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Conserved domains on  [gi|2361082295|emb|CAI4551087|]
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BAL_1a_G0030330.mRNA.1.CDS.1 [Saccharomyces cerevisiae]

Protein Classification

Graphical summary

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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 ...
 1752-1982 2.47e-89

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: 292.66  E-value: 2.47e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1752 YNIKEMSSVEVSIPGI-FTEGEIIIGAHRDSlASSSAGDANSGSAILLEIARAMSKLLKH-GWKPLRPIKLISWDGERSG 1829
Cdd:cd03874     52 EEYSPITNVVGKIEGIeQPDRAIIIGAHRDS-WGYGAGYPNSGTAVLLEIARLFQQLKKKfGWKPLRTIYFISWDGSEFG 130

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1830 LLGSTDYAEAHAAILRRRALVYLNLDNAISG-TNFHCKANPLLQDVIYEAAKLTEFNGHEDWslfdhWKYTSNATISLLD 1908
Cdd:cd03874    131 LAGSTELGEDRKASLKDEVYAYINIDQLVIGnSELDVDAHPLLQSLFRKASKKVKFPGNEDW-----WKHSPNAKVSNLH 205

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2361082295 1909 GLSSYTSFQYHLGVPAAHFQFNANDtsGAVYHSNSVFDSPTWLEKFTNSDYKLHNTMAMFVGLTTLMLSENELA 1982
Cdd:cd03874    206 QYGDWTPFLNHLGIPVAVFSFKNDR--NASYPINSSYDTFEWLEKFLDPDFELHSTLAEFVGLLVLSLAEDPLL 277
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 1525-1746 2.25e-87

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: 284.57  E-value: 2.25e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1525 PVDTNVALLENGKVVYeaSMIEDRVKSDPAShaRKRQKGFHQYSKNGSVTARYVFCNYGSISDYKLLLKKNIDIEDKIHI 1604
Cdd:cd02121      1 PVKRSLILTKPDGATG--KLIEDTVLEEPPS--PDVVPPFHAYSASGNVTAELVYANYGSPEDFEYLEDLGIDVKGKIVI 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1605 VRSGKILPGLKVKNAELYGASSVIIYTDPFDDGKVTEENGfLHYPYGPARNPSYIKRDSVNYFSDTPGDPTTPGYPSKDS 1684
Cdd:cd02121     77 ARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYITGENG-KTYPDGPARPPSGVQRGSVLFMSIGPGDPLTPGYPSKPG 155

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2361082295 1685 DTEHM-SPVGRVPRIPSVPMSARDVQPILERLNGRG----FQIGPGSNIKDFgsFTGPSSSIDKVHL 1746
Cdd:cd02121    156 AERRDkEESKGLPKIPSLPISYRDAQPLLKALGGPGapsdWQGGLPVTYRLG--FGGPSPGKVRVNL 220
COG5048 COG5048
FOG: Zn-finger [General function prediction only];
420-960 2.13e-32

FOG: Zn-finger [General function prediction only];


:

Pssm-ID: 227381 [Multi-domain]  Cd Length: 467  Bit Score: 133.28  E-value: 2.13e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  420 ATPGVYLLSSGPSLTDLLTMNSAHAGAGGYMSSHHSPFDLGCFSHDKPTVSELNLPSSFPNTIPSNSTTASNSYSNLANQ 499
Cdd:COG5048      1 ATLTSSQSSSSNNSVLSSTPKSTLKSLSNAPRPDSCPNCTDSFSRLEHLTRHIRSHTGEKPSQCSYSGCDKSFSRPLELS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  500 TYTQMSNEQPLMSLSPKNPPTTVSDSSSTINFNPSANNLLEPSMEPNDKDSNIDPAAIDDKWLSEFINNSDPKST-FKIN 578
Cdd:COG5048     81 RHLRTHHNNPSDLNSKSLPLSNSKASSSSLSSSSSNSNDNNLLSSHSLPPSSRDPQLPDLLSISNLRNNPLPGNNsSSVN 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  579 FNHFNDIGFiysppssrssipsksppNHSATSLNHEKASLSPrLNLSLNESTDLPSTPQNQLKEPSYSDPISHSSHKRRR 658
Cdd:COG5048    161 TPQSNSLHP-----------------PLPANSLSKDPSSNLS-LLISSNVSTSIPSSSENSPLSSSYSIPSSSSDQNLEN 222

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  659 DSVMMDYDLSNFFSSRQLDISKVLNGTEQNNSHVNDDVLTLSFPGETDSNATQKQLPVLTPSDLLSPFSvpsvsqvlftn 738
Cdd:COG5048    223 SSSSLPLTTNSQLSPKSLLSQSPSSLSSSDSSSSASESPRSSLPTASSQSSSPNESDSSSEKGFSLPIK----------- 291

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  739 elrsmMLADNNIDSGAFPTTSQLNDYVTYYKEefhpffsfiHLPSIIFNMDSyplLLSISMVGALYGFHSTHAKVLANVA 818
Cdd:COG5048    292 -----SKQCNISFSRSSPLTRHLRSVNHSGES---------LKPFSCPYSLC---GKLFSRNDALKRHILLHTSISPAKE 354

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  819 STQIRKSLKASEKNPEttelwviqtlvlltfycifnkntavikgmHGQLTTIIRLLKASRLNLPLESLRQPPIESDHIME 898
Cdd:COG5048    355 KLLNSSSKFSPLLNNE-----------------------------PPQSLQQYKDLKNDKKSETLSNSCIRNFKRDSNLS 405

                          490       500       510       520       530       540
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2361082295  899 YENSPHMFSKIREQYNAPNQMNKNYQYFVLAQSRIRTCHAVLLISNLFSSLVGADCCFHSVD 960
Cdd:COG5048    406 LHIITHLSFRPYNCKNPPCSKSFNRHYNLIPHKKIHTNHAPLLCSILKSFRRDLDLSNHGKD 467
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 2058-2132 2.51e-08

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: 54.13  E-value: 2.51e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2361082295 2058 KKIKSYIKLQRSNSKSKQIDQLFITHRGLKDREWMKYSLLAPSKFEGSVGEVLPGLHEGLADKDRNEVIQWLTIL 2132
Cdd:pfam04253   30 IKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGATFPGIRDAIEAGDWELAQKQISIV 104
fungal_TF_MHR cd12148
fungal transcription factor regulatory middle homology region; This domain is present in the ...
 756-1248 1.36e-05

fungal transcription factor regulatory middle homology region; This domain is present in the large family of fungal zinc cluster transcription factors that contain an N-terminal GAL4-like C6 zinc binuclear cluster DNA-binding domain. Examples of members of this large fungal group are the following Saccharomyces cerevisiae transcription factors, GAL4, STB5, DAL81, CAT8, RDR1, HAL9, PUT3, PPR1, ASG1, RSF2, PIP2, as well as the C-terminal domain of the Cep3, a subunit of the yeast centromere-binding factor 3. It has been suggested that this region plays a regulatory role.


:

Pssm-ID: 213391  Cd Length: 410  Bit Score: 49.75  E-value: 1.36e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  756 PTTSQLNDYVTYYKEEFHPFFSFIHLPSIIFNMDSYP------------LLLSISMVGALYGFHSTHAKVLANVASTQIR 823
Cdd:cd12148      1 PPREVADRLLDLYFENVHPLFPILHRPTFLRDLESLYsdpsslspaslaLLLAVLALAALSLPDSELRGESRRSLAERYY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  824 KSLKA--SEKNPETTELWVIQTLVLLTFYCIFNKNTAVIKGMHGQLttiIRLlkASRLNLPLESLRQPPIEsdhimeyen 901
Cdd:cd12148     81 EAARQllDLALFLPPSLETLQALLLLALYLLGTGDPSSAWLLLGLA---IRL--AQSLGLHRDPSSLPGLS--------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  902 sphmfskireqynapnqmnknyqyFVLAQSRIRTCHAVLLISNLFSSLVGADCCFHSVDLKCGVPCYKEELYQCRNSDEW 981
Cdd:cd12148    147 ------------------------PFERELRRRLWWSLYILDRLLSLSLGRPPSISDEDIDVPLPSNEDDELSPSSSPPP 202

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  982 SDllcqhkitldskfslielsngneayenclRFLSTGDSFFYGHARvslstclslLISIHEKILIERNNARIsnnntnsn 1061
Cdd:cd12148    203 PP-----------------------------SEEPTSLSFFIALIR---------LARILGRILRLLYSPRA-------- 236

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1062 nielDDIEWKMTSRQRIDTMLKYWENLYLKNGGILTPTENSMSTINANPAMRLIipvYLFAKMrrCLDLAHVIEKIWLKD 1141
Cdd:cd12148    237 ----SSPEDSLETILELDAELEEWRASLPPELRLDSSSLESPSLLPQRLLLHLL---YHLLLI--LLHRPFLLRSLSSLS 307

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1142 WSNMNKAleevcydmgSLREATEYALNMVDAWTSFFTyikrgKRRIFNTPVFATTCMFTAVLVISEYMKCVEDWARGYNA 1221
Cdd:cd12148    308 PSSSSAE---------SRRACLEAAREILELLRLLLS-----SSLLLLLWWFLLYYLFSAALVLLLALLLRPSSSELEEA 373

                          490       500       510
                   ....*....|....*....|....*....|...
gi 2361082295 1222 NNPNSALLDFSDRV------LWLKAERILRRLQ 1248
Cdd:cd12148    374 RSLLERALELLERLserwprLARRALRLLERLL 406
zf-H2C2_2 pfam13465
Zinc-finger double domain;
134-159 1.92e-05

Zinc-finger double domain;


:

Pssm-ID: 463886 [Multi-domain]  Cd Length: 26  Bit Score: 43.13  E-value: 1.92e-05
                           10        20
                   ....*....|....*....|....*.
gi 2361082295  134 HLKRHQHSHTREKPYLCIFCGRCFAR 159
Cdd:pfam13465    1 NLKRHMRTHTGEKPYKCPECGKSFKS 26
Zinc_peptidase_like super family cl14876
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ...
 1468-1520 2.27e-05

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: 48.45  E-value: 2.27e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2361082295 1468 YLNSLQQENRAKEHVYKYA--GYMSNGASDSSTFKYTLDEFLDMG-YKPKVEKYFP 1520
Cdd:cd03874      1 YARKLVDLAKIKEDLEYLSsmPHMAGTKGDAALAKYIENSFKNNGlFEVELEEYSP 56
COG5048 super family cl34881
FOG: Zn-finger [General function prediction only];
106-539 3.96e-03

FOG: Zn-finger [General function prediction only];


The actual alignment was detected with superfamily member COG5048:

Pssm-ID: 227381 [Multi-domain]  Cd Length: 467  Bit Score: 41.99  E-value: 3.96e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  106 PKKSRIIKTDKPRPFLCPTCTRGFVRQEHLKRHQHSHTREKPYLCIFCGRCFARRDLVLRHQQKLHaalvgtgdprrmtp 185
Cdd:COG5048     20 PKSTLKSLSNAPRPDSCPNCTDSFSRLEHLTRHIRSHTGEKPSQCSYSGCDKSFSRPLELSRHLRT-------------- 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  186 APNSTSSFASKRRHSVAADDPTDLHIIKIAGNKETILPTPKNLTGktseelkeavvalaKSNNVELPVSAPVMNDKREKT 265
Cdd:COG5048     86 HHNNPSDLNSKSLPLSNSKASSSSLSSSSSNSNDNNLLSSHSLPP--------------SSRDPQLPDLLSISNLRNNPL 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  266 PPSKAGSLGFREFKFSTKGVPVHSASSDAVIDRASTPSS--MHKTKRHASFSAssamtyMSSSNSPHHSITNFELVEDAP 343
Cdd:COG5048    152 PGNNSSSVNTPQSNSLHPPLPANSLSKDPSSNLSLLISSnvSTSIPSSSENSP------LSSSYSIPSSSSDQNLENSSS 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  344 HqVGFSTPQMTAKQLMESVSELDLPPltLDEPPQAIKFNLNLFNNDPS---GQQQQQQQQQQQNSTSSTIVNSNNGSTVA 420
Cdd:COG5048    226 S-LPLTTNSQLSPKSLLSQSPSSLSS--SDSSSSASESPRSSLPTASSqssSPNESDSSSEKGFSLPIKSKQCNISFSRS 302

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  421 TPGVYLLSSGP-SLTDLLTMNSAHAGAG--GYMSSHHSPFDLgcFSHDKPTVSELNLPSSFPNTIPSNS---TTASNSYS 494
Cdd:COG5048    303 SPLTRHLRSVNhSGESLKPFSCPYSLCGklFSRNDALKRHIL--LHTSISPAKEKLLNSSSKFSPLLNNeppQSLQQYKD 380

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*..
gi 2361082295  495 NLANQTYTQMSNEQPLMSLSPKNP--PTTVSDSSSTINFNPSANNLL 539
Cdd:COG5048    381 LKNDKKSETLSNSCIRNFKRDSNLslHIITHLSFRPYNCKNPPCSKS 427
 
Name Accession Description Interval E-value
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 1752-1982 2.47e-89

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: 292.66  E-value: 2.47e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1752 YNIKEMSSVEVSIPGI-FTEGEIIIGAHRDSlASSSAGDANSGSAILLEIARAMSKLLKH-GWKPLRPIKLISWDGERSG 1829
Cdd:cd03874     52 EEYSPITNVVGKIEGIeQPDRAIIIGAHRDS-WGYGAGYPNSGTAVLLEIARLFQQLKKKfGWKPLRTIYFISWDGSEFG 130

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1830 LLGSTDYAEAHAAILRRRALVYLNLDNAISG-TNFHCKANPLLQDVIYEAAKLTEFNGHEDWslfdhWKYTSNATISLLD 1908
Cdd:cd03874    131 LAGSTELGEDRKASLKDEVYAYINIDQLVIGnSELDVDAHPLLQSLFRKASKKVKFPGNEDW-----WKHSPNAKVSNLH 205

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2361082295 1909 GLSSYTSFQYHLGVPAAHFQFNANDtsGAVYHSNSVFDSPTWLEKFTNSDYKLHNTMAMFVGLTTLMLSENELA 1982
Cdd:cd03874    206 QYGDWTPFLNHLGIPVAVFSFKNDR--NASYPINSSYDTFEWLEKFLDPDFELHSTLAEFVGLLVLSLAEDPLL 277
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 1525-1746 2.25e-87

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: 284.57  E-value: 2.25e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1525 PVDTNVALLENGKVVYeaSMIEDRVKSDPAShaRKRQKGFHQYSKNGSVTARYVFCNYGSISDYKLLLKKNIDIEDKIHI 1604
Cdd:cd02121      1 PVKRSLILTKPDGATG--KLIEDTVLEEPPS--PDVVPPFHAYSASGNVTAELVYANYGSPEDFEYLEDLGIDVKGKIVI 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1605 VRSGKILPGLKVKNAELYGASSVIIYTDPFDDGKVTEENGfLHYPYGPARNPSYIKRDSVNYFSDTPGDPTTPGYPSKDS 1684
Cdd:cd02121     77 ARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYITGENG-KTYPDGPARPPSGVQRGSVLFMSIGPGDPLTPGYPSKPG 155

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2361082295 1685 DTEHM-SPVGRVPRIPSVPMSARDVQPILERLNGRG----FQIGPGSNIKDFgsFTGPSSSIDKVHL 1746
Cdd:cd02121    156 AERRDkEESKGLPKIPSLPISYRDAQPLLKALGGPGapsdWQGGLPVTYRLG--FGGPSPGKVRVNL 220
COG5048 COG5048
FOG: Zn-finger [General function prediction only];
420-960 2.13e-32

FOG: Zn-finger [General function prediction only];


Pssm-ID: 227381 [Multi-domain]  Cd Length: 467  Bit Score: 133.28  E-value: 2.13e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  420 ATPGVYLLSSGPSLTDLLTMNSAHAGAGGYMSSHHSPFDLGCFSHDKPTVSELNLPSSFPNTIPSNSTTASNSYSNLANQ 499
Cdd:COG5048      1 ATLTSSQSSSSNNSVLSSTPKSTLKSLSNAPRPDSCPNCTDSFSRLEHLTRHIRSHTGEKPSQCSYSGCDKSFSRPLELS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  500 TYTQMSNEQPLMSLSPKNPPTTVSDSSSTINFNPSANNLLEPSMEPNDKDSNIDPAAIDDKWLSEFINNSDPKST-FKIN 578
Cdd:COG5048     81 RHLRTHHNNPSDLNSKSLPLSNSKASSSSLSSSSSNSNDNNLLSSHSLPPSSRDPQLPDLLSISNLRNNPLPGNNsSSVN 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  579 FNHFNDIGFiysppssrssipsksppNHSATSLNHEKASLSPrLNLSLNESTDLPSTPQNQLKEPSYSDPISHSSHKRRR 658
Cdd:COG5048    161 TPQSNSLHP-----------------PLPANSLSKDPSSNLS-LLISSNVSTSIPSSSENSPLSSSYSIPSSSSDQNLEN 222

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  659 DSVMMDYDLSNFFSSRQLDISKVLNGTEQNNSHVNDDVLTLSFPGETDSNATQKQLPVLTPSDLLSPFSvpsvsqvlftn 738
Cdd:COG5048    223 SSSSLPLTTNSQLSPKSLLSQSPSSLSSSDSSSSASESPRSSLPTASSQSSSPNESDSSSEKGFSLPIK----------- 291

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  739 elrsmMLADNNIDSGAFPTTSQLNDYVTYYKEefhpffsfiHLPSIIFNMDSyplLLSISMVGALYGFHSTHAKVLANVA 818
Cdd:COG5048    292 -----SKQCNISFSRSSPLTRHLRSVNHSGES---------LKPFSCPYSLC---GKLFSRNDALKRHILLHTSISPAKE 354

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  819 STQIRKSLKASEKNPEttelwviqtlvlltfycifnkntavikgmHGQLTTIIRLLKASRLNLPLESLRQPPIESDHIME 898
Cdd:COG5048    355 KLLNSSSKFSPLLNNE-----------------------------PPQSLQQYKDLKNDKKSETLSNSCIRNFKRDSNLS 405

                          490       500       510       520       530       540
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2361082295  899 YENSPHMFSKIREQYNAPNQMNKNYQYFVLAQSRIRTCHAVLLISNLFSSLVGADCCFHSVD 960
Cdd:COG5048    406 LHIITHLSFRPYNCKNPPCSKSFNRHYNLIPHKKIHTNHAPLLCSILKSFRRDLDLSNHGKD 467
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 1760-1943 2.60e-23

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: 101.36  E-value: 2.60e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1760 VEVSIPGI-FTEGEIIIGAHRDSLASSSAG--DANSGSAILLEIARAMSKllkHGWKPLRPIKLISWDGERSGLLGSTDY 1836
Cdd:COG2234     49 VIAEIPGTdPPDEVVVLGAHYDSVGSIGPGadDNASGVAALLELARALAA---LGPKPKRTIRFVAFGAEEQGLLGSRYY 125

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1837 AEAHAAILrRRALVYLNLDNAISGTNFH------CKANPLLQDVIYEAAKltefnghedwSLFDHWKYTSNATISLLDGl 1910
Cdd:COG2234    126 AENLKAPL-EKIVAVLNLDMIGRGGPRNylyvdgDGGSPELADLLEAAAK----------AYLPGLGVDPPEETGGYGR- 193

                          170       180       190
                   ....*....|....*....|....*....|...
gi 2361082295 1911 SSYTSFqYHLGVPAAHFqFNANDTSGAVYHSNS 1943
Cdd:COG2234    194 SDHAPF-AKAGIPALFL-FTGAEDYHPDYHTPS 224
Peptidase_M28 pfam04389
Peptidase family M28;
1762-1941 1.54e-19

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 88.50  E-value: 1.54e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1762 VSIPGIFTEGEIIIGAHRDSLASSS-AGDANSGSAILLEIARAmsklLKHGWKPLRPIKLISWDGERSGLLGSTDYAEAH 1840
Cdd:pfam04389    4 AKLPGKAPDEVVLLSAHYDSVGTGPgADDNASGVAALLELARV----LAAGQRPKRSVRFLFFDAEEAGLLGSHHFAKSH 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1841 AAILRRRAlvYLNLDNAISGtnfhckaNPLLQDVIYEAakltefNGHEDWSLFDHWKYTSNATI-------SLLDGLSSY 1913
Cdd:pfam04389   80 PPLKKIRA--VINLDMIGSG-------GPALLFQSGPK------GSSLLEKYLKAAAKPYGVTLaedpfqeRGGPGRSDH 144

                          170       180
                   ....*....|....*....|....*...
gi 2361082295 1914 TSFQyHLGVPAAHFQFNANdtsGAVYHS 1941
Cdd:pfam04389  145 APFI-KAGIPGLDLAFTDF---GYRYHT 168
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 2058-2132 2.51e-08

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: 54.13  E-value: 2.51e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2361082295 2058 KKIKSYIKLQRSNSKSKQIDQLFITHRGLKDREWMKYSLLAPSKFEGSVGEVLPGLHEGLADKDRNEVIQWLTIL 2132
Cdd:pfam04253   30 IKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGATFPGIRDAIEAGDWELAQKQISIV 104
Fungal_trans pfam04082
Fungal specific transcription factor domain; This domain is found in a number of fungal ...
 767-881 4.16e-08

Fungal specific transcription factor domain; This domain is found in a number of fungal transcription factors including transcriptional activator xlnR, yeast regulatory protein GAL4, and nicotinate catabolism cluster-specific transcription factor HxnR.


Pssm-ID: 397964  Cd Length: 262  Bit Score: 56.73  E-value: 4.16e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  767 YYKEEFHPFFSFIHLPSI---IFNMDSYP-------LLLSISMVGALY------GFHSTHAKVLANVASTQIR-KSLKAS 829
Cdd:pfam04082    3 LFFKNFHPQFPILHRPSFlrdYFELFSSPsnyasplLLLAILALGALFsesptaRSSSSLTDEAADGIHFFLRaLILIHE 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2361082295  830 EKNPETTELWVIQTLVLLTFYCIFNKNTAVIKGMHGqltTIIRLLKASRLNL 881
Cdd:pfam04082   83 DFSSPSSSLWILQALLLLELYELGTGDRKLHWRYHG---LAIRLARSLGLHR 131
fungal_TF_MHR cd12148
fungal transcription factor regulatory middle homology region; This domain is present in the ...
 756-1248 1.36e-05

fungal transcription factor regulatory middle homology region; This domain is present in the large family of fungal zinc cluster transcription factors that contain an N-terminal GAL4-like C6 zinc binuclear cluster DNA-binding domain. Examples of members of this large fungal group are the following Saccharomyces cerevisiae transcription factors, GAL4, STB5, DAL81, CAT8, RDR1, HAL9, PUT3, PPR1, ASG1, RSF2, PIP2, as well as the C-terminal domain of the Cep3, a subunit of the yeast centromere-binding factor 3. It has been suggested that this region plays a regulatory role.


Pssm-ID: 213391  Cd Length: 410  Bit Score: 49.75  E-value: 1.36e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  756 PTTSQLNDYVTYYKEEFHPFFSFIHLPSIIFNMDSYP------------LLLSISMVGALYGFHSTHAKVLANVASTQIR 823
Cdd:cd12148      1 PPREVADRLLDLYFENVHPLFPILHRPTFLRDLESLYsdpsslspaslaLLLAVLALAALSLPDSELRGESRRSLAERYY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  824 KSLKA--SEKNPETTELWVIQTLVLLTFYCIFNKNTAVIKGMHGQLttiIRLlkASRLNLPLESLRQPPIEsdhimeyen 901
Cdd:cd12148     81 EAARQllDLALFLPPSLETLQALLLLALYLLGTGDPSSAWLLLGLA---IRL--AQSLGLHRDPSSLPGLS--------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  902 sphmfskireqynapnqmnknyqyFVLAQSRIRTCHAVLLISNLFSSLVGADCCFHSVDLKCGVPCYKEELYQCRNSDEW 981
Cdd:cd12148    147 ------------------------PFERELRRRLWWSLYILDRLLSLSLGRPPSISDEDIDVPLPSNEDDELSPSSSPPP 202

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  982 SDllcqhkitldskfslielsngneayenclRFLSTGDSFFYGHARvslstclslLISIHEKILIERNNARIsnnntnsn 1061
Cdd:cd12148    203 PP-----------------------------SEEPTSLSFFIALIR---------LARILGRILRLLYSPRA-------- 236

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1062 nielDDIEWKMTSRQRIDTMLKYWENLYLKNGGILTPTENSMSTINANPAMRLIipvYLFAKMrrCLDLAHVIEKIWLKD 1141
Cdd:cd12148    237 ----SSPEDSLETILELDAELEEWRASLPPELRLDSSSLESPSLLPQRLLLHLL---YHLLLI--LLHRPFLLRSLSSLS 307

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1142 WSNMNKAleevcydmgSLREATEYALNMVDAWTSFFTyikrgKRRIFNTPVFATTCMFTAVLVISEYMKCVEDWARGYNA 1221
Cdd:cd12148    308 PSSSSAE---------SRRACLEAAREILELLRLLLS-----SSLLLLLWWFLLYYLFSAALVLLLALLLRPSSSELEEA 373

                          490       500       510
                   ....*....|....*....|....*....|...
gi 2361082295 1222 NNPNSALLDFSDRV------LWLKAERILRRLQ 1248
Cdd:cd12148    374 RSLLERALELLERLserwprLARRALRLLERLL 406
PRK10199 PRK10199
alkaline phosphatase isozyme conversion aminopeptidase; Provisional
 1683-1860 1.74e-05

alkaline phosphatase isozyme conversion aminopeptidase; Provisional


Pssm-ID: 182299 [Multi-domain]  Cd Length: 346  Bit Score: 49.35  E-value: 1.74e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1683 DSDTEHMSPV--GRVPRIPSVPMSArdvqpilERLNGRGFQIGPGSNIKDFGSFTGPSSSIDKVHLHNeLTynikeMSSV 1760
Cdd:PRK10199    34 NTQARHIATFfpGRMTGSPAEMLSA-------DYLRQQFQQMGYQSDIRTFNSRYIYTARDNRKNWHN-VT-----GSTV 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1761 ----EVSIPGiftegEIIIGAHRDSLASSSAGDAN---------------SGSAILLEIARAMSKllkhgwKPLR-PIKL 1820
Cdd:PRK10199   101 iaahEGKAPQ-----QIIIMAHLDTYAPQSDADVDanlggltlqgmddnaAGLGVMLELAERLKN------VPTEyGIRF 169

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 2361082295 1821 ISWDGERSGLLGSTDYAEAHAAILRRRALVYLNLDNAISG 1860
Cdd:PRK10199   170 VATSGEEEGKLGAENLLKRMSDTEKKNTLLVINLDNLIVG 209
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
 1573-1652 1.88e-05

PA domain; The PA (Protease associated) domain is found as an insert domain in diverse proteases. The PA domain is also found in a plant vacuolar sorting receptor Swiss:O22925 and members of the RZF family Swiss:O43567. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors.


Pssm-ID: 460499 [Multi-domain]  Cd Length: 91  Bit Score: 45.20  E-value: 1.88e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1573 VTARYVFCNYGSISDYklllkkniDIEDKIHIVRSGKILPGLKVKNAELYGASSVIIYTDPFDDGKVTEENGFLHYPYGP 1652
Cdd:pfam02225    5 VLAPGCYAGDGIPADF--------DVKGKIVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVEGLGGPPGAGGNELYPDGI 76
zf-H2C2_2 pfam13465
Zinc-finger double domain;
134-159 1.92e-05

Zinc-finger double domain;


Pssm-ID: 463886 [Multi-domain]  Cd Length: 26  Bit Score: 43.13  E-value: 1.92e-05
                           10        20
                   ....*....|....*....|....*.
gi 2361082295  134 HLKRHQHSHTREKPYLCIFCGRCFAR 159
Cdd:pfam13465    1 NLKRHMRTHTGEKPYKCPECGKSFKS 26
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 1468-1520 2.27e-05

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: 48.45  E-value: 2.27e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2361082295 1468 YLNSLQQENRAKEHVYKYA--GYMSNGASDSSTFKYTLDEFLDMG-YKPKVEKYFP 1520
Cdd:cd03874      1 YARKLVDLAKIKEDLEYLSsmPHMAGTKGDAALAKYIENSFKNNGlFEVELEEYSP 56
COG5048 COG5048
FOG: Zn-finger [General function prediction only];
106-539 3.96e-03

FOG: Zn-finger [General function prediction only];


Pssm-ID: 227381 [Multi-domain]  Cd Length: 467  Bit Score: 41.99  E-value: 3.96e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  106 PKKSRIIKTDKPRPFLCPTCTRGFVRQEHLKRHQHSHTREKPYLCIFCGRCFARRDLVLRHQQKLHaalvgtgdprrmtp 185
Cdd:COG5048     20 PKSTLKSLSNAPRPDSCPNCTDSFSRLEHLTRHIRSHTGEKPSQCSYSGCDKSFSRPLELSRHLRT-------------- 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  186 APNSTSSFASKRRHSVAADDPTDLHIIKIAGNKETILPTPKNLTGktseelkeavvalaKSNNVELPVSAPVMNDKREKT 265
Cdd:COG5048     86 HHNNPSDLNSKSLPLSNSKASSSSLSSSSSNSNDNNLLSSHSLPP--------------SSRDPQLPDLLSISNLRNNPL 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  266 PPSKAGSLGFREFKFSTKGVPVHSASSDAVIDRASTPSS--MHKTKRHASFSAssamtyMSSSNSPHHSITNFELVEDAP 343
Cdd:COG5048    152 PGNNSSSVNTPQSNSLHPPLPANSLSKDPSSNLSLLISSnvSTSIPSSSENSP------LSSSYSIPSSSSDQNLENSSS 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  344 HqVGFSTPQMTAKQLMESVSELDLPPltLDEPPQAIKFNLNLFNNDPS---GQQQQQQQQQQQNSTSSTIVNSNNGSTVA 420
Cdd:COG5048    226 S-LPLTTNSQLSPKSLLSQSPSSLSS--SDSSSSASESPRSSLPTASSqssSPNESDSSSEKGFSLPIKSKQCNISFSRS 302

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  421 TPGVYLLSSGP-SLTDLLTMNSAHAGAG--GYMSSHHSPFDLgcFSHDKPTVSELNLPSSFPNTIPSNS---TTASNSYS 494
Cdd:COG5048    303 SPLTRHLRSVNhSGESLKPFSCPYSLCGklFSRNDALKRHIL--LHTSISPAKEKLLNSSSKFSPLLNNeppQSLQQYKD 380

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*..
gi 2361082295  495 NLANQTYTQMSNEQPLMSLSPKNP--PTTVSDSSSTINFNPSANNLL 539
Cdd:COG5048    381 LKNDKKSETLSNSCIRNFKRDSNLslHIITHLSFRPYNCKNPPCSKS 427
 
Name Accession Description Interval E-value
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 1752-1982 2.47e-89

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: 292.66  E-value: 2.47e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1752 YNIKEMSSVEVSIPGI-FTEGEIIIGAHRDSlASSSAGDANSGSAILLEIARAMSKLLKH-GWKPLRPIKLISWDGERSG 1829
Cdd:cd03874     52 EEYSPITNVVGKIEGIeQPDRAIIIGAHRDS-WGYGAGYPNSGTAVLLEIARLFQQLKKKfGWKPLRTIYFISWDGSEFG 130

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1830 LLGSTDYAEAHAAILRRRALVYLNLDNAISG-TNFHCKANPLLQDVIYEAAKLTEFNGHEDWslfdhWKYTSNATISLLD 1908
Cdd:cd03874    131 LAGSTELGEDRKASLKDEVYAYINIDQLVIGnSELDVDAHPLLQSLFRKASKKVKFPGNEDW-----WKHSPNAKVSNLH 205

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2361082295 1909 GLSSYTSFQYHLGVPAAHFQFNANDtsGAVYHSNSVFDSPTWLEKFTNSDYKLHNTMAMFVGLTTLMLSENELA 1982
Cdd:cd03874    206 QYGDWTPFLNHLGIPVAVFSFKNDR--NASYPINSSYDTFEWLEKFLDPDFELHSTLAEFVGLLVLSLAEDPLL 277
PA_GCPII_like cd02121
PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II ...
 1525-1746 2.25e-87

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: 284.57  E-value: 2.25e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1525 PVDTNVALLENGKVVYeaSMIEDRVKSDPAShaRKRQKGFHQYSKNGSVTARYVFCNYGSISDYKLLLKKNIDIEDKIHI 1604
Cdd:cd02121      1 PVKRSLILTKPDGATG--KLIEDTVLEEPPS--PDVVPPFHAYSASGNVTAELVYANYGSPEDFEYLEDLGIDVKGKIVI 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1605 VRSGKILPGLKVKNAELYGASSVIIYTDPFDDGKVTEENGfLHYPYGPARNPSYIKRDSVNYFSDTPGDPTTPGYPSKDS 1684
Cdd:cd02121     77 ARYGGIFRGLKVKNAQLAGAVGVIIYSDPADDGYITGENG-KTYPDGPARPPSGVQRGSVLFMSIGPGDPLTPGYPSKPG 155

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2361082295 1685 DTEHM-SPVGRVPRIPSVPMSARDVQPILERLNGRG----FQIGPGSNIKDFgsFTGPSSSIDKVHL 1746
Cdd:cd02121    156 AERRDkEESKGLPKIPSLPISYRDAQPLLKALGGPGapsdWQGGLPVTYRLG--FGGPSPGKVRVNL 220
M28_PSMA_like cd08022
M28 Zn-peptidase prostate-specific membrane antigen; Peptidase M28 family; prostate-specific ...
 1764-1981 9.36e-63

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: 216.33  E-value: 9.36e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1764 IPGIFTEGE-IIIGAHRDSLaSSSAGDANSGSAILLEIARAMSKLLKHGWKPLRPIKLISWDGERSGLLGSTDYAEAHAA 1842
Cdd:cd08022     67 IRGSEEPDEyIILGNHRDAW-VFGAGDPNSGTAVLLEVARALGTLLKKGWRPRRTIIFASWDAEEYGLIGSTEWVEENAD 145

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1843 ILRRRALVYLNLDNAISGTNFHCKANPLLQDVIYEAAKLTEF-NGHEDWSLFDHWKYTSNATISLLDGLSSYTSFQYHLG 1921
Cdd:cd08022    146 WLQERAVAYLNVDVAVSGSTLRAAGSPLLQNLLREAAKEVQDpDEGATLKYLPSWWDDTGGEIGNLGSGSDYTPFLDHLG 225

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1922 VPAAHFQFnANDTSGAVYHSNSVFDSPTWLEKFTNSDYKLHNTMAMFVGLTTLMLSENEL 1981
Cdd:cd08022    226 IASIDFGF-SGGPTDPYPHYHSNYDSFEWMEKFGDPGFKYHVAIAQVWGLLALRLADDPI 284
COG5048 COG5048
FOG: Zn-finger [General function prediction only];
420-960 2.13e-32

FOG: Zn-finger [General function prediction only];


Pssm-ID: 227381 [Multi-domain]  Cd Length: 467  Bit Score: 133.28  E-value: 2.13e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  420 ATPGVYLLSSGPSLTDLLTMNSAHAGAGGYMSSHHSPFDLGCFSHDKPTVSELNLPSSFPNTIPSNSTTASNSYSNLANQ 499
Cdd:COG5048      1 ATLTSSQSSSSNNSVLSSTPKSTLKSLSNAPRPDSCPNCTDSFSRLEHLTRHIRSHTGEKPSQCSYSGCDKSFSRPLELS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  500 TYTQMSNEQPLMSLSPKNPPTTVSDSSSTINFNPSANNLLEPSMEPNDKDSNIDPAAIDDKWLSEFINNSDPKST-FKIN 578
Cdd:COG5048     81 RHLRTHHNNPSDLNSKSLPLSNSKASSSSLSSSSSNSNDNNLLSSHSLPPSSRDPQLPDLLSISNLRNNPLPGNNsSSVN 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  579 FNHFNDIGFiysppssrssipsksppNHSATSLNHEKASLSPrLNLSLNESTDLPSTPQNQLKEPSYSDPISHSSHKRRR 658
Cdd:COG5048    161 TPQSNSLHP-----------------PLPANSLSKDPSSNLS-LLISSNVSTSIPSSSENSPLSSSYSIPSSSSDQNLEN 222

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  659 DSVMMDYDLSNFFSSRQLDISKVLNGTEQNNSHVNDDVLTLSFPGETDSNATQKQLPVLTPSDLLSPFSvpsvsqvlftn 738
Cdd:COG5048    223 SSSSLPLTTNSQLSPKSLLSQSPSSLSSSDSSSSASESPRSSLPTASSQSSSPNESDSSSEKGFSLPIK----------- 291

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  739 elrsmMLADNNIDSGAFPTTSQLNDYVTYYKEefhpffsfiHLPSIIFNMDSyplLLSISMVGALYGFHSTHAKVLANVA 818
Cdd:COG5048    292 -----SKQCNISFSRSSPLTRHLRSVNHSGES---------LKPFSCPYSLC---GKLFSRNDALKRHILLHTSISPAKE 354

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  819 STQIRKSLKASEKNPEttelwviqtlvlltfycifnkntavikgmHGQLTTIIRLLKASRLNLPLESLRQPPIESDHIME 898
Cdd:COG5048    355 KLLNSSSKFSPLLNNE-----------------------------PPQSLQQYKDLKNDKKSETLSNSCIRNFKRDSNLS 405

                          490       500       510       520       530       540
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2361082295  899 YENSPHMFSKIREQYNAPNQMNKNYQYFVLAQSRIRTCHAVLLISNLFSSLVGADCCFHSVD 960
Cdd:COG5048    406 LHIITHLSFRPYNCKNPPCSKSFNRHYNLIPHKKIHTNHAPLLCSILKSFRRDLDLSNHGKD 467
M28_TfR cd09848
M28 Zn-peptidase Transferrin Receptor family; Peptidase M28 family; Transferrin Receptor (TfR) ...
 1773-1985 1.40e-29

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: 120.56  E-value: 1.40e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1773 IIIGAHRDSLASSSAgDANSGSAILLEIARAMSKLLKH-GWKPLRPIKLISWDGERSGLLGSTDYAEAHAAILRRRALVY 1851
Cdd:cd09848     73 VVIGAQRDAWGPGAA-KSGVGTALLLELARTFSDMVKNdGFKPRRSIVFASWSAGDFGSVGATEWLEGYLSSLHLKAFTY 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1852 LNLDNAISGT-NFHCKANPLLQDVIYEAAKLTEFNGHEDWSLFDHWKYTSNATISLLDGLSSYTSFQYHLGVPAAHFQFN 1930
Cdd:cd09848    152 ISLDGAVLGDdSFKASASPLLYTLIESTMKQVKSPVHSGQSYYETRSSWWASIVEPLGLDSAAYPFLAFSGIPSVSFHFT 231

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2361082295 1931 ANDTSGAVYHSNsvFDSPTWLEKFTNSDY-KLHNTMAMFVGLTTLMLSENELARFN 1985
Cdd:cd09848    232 EDDEDYPFLGTK--EDTKENLDKFTNGELwEVAAAAAEVAGQMALRLVHDHLLPLD 285
Iap COG2234
Zn-dependent amino- or carboxypeptidase, M28 family [Posttranslational modification, protein ...
 1760-1943 2.60e-23

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: 101.36  E-value: 2.60e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1760 VEVSIPGI-FTEGEIIIGAHRDSLASSSAG--DANSGSAILLEIARAMSKllkHGWKPLRPIKLISWDGERSGLLGSTDY 1836
Cdd:COG2234     49 VIAEIPGTdPPDEVVVLGAHYDSVGSIGPGadDNASGVAALLELARALAA---LGPKPKRTIRFVAFGAEEQGLLGSRYY 125

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1837 AEAHAAILrRRALVYLNLDNAISGTNFH------CKANPLLQDVIYEAAKltefnghedwSLFDHWKYTSNATISLLDGl 1910
Cdd:COG2234    126 AENLKAPL-EKIVAVLNLDMIGRGGPRNylyvdgDGGSPELADLLEAAAK----------AYLPGLGVDPPEETGGYGR- 193

                          170       180       190
                   ....*....|....*....|....*....|...
gi 2361082295 1911 SSYTSFqYHLGVPAAHFqFNANDTSGAVYHSNS 1943
Cdd:COG2234    194 SDHAPF-AKAGIPALFL-FTGAEDYHPDYHTPS 224
Peptidase_M28 pfam04389
Peptidase family M28;
1762-1941 1.54e-19

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 88.50  E-value: 1.54e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1762 VSIPGIFTEGEIIIGAHRDSLASSS-AGDANSGSAILLEIARAmsklLKHGWKPLRPIKLISWDGERSGLLGSTDYAEAH 1840
Cdd:pfam04389    4 AKLPGKAPDEVVLLSAHYDSVGTGPgADDNASGVAALLELARV----LAAGQRPKRSVRFLFFDAEEAGLLGSHHFAKSH 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1841 AAILRRRAlvYLNLDNAISGtnfhckaNPLLQDVIYEAakltefNGHEDWSLFDHWKYTSNATI-------SLLDGLSSY 1913
Cdd:pfam04389   80 PPLKKIRA--VINLDMIGSG-------GPALLFQSGPK------GSSLLEKYLKAAAKPYGVTLaedpfqeRGGPGRSDH 144

                          170       180
                   ....*....|....*....|....*...
gi 2361082295 1914 TSFQyHLGVPAAHFQFNANdtsGAVYHS 1941
Cdd:pfam04389  145 APFI-KAGIPGLDLAFTDF---GYRYHT 168
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 1758-1942 2.23e-19

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: 88.55  E-value: 2.23e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1758 SSVEVSIPGIFTEGEII-IGAHRDSLASSSAGDAN-SGSAILLEIARAMSKLLKhgwKPLRPIKLISWDGERSGLLGSTD 1835
Cdd:cd02690      2 YNVIATIKGSDKPDEVIlIGAHYDSVPLSPGANDNaSGVAVLLELARVLSKLQL---KPKRSIRFAFWDAEELGLLGSKY 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1836 YAEAHAAILRRRALvYLNLDNAISGTNfhckanpllqDVIYEAAKLTEFNGHED-WSLFDHWKYTSNATISLLDGLSSYT 1914
Cdd:cd02690     79 YAEQLLSSLKNIRA-ALNLDMIGGAGP----------DLYLQTAPGNDALVEKLlRALAHELENVVYTVVYKEDGGTGGS 147

                          170       180       190
                   ....*....|....*....|....*....|
gi 2361082295 1915 SFQYHL--GVPAAHFQFNANDtSGAVYHSN 1942
Cdd:cd02690    148 DHRPFLarGIPAASLIQSESY-NFPYYHTT 176
PA_TfR cd02128
PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This ...
 1562-1718 5.95e-18

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: 83.60  E-value: 5.95e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1562 KGFHQYSKNGSVTARYVFCNYGSISDYKLLLKKNIDIEDKIHIVRSGKILPGLKVKNAELYGASSVIIYTDPFDDGKVTE 1641
Cdd:cd02128     18 GGYVAYSAAGTVTGKLVYANYGRKKDFEDLQSVGVSVNGSVVLVRAGKISFAEKVANAEKLGAVGVLIYPDPADFPIDPS 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1642 ENGflhyPYGPARNPSyikrdsvnyfsdtpGDPTTPGYPSKDsdteH--MSPVGR--VPRIPSVPMSARDVQPILERLNG 1717
Cdd:cd02128     98 ETA----LFGHVHLGT--------------GDPYTPGFPSFN----HtqFPPSQSsgLPNIPAQTISAAAAAKLLSKMGG 155


                   .
gi 2361082295 1718 R 1718
Cdd:cd02128    156 P 156
M28_like cd08015
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 1764-1946 2.27e-12

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: 68.39  E-value: 2.27e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1764 IPGIFTEGE-IIIGAHRDSL-ASSSAGDANSGSAILLEiarAMSKLLKHGWKPLRPIKLISWDGERSGLLGSTDYAEAHA 1841
Cdd:cd08015      8 IPGSDKKDEvVILGAHLDSWhGATGATDNGAGTAVMME---AMRILKAIGSKPKRTIRVALWGSEEQGLHGSRAYVEKHF 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1842 AILRRRAL--------VYLNLDNA------ISGTNFHcKANPLLQDVIYE-----AAKLTEFN-GHEDWSLFDhwkytsn 1901
Cdd:cd08015     85 GDPPTMQLqrdhkkisAYFNLDNGtgrirgIYLQGNL-AAYPIFSAWLYPfhdlgATTVIERNtGGTDHAAFD------- 156

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 2361082295 1902 atislldglssytsfqyHLGVPAahFQFNAN--DTSGAVYHSN-SVFD 1946
Cdd:cd08015    157 -----------------AVGIPA--FQFIQDpwDYWTRTHHTNrDTYD 185
M28_AAP cd03879
M28 Zn-peptidase Aeromonas (Vibrio) proteolytica aminopeptidase; Peptidase family M28; ...
 1758-1855 1.37e-10

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: 64.57  E-value: 1.37e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1758 SSVEVSIPGIFTEGE-IIIGAHRDSLASSS--------AGDANSGSAILLEIARAmskLLKHGWKPLRPIKLISWDGERS 1828
Cdd:cd03879     75 PSIIATIPGSEKSDEiVVIGAHQDSINGSNpsngrapgADDDGSGTVTILEALRV---LLESGFQPKNTIEFHWYAAEEG 151

                           90       100
                   ....*....|....*....|....*..
gi 2361082295 1829 GLLGSTDYAEAHAAiLRRRALVYLNLD 1855
Cdd:cd03879    152 GLLGSQAIATQYKS-EGKNVKAMLQLD 177
M28_like_PA cd05661
M28 Zn-peptidase containing a PA domain insert; Peptidase family M28 (also called ...
 1773-1948 1.73e-10

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: 63.74  E-value: 1.73e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1773 IIIGAHRDSLASS-SAGDANSGSAILLEIARAMSKLlkhgwKPLRPIKLISWDGERSGLLGSTDYAEAHAAILRRRALVY 1851
Cdd:cd05661     79 IIVTSHYDSVVKApGANDNASGTAVTLELARVFKKV-----KTDKELRFIAFGAEENGLLGSKYYVASLSEDEIKRTIGV 153

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1852 LNLDnaISGTNFHCKANPLLQDVIYEAAKLTEFNGHEDWSLFDHWKYTsnatislLDGLSSYTSFqYHLGVPAAHFQFna 1931
Cdd:cd05661    154 FNLD--MVGTSDAKAGDLYAYTIDGKPNLVTDSGAAASKRLSGVLPLV-------QQGSSDHVPF-HEAGIPAALFIH-- 221

                          170
                   ....*....|....*..
gi 2361082295 1932 ndTSGAVYHSNSVFDSP 1948
Cdd:cd05661    222 --MDPETEPVEPWYHTP 236
TFR_dimer pfam04253
Transferrin receptor-like dimerization domain; This domain is involved in dimerization of the ...
 2058-2132 2.51e-08

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: 54.13  E-value: 2.51e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2361082295 2058 KKIKSYIKLQRSNSKSKQIDQLFITHRGLKDREWMKYSLLAPSKFEGSVGEVLPGLHEGLADKDRNEVIQWLTIL 2132
Cdd:pfam04253   30 IKEPDLLAVRAVNDKLMLFERAFLDPEGLPGRPWFKHVVFAPGLWTGYAGATFPGIRDAIEAGDWELAQKQISIV 104
M28_like_PA_PDZ_associated cd05663
M28 Zn-peptidase containing a protease-associated (PA) domain insert and associated with a PDZ ...
 1773-1927 3.35e-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: 57.08  E-value: 3.35e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1773 IIIGAHRD--------SLASSS-------AGDANSGSAILLEIARAMSKLLKHGWKPlRPIKLISWDGERSGLLGSTDYA 1837
Cdd:cd05663     73 VVVGAHYDhlgyggegSLARGDeslihngADDNASGVAAMLELAAKLVDSDTSLALS-RNLVFIAFSGEELGLLGSKHFV 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1838 EAhAAILRRRALVYLNLDN---------AISGTNfhckANPLLQDVIYEAAKLTEFNGHEDWSLFdhwkytsnatislld 1908
Cdd:cd05663    152 KN-PPFPIKNTVYMINMDMvgrlrdnklIVQGTG----TSPGWEQLVQARNKATGFKLILDPTGY--------------- 211

                          170
                   ....*....|....*....
gi 2361082295 1909 GLSSYTSFqYHLGVPAAHF 1927
Cdd:cd05663    212 GPSDHTSF-YLDDVPVLHF 229
Fungal_trans pfam04082
Fungal specific transcription factor domain; This domain is found in a number of fungal ...
 767-881 4.16e-08

Fungal specific transcription factor domain; This domain is found in a number of fungal transcription factors including transcriptional activator xlnR, yeast regulatory protein GAL4, and nicotinate catabolism cluster-specific transcription factor HxnR.


Pssm-ID: 397964  Cd Length: 262  Bit Score: 56.73  E-value: 4.16e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  767 YYKEEFHPFFSFIHLPSI---IFNMDSYP-------LLLSISMVGALY------GFHSTHAKVLANVASTQIR-KSLKAS 829
Cdd:pfam04082    3 LFFKNFHPQFPILHRPSFlrdYFELFSSPsnyasplLLLAILALGALFsesptaRSSSSLTDEAADGIHFFLRaLILIHE 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2361082295  830 EKNPETTELWVIQTLVLLTFYCIFNKNTAVIKGMHGqltTIIRLLKASRLNL 881
Cdd:pfam04082   83 DFSSPSSSLWILQALLLLELYELGTGDRKLHWRYHG---LAIRLARSLGLHR 131
M28_like cd03877
M28 Zn-peptidase, many containing a protease-associated (PA) domain insert; Peptidase family ...
 1773-1855 4.36e-08

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: 55.71  E-value: 4.36e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1773 IIIGAHRDSL--ASSSAGD-----AN---SGSAILLEIARAmsklLKHGWKPLRPIKLISWDGERSGLLGSTDYAEaHAA 1842
Cdd:cd03877     18 IVIGAHYDHLgiGGGDSGDkiyngADdnaSGVAAVLELARY----FAKQKTPKRSIVFAAFTAEEKGLLGSKYFAE-NPK 92

                           90
                   ....*....|...
gi 2361082295 1843 ILRRRALVYLNLD 1855
Cdd:cd03877     93 FPLDKIVAMLNLD 105
PA cd00538
PA: Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction ...
 1570-1637 4.55e-08

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: 53.67  E-value: 4.55e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2361082295 1570 NGSVTARYVFCNYGSISDyklllkKNIDIEDKIHIVRSGKILPGLKVKNAELYGASSVIIYTDPFDDG 1637
Cdd:cd00538     23 VGVVAGPLVGCGYGTTDD------SGADVKGKIVLVRRGGCSFSEKVKNAQKAGAKAVIIYNNGDDPG 84
M28_SGAP_like cd03876
M28 Zn-peptidase Streptomyces griseus aminopeptidase and similar proteins; Peptidase family ...
 1773-1863 9.51e-08

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


Pssm-ID: 349873 [Multi-domain]  Cd Length: 289  Bit Score: 55.77  E-value: 9.51e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1773 IIIGAHRDSLassSAG----DANSGSAILLEIARAMSKllkhgWKPLRPIKLISWDGERSGLLGSTDYAEAHAAILRRRA 1848
Cdd:cd03876     79 VMLGAHLDSV---SAGpginDNGSGSAALLEVALALAK-----FKVKNAVRFAWWTAEEFGLLGSKFYVNNLSSEERSKI 150

                           90
                   ....*....|....*
gi 2361082295 1849 LVYLNLDnAISGTNF 1863
Cdd:cd03876    151 RLYLNFD-MIASPNY 164
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
 1737-1860 7.43e-07

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: 53.36  E-value: 7.43e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1737 PSSSIDKVHLHNELTYNIKEMSSVEVSIPGIFTEGE--IIIGAHRDSLASS-SAGDANSGSAILLEIARAMSkllKHGWK 1813
Cdd:cd03875     59 DTGSGSFNFLSSGMTLVYFEVTNIVVRISGKNSNSLpaLLLNAHFDSVPTSpGATDDGMGVAVMLEVLRYLS---KSGHQ 135

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2361082295 1814 PLRPIKLISWDGERSGLLGSTDYAEAHaaILRRRALVYLNLDNAISG 1860
Cdd:cd03875    136 PKRDIIFLFNGAEENGLLGAHAFITQH--PWAKNVRAFINLEAAGAG 180
PA_hNAALADL2_like cd02131
PA_hNAALADL2_like: Protease-associated domain containing proteins like human N-acetylated ...
 1567-1683 2.30e-06

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: 49.55  E-value: 2.30e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1567 YSKNGSVTARYVFCNYGSISDYKLLlKKNIDIEDKIHIVRSGKiLPGL-KVKNAELYGASSVIIYTDPFDDGKVTEENgf 1645
Cdd:cd02131      9 YSAKGTLQAEVVDVQYGSVEDLRRI-RDNMNVTNQIALLKLGQ-APLLyKLSLLEEAGFGGVLLYVDPCDLPKTRHTW-- 84

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2361082295 1646 lHYPYGPARNPSyikrdsvnyfsdtpGDPTTPGYPSKD 1683
Cdd:cd02131     85 -HQAFMVSLNPG--------------GDPSTPGYPSAD 107
M28_Pgcp_like cd03883
M28 Zn-Peptidase Plasma glutamate carboxypeptidase; Peptidase M28 family; Plasma glutamate ...
 1773-1881 3.33e-06

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: 51.93  E-value: 3.33e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1773 IIIGAHRDSL-ASSSAGDANSGSAILLEIAramsKLLKH-GWKPLRPIKLISWDGERSGLLGSTDYAEAHAAILRRRALV 1850
Cdd:cd03883    243 VLVGGHLDSWdVGTGAMDDGGGVAISWEAL----KLIKDlGLKPKRTIRVVLWTGEEQGLVGAKAYAEAHKDELENHVFA 318

                           90       100       110
                   ....*....|....*....|....*....|.
gi 2361082295 1851 YLNLDNAISGTNFHCKANPLLQDVIYEAAKL 1881
Cdd:cd03883    319 MESDIGTFTPYGLQFTGSDTARAIVKEVMKL 349
M28_like cd05640
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
 1770-1839 4.88e-06

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: 50.52  E-value: 4.88e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2361082295 1770 EGEIIIGAHRDSLASSSAGDAN-SGSAILLEIARAMSKLlkhgwKPLRPIKLISWDGE-----RSGLLGSTDYAEA 1839
Cdd:cd05640     66 DKLILIGAHYDTVPGSPGADDNaSGVAALLELARLLATL-----DPNHTLRFVAFDLEeypffARGLMGSHAYAED 136
M28_like_PA cd05660
M28 Zn-peptidase containing a protease-associated (PA) domain insert; Peptidase family M28 ...
 1773-1838 6.96e-06

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: 50.05  E-value: 6.96e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2361082295 1773 IIIGAHRDSLA--SSSAGDA--------NSGSAILLEIARAMSKLLKhgwKPLRPIKLISWDGERSGLLGSTDYAE 1838
Cdd:cd05660     76 IVLSAHWDHLGigPPIGGDEiyngavdnASGVAAVLELARVFAAQDQ---RPKRSIVFLAVTAEEKGLLGSRYYAA 148
fungal_TF_MHR cd12148
fungal transcription factor regulatory middle homology region; This domain is present in the ...
 756-1248 1.36e-05

fungal transcription factor regulatory middle homology region; This domain is present in the large family of fungal zinc cluster transcription factors that contain an N-terminal GAL4-like C6 zinc binuclear cluster DNA-binding domain. Examples of members of this large fungal group are the following Saccharomyces cerevisiae transcription factors, GAL4, STB5, DAL81, CAT8, RDR1, HAL9, PUT3, PPR1, ASG1, RSF2, PIP2, as well as the C-terminal domain of the Cep3, a subunit of the yeast centromere-binding factor 3. It has been suggested that this region plays a regulatory role.


Pssm-ID: 213391  Cd Length: 410  Bit Score: 49.75  E-value: 1.36e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  756 PTTSQLNDYVTYYKEEFHPFFSFIHLPSIIFNMDSYP------------LLLSISMVGALYGFHSTHAKVLANVASTQIR 823
Cdd:cd12148      1 PPREVADRLLDLYFENVHPLFPILHRPTFLRDLESLYsdpsslspaslaLLLAVLALAALSLPDSELRGESRRSLAERYY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  824 KSLKA--SEKNPETTELWVIQTLVLLTFYCIFNKNTAVIKGMHGQLttiIRLlkASRLNLPLESLRQPPIEsdhimeyen 901
Cdd:cd12148     81 EAARQllDLALFLPPSLETLQALLLLALYLLGTGDPSSAWLLLGLA---IRL--AQSLGLHRDPSSLPGLS--------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  902 sphmfskireqynapnqmnknyqyFVLAQSRIRTCHAVLLISNLFSSLVGADCCFHSVDLKCGVPCYKEELYQCRNSDEW 981
Cdd:cd12148    147 ------------------------PFERELRRRLWWSLYILDRLLSLSLGRPPSISDEDIDVPLPSNEDDELSPSSSPPP 202

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  982 SDllcqhkitldskfslielsngneayenclRFLSTGDSFFYGHARvslstclslLISIHEKILIERNNARIsnnntnsn 1061
Cdd:cd12148    203 PP-----------------------------SEEPTSLSFFIALIR---------LARILGRILRLLYSPRA-------- 236

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1062 nielDDIEWKMTSRQRIDTMLKYWENLYLKNGGILTPTENSMSTINANPAMRLIipvYLFAKMrrCLDLAHVIEKIWLKD 1141
Cdd:cd12148    237 ----SSPEDSLETILELDAELEEWRASLPPELRLDSSSLESPSLLPQRLLLHLL---YHLLLI--LLHRPFLLRSLSSLS 307

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1142 WSNMNKAleevcydmgSLREATEYALNMVDAWTSFFTyikrgKRRIFNTPVFATTCMFTAVLVISEYMKCVEDWARGYNA 1221
Cdd:cd12148    308 PSSSSAE---------SRRACLEAAREILELLRLLLS-----SSLLLLLWWFLLYYLFSAALVLLLALLLRPSSSELEEA 373

                          490       500       510
                   ....*....|....*....|....*....|...
gi 2361082295 1222 NNPNSALLDFSDRV------LWLKAERILRRLQ 1248
Cdd:cd12148    374 RSLLERALELLERLserwprLARRALRLLERLL 406
PRK10199 PRK10199
alkaline phosphatase isozyme conversion aminopeptidase; Provisional
 1683-1860 1.74e-05

alkaline phosphatase isozyme conversion aminopeptidase; Provisional


Pssm-ID: 182299 [Multi-domain]  Cd Length: 346  Bit Score: 49.35  E-value: 1.74e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1683 DSDTEHMSPV--GRVPRIPSVPMSArdvqpilERLNGRGFQIGPGSNIKDFGSFTGPSSSIDKVHLHNeLTynikeMSSV 1760
Cdd:PRK10199    34 NTQARHIATFfpGRMTGSPAEMLSA-------DYLRQQFQQMGYQSDIRTFNSRYIYTARDNRKNWHN-VT-----GSTV 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1761 ----EVSIPGiftegEIIIGAHRDSLASSSAGDAN---------------SGSAILLEIARAMSKllkhgwKPLR-PIKL 1820
Cdd:PRK10199   101 iaahEGKAPQ-----QIIIMAHLDTYAPQSDADVDanlggltlqgmddnaAGLGVMLELAERLKN------VPTEyGIRF 169

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 2361082295 1821 ISWDGERSGLLGSTDYAEAHAAILRRRALVYLNLDNAISG 1860
Cdd:PRK10199   170 VATSGEEEGKLGAENLLKRMSDTEKKNTLLVINLDNLIVG 209
PA pfam02225
PA domain; The PA (Protease associated) domain is found as an insert domain in diverse ...
 1573-1652 1.88e-05

PA domain; The PA (Protease associated) domain is found as an insert domain in diverse proteases. The PA domain is also found in a plant vacuolar sorting receptor Swiss:O22925 and members of the RZF family Swiss:O43567. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors.


Pssm-ID: 460499 [Multi-domain]  Cd Length: 91  Bit Score: 45.20  E-value: 1.88e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1573 VTARYVFCNYGSISDYklllkkniDIEDKIHIVRSGKILPGLKVKNAELYGASSVIIYTDPFDDGKVTEENGFLHYPYGP 1652
Cdd:pfam02225    5 VLAPGCYAGDGIPADF--------DVKGKIVLVRCTFGFRAEKVRNAQAAGAAGVIIYNNVEGLGGPPGAGGNELYPDGI 76
zf-H2C2_2 pfam13465
Zinc-finger double domain;
134-159 1.92e-05

Zinc-finger double domain;


Pssm-ID: 463886 [Multi-domain]  Cd Length: 26  Bit Score: 43.13  E-value: 1.92e-05
                           10        20
                   ....*....|....*....|....*.
gi 2361082295  134 HLKRHQHSHTREKPYLCIFCGRCFAR 159
Cdd:pfam13465    1 NLKRHMRTHTGEKPYKCPECGKSFKS 26
M28_PMSA_TfR_like cd03874
M28 Zn-peptidase Transferrin Receptor-like family; Peptidase M28 family; Transferrin Receptor ...
 1468-1520 2.27e-05

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: 48.45  E-value: 2.27e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2361082295 1468 YLNSLQQENRAKEHVYKYA--GYMSNGASDSSTFKYTLDEFLDMG-YKPKVEKYFP 1520
Cdd:cd03874      1 YARKLVDLAKIKEDLEYLSsmPHMAGTKGDAALAKYIENSFKNNGlFEVELEEYSP 56
M28_like cd05643
M28 Zn-peptidase-like; Peptidase family M28 (also called aminopeptidase Y family), ...
 1711-1808 1.82e-03

M28 Zn-peptidase-like; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They typically 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 protein subfamily conserves some of the metal-coordinating residues of the typically co-catalytic M28 family which might suggest binding of a single metal ion.


Pssm-ID: 349895 [Multi-domain]  Cd Length: 290  Bit Score: 42.78  E-value: 1.82e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295 1711 ILERLNGRGFQIGPGSNIKDFGS-----FTGPSSSIDKVHLHNELTynikemssVEVSIPGIFTEGEIIIGAHrdsLASS 1785
Cdd:cd05643     27 VKELLEELGLEAKLISDIYDGGEriltpQSPISWELIEGELNETLP--------ILYAIIGKETPPEIAFVAH---LCHP 95

                           90       100
                   ....*....|....*....|....*
gi 2361082295 1786 SAG--DANSGSAILLEIARAMSKLL 1808
Cdd:cd05643     96 KPGanDNASGSALLLEVARVLAKLI 120
PA_C5a_like cd02133
PA_C5a_like: Protease-associated domain containing proteins like Streptococcus pyogenes C5a ...
 1574-1630 2.15e-03

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: 40.73  E-value: 2.15e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2361082295 1574 TARYVFCNYGSISDYKlllkkNIDIEDKIHIVRSGKILPGLKVKNAELYGASSVIIY 1630
Cdd:cd02133     27 TYELVDAGLGTPEDFE-----GKDVKGKIALIQRGEITFVEKIANAKAAGAVGVIIY 78
COG5048 COG5048
FOG: Zn-finger [General function prediction only];
106-539 3.96e-03

FOG: Zn-finger [General function prediction only];


Pssm-ID: 227381 [Multi-domain]  Cd Length: 467  Bit Score: 41.99  E-value: 3.96e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  106 PKKSRIIKTDKPRPFLCPTCTRGFVRQEHLKRHQHSHTREKPYLCIFCGRCFARRDLVLRHQQKLHaalvgtgdprrmtp 185
Cdd:COG5048     20 PKSTLKSLSNAPRPDSCPNCTDSFSRLEHLTRHIRSHTGEKPSQCSYSGCDKSFSRPLELSRHLRT-------------- 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  186 APNSTSSFASKRRHSVAADDPTDLHIIKIAGNKETILPTPKNLTGktseelkeavvalaKSNNVELPVSAPVMNDKREKT 265
Cdd:COG5048     86 HHNNPSDLNSKSLPLSNSKASSSSLSSSSSNSNDNNLLSSHSLPP--------------SSRDPQLPDLLSISNLRNNPL 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  266 PPSKAGSLGFREFKFSTKGVPVHSASSDAVIDRASTPSS--MHKTKRHASFSAssamtyMSSSNSPHHSITNFELVEDAP 343
Cdd:COG5048    152 PGNNSSSVNTPQSNSLHPPLPANSLSKDPSSNLSLLISSnvSTSIPSSSENSP------LSSSYSIPSSSSDQNLENSSS 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  344 HqVGFSTPQMTAKQLMESVSELDLPPltLDEPPQAIKFNLNLFNNDPS---GQQQQQQQQQQQNSTSSTIVNSNNGSTVA 420
Cdd:COG5048    226 S-LPLTTNSQLSPKSLLSQSPSSLSS--SDSSSSASESPRSSLPTASSqssSPNESDSSSEKGFSLPIKSKQCNISFSRS 302

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2361082295  421 TPGVYLLSSGP-SLTDLLTMNSAHAGAG--GYMSSHHSPFDLgcFSHDKPTVSELNLPSSFPNTIPSNS---TTASNSYS 494
Cdd:COG5048    303 SPLTRHLRSVNhSGESLKPFSCPYSLCGklFSRNDALKRHIL--LHTSISPAKEKLLNSSSKFSPLLNNeppQSLQQYKD 380

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*..
gi 2361082295  495 NLANQTYTQMSNEQPLMSLSPKNP--PTTVSDSSSTINFNPSANNLL 539
Cdd:COG5048    381 LKNDKKSETLSNSCIRNFKRDSNLslHIITHLSFRPYNCKNPPCSKS 427
 
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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