3OE0,3OE6,4RWS


Conserved Protein Domain Family
7tmA_CXCR4

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cd15179: 7tmA_CXCR4 
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CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors
CXCR4 is the only known G protein-coupled chemokine receptor for the key homeostatic ligand CXCL12, which is constitutively secreted by bone marrow stromal cells. Atypical chemokine receptor CXCR7 (ACKR3) also binds CXCL12, but activates signaling in a G protein-independent manner. CXCR4 is also a co-receptor for HIV infection and plays critical roles in the development of immune system during both lymphopoiesis and myelopoiesis. 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: 341334
Aligned: 10 rows
Threshold Bit Score: 434.581
Created: 9-Dec-2008
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:chemokine binding site [polypeptide binding site]
Evidence:
  • Comment:based on structures of chemokine receptors with bound ligands (chemokines, peptides, or chemical antagonists/agonists)
  • Structure:4RWS: Human chemokine receptor CXCR4 binds a viral chemokine; contacts at 4A
  • Structure:3OE0: Human CXCR4 chemokine receptor in complex with a cyclic peptide antagonist, contacts at 4A.
  • Structure:3OE6: Human CXCR4 chemokine receptor in complex with a small molecule antagonist, 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              #                                                #  #               #  ## 
3OE0_A        49 IFLPTIYSIIFLTGIVGNGLVILVMGYQKKlrsmTDKYRLHLSVADLLFVITLPFWAVDAvanWYFGnflCKAVHVIYTV 128
3OE6_A        49 IFLPTIYSIIFLTGIVGNGLVILVMGYQKKlrsmTDKYRLHLSVADLLFVITLPFWAVDAvanWYFGnflCKAVHVIYTV 128
4RWS_A        48 IFLPTIYSIIFLTGIVGNGLVILVMGYQKKlrsmTDKYRLHLSVADLLFVITLPFWAVDAvanWYFGnflCKAVHVIYTV 127
P25930        40 IFLPTVYSIIFLTGIVGNGLVILVMGYQKKlrsmTDKYRLHLSVADLLFVLTLPFWAVDAvanWYFGkflCKAVHVIYTV 119 cow
AAL18011      45 IFLPTVYGIIFVLGLIGNGLVVLVMGCQKKsrtmTDKYRLHLSVADLLFVLTLPFWAVDAakdWYFGgfmCVAVHMIYTV 124 zebrafish
AAH44963      43 IFLPTIYSFIFLLGIIGNGLVVVVMGYQKKsrtmTDKYRLHLSVADLLFVFTLPFWSVDAaigWYFKeflCKAVHVIYTV 122 African clawed ...
AAO21209      50 VFLPVVYGLVCLLGFAGNGLILVILTCFTKkrtsSDLYLMHLAAADLLFVLTMPFWAVGSateWVFGnvlCCLVNFTFTV 129 sea lamprey
NP_989948     45 IFLPTIYSIIFLTGIIGNGLVIIVMGYQKKqrsmTDKYRLHLSVADLLFVITLPFWSVDAaisWYFGnvlCKAVHVIYTV 124 chicken
XP_006006253  45 IFLPIVYSIIFLMGITGNILVIIVMGYQKRsrtmTDKYRLHLSVADLLFVLTLPFWSVSAassWFFGnflCKALHFIYTV 124 coelacanth
NP_001279396  40 ILIPLFYSLIFILGIVGNGLVVLVMGYHKRyrsmTDKYRLHLSVADLLFVLTLPFWAIDTv-nWYFGditCKIVHVIYTM 118 elephant shark
Feature 1                                                                             ######     
3OE0_A       129 NLYSSVWILAFISLDRYLAIVHatnSQRPRKlLAEKVVYVGVWIPALLLTIPDFIFanvse--addryICDRFYPnd--- 203
3OE6_A       129 NLYSSVWILAFISLDRYLAIVHatnSQRPRKlLAEKVVYVGVWIPALLLTIPDFIFanvse--addryICDRFYPnd--- 203
4RWS_A       128 NLYSSVWILAFISLDRYLAIVHatnSQRPRKlLAEKVVYVGVWIPALLLTIPDFIFanvse--addryICCRFYPnd--- 202
P25930       120 NLYSSVLILAFISLDRYLAIVHatnSQKPRKlLAEKVVYVGVWLPAVLLTIPDLIFadike--vderyICDRFYPsd--- 194 cow
AAL18011     125 NLYSSVLILAFISLDRYLAVVRatnSQGPRKlLANRIIYVGVWLPAALLTVPDLVFakaes--sairtFCERIYPqdsfv 202 zebrafish
AAH44963     123 NLYSSVLILAFISLDRYLAIVHatnSQGSRKmLADKVVYAGVWLPALLLTVPDLVFasvsn--engqfVCDRIYPidnre 200 African clawed ...
AAO21209     130 NLASSILLLACISIERYLAIVRatkTDKVRRkFATKVTCGAVWALSLLLAMPDLVFshvyiaplsghqLCEHVYPesase 209 sea lamprey
NP_989948    125 NLYSSVLILAFISLDRYLAIVHatnSQRPRKlLAEKIVYVGVWLPAVLLTVPDIIFastse--vegryLCDRMYPhd--- 199 chicken
XP_006006253 125 NLYSSVLILAFISIDRYLAIVHatnSQRPRKiLAERVVYVGVWLPAILMTVPDIVFakveesglqdlfICERIYPqetht 204 coelacanth
NP_001279396 119 NLYSTVLIMAFISLDRYYAVVHatnSTRQRKmLANRFVYVGVWLPSILLTVPDMVFakttq--lmdriVCDRIYPtetfq 196 elephant shark
Feature 1          #  ##                                                                         
3OE0_A       204 lWVVVFQFQHIMVGLILPGIVILSCYCIIISKLShnifemlrideglrlkiykdtegyytigighlltkspslnaaksel 283
3OE6_A       204 lWVVVFQFQHIMVGLILPGIVILSCYCIIISKLShsgsnifemlrideglrlkiykdtegyytigighlltkspslnaak 283
4RWS_A       203 lWVVVFQFQHIMVGLILPGIVILSCYCIIISKLShnifemlrideglrlkiykdtegyytigighlltkspslnaaksel 282
P25930       195 lWLVVFQFQHIVVGLLLPGIVILSCYCIIISKLShs-------------------------------------------- 230 cow
AAL18011     203 tWVVAFRFQHILVGFVLPGLVILICYCIIISKLSrgs------------------------------------------- 239 zebrafish
AAH44963     201 tWTVGFRFLHITVGLILPGLIILVCYCVIISKLShs-------------------------------------------- 236 African clawed ...
AAO21209     210 lWRTSLRALHHVLAFALPGIVIVFCYVMVIRTLSql-------------------------------------------- 245 sea lamprey
NP_989948    200 nWLISFRFQHILVGLVLPGLIILTCYCIIISKLShs-------------------------------------------- 235 chicken
XP_006006253 205 iWMIAFRFQHILVGLVFPGLIILTCYCIIISRLShs-------------------------------------------- 240 coelacanth
NP_001279396 197 tWLVAFRMKGVLVGFVLPALVILTCYCIIISKLSqs-------------------------------------------- 232 elephant shark
Feature 1                                                                                        
3OE0_A       284 dkaigrntngvitkdeaeklfnqdvdaavrgilrnak---lkpvydsldavrraalinmvfqmgetgvagftnslrmlqq 360
3OE6_A       284 seldkaigrntngvitkdeaeklfnqdvdaavrgilrnaklkpvydsldavrraalinmvfqmgetgvagftnslrmlqq 363
4RWS_A       283 dkaigrntngvitkdeaeklfnqdvdaavrgilrnak---lkpvydsldavrraalinmvfqmgetgvagftnslrmlqq 359
P25930           --------------------------------------------------------------------------------     cow
AAL18011         --------------------------------------------------------------------------------     zebrafish
AAH44963         --------------------------------------------------------------------------------     African clawed ...
AAO21209         --------------------------------------------------------------------------------     sea lamprey
NP_989948        --------------------------------------------------------------------------------     chicken
XP_006006253     --------------------------------------------------------------------------------     coelacanth
NP_001279396     --------------------------------------------------------------------------------     elephant shark
Feature 1                                                                         #      #  #    
3OE0_A       361 krwdeaavnlaksrwynqtpnrakrvittfrtgtwdaysgsgHQKRKALKPTVILILAFFACWLPYYIGISIDSFILlei 440
3OE6_A       364 krwdeaavnlaksrwynqtpnrakrvittfrtgtwdaygskgHQKRKALKTTVILILAFFACWLPYYIGISIDSFILlei 443
4RWS_A       360 krwdeaavnlaksrwynqtpnrakrvittfrtgtwdaysgsgHQKRKALKPTVILILAFFACWLPYYIGISIDSFILlei 439
P25930       231 ----------------------------------------kgYQKRKALKTTVILILTFFACWLPYYIGISIDSFILlei 270 cow
AAL18011     240 ----------------------------------------kgTQKRKALKTTVVLIVCFFVCWLPYCGGILLDTLMMlev 279 zebrafish
AAH44963     237 ----------------------------------------kgHQKRKALKTTVILILAFFACWLPYYVCLTTDTFMMlgl 276 African clawed ...
AAO21209     246 ----------------------------------------hnHEKRKALKVVVAIVAAFFVCWLPYNVVTLLDTLMRlda 285 sea lamprey
NP_989948    236 ----------------------------------------kgHQKRKALKTTVILILTFFACWLPYYIGISIDTFILlgv 275 chicken
XP_006006253 241 ----------------------------------------kgQQKRKALKTTVILILAFFACWLPYYIGISVDVFMLlgv 280 coelacanth
NP_001279396 233 ----------------------------------------tgLQKRKALKITIILIVIFFTCWLPYYIVILIDTVMLmrg 272 elephant shark
Feature 1                #   #  ##  #                         
3OE0_A       441 i-kqgCEFENTVHKWISITEALAFFHCCLNPILYAFLGaKFKTSA 484
3OE6_A       444 i-kqgCEFENTVHKWISITEALAFFHCCLNPILYAFLGaKFKTSA 487
4RWS_A       440 i-kqgCEFENTVHKWISITEALAFFHCCLNPILYAFLGaKFKTSA 483
P25930       271 i-qqgCEFESTVHKWISITEALAFFHCCLNPILYAFLGaKFKTSA 314 cow
AAL18011     280 i-phsCELEQGLQKWIFVTEALAYFHCCLNPILYAFLGvKFKKSA 323 zebrafish
AAH44963     277 v-kadCIWENTLHKAISITEALAFFHCCLNPILYAFLGaKFKKSA 320 African clawed frog
AAO21209     286 vvnsdCEMEQRLGVAVAVTEGVGFSHCCFIPVLYAFVGkKFKENL 330 sea lamprey
NP_989948    276 i-rhrCSLDTIVHKWISITEALAFFHCCLNPILYAFLGaKFKTSA 319 chicken
XP_006006253 281 i-khsCDLESFVAKWISITEALAFFHCCLNPILYAFLGaNFKTSA 324 coelacanth
NP_001279396 273 r-eysCVMEQMVIMAMNLTEAVAYCHCCLNPILYAFVGvNFKSYT 316 elephant shark

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