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Conserved domains on  [gi|1034571481|ref|XP_016872532|]
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N-acetylated-alpha-linked acidic dipeptidase 2 isoform X1 [Homo sapiens]

Protein Classification

M28 family metallopeptidase( domain architecture ID 10114706)

M28 family metallopeptidase is a zinc-dependent peptidase that may be an aminopeptidase or a carboxypeptidase with co-catalytic zinc ions; contains a protease-associated (PA) domain insert which may participate in substrate binding and/or promote conformational changes; similar to Homo sapiens glutamate carboxypeptidase 2, N-acetylated-alpha-linked acidic dipeptidase 2 and N-acetylated-alpha-linked acidic dipeptidase-like protein

CATH:  3.40.630.10
EC:  3.4.-.-
MEROPS:  M28

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
366-620 8.73e-124

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: 371.95  E-value: 8.73e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 366 KVRMHVYNInkitRIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIARSFGKLMSKGWRPRRTIIFAS 445
Cdd:cd08022    50 DVELEEYDV----PIWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFAS 125
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 446 WDAEEFGLLGSTEWAEENVKILQERSIAYINSDSSIEGnYTLRVDCTPLLYQLVYKLTKEIPSPDDGFESKSlyeswlek 525
Cdd:cd08022   126 WDAEEYGLIGSTEWVEENADWLQERAVAYLNVDVAVSG-STLRAAGSPLLQNLLREAAKEVQDPDEGATLKY-------- 196
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 526 DPSPENKNLPRINKLGSGSDFEAYFQRLGIASGRARYTKNKKtdkySSYPVYHTIYETFELVEKFYDPTFKKQLSVAQLR 605
Cdd:cd08022   197 LPSWWDDTGGEIGNLGSGSDYTPFLDHLGIASIDFGFSGGPT----DPYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVW 272
                         250
                  ....*....|....*
gi 1034571481 606 GALVYELVDSKIIPF 620
Cdd:cd08022   273 GLLALRLADDPILPF 287
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
145-371 3.01e-95

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: 295.74  E-value: 3.01e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 145 PNETNANYISIVDEHETEIFKTsYLEPPPDgyenvTNIVPPYNAFSAQGMPEGDLVYVNYARTEDFFKLEReMGINCTGK 224
Cdd:cd02121     1 PVKRSLILTKPDGATGKLIEDT-VLEEPPS-----PDVVPPFHAYSASGNVTAELVYANYGSPEDFEYLED-LGIDVKGK 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 225 IVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPEV---QPYPKGWNLPGTAAQRGNVLNL-NGAGDPLTPGYPAK 300
Cdd:cd02121    74 IVIARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYITGengKTYPDGPARPPSGVQRGSVLFMsIGPGDPLTPGYPSK 153
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034571481 301 EYTFRLDVEEGVGIPRIPVHPIGYNDAEILLRYLGGIAPPDkSWKGALNVSYSIGPgftGSDSFRKVRMHV 371
Cdd:cd02121   154 PGAERRDKEESKGLPKIPSLPISYRDAQPLLKALGGPGAPS-DWQGGLPVTYRLGF---GGPSPGKVRVNL 220
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
652-772 1.06e-42

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


:

Pssm-ID: 461238  Cd Length: 116  Bit Score: 150.43  E-value: 1.06e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 652 VSFDSLFSAVKNFSEAASDFHKR---LIQVDLNNPIAVRMMNDQLMLLERAFIDPLGLPGKLFYRHIIFAPSSHNKYAGE 728
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWakkWEDIKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGA 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1034571481 729 SFPGIYDAIFDIenkansrlAWKEVKKHISIAAFTIQAAAGTLK 772
Cdd:pfam04253  81 TFPGIRDAIEAG--------DWELAQKQISIVAKAIQSAAETLK 116
Zinc_peptidase_like super family cl14876
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ...
94-139 9.07e-09

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).


The actual alignment was detected with superfamily member cd03874:

Pssm-ID: 472712 [Multi-domain]  Cd Length: 278  Bit Score: 57.31  E-value: 9.07e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1034571481  94 NIKSFLRSFTKLPHLAGTEQNFLLAKKIQTQWKKFGLDSAKLVHYD 139
Cdd:cd03874    10 KIKEDLEYLSSMPHMAGTKGDAALAKYIENSFKNNGLFEVELEEYS 55
 
Name Accession Description Interval E-value
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
366-620 8.73e-124

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: 371.95  E-value: 8.73e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 366 KVRMHVYNInkitRIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIARSFGKLMSKGWRPRRTIIFAS 445
Cdd:cd08022    50 DVELEEYDV----PIWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFAS 125
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 446 WDAEEFGLLGSTEWAEENVKILQERSIAYINSDSSIEGnYTLRVDCTPLLYQLVYKLTKEIPSPDDGFESKSlyeswlek 525
Cdd:cd08022   126 WDAEEYGLIGSTEWVEENADWLQERAVAYLNVDVAVSG-STLRAAGSPLLQNLLREAAKEVQDPDEGATLKY-------- 196
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 526 DPSPENKNLPRINKLGSGSDFEAYFQRLGIASGRARYTKNKKtdkySSYPVYHTIYETFELVEKFYDPTFKKQLSVAQLR 605
Cdd:cd08022   197 LPSWWDDTGGEIGNLGSGSDYTPFLDHLGIASIDFGFSGGPT----DPYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVW 272
                         250
                  ....*....|....*
gi 1034571481 606 GALVYELVDSKIIPF 620
Cdd:cd08022   273 GLLALRLADDPILPF 287
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
145-371 3.01e-95

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: 295.74  E-value: 3.01e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 145 PNETNANYISIVDEHETEIFKTsYLEPPPDgyenvTNIVPPYNAFSAQGMPEGDLVYVNYARTEDFFKLEReMGINCTGK 224
Cdd:cd02121     1 PVKRSLILTKPDGATGKLIEDT-VLEEPPS-----PDVVPPFHAYSASGNVTAELVYANYGSPEDFEYLED-LGIDVKGK 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 225 IVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPEV---QPYPKGWNLPGTAAQRGNVLNL-NGAGDPLTPGYPAK 300
Cdd:cd02121    74 IVIARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYITGengKTYPDGPARPPSGVQRGSVLFMsIGPGDPLTPGYPSK 153
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034571481 301 EYTFRLDVEEGVGIPRIPVHPIGYNDAEILLRYLGGIAPPDkSWKGALNVSYSIGPgftGSDSFRKVRMHV 371
Cdd:cd02121   154 PGAERRDKEESKGLPKIPSLPISYRDAQPLLKALGGPGAPS-DWQGGLPVTYRLGF---GGPSPGKVRVNL 220
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
652-772 1.06e-42

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


Pssm-ID: 461238  Cd Length: 116  Bit Score: 150.43  E-value: 1.06e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 652 VSFDSLFSAVKNFSEAASDFHKR---LIQVDLNNPIAVRMMNDQLMLLERAFIDPLGLPGKLFYRHIIFAPSSHNKYAGE 728
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWakkWEDIKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGA 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1034571481 729 SFPGIYDAIFDIenkansrlAWKEVKKHISIAAFTIQAAAGTLK 772
Cdd:pfam04253  81 TFPGIRDAIEAG--------DWELAQKQISIVAKAIQSAAETLK 116
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
335-615 7.18e-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: 136.41  E-value: 7.18e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 335 GGIAPPDKSWKGALNVSYSIGPGFTGSDSFRKVRMHVYNINKITRIYNVVGTIRGSVEPDRYVILGGHRDSWVF---GAI 411
Cdd:COG2234     1 ALAAAGGGGGTTAGAAAAAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPDEVVVLGAHYDSVGSigpGAD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 412 DPTSGVAVLQEIARSFGKLmskGWRPRRTIIFASWDAEEFGLLGSTEWAeENVKILQERSIAYINSDSSIEGNYTLRVDc 491
Cdd:COG2234    81 DNASGVAALLELARALAAL---GPKPKRTIRFVAFGAEEQGLLGSRYYA-ENLKAPLEKIVAVLNLDMIGRGGPRNYLY- 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 492 tpllyqlvykLTKEIPSPddgfESKSLYESWLEKDPSPENKNLPRINKLGSGSDFeAYFQRLGIASGRARytknkkTDKY 571
Cdd:COG2234   156 ----------VDGDGGSP----ELADLLEAAAKAYLPGLGVDPPEETGGYGRSDH-APFAKAGIPALFLF------TGAE 214
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1034571481 572 SSYPVYHTIYETFELVekfyDPTFKKQlsVAQLRGALVYELVDS 615
Cdd:COG2234   215 DYHPDYHTPSDTLDKI----DLDALAK--VAQLLAALVYELANA 252
Peptidase_M28 pfam04389
Peptidase family M28;
382-585 1.91e-25

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 104.29  E-value: 1.91e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 382 NVVGTIRGSvEPDRYVILGGHRDSWVF--GAIDPTSGVAVLQEIARSFGKlmskGWRPRRTIIFASWDAEEFGLLGSTEW 459
Cdd:pfam04389   1 NVIAKLPGK-APDEVVLLSAHYDSVGTgpGADDNASGVAALLELARVLAA----GQRPKRSVRFLFFDAEEAGLLGSHHF 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 460 AEENvkILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLTKEIPSPddgfeskslYESWLEKDPSPENkNLPrink 539
Cdd:pfam04389  76 AKSH--PPLKKIRAVINLDMIGSGGPALLFQSGPKGSSLLEKYLKAAAKP---------YGVTLAEDPFQER-GGP---- 139
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1034571481 540 lgSGSDFEAyFQRLGIASGRARYTKNKktdkyssyPVYHTIYETFE 585
Cdd:pfam04389 140 --GRSDHAP-FIKAGIPGLDLAFTDFG--------YRYHTPADTID 174
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
196-286 1.05e-14

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: 70.24  E-value: 1.05e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 196 EGDLV-----YVNYARTEDFfkleremgiNCTGKIVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPE----VQP 266
Cdd:pfam02225   1 TGPLVlapgcYAGDGIPADF---------DVKGKIVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVEGLGGPPgaggNEL 71
                          90       100
                  ....*....|....*....|
gi 1034571481 267 YPKGWNLPGTAAQRGNVLNL 286
Cdd:pfam02225  72 YPDGIYIPAVGVSRADGEAL 91
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
94-139 9.07e-09

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


Pssm-ID: 349871 [Multi-domain]  Cd Length: 278  Bit Score: 57.31  E-value: 9.07e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1034571481  94 NIKSFLRSFTKLPHLAGTEQNFLLAKKIQTQWKKFGLDSAKLVHYD 139
Cdd:cd03874    10 KIKEDLEYLSSMPHMAGTKGDAALAKYIENSFKNNGLFEVELEEYS 55
PRK08262 PRK08262
M20 family peptidase;
406-472 6.25e-04

M20 family peptidase;


Pssm-ID: 236208 [Multi-domain]  Cd Length: 486  Bit Score: 43.01  E-value: 6.25e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034571481 406 WVFGAIDPTSGVAVLQEIARSfgkLMSKGWRPRRTIIFASWDAEEFGLLGstewAEENVKILQERSI 472
Cdd:PRK08262  148 WGRGALDDKGSLVAILEAAEA---LLAQGFQPRRTIYLAFGHDEEVGGLG----ARAIAELLKERGV 207
 
Name Accession Description Interval E-value
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
366-620 8.73e-124

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: 371.95  E-value: 8.73e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 366 KVRMHVYNInkitRIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIARSFGKLMSKGWRPRRTIIFAS 445
Cdd:cd08022    50 DVELEEYDV----PIWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFAS 125
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 446 WDAEEFGLLGSTEWAEENVKILQERSIAYINSDSSIEGnYTLRVDCTPLLYQLVYKLTKEIPSPDDGFESKSlyeswlek 525
Cdd:cd08022   126 WDAEEYGLIGSTEWVEENADWLQERAVAYLNVDVAVSG-STLRAAGSPLLQNLLREAAKEVQDPDEGATLKY-------- 196
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 526 DPSPENKNLPRINKLGSGSDFEAYFQRLGIASGRARYTKNKKtdkySSYPVYHTIYETFELVEKFYDPTFKKQLSVAQLR 605
Cdd:cd08022   197 LPSWWDDTGGEIGNLGSGSDYTPFLDHLGIASIDFGFSGGPT----DPYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVW 272
                         250
                  ....*....|....*
gi 1034571481 606 GALVYELVDSKIIPF 620
Cdd:cd08022   273 GLLALRLADDPILPF 287
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
145-371 3.01e-95

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: 295.74  E-value: 3.01e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 145 PNETNANYISIVDEHETEIFKTsYLEPPPDgyenvTNIVPPYNAFSAQGMPEGDLVYVNYARTEDFFKLEReMGINCTGK 224
Cdd:cd02121     1 PVKRSLILTKPDGATGKLIEDT-VLEEPPS-----PDVVPPFHAYSASGNVTAELVYANYGSPEDFEYLED-LGIDVKGK 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 225 IVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPEV---QPYPKGWNLPGTAAQRGNVLNL-NGAGDPLTPGYPAK 300
Cdd:cd02121    74 IVIARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYITGengKTYPDGPARPPSGVQRGSVLFMsIGPGDPLTPGYPSK 153
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034571481 301 EYTFRLDVEEGVGIPRIPVHPIGYNDAEILLRYLGGIAPPDkSWKGALNVSYSIGPgftGSDSFRKVRMHV 371
Cdd:cd02121   154 PGAERRDKEESKGLPKIPSLPISYRDAQPLLKALGGPGAPS-DWQGGLPVTYRLGF---GGPSPGKVRVNL 220
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
362-619 1.51e-77

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: 251.06  E-value: 1.51e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 362 DSFRKVRMHVYNINKITRIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIARSFGKLMSK-GWRPRRT 440
Cdd:cd03874    39 NSFKNNGLFEVELEEYSPITNVVGKIEGIEQPDRAIIIGAHRDSWGYGAGYPNSGTAVLLEIARLFQQLKKKfGWKPLRT 118
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 441 IIFASWDAEEFGLLGSTEWAEENVKILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLTKEIPSPDDGFESKSLYE 520
Cdd:cd03874   119 IYFISWDGSEFGLAGSTELGEDRKASLKDEVYAYINIDQLVIGNSELDVDAHPLLQSLFRKASKKVKFPGNEDWWKHSPN 198
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 521 swlekdpspenknlPRINKLGSGSDFEAYFQRLGIASGRARYTKNKktdkySSYPVYHTIYETFELVEKFYDPTFKKQLS 600
Cdd:cd03874   199 --------------AKVSNLHQYGDWTPFLNHLGIPVAVFSFKNDR-----NASYPINSSYDTFEWLEKFLDPDFELHST 259
                         250
                  ....*....|....*....
gi 1034571481 601 VAQLRGALVYELVDSKIIP 619
Cdd:cd03874   260 LAEFVGLLVLSLAEDPLLP 278
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
379-621 8.56e-43

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: 156.77  E-value: 8.56e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 379 RIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIARSFGKLMSK-GWRPRRTIIFASWDAEEFGLLGST 457
Cdd:cd09848    55 KIHNIFGVIKGFVEPDRYVVIGAQRDAWGPGAAKSGVGTALLLELARTFSDMVKNdGFKPRRSIVFASWSAGDFGSVGAT 134
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 458 EWAEENVKILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLTKEIPSPDDGfeskslYESWLEKDPSPENKNLpRI 537
Cdd:cd09848   135 EWLEGYLSSLHLKAFTYISLDGAVLGDDSFKASASPLLYTLIESTMKQVKSPVHS------GQSYYETRSSWWASIV-EP 207
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 538 NKLGSGS-DFEAYfqrLGIASGRARYTKNkktdkYSSYPVYHTIYETFELVEKFYDP-TFKKQLSVAQLRGALVYELVDS 615
Cdd:cd09848   208 LGLDSAAyPFLAF---SGIPSVSFHFTED-----DEDYPFLGTKEDTKENLDKFTNGeLWEVAAAAAEVAGQMALRLVHD 279

                  ....*.
gi 1034571481 616 KIIPFN 621
Cdd:cd09848   280 HLLPLD 285
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
652-772 1.06e-42

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


Pssm-ID: 461238  Cd Length: 116  Bit Score: 150.43  E-value: 1.06e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 652 VSFDSLFSAVKNFSEAASDFHKR---LIQVDLNNPIAVRMMNDQLMLLERAFIDPLGLPGKLFYRHIIFAPSSHNKYAGE 728
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWakkWEDIKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGA 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1034571481 729 SFPGIYDAIFDIenkansrlAWKEVKKHISIAAFTIQAAAGTLK 772
Cdd:pfam04253  81 TFPGIRDAIEAG--------DWELAQKQISIVAKAIQSAAETLK 116
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
335-615 7.18e-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: 136.41  E-value: 7.18e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 335 GGIAPPDKSWKGALNVSYSIGPGFTGSDSFRKVRMHVYNINKITRIYNVVGTIRGSVEPDRYVILGGHRDSWVF---GAI 411
Cdd:COG2234     1 ALAAAGGGGGTTAGAAAAAAAAAAAAAGLALLKLKGLLLEAAGGDSRNVIAEIPGTDPPDEVVVLGAHYDSVGSigpGAD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 412 DPTSGVAVLQEIARSFGKLmskGWRPRRTIIFASWDAEEFGLLGSTEWAeENVKILQERSIAYINSDSSIEGNYTLRVDc 491
Cdd:COG2234    81 DNASGVAALLELARALAAL---GPKPKRTIRFVAFGAEEQGLLGSRYYA-ENLKAPLEKIVAVLNLDMIGRGGPRNYLY- 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 492 tpllyqlvykLTKEIPSPddgfESKSLYESWLEKDPSPENKNLPRINKLGSGSDFeAYFQRLGIASGRARytknkkTDKY 571
Cdd:COG2234   156 ----------VDGDGGSP----ELADLLEAAAKAYLPGLGVDPPEETGGYGRSDH-APFAKAGIPALFLF------TGAE 214
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1034571481 572 SSYPVYHTIYETFELVekfyDPTFKKQlsVAQLRGALVYELVDS 615
Cdd:COG2234   215 DYHPDYHTPSDTLDKI----DLDALAK--VAQLLAALVYELANA 252
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
380-585 4.77e-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 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: 114.75  E-value: 4.77e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 380 IYNVVGTIRGSVEPDRYVILGGHRDSWVF--GAIDPTSGVAVLQEIARSFGKLmskGWRPRRTIIFASWDAEEFGLLGST 457
Cdd:cd02690     1 GYNVIATIKGSDKPDEVILIGAHYDSVPLspGANDNASGVAVLLELARVLSKL---QLKPKRSIRFAFWDAEELGLLGSK 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 458 EWAEENvKILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLTKEIpspddgfesKSLYESWLEKDPSPENKNLPRi 537
Cdd:cd02690    78 YYAEQL-LSSLKNIRAALNLDMIGGAGPDLYLQTAPGNDALVEKLLRAL---------AHELENVVYTVVYKEDGGTGG- 146
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 1034571481 538 nklgsgSDFEaYFQRLGIASGRARytknkkTDKYSSYPVYHTIYETFE 585
Cdd:cd02690   147 ------SDHR-PFLARGIPAASLI------QSESYNFPYYHTTQDTLE 181
PA_TfR cd02128
PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This ...
152-371 6.58e-29

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


Pssm-ID: 239043 [Multi-domain]  Cd Length: 183  Bit Score: 114.03  E-value: 6.58e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 152 YISIVDEHETEifktsYLEPPPDGYEnvtnivppynAFSAQGMPEGDLVYVNYARTEDFFKLeREMGINCTGKIVIARYG 231
Cdd:cd02128     1 SVIIGDAGRLN-----ELVENPGGYV----------AYSAAGTVTGKLVYANYGRKKDFEDL-QSVGVSVNGSVVLVRAG 64
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 232 KIFRGNKVKNAMLAGAIGIILYSDPADYfaPEVqpypkgwnlPGTAAQRGNVlNLnGAGDPLTPGYPAKEYTFRLDVEEG 311
Cdd:cd02128    65 KISFAEKVANAEKLGAVGVLIYPDPADF--PID---------PSETALFGHV-HL-GTGDPYTPGFPSFNHTQFPPSQSS 131
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034571481 312 vGIPRIPVHPIGYNDAEILLRYLGG-IAPPDksWKGAlNVSYSIGPgftgsDSFRKVRMHV 371
Cdd:cd02128   132 -GLPNIPAQTISAAAAAKLLSKMGGpVCPSG--WKGG-DSTCRLGT-----SSSKNVKLTV 183
Peptidase_M28 pfam04389
Peptidase family M28;
382-585 1.91e-25

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 104.29  E-value: 1.91e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 382 NVVGTIRGSvEPDRYVILGGHRDSWVF--GAIDPTSGVAVLQEIARSFGKlmskGWRPRRTIIFASWDAEEFGLLGSTEW 459
Cdd:pfam04389   1 NVIAKLPGK-APDEVVLLSAHYDSVGTgpGADDNASGVAALLELARVLAA----GQRPKRSVRFLFFDAEEAGLLGSHHF 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 460 AEENvkILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLTKEIPSPddgfeskslYESWLEKDPSPENkNLPrink 539
Cdd:pfam04389  76 AKSH--PPLKKIRAVINLDMIGSGGPALLFQSGPKGSSLLEKYLKAAAKP---------YGVTLAEDPFQER-GGP---- 139
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1034571481 540 lgSGSDFEAyFQRLGIASGRARYTKNKktdkyssyPVYHTIYETFE 585
Cdd:pfam04389 140 --GRSDHAP-FIKAGIPGLDLAFTDFG--------YRYHTPADTID 174
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
205-506 4.15e-18

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: 87.75  E-value: 4.15e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 205 ARTEDFFKLEREMGiNCTGKIVI-----ARYGK--IFRGNKVKNAMLAGAIGIILYSdpadyfapeVQPYpkGWNLPGTA 277
Cdd:cd03883   109 VVVFSFEELQAKAD-EVKGKIVVynqpfKGYGEtvKYRGQGAVEAAKYGAVAVLIRS---------ITPF--SIYSPHTG 176
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 278 AQRgnvlnlngagdpltpgypakeytfrldveEGVGIPRIPVHPIGYNDAEILLRYlggiappdkswkgalnvsYSIGPg 357
Cdd:cd03883   177 IMR-----------------------------YQDGVTKIPAAAITVEDAEMLSRM------------------AARGQ- 208
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 358 ftgsdsfrKVRMHVYNINKI---TRIYNVVGTIRGSVEPDRYVILGGHRDSWVF--GAIDPTSGVAVLQEIARSFGKLms 432
Cdd:cd03883   209 --------KIVIELKMEAKTypdATSRNVIAEITGSKYPDEVVLVGGHLDSWDVgtGAMDDGGGVAISWEALKLIKDL-- 278
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034571481 433 kGWRPRRTIIFASWDAEEFGLLGSTEWAEENVKILQERSIAyINSDSSIEGNYTLRVDCTP---LLYQLVYKLTKEI 506
Cdd:cd03883   279 -GLKPKRTIRVVLWTGEEQGLVGAKAYAEAHKDELENHVFA-MESDIGTFTPYGLQFTGSDtarAIVKEVMKLLSPL 353
M28_like cd03877
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
381-478 8.17e-17

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: 79.59  E-value: 8.17e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 381 YNVVGTIRGSVEPDRYVILGGHRDSWVF-----------GAIDPTSGVAVLQEIARSFgklmSKGWRPRRTIIFASWDAE 449
Cdd:cd03877     2 HNVVGVLEGSDLPDETIVIGAHYDHLGIgggdsgdkiynGADDNASGVAAVLELARYF----AKQKTPKRSIVFAAFTAE 77
                          90       100
                  ....*....|....*....|....*....
gi 1034571481 450 EFGLLGSTEWAeENVKILQERSIAYINSD 478
Cdd:cd03877    78 EKGLLGSKYFA-ENPKFPLDKIVAMLNLD 105
M28_like cd08015
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
381-479 4.52e-16

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: 78.02  E-value: 4.52e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 381 YNVVGTIRGSVEPDRYVILGGHRDSW--VFGAIDPTSGVAVLQEIARSFGKLMSKgwrPRRTIIFASWDAEEFGLLGSTE 458
Cdd:cd08015     2 YNVIAEIPGSDKKDEVVILGAHLDSWhgATGATDNGAGTAVMMEAMRILKAIGSK---PKRTIRVALWGSEEQGLHGSRA 78
                          90       100
                  ....*....|....*....|....*....
gi 1034571481 459 WAE---ENVKILQERSI-----AYINSDS 479
Cdd:cd08015    79 YVEkhfGDPPTMQLQRDhkkisAYFNLDN 107
M28_like_PA cd05660
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ...
356-479 1.07e-15

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: 78.17  E-value: 1.07e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 356 PGFTGSDSFRKVRMhVYNINKITRiYNVVGTIRGSVEPDRYVILGGHRDSW----------VF-GAIDPTSGVAVLQEIA 424
Cdd:cd05660    37 PAGSDGSYLQAVPL-VSKIEYSTS-HNVVAILPGSKLPDEYIVLSAHWDHLgigppiggdeIYnGAVDNASGVAAVLELA 114
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034571481 425 RSFGKlmsKGWRPRRTIIFASWDAEEFGLLGSTEWAE-ENVKIlqERSIAYINSDS 479
Cdd:cd05660   115 RVFAA---QDQRPKRSIVFLAVTAEEKGLLGSRYYAAnPIFPL--DKIVANLNIDM 165
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
180-336 1.86e-15

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: 73.32  E-value: 1.86e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 180 TNIVPPYNAFSAQGMPEGDLVYVNYARTEDFfkleremGINCTGKIVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADy 259
Cdd:cd00538    11 GSALLFNPPSSPVGVVAGPLVGCGYGTTDDS-------GADVKGKIVLVRRGGCSFSEKVKNAQKAGAKAVIIYNNGDD- 82
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034571481 260 fapevqPYPKGWNlpgtaaqrgnvlnlngagdpltpgypakeytfrldVEEGVGIPRIPVHPIGYNDAEILLRYLGG 336
Cdd:cd00538    83 ------PGPQMGS-----------------------------------VGLESTDPSIPTVGISYADGEALLSLLEA 118
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
196-286 1.05e-14

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: 70.24  E-value: 1.05e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 196 EGDLV-----YVNYARTEDFfkleremgiNCTGKIVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPE----VQP 266
Cdd:pfam02225   1 TGPLVlapgcYAGDGIPADF---------DVKGKIVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVEGLGGPPgaggNEL 71
                          90       100
                  ....*....|....*....|
gi 1034571481 267 YPKGWNLPGTAAQRGNVLNL 286
Cdd:pfam02225  72 YPDGIYIPAVGVSRADGEAL 91
M28_like cd05642
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
378-461 7.59e-14

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


Pssm-ID: 349894 [Multi-domain]  Cd Length: 347  Bit Score: 73.68  E-value: 7.59e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 378 TRIYNVVGTIRGSVEPDRYVILGGHRDSWVF----------GAIDPTSGVAVLQEIARSFGKlmskgWRPRRTIIFASWD 447
Cdd:cd05642    86 VNISNVVATLKGSEDPDRVYVVSGHYDSRVSdvmdyesdapGANDDASGVAVSMELARIFAK-----HRPKATIVFTAVA 160
                          90
                  ....*....|....
gi 1034571481 448 AEEFGLLGSTEWAE 461
Cdd:cd05642   161 GEEQGLYGSTFLAQ 174
PA_hNAALADL2_like cd02131
PA_hNAALADL2_like: Protease-associated domain containing proteins like human N-acetylated ...
185-347 7.59e-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: 66.88  E-value: 7.59e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 185 PYNAFSAQGMPEGDLVYVNYARTEDFFKLEREMgiNCTGKIVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADyfapev 264
Cdd:cd02131     5 SYAAYSAKGTLQAEVVDVQYGSVEDLRRIRDNM--NVTNQIALLKLGQAPLLYKLSLLEEAGFGGVLLYVDPCD------ 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 265 qpYPKGWNLpgtaAQRGNVLNLNGAGDPLTPGYPAKEYTFRldvEEGVGIPRIPVHPIGYNDAEILLRylggiAPPDKSW 344
Cdd:cd02131    77 --LPKTRHT----WHQAFMVSLNPGGDPSTPGYPSADQSCR---QCRGNLTSLLVQPISAYLAKKLLS-----APPSRRK 142

                  ...
gi 1034571481 345 KGA 347
Cdd:cd02131   143 EGS 145
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
381-467 7.97e-12

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: 66.50  E-value: 7.97e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 381 YNVVGTIRGSVEPDRYVILGGHRDS---WVF------GAIDPTSGVAVLQEIARSfgkLMSKGWRPRRTIIFASWDAEEF 451
Cdd:cd03879    75 PSIIATIPGSEKSDEIVVIGAHQDSingSNPsngrapGADDDGSGTVTILEALRV---LLESGFQPKNTIEFHWYAAEEG 151
                          90       100
                  ....*....|....*....|
gi 1034571481 452 GLLGS----TEWAEENVKIL 467
Cdd:cd03879   152 GLLGSqaiaTQYKSEGKNVK 171
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
358-476 1.35e-11

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: 66.46  E-value: 1.35e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 358 FTGSDSFRKVRMHVYNINKITRIYNVVGTIRGSV-EPDRYVILGGHRDSWV--FGAIDPTSGVAVLQEIARSFGKlmsKG 434
Cdd:cd03875    57 QDDTGSGSFNFLSSGMTLVYFEVTNIVVRISGKNsNSLPALLLNAHFDSVPtsPGATDDGMGVAVMLEVLRYLSK---SG 133
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1034571481 435 WRPRRTIIFASWDAEEFGLLGST-----EWAEENVKilqersiAYIN 476
Cdd:cd03875   134 HQPKRDIIFLFNGAEENGLLGAHafitqHPWAKNVR-------AFIN 173
M28_SGAP_like cd03876
M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family ...
381-558 8.33e-10

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: 60.77  E-value: 8.33e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 381 YNVVGTIRGSvEPDRYVILGGHRDSwVF---GAIDPTSGVAVLQEIARSFGKlmskgWRPRRTIIFASWDAEEFGLLGST 457
Cdd:cd03876    64 YNVIAETKGG-DPNNVVMLGAHLDS-VSagpGINDNGSGSAALLEVALALAK-----FKVKNAVRFAWWTAEEFGLLGSK 136
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 458 EWA-----EENVKILqersiAYINSD---SSIEGNYTLRVDCTpllyqlvyklTKEIPSPDDGFESKSLYESWLEKdpsp 529
Cdd:cd03876   137 FYVnnlssEERSKIR-----LYLNFDmiaSPNYGYFIYDGDGS----------AFNLTGPPGSAEIERLFEAYFTS---- 197
                         170       180       190
                  ....*....|....*....|....*....|
gi 1034571481 530 enKNLPRINKLGSG-SDFEAyFQRLGIASG 558
Cdd:cd03876   198 --LGLPSTPTEFDGrSDYAP-FIEAGIPAG 224
M28_like_PA cd05661
M28 Zn-peptidase containing a PA domain insert; Peptidase family M28 (also called ...
381-611 5.80e-09

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


Pssm-ID: 349911 [Multi-domain]  Cd Length: 262  Bit Score: 57.58  E-value: 5.80e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 381 YNVVGTIR--GSVEPDRYVILGGHRDSWVF--GAIDPTSGVAVLQEIARSFGKLMSKgwrprRTIIFASWDAEEFGLLGS 456
Cdd:cd05661    61 HNVIATKKpdNNKNNNDIIIVTSHYDSVVKapGANDNASGTAVTLELARVFKKVKTD-----KELRFIAFGAEENGLLGS 135
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 457 TEWAEENVKILQERSIAYIN------SDSSIEGNYTLRVDCTPllyQLVYKLTKEipspddgfeskslyeswlekdpspE 530
Cdd:cd05661   136 KYYVASLSEDEIKRTIGVFNldmvgtSDAKAGDLYAYTIDGKP---NLVTDSGAA------------------------A 188
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 531 NKNLPRINKLGSG--SDFEAyFQRLGIASgrARYTKNKKTDKYSSyPVYHTIYETFELVEKfydptfKKQLSVAQLRGAL 608
Cdd:cd05661   189 SKRLSGVLPLVQQgsSDHVP-FHEAGIPA--ALFIHMDPETEPVE-PWYHTPNDTVENISK------ERLDNALDIVGTA 258

                  ...
gi 1034571481 609 VYE 611
Cdd:cd05661   259 VYQ 261
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
94-139 9.07e-09

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


Pssm-ID: 349871 [Multi-domain]  Cd Length: 278  Bit Score: 57.31  E-value: 9.07e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1034571481  94 NIKSFLRSFTKLPHLAGTEQNFLLAKKIQTQWKKFGLDSAKLVHYD 139
Cdd:cd03874    10 KIKEDLEYLSSMPHMAGTKGDAALAKYIENSFKNNGLFEVELEEYS 55
M28_like cd05640
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
382-462 1.85e-08

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: 56.30  E-value: 1.85e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 382 NVVGTIRGSVEPDRYVILGGHRDSW--VFGAIDPTSGVAVLQEIARSFGKLmskgwRPRRTIIFASWDAEEF-----GLL 454
Cdd:cd05640    54 NLIADLPGSYSQDKLILIGAHYDTVpgSPGADDNASGVAALLELARLLATL-----DPNHTLRFVAFDLEEYpffarGLM 128

                  ....*...
gi 1034571481 455 GSTEWAEE 462
Cdd:cd05640   129 GSHAYAED 136
M28_like_PA_PDZ_associated cd05663
M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ ...
382-478 1.93e-08

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


Pssm-ID: 349913 [Multi-domain]  Cd Length: 266  Bit Score: 56.31  E-value: 1.93e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 382 NVVGTI-RGSVEPDRYVILGGHRDSWVFG----------------AIDPTSGVAVLQEIARSFGKLMSKGWRPRRtIIFA 444
Cdd:cd05663    57 NVIGVLpGKGDVADETVVVGAHYDHLGYGgegslargdeslihngADDNASGVAAMLELAAKLVDSDTSLALSRN-LVFI 135
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1034571481 445 SWDAEEFGLLGSTEWAeENVKILQERSIAYINSD 478
Cdd:cd05663   136 AFSGEELGLLGSKHFV-KNPPFPIKNTVYMINMD 168
M28_like cd05662
M28 Zn-Peptidases; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized ...
382-478 4.05e-08

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


Pssm-ID: 349912 [Multi-domain]  Cd Length: 268  Bit Score: 55.17  E-value: 4.05e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 382 NVVGTIRGSVEPDRYVILGGHRD------SWVF-GAIDPTSGVAVLQEIARSFgklmsKGWRPRRTIIFASWDAEEFGLL 454
Cdd:cd05662    64 NVLAVIKGSEPPTKWRVVSAHYDhlgirgGKIYnGADDNASGVAALLALAEYF-----KKHPPKHNVIFAATDAEEPGLR 138
                          90       100
                  ....*....|....*....|....*
gi 1034571481 455 GSTEWAEEnvKILQERSIAY-INSD 478
Cdd:cd05662   139 GSYAFVEA--LKVPRAQIELnINLD 161
PA_C5a_like cd02133
PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a ...
198-253 8.04e-06

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


Pssm-ID: 239048 [Multi-domain]  Cd Length: 143  Bit Score: 46.13  E-value: 8.04e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034571481 198 DLVYVNYARTEDFFKLEREmginctGKIV-IARyGKIFRGNKVKNAMLAGAIGIILY 253
Cdd:cd02133    29 ELVDAGLGTPEDFEGKDVK------GKIAlIQR-GEITFVEKIANAKAAGAVGVIIY 78
PRK08262 PRK08262
M20 family peptidase;
406-472 6.25e-04

M20 family peptidase;


Pssm-ID: 236208 [Multi-domain]  Cd Length: 486  Bit Score: 43.01  E-value: 6.25e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034571481 406 WVFGAIDPTSGVAVLQEIARSfgkLMSKGWRPRRTIIFASWDAEEFGLLGstewAEENVKILQERSI 472
Cdd:PRK08262  148 WGRGALDDKGSLVAILEAAEA---LLAQGFQPRRTIYLAFGHDEEVGGLG----ARAIAELLKERGV 207
PA_M28_1_3 cd04822
PA_M28_1_3: Protease-associated (PA) domain, peptidase family M28, subfamily-1, subgroup 3. A ...
188-294 6.50e-04

PA_M28_1_3: Protease-associated (PA) domain, peptidase family M28, subfamily-1, subgroup 3. A subgroup 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 subgroups; relatively little is known about proteins in this subgroup.


Pssm-ID: 240126 [Multi-domain]  Cd Length: 151  Bit Score: 40.90  E-value: 6.50e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 188 AFSAQGMPEGDLVYVNYARTEDFFKLEREMGINCTGKIV-IARY-------GKIFRGN----------KVKNAMLAGAIG 249
Cdd:cd04822    13 AFSRSGAVTAPVVFAGYGITAPELGYDDYAGLDVKGKIVlVLRHepqeddaNSRFNGPgltrhaglryKATNARRHGAAA 92
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1034571481 250 IILYSDPAD--YFAPEVQPYPkGWNLP--GTAAQRGNVLNLNGAGDPLT 294
Cdd:cd04822    93 VIVVNGPNShsGDADRLPRFG-GTAPQrvDIAAADPWFTAAEAAGKDLT 140
PA_subtilisin_like cd02120
PA_subtilisin_like: Protease-associated domain containing subtilisin-like proteases. This ...
222-258 1.35e-03

PA_subtilisin_like: Protease-associated domain containing subtilisin-like proteases. This group contains various PA domain-containing subtilisin-like proteases including melon cucumisin, Arabidopsis thaliana Ara12, a nodule specific serine protease from Alnus glutinosa ag12, members of the tomato P69 family, and tomato LeSBT2. These proteins belong to the peptidase S8 family. Cucumisin from the juice of melon fruits is a thermostable serine peptidase, with a broad substrate specificity for oligopeptides and proteins. A. thaliana Ara12 is a thermostable, extracellular serine protease, found chiefly in silique tissue and stem tissue. Ara12 is stimulated by Ca2+ ions. A. glutinosa ag12 is expressed at high levels in the nodules, and at low levels in the shoot tips; it is implicated in both symbiotic and non-symbiotic processes in plant development. The tomato P69 protease family is comprised of various protein isoforms of approximately 69KDa. These isoforms accumulate extracellularly. Some of the P69 genes are tightly regulated in a tissue specific fashion, and by environmental and developmental signals. For example: infection with avirulent bacteria activates transcription of the genes for the P69 B and C isoforms, the P69 E transcript was detected only in roots, and the P69F transcript only in hydathodes. The Tomato LeSBT2 subtilase transcript was not detected in flowers and roots, but was present in cotyledons and leaves. 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: 239035 [Multi-domain]  Cd Length: 126  Bit Score: 39.32  E-value: 1.35e-03
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1034571481 222 TGKIVIARYGKIF-RGNKVKNAMLAGAIGIILYSDPAD 258
Cdd:cd02120    51 KGKIVLCDRGGNTsRVAKGDAVKAAGGAGMILANDPTD 88
PRK09133 PRK09133
hypothetical protein; Provisional
382-498 1.96e-03

hypothetical protein; Provisional


Pssm-ID: 236388 [Multi-domain]  Cd Length: 472  Bit Score: 41.53  E-value: 1.96e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 382 NVVGTIRGSvEPDRYVILGGH-------RDSWV---F------------GAIDPTSGVAVLqeIArSFGKLMSKGWRPRR 439
Cdd:PRK09133   90 NLVARLRGT-DPKKPILLLAHmdvveakREDWTrdpFklveengyfygrGTSDDKADAAIW--VA-TLIRLKREGFKPKR 165
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034571481 440 TIIFASWDAEEFGLLGSTEWAEENVKILQERSIAyINSDssieGNYTLRVDCTPLLYQL 498
Cdd:PRK09133  166 DIILALTGDEEGTPMNGVAWLAENHRDLIDAEFA-LNEG----GGGTLDEDGKPVLLTV 219
Zinc_peptidase_like cd03873
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ...
382-462 3.10e-03

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: 39.72  E-value: 3.10e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 382 NVVGTIRGSvEPDRYVILGGHRDS-------WVF----------------GAIDPTSGVAVLQEIARSFGKlmsKGWRPR 438
Cdd:cd03873     1 NLIARLGGG-EGGKSVALGAHLDVvpagegdNRDppfaedteeegrlygrGALDDKGGVAAALEALKRLKE---NGFKPK 76
                          90       100
                  ....*....|....*....|....
gi 1034571481 439 RTIIFASWDAEEFGLLGSTEWAEE 462
Cdd:cd03873    77 GTIVVAFTADEEVGSGGGKGLLSK 100
M28_nicalin_like cd03882
M28 Zn-Peptidase Nicalin, Nicastrin-like protein; Peptidase M28 family, Nicalin ...
374-514 8.05e-03

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: 349878  Cd Length: 296  Bit Score: 38.89  E-value: 8.05e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034571481 374 INKITRIYNVVG--TIRGSVEPDRYVILGGHRDSwvFGAI-------DPT-SGVAVLQEIARSFGKLMS-KGWRPRRTII 442
Cdd:cd03882    67 AISDWKITTIEGrlTGLGDGEKLPTIVIVAHYDT--FGVApwlssgaDSNgSGVAALLELMRLFSRLYSnPRTRAKYNLL 144
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034571481 443 FASWDAEEFGLLGSTEWAEENVKILQErSIAY---INSDSSIEGNYTLRVDCTP----LLYQLVYKLTKEIPSPDDGFE 514
Cdd:cd03882   145 FLLTGGGKLNYQGTKHWLESNLDHFLD-NVEFvlcLDSIGSKDSDLYLHVSKPPkegtHIQQFLEELKSVAKAPDKNLT 222
 
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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