Cd Length: 435  Bit Score: 60.31  E-value: 9.79e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 382 GSLLGSPYHLGPGPRLRLVVNNHRTStpiNNIFGCIEGRSEPDHYVVIGAQRDAW--GPGAAKSAVGTAILLELVRTFSs 459
Cdd:COG2234  169 GNRLIFYKQAGGGLTSKNVAATISGS---SQIIEAIIGTAHSDSLGLLGAHIDSVptGPGADDNASGVAALLELARVLK- 244
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530386343 460 mvsnGFRPRRSLLFISWDGGDFGSVGSTEWLEGYLSVLHLKAVVYVSLDNAVLGDdkfHAKTSPLLTSLIESVLkqvDSP 539
Cdd:COG2234  245 ----GNPPKRTVRFVAFGAEESGLLGSEAYVKRLSKDLDKKIALVINLDMLGSPN---PTPTLILYGNGLERVP---PGL 314
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530386343 540 NHSGQTLYEQVVFtnpswdAEVIRPLPMdSSAYSFTaFVGVPAVEFSFMED--DQAYPFLHTKEDT 603
Cdd:COG2234  315 RAVAALIGRPVDP------STVQDFDPR-SDHYPFT-EAGIPSLFLFSGAPggVEAVAWGHTAADT 372
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.11
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A et al. (2009), "CDD: specific functional annotation with the Conserved Domain Database.", Nucleic Acids Res.37(D)205-10.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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