NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|50287391|ref|XP_446125|]
View 

uncharacterized protein GVI51_F03267 [Nakaseomyces glabratus]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

Name Accession Description Interval E-value
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
150-599 1.93e-74

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: 242.59  E-value: 1.93e-74
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 150 YARRSVDLSKLEKDWEYLSSMPHSSGTRSDMALSEFIHDTFKNNGISLLEKYQYetlvnypgssylsikvgekvlnfelt 229
Cdd:cd03874   1 YARKLVDLAKIKEDLEYLSSMPHMAGTKGDAALAKYIENSFKNNGLFEVELEEY-------------------------- 54
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 230 ednfnplspngevkdarlvdggygtlkeledlknggnlhsnfvlllkygnvvseqvlaaqkygasgilfvsnswndnndi 309
Cdd:cd03874     --------------------------------------------------------------------------------
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 310 vekrsvalpqyglgnplkpswdrnpadpnspqarpsipsipisnkqgnellslindksvsvtaslkvdavikeeQPIVDI 389
Cdd:cd03874  55 --------------------------------------------------------------------------SPITNV 60
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 390 IAKINGNEQADRSIIIMASRNSIDNGAAYPNSGTASLLSLVQLMQELRYKFNWEPLRSIYFISIGGSEFNSAGAAELIKE 469
Cdd:cd03874  61 VGKIEGIEQPDRAIIIGAHRDSWGYGAGYPNSGTAVLLEIARLFQQLKKKFGWKPLRTIYFISWDGSEFGLAGSTELGED 140
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 470 KYQSIIDGVYSIIDISEFNVWdsSKELNIETHPLLFSLFNEEEVKRGY-----------NLDVHSVHHYGDWVPYLAA-G 537
Cdd:cd03874 141 RKASLKDEVYAYINIDQLVIG--NSELDVDAHPLLQSLFRKASKKVKFpgnedwwkhspNAKVSNLHQYGDWTPFLNHlG 218
                       410       420       430       440       450       460
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 50287391 538 VPVTVLTSKSLRTKSAPIFTKEDTYSAFKDSFEKaaKEGIIHDNLLFLVNLVLQVGDKPLIP 599
Cdd:cd03874 219 IPVAVFSFKNDRNASYPINSSYDTFEWLEKFLDP--DFELHSTLAEFVGLLVLSLAEDPLLP 278
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
226-372 1.50e-17

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: 79.48  E-value: 1.50e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 226 FELTEDNFNPLSPNGEVKDARLVDGGYGTLKELedlkngGNLHSNFVLLLKYGNV-VSEQVLAAQKYGASGILFVSNSWN 304
Cdd:cd00538   9 YAGSALLFNPPSSPVGVVAGPLVGCGYGTTDDS------GADVKGKIVLVRRGGCsFSEKVKNAQKAGAKAVIIYNNGDD 82
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 50287391 305 DnndivekrsvaLPQYGlgnplkpswdrnpaDPNSPQARPSIPSIPISNKQGNELLSLIN-DKSVSVTA 372
Cdd:cd00538  83 P-----------GPQMG--------------SVGLESTDPSIPTVGISYADGEALLSLLEaGKTVTVDL 126
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
624-751 4.86e-16

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: 74.54  E-value: 4.86e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391   624 LDLMHVMSGMSSWMAIGKQWAEGVEAWKVVviehdggFEPTLiyLDRTQWNIQVSNVARYLVSWEGVPGRAHYRNLFLGP 703
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWAKKWEDI-------KEPDL--LAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAP 71
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 50287391   704 ELWTqlddDEKSWVLPGLKDLLHNGQIDEANDHLKLIGKVLNDAAVMF 751
Cdd:pfam04253  72 GLWT----GYAGATFPGIRDAIEAGDWELAQKQISIVAKAIQSAAETL 115
 
Name Accession Description Interval E-value
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
150-599 1.93e-74

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: 242.59  E-value: 1.93e-74
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 150 YARRSVDLSKLEKDWEYLSSMPHSSGTRSDMALSEFIHDTFKNNGISLLEKYQYetlvnypgssylsikvgekvlnfelt 229
Cdd:cd03874   1 YARKLVDLAKIKEDLEYLSSMPHMAGTKGDAALAKYIENSFKNNGLFEVELEEY-------------------------- 54
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 230 ednfnplspngevkdarlvdggygtlkeledlknggnlhsnfvlllkygnvvseqvlaaqkygasgilfvsnswndnndi 309
Cdd:cd03874     --------------------------------------------------------------------------------
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 310 vekrsvalpqyglgnplkpswdrnpadpnspqarpsipsipisnkqgnellslindksvsvtaslkvdavikeeQPIVDI 389
Cdd:cd03874  55 --------------------------------------------------------------------------SPITNV 60
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 390 IAKINGNEQADRSIIIMASRNSIDNGAAYPNSGTASLLSLVQLMQELRYKFNWEPLRSIYFISIGGSEFNSAGAAELIKE 469
Cdd:cd03874  61 VGKIEGIEQPDRAIIIGAHRDSWGYGAGYPNSGTAVLLEIARLFQQLKKKFGWKPLRTIYFISWDGSEFGLAGSTELGED 140
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 470 KYQSIIDGVYSIIDISEFNVWdsSKELNIETHPLLFSLFNEEEVKRGY-----------NLDVHSVHHYGDWVPYLAA-G 537
Cdd:cd03874 141 RKASLKDEVYAYINIDQLVIG--NSELDVDAHPLLQSLFRKASKKVKFpgnedwwkhspNAKVSNLHQYGDWTPFLNHlG 218
                       410       420       430       440       450       460
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 50287391 538 VPVTVLTSKSLRTKSAPIFTKEDTYSAFKDSFEKaaKEGIIHDNLLFLVNLVLQVGDKPLIP 599
Cdd:cd03874 219 IPVAVFSFKNDRNASYPINSSYDTFEWLEKFLDP--DFELHSTLAEFVGLLVLSLAEDPLLP 278
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
226-372 1.50e-17

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: 79.48  E-value: 1.50e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 226 FELTEDNFNPLSPNGEVKDARLVDGGYGTLKELedlkngGNLHSNFVLLLKYGNV-VSEQVLAAQKYGASGILFVSNSWN 304
Cdd:cd00538   9 YAGSALLFNPPSSPVGVVAGPLVGCGYGTTDDS------GADVKGKIVLVRRGGCsFSEKVKNAQKAGAKAVIIYNNGDD 82
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 50287391 305 DnndivekrsvaLPQYGlgnplkpswdrnpaDPNSPQARPSIPSIPISNKQGNELLSLIN-DKSVSVTA 372
Cdd:cd00538  83 P-----------GPQMG--------------SVGLESTDPSIPTVGISYADGEALLSLLEaGKTVTVDL 126
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
624-751 4.86e-16

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: 74.54  E-value: 4.86e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391   624 LDLMHVMSGMSSWMAIGKQWAEGVEAWKVVviehdggFEPTLiyLDRTQWNIQVSNVARYLVSWEGVPGRAHYRNLFLGP 703
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWAKKWEDI-------KEPDL--LAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAP 71
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 50287391   704 ELWTqlddDEKSWVLPGLKDLLHNGQIDEANDHLKLIGKVLNDAAVMF 751
Cdd:pfam04253  72 GLWT----GYAGATFPGIRDAIEAGDWELAQKQISIVAKAIQSAAETL 115
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
389-540 2.60e-07

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: 52.44  E-value: 2.60e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 389 IIAKINGNEQADRSIIIMA---SRNSIDNGAAYPNSGTASLLSLVQLMQELRYKFNweplRSIYFISIGGSEFNSAGAAE 465
Cdd:COG2234  49 VIAEIPGTDPPDEVVVLGAhydSVGSIGPGADDNASGVAALLELARALAALGPKPK----RTIRFVAFGAEEQGLLGSRY 124
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 466 LIKEKYQSIIDGVYSI-ID-ISEFNVWDS----SKELNIETHPLLFSLFNEEEVKRGYNLDVHSVHHYG-DWVPYLAAGV 538
Cdd:COG2234 125 YAENLKAPLEKIVAVLnLDmIGRGGPRNYlyvdGDGGSPELADLLEAAAKAYLPGLGVDPPEETGGYGRsDHAPFAKAGI 204

                ..
gi 50287391 539 PV 540
Cdd:COG2234 205 PA 206
 
Name Accession Description Interval E-value
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
150-599 1.93e-74

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: 242.59  E-value: 1.93e-74
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 150 YARRSVDLSKLEKDWEYLSSMPHSSGTRSDMALSEFIHDTFKNNGISLLEKYQYetlvnypgssylsikvgekvlnfelt 229
Cdd:cd03874   1 YARKLVDLAKIKEDLEYLSSMPHMAGTKGDAALAKYIENSFKNNGLFEVELEEY-------------------------- 54
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 230 ednfnplspngevkdarlvdggygtlkeledlknggnlhsnfvlllkygnvvseqvlaaqkygasgilfvsnswndnndi 309
Cdd:cd03874     --------------------------------------------------------------------------------
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 310 vekrsvalpqyglgnplkpswdrnpadpnspqarpsipsipisnkqgnellslindksvsvtaslkvdavikeeQPIVDI 389
Cdd:cd03874  55 --------------------------------------------------------------------------SPITNV 60
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 390 IAKINGNEQADRSIIIMASRNSIDNGAAYPNSGTASLLSLVQLMQELRYKFNWEPLRSIYFISIGGSEFNSAGAAELIKE 469
Cdd:cd03874  61 VGKIEGIEQPDRAIIIGAHRDSWGYGAGYPNSGTAVLLEIARLFQQLKKKFGWKPLRTIYFISWDGSEFGLAGSTELGED 140
                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 470 KYQSIIDGVYSIIDISEFNVWdsSKELNIETHPLLFSLFNEEEVKRGY-----------NLDVHSVHHYGDWVPYLAA-G 537
Cdd:cd03874 141 RKASLKDEVYAYINIDQLVIG--NSELDVDAHPLLQSLFRKASKKVKFpgnedwwkhspNAKVSNLHQYGDWTPFLNHlG 218
                       410       420       430       440       450       460
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 50287391 538 VPVTVLTSKSLRTKSAPIFTKEDTYSAFKDSFEKaaKEGIIHDNLLFLVNLVLQVGDKPLIP 599
Cdd:cd03874 219 IPVAVFSFKNDRNASYPINSSYDTFEWLEKFLDP--DFELHSTLAEFVGLLVLSLAEDPLLP 278
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
226-372 1.50e-17

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: 79.48  E-value: 1.50e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 226 FELTEDNFNPLSPNGEVKDARLVDGGYGTLKELedlkngGNLHSNFVLLLKYGNV-VSEQVLAAQKYGASGILFVSNSWN 304
Cdd:cd00538   9 YAGSALLFNPPSSPVGVVAGPLVGCGYGTTDDS------GADVKGKIVLVRRGGCsFSEKVKNAQKAGAKAVIIYNNGDD 82
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 50287391 305 DnndivekrsvaLPQYGlgnplkpswdrnpaDPNSPQARPSIPSIPISNKQGNELLSLIN-DKSVSVTA 372
Cdd:cd00538  83 P-----------GPQMG--------------SVGLESTDPSIPTVGISYADGEALLSLLEaGKTVTVDL 126
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
624-751 4.86e-16

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: 74.54  E-value: 4.86e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391   624 LDLMHVMSGMSSWMAIGKQWAEGVEAWKVVviehdggFEPTLiyLDRTQWNIQVSNVARYLVSWEGVPGRAHYRNLFLGP 703
Cdd:pfam04253   1 LSLEPLRKAIEKFKKAAKEFDAWAKKWEDI-------KEPDL--LAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAP 71
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 50287391   704 ELWTqlddDEKSWVLPGLKDLLHNGQIDEANDHLKLIGKVLNDAAVMF 751
Cdd:pfam04253  72 GLWT----GYAGATFPGIRDAIEAGDWELAQKQISIVAKAIQSAAETL 115
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
233-368 1.43e-13

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: 70.40  E-value: 1.43e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 233 FNPLSPNGEVKdARLVDGGYGTLKELEDLKNGG-NLHSNFVLLLKYGNVVSEQVLAAQKYGASGILFVS----------- 300
Cdd:cd02121  36 FHAYSASGNVT-AELVYANYGSPEDFEYLEDLGiDVKGKIVIARYGGIFRGLKVKNAQLAGAVGVIIYSdpaddgyitge 114
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 301 ------NSWNDNNDIVEKRSVALPQYGLGNPLKPSWdrnPADPNSPQAR-------PSIPSIPISNKQGNELLSLINDKS 367
Cdd:cd02121 115 ngktypDGPARPPSGVQRGSVLFMSIGPGDPLTPGY---PSKPGAERRDkeeskglPKIPSLPISYRDAQPLLKALGGPG 191

                .
gi 50287391 368 V 368
Cdd:cd02121 192 A 192
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
382-563 5.25e-13

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: 70.10  E-value: 5.25e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 382 EEQPIVDIIAKINGNEQADRSIIIMASRNSIDNGAAYPNSGTASLLSLVQLMQELRYKFNWEPLRSIYFISIGGSEFNSA 461
Cdd:cd09848  52 EHYKIHNIFGVIKGFVEPDRYVVIGAQRDAWGPGAAKSGVGTALLLELARTFSDMVKNDGFKPRRSIVFASWSAGDFGSV 131
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 462 GAAELIkEKYQSIID-GVYSIIDISEFNVWDSSkeLNIETHPLLFSLFneEEVKRGYNLDVHSVHHY-----GDWV---- 531
Cdd:cd09848 132 GATEWL-EGYLSSLHlKAFTYISLDGAVLGDDS--FKASASPLLYTLI--ESTMKQVKSPVHSGQSYyetrsSWWAsive 206
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 50287391 532 ---------PYLA-AGVPVTVLTSKSLRTKSAPIFTKEDTYS 563
Cdd:cd09848 207 plgldsaayPFLAfSGIPSVSFHFTEDDEDYPFLGTKEDTKE 248
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
383-469 2.18e-12

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: 68.41  E-value: 2.18e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 383 EQPIVDIIAKINGNEQADRSIIIMASRNSIDNGAAYPNSGTASLLSLVQLMQELRyKFNWEPLRSIYFISIGGSEFNSAG 462
Cdd:cd08022  57 DVPIWNVIGTIRGSEEPDEYIILGNHRDAWVFGAGDPNSGTAVLLEVARALGTLL-KKGWRPRRTIIFASWDAEEYGLIG 135

                ....*..
gi 50287391 463 AAELIKE 469
Cdd:cd08022 136 STEWVEE 142
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
389-540 2.60e-07

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: 52.44  E-value: 2.60e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 389 IIAKINGNEQADRSIIIMA---SRNSIDNGAAYPNSGTASLLSLVQLMQELRYKFNweplRSIYFISIGGSEFNSAGAAE 465
Cdd:COG2234  49 VIAEIPGTDPPDEVVVLGAhydSVGSIGPGADDNASGVAALLELARALAALGPKPK----RTIRFVAFGAEEQGLLGSRY 124
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 466 LIKEKYQSIIDGVYSI-ID-ISEFNVWDS----SKELNIETHPLLFSLFNEEEVKRGYNLDVHSVHHYG-DWVPYLAAGV 538
Cdd:COG2234 125 YAENLKAPLEKIVAVLnLDmIGRGGPRNYlyvdGDGGSPELADLLEAAAKAYLPGLGVDPPEETGGYGRsDHAPFAKAGI 204

                ..
gi 50287391 539 PV 540
Cdd:COG2234 205 PA 206
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
388-573 7.79e-06

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: 47.34  E-value: 7.79e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 388 DIIAKINGNEQADRSIIIMASRNS-------IDNGaaypnSGTASLLSLVQLMQELRYKFNweplRSIYFISIGGSEFNS 460
Cdd:cd02690   3 NVIATIKGSDKPDEVILIGAHYDSvplspgaNDNA-----SGVAVLLELARVLSKLQLKPK----RSIRFAFWDAEELGL 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 461 AGAAELIkEKYQSIIDGVYSIIDISefNVWDSSKELNIETHPLLFSLFNE--EEVKRGYNLDVHSVHHY-------GDWV 531
Cdd:cd02690  74 LGSKYYA-EQLLSSLKNIRAALNLD--MIGGAGPDLYLQTAPGNDALVEKllRALAHELENVVYTVVYKedggtggSDHR 150
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 50287391 532 PYLAAGVPVTVLTskslRTKSAP---IFTKEDTYSAFKDSFEKAA 573
Cdd:cd02690 151 PFLARGIPAASLI----QSESYNfpyYHTTQDTLENIDKDTLKRA 191
PA_TfR cd02128
PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This ...
220-361 1.21e-05

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: 46.62  E-value: 1.21e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 220 GEKVLNFElTEDNFNPLSPNGEVKdARLVDGGYGTLKELEDLKNGGNLHSNFVLLLKYG-NVVSEQVLAAQKYGASGILF 298
Cdd:cd02128   8 GRLNELVE-NPGGYVAYSAAGTVT-GKLVYANYGRKKDFEDLQSVGVSVNGSVVLVRAGkISFAEKVANAEKLGAVGVLI 85
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 50287391 299 VSNSWN---DNNDIVEKRSVALpqyGLGNPLKP---SWDRNPADPNSPQARPSIPSIPISNKQGNELLS 361
Cdd:cd02128  86 YPDPADfpiDPSETALFGHVHL---GTGDPYTPgfpSFNHTQFPPSQSSGLPNIPAQTISAAAAAKLLS 151
PA_2 cd04819
PA_2: Protease-associated (PA) domain subgroup 2. A subgroup of PA-domain containing proteins. ...
234-366 2.35e-04

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 [Multi-domain]  Cd Length: 127  Bit Score: 41.61  E-value: 2.35e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50287391 234 NPLSPNGEVKdARLVDGGYGTLKELEDLknggNLHSNFVLLLKYGNVVS--EQVLAAQKYGASGILFVsnswnDNNDIVe 311
Cdd:cd04819  15 LPRSPSGEAK-GEPVDAGYGLPKDFDGL----DLEGKIAVVKRDDPDVDrkEKYAKAVAAGAAAFVVV-----NTVPGV- 83
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 50287391 312 krsvaLPQYGlgnplkpswdrnpADPNSPQARPSIPSIPISNKQGNELLSLINDK 366
Cdd:cd04819  84 -----LPATG-------------DEGTEDGPPSPIPAASVSGEDGLRLARVAERN 120
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH
HHS Vulnerability Disclosure