Conserved Protein Domain Family
PA_TfR

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cd02128: PA_TfR 
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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.
Statistics
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PSSM-Id: 239043
View PSSM: cd02128
Aligned: 12 rows
Threshold Bit Score: 265.032
Threshold Setting Gi: 47210672
Created: 18-Jan-2005
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
Hierarchy
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Display:
 
Conserved site includes 14 residues -Click on image for an interactive view with Cn3D
Feature 1:PA/protease-like domain interface [polypeptide binding site]
Evidence:
  • Structure:1SUV_A, human transferrin receptor TfR1 in complex with transferrin, contacts of PA domain with protease-like domain at 3.5A.
    View structure with Cn3D

cd02128 is part of a hierarchy of related CD models.
Use the graphical representation to navigate this hierarchy.
cd02128 is a member of the superfamily cl28883.
cd00538:PAcd02120:PA_subtilisin_likecd02121:PA_GCPII_likecd02122:PA_GRAIL_likecd02123:PA_C_RZF_likecd02124:PA_PoS1_likecd02125:PA_VSRcd02126:PA_EDEM3_likecd02127:PA_hPAP21_likecd02128:PA_TfRcd02129:PA_hSPPL_likecd02130:PA_ScAPY_likecd02131:PA_hNAALADL2_likecd02132:PA_GO-likecd02133:PA_C5a_likecd04813:PA_1cd04814:PA_M28_1cd04815:PA_M28_2cd04816:PA_SaNapH_likecd04817:PA_VapT_likecd04818:PA_subtilisin_1cd04819:PA_2cd04820:PA_M28_1_1cd04821:PA_M28_1_2cd04822:PA_M28_1_347210672558319931DE4 C1SUV B1SUV A1DE4 F126325789201406354722799557770576558319912014091247210672558319931DE4 C1SUV B1SUV A1DE4 F1263257892014063547227995577705765583199120140912
cd02128 Sequence Cluster
cd02128 Sequence Cluster
Sub-family Hierarchy
 cd02128 Branch
 Whole Hierarchy
 [Download CDTree]
Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
1DE4_C        79 SVIIvdkn-grlvYLVenPGGYVAYSkAATVTGKLVHANFGtkKDFEDLy---tPVNGSIVIVRAGki-tFAEKVANAES 153
1SUV_B        78 SVIIvdkn-grlvYLVenPGGYVAYSkAATVTGKLVHANFGtkKDFEDLy---tPVNGSIVIVRAGki-tFAEKVANAES 152
1SUV_A        78 SVIIvdkn-grlvYLVenPGGYVAYSkAATVTGKLVHANFGtkKDFEDLy---tPVNGSIVIVRAGki-tFAEKVANAES 152
1DE4_F        79 SVIIvdkn-grlvYLVenPGGYVAYSkAATVTGKLVHANFGtkKDFEDLy---tPVNGSIVIVRAGki-tFAEKVANAES 153
gi 20140635  210 SISIng-----keEILetPDAIVAYSeSGSVSGKPVYVNYGlkKDFEIIqkvvaSLNGTIVIVRAGki-tLAEKVANAKE 283
gi 47210672   64 YCPYgaag--taqVRQpvAMPTAAASrALCLQGGVVYANYGrqQDFHWLqssgvSVGGAVVVIRVGggvsFAEKVWLAEK 141
gi 20140912  211 LHWVdeagkvgeqLPLedPDVYCPYSaIGNVTGELVYAHYGrpEDLQDLrargvDPVGRLLLVRVGvi-sFAQKVTNAQD 289
gi 47227995  189 SIVFk-------dGNEerPSGFLSYSaCGRVMGAVLYGHYGqeSDLMMLqnknlDLSGRVLLLRAGrn-sFAEKVANAAK 260
gi 55831991  209 KVWFg-------nEEIgsPKGFLAYSeTGRREGRVVYANYGepADLQAVqanevSLNGTVVLMRAGri-sMAQKVMNVAK 280
gi 55831993  198 LWLVdseg-aeleEIRldSEGYCAYSaTGTATGGLVYVNYGrrEDFDQLrvmgvSLNGSIAMVRVGggvsFAEKVWLAQE 276
gi 57770576  198 RVLFr-------nNVVgtTEGYLAYSaIKTVQGAALYAHYGraEDFRRLqevsaDVSEKVVLVRAGll-sYAEKVANAAS 269
gi 126325789 208 NVVTiln---esnDLMe-MNGYVAYSvNSTANGTLIYANYGskNDFEQLksqqvTIDGSMVLVRAGkl-sFAEKVENAEA 282
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                     #             #### #   ####  # ###                                 
1DE4_C       154 LNAIGVLIYMDqTKFPivn------aeLSFFGHAHLGTGDPYTPGFPSFNHTQFPPSRSSGLPNIPVQTISRAAAEKLFG 227
1SUV_B       153 LNAIGVLIYMDqTKFPivn------aeLSFFGHAHLGTGDPYTPGFPSFNHTQFPPSRSSGLPNIPVQTISRAAAEKLFG 226
1SUV_A       153 LNAIGVLIYMDqTKFPivn------aeLSFFGHAHLGTGDPYTPGFPSFNHTQFPPSRSSGLPNIPVQTISRAAAEKLFG 226
1DE4_F       154 LNAIGVLIYMDqTKFPivn------aeLSFFGHAHLGTGDPYTPGFPSFNHTQFPPSRSSGLPNIPVQTISRAAAEKLFG 227
gi 20140635  284 AGAAGVLMYVDsLMYGit-------dtLIPFGHAHLGTGDPYTPGFPSFNHTQFPPVESSGLPHIAVQTISSSAAARLFS 356
gi 47210672  142 SGAGGVLIYPDpADLPqdprrlglsshTAVSEHVHLGSGDPFTPGFPSFNHSLVPPLQSSGLPLIPALPVSAAVAAKLLS 221
gi 20140912  290 FGAQGVLIYPEpADFSqdppkpslssqQAVYGHVHLGTGDPYTPGFPSFNQTQFPPVASSGLPSIPAQPISADIASRLLR 369
gi 47227995  261 LNASAVLIYPDpADYAlq-------dtTELFGHVHLGSGDPYTPGFPSFNHTQFPPVVSSGLPKIPAQTITAGMASKILR 333
gi 55831991  281 LGAVAALIYPDpADYDgm--------dTELYGHVHLGSGDPYTPGFPSFNHTQFAPAKSSGLPEILAQTIPASMARKILS 352
gi 55831993  277 AGHVGVLIYPDpADVPqdprrlglhsnAVISEHVHLGSGDPFTPGFPSFNHTQFPSTQSSGLPIIPAQPISANVAAKLLS 356
gi 57770576  270 LNASAVLIYPDpVNYQik-------enTALFGHVHLGTGDPYTPGFPSFNHTQFPPAQSSGLPSIPAQTITTKQASEIMS 342
gi 126325789 283 YNAVGVLIYLArGDFDiid------adIVPFGHAHLGTGDPFTPGFPSFNHTQFPPSQSSGLPTIPVQTISRSQALKLFS 356
                        170       180       190
                 ....*....|....*....|....*....|....*....
Feature 1                                               
1DE4_C       228 NMEGd-CPSDWkt----dsTCRMvts----eskNVKLTV 257
1SUV_B       227 NMEGd-CPSDWkt----dsTCRMvts----eskNVKLTV 256
1SUV_A       227 NMEGd-CPSDWkt----dsTCRMvts----eskNVKLTV 256
1DE4_F       228 NMEGd-CPSDWkt----dsTCRMvts----eskNVKLTV 257
gi 20140635  357 KMDGdtCSEGWkga---ihSCKVttkq--esqiMVKLDV 390
gi 47210672  222 QLTGpsCPPLWrpql-pyvRCLVgpdl--ssgrRVRMSV 257
gi 20140912  370 KLKGpvAPQEWqgsl-lgsPYHLgp------gpRLRLVV 401
gi 47227995  334 QLGGpvVPAGWt------gALRLgde-----kdIITMEV 361
gi 55831991  353 KMGGseVPSKFkgg---ftSYKFgde-----snKVALSI 383
gi 55831993  357 QLSGavCPRGWqgrl-pyvQCVLgpgfsgvgvrQLKMAV 394
gi 57770576  343 KLGGrsSPREWsdgmladtQYLLgdk-----ddIITVEV 376
gi 126325789 357 KMNGadCPQGWdg----dsKCKIss------evNVRLTV 385

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