4MBS,5T1A


Conserved Protein Domain Family
7tmA_CCR5_CCR2

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cd15184: 7tmA_CCR5_CCR2 
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CC chemokine receptor types 5 and 2, member of the class A family of seven-transmembrane G protein-coupled receptors
CCR2 and CCR5 share very high amino acid sequence identity. Both receptors play important roles in the trafficking of monocytes/macrophages and are implicated in the pathogenesis of immunologic diseases (rheumatoid arthritis, celiac disease, and transplant rejection) and cardiovascular diseases (atherosclerosis and autoimmune hepatitis). CCR2 is a receptor specific for members of the monocyte chemotactic protein family, including CCL2, CCL7, and CCL13. Conversely, CCR5 is a major co-receptor for HIV infection and binds many CC chemokine ligands, including CC chemokine ligands including CCL2, CCL3, CCL4, CCL5, CCL11, CCL13, CCL14, and CCL16. CCR2 is expressed primarily on blood monocytes and memory T cells, whereas CCR5 is expressed on antigen-presenting cells (macrophages and dendritic cells) and activated T effector cells. Chemokines are principal regulators for leukocyte trafficking, recruitment, and activation. Chemokine family membership is defined on the basis of sequence homology and on the presence of variations on a conserved cysteine motif, which allows the family to further divide into four subfamilies (CC, CXC, XC, and CX3C). Chemokines interact with seven-transmembrane receptors which are typically coupled to G protein for signaling. Currently, there are ten known receptors for CC chemokines, seven for CXC chemokines, and single receptors for the XC and CX3C chemokines.
Statistics
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PSSM-Id: 341338
Aligned: 9 rows
Threshold Bit Score: 466.538
Created: 16-Dec-2013
Updated: 25-Oct-2021
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 23 residues -Click on image for an interactive view with Cn3D
Feature 1:putative chemokine binding site [polypeptide binding site]
Evidence:
  • Comment:based on structures of chemokine receptors with bound ligands (chemokines, peptides, or chemical antagonists/agonists)
  • Structure:4MBS: Human Ccr5 chemokine receptor binds the HIV entry inhibitor maraviroc, contacts at 4A.
  • Structure:5T1A: Human CC chemokine receptor 2 (CCR2) binds an orthosteric antagonist (BMS-681), contacts at 4A
  • Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracellular surface of its receptor.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1              #                                                #  #               #  ## 
4MBS_A        33 RLLPPLYSLVFIFGFVGNMLVILILINYKRlksmTDIYLLNLAISDLFFLLTVPFWAHYAaaqWDFGntmCQLLTGLYFI 112
5T1A_A        53 QLLPPLYSLVFIFGFVGNMLVVLILINCKKlkclTDIYLLNLAISDLLFLITLPLWAHSAaneWVFGnamCKLFTGLYHI 132
P51682        33 QLLPPLYSLVFIFGFVGNMMVFLILISCKKlksvTDIYLLNLAISDLLFLLTLPFWAHYAaneWVFGnimCKVFTGLYHI 112 house mouse
Q5ECR9        31 RLLPPLYSLVFIFGFVGNVLVVLILIDCKKlksmTDIYLLNLAISDLLFLLTIPFWAHYAadqWTFGnkmCQLLTGLYYI 110 dog
Q1ZY22        31 RLLPPLYSLVFIFGFVGNLLVVLILITCKKlksmTDIYLLNLAISDLLFLLTLPLWAHYAaaeWDFGgamCKVFTGMYHM 110 rabbit
P51681        31 RLLPPLYSLVFIFGFVGNMLVILILINCKRlksmTDIYLLNLAISDLFFLLTVPFWAHYAaaqWDFGntmCQLLTGLYFI 110 human
ABS86967      35 NFLPPLYSLVVIFGFIGNILVVLILVKYKKlksmTDIYLLNLAISDLLFIFSLPFWAYYAahdWIFGdalCRILSGVYLL 114 chicken
P41597        43 QLLPPLYSLVFIFGFVGNMLVVLILINCKKlkclTDIYLLNLAISDLLFLITLPLWAHSAaneWVFGnamCKLFTGLYHI 122 human
XP_003225806  37 HVLPTLYSLVLVFGMLGNALVVLILIRYKKlksmTDIYLLNLAISDLLFVVSLPFWAYSAaheWIFEdamCKILSGIYVV 116 green anole
Feature 1                                                                           ######       
4MBS_A       113 GFFSGIFFIILLTIDRYLAVVHavfALKARtvTFGVVTSVITWVVAVFASLPNIIFtRSQKEglhYTCSSHFPysqyqfW 192
5T1A_A       133 GYFGGIFFIILLTIDRYLAIVHavfALKARtvTFGVVTSVITWLVAVFASVPGIIFtKXQKEdsvYVCGPYFPr----gW 208
P51682       113 GYFGGIFFIILLTIDRYLAIVHavfALKVRtvNFGVITSVVTWAVAVFASLPEIIFtRSQKEgfhYTCSPHFPhtqyhfW 192 house mouse
Q5ECR9       111 GFFTGNFFIILLTMDRYLAIVHavsASKARtvTFGVVTSGIAWVVAVLASFPRIIFtRSQKEgsrFTCSPHFPpsqhhfW 190 dog
Q1ZY22       111 GYFGGIFFIILLTIDRYLAIVHavfALKARtvTFGVVTSGVTWVAAILVSLPDIIFtRSQKEgfrCSCSPHFPasqyqfW 190 rabbit
P51681       111 GFFSGIFFIILLTIDRYLAVVHavfALKARtvTFGVVTSVITWVVAVFASLPGIIFtRSQKEglhYTCSSHFPysqyqfW 190 human
ABS86967     115 GFYSGIFFIILLTVDRYLAIVHavfALKARtvTYGILTSIVTWAVALFASVPGIVFhKTQQEhtrYTCSAHYPqeqrdeW 194 chicken
P41597       123 GYFGGIFFIILLTIDRYLAIVHavfALKARtvTFGVVTSVITWLVAVFASVPGIIFtKCQKEdsvYVCGPYFPr----gW 198 human
XP_003225806 117 GFYSGSFFIILLTIDRYLAIVHavfALKARtvTYGIVTSAVTWCVAILASIPWLIFnKLQREnnhCRCTLSFPpethvnW 196 green anole
Feature 1        #  ##                                                                           
4MBS_A       193 KNFQTLKIVILGLVLPLLVMVICYSGILKTllrmkkytctvcgyiynpedgdpdngvnp--------------------- 251
5T1A_A       209 NNFHTIMRNILGLVLPLLIMVICYSGISRAsksrinifemlrideglrlkiykdtegyytigighlltkspslnaaksel 288
P51682       193 KSFQTLKMVILSLILPLLVMVICYSGILHTlfrc---------------------------------------------- 226 house mouse
Q5ECR9       191 KNFQALKMSVLGLILPLLVMIIGYSAILKTllrc---------------------------------------------- 224 dog
Q1ZY22       191 KNFHTIMRNILSLVLPLLVMIVCYSGILKTllrc---------------------------------------------- 224 rabbit
P51681       191 KNFQTLKIVILGLVLPLLVMVICYSGILKTllrc---------------------------------------------- 224 human
ABS86967     195 KQFLALKMNILGLVIPMIIMICSYTQIIKTllq----------------------------------------------- 227 chicken
P41597       199 NNFHTIMRNILGLVLPLLIMVICYSGILKTllrc---------------------------------------------- 232 human
XP_003225806 197 NQFLTLKINLIGLIFPMIVMIFCYTQIIITlmr----------------------------------------------- 229 green anole
Feature 1                                                                                        
4MBS_A           --------------------------------------------------------------------------------    
5T1A_A       289 dkaigrntngvitkdeaeklfnqdvdaavrgilrnaklkpvydsldavrraalinmvfqmgetgvagftnslrmlqqkrw 368
P51682           --------------------------------------------------------------------------------     house mouse
Q5ECR9           --------------------------------------------------------------------------------     dog
Q1ZY22           --------------------------------------------------------------------------------     rabbit
P51681           --------------------------------------------------------------------------------     human
ABS86967         --------------------------------------------------------------------------------     chicken
P41597           --------------------------------------------------------------------------------     human
XP_003225806     --------------------------------------------------------------------------------     green anole
Feature 1                                                                     #      #  #        
4MBS_A       252 ---------gtdfkdipddwvcplcgvgkdqfeeveeeKKRHRDVRLIFTIMIVYFLFWAPYNIVLLLNTFQEFFGLNNC 322
5T1A_A       369 deaavnlaksrwynqtpnrakrvittfrtgtwdaypppSREKKAVRVIFTIMIVYFLFWTPYNIVILLNTFQEFFGLSNC 448
P51682       227 -----------------------------------rneKKRHRAVRLIFAIMIVYFLFWTPYNIVLLLTTFQEFFGLNNC 271 house mouse
Q5ECR9       225 -----------------------------------rneKKRHKAERLIFVIMIVYFLFWAPYNIVLLLSTFQEFFGLNNC 269 dog
Q1ZY22       225 -----------------------------------rneKRRHRAVRLIFAIMVVYFLFWAPYNVVLLLNTFQEFFGLNNC 269 rabbit
P51681       225 -----------------------------------rneKKRHRAVRLIFTIMIVYFLFWAPYNIVLLLNTFQEFFGLNNC 269 human
ABS86967     228 -----------------------------------crnEKKNKAVRLIFIIMIVYFFFWAPYNICILLRDFQDSFSITSC 272 chicken
P41597       233 -----------------------------------rneKKRHRAVRVIFTIMIVYFLFWTPYNIVILLNTFQEFFGLSNC 277 human
XP_003225806 230 -----------------------------------crnDKKNKAVRLIFIIMIIYFLFWAPYNIVLLLQTFQTSFRLDNC 274 green anole
Feature 1          #   #  ##  #                         
4MBS_A       323 ssSNRLDQAMQVTETLGMTHCCINPIIYAFVGeeFRNYL 361
5T1A_A       449 esTSQLDQATQVTETLGMTHCCINPIIYAFVGekFRRYL 487
P51682       272 ssSNRLDQAMQATETLGMTHCCLNPVIYAFVGekFRSYL 310 house mouse
Q5ECR9       270 nsSNRLDQAMQITETLGMTHCCINPIIYAFVGekFRRYL 308 dog
Q1ZY22       270 ssSNRLDRAMQVTETLGMTHCCINPVVYAFVGekFRSYL 308 rabbit
P51681       270 ssSNRLDQAMQVTETLGMTHCCINPIIYAFVGekFRNYL 308 human
ABS86967     273 eiSGQLQKATQVTETISMIHCCINPVIYAFAGekFRKYL 311 chicken
P41597       278 esTSQLDQATQVTETLGMTHCCINPIIYAFVGekFRSLF 316 human
XP_003225806 275 ysYSNLGVALQVTETLAMAHCCINPVIYAFAGekFRKYT 313 green anole

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