Conserved Protein Domain Family
7tmB1_VIP-R2

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cd15986: 7tmB1_VIP-R2 
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors
Vasoactive intestinal peptide (VIP) receptor 2 is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. VIP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. However, depending on its cellular location, VIP-R1 is also capable of coupling to additional G proteins such as G(q) protein, thus leading to the activation of phospholipase C and intracellular calcium influx.
Statistics
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PSSM-Id: 320652
View PSSM: cd15986
Aligned: 5 rows
Threshold Bit Score: 442.321
Threshold Setting Gi: 187607730
Created: 7-Jul-2014
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative polypeptide ligand binding pocket [polypeptide binding site]
Evidence:
  • Comment:based on mutagenesis of human glucagon receptor (GCGR), and modeling studies of GCGR and other related class B GPCRs
  • Comment:Residues in the globular N-terminal extracellular domain and the extracellular loops of the 7TM domain may also be involved in ligand binding.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1               #   #                                         #  ##  #                   
gi 2506490   123 YILVKAIYTLGYSVSLMSLATGSIILCLFRKLHCTRNYIHLNLFLSFILRAISVLVKDDVLYSSsgtlhcpdqpsswVGC 202
gi 62461590  125 YVRVKAIYTLGHSVSLIALTTGSIILCLFRKLHCTRNYIHLNLFLSFILRAISVLVKDDILYSSsntahcpedqtswVGC 204
gi 187607730 125 YIIVQTIYTFGHSVSLIALTIGSTILCLFRKLHCTRNYIHLNMFISFILKAISVLIKDGFLFSNpesc-----peslIGC 199
gi 161878876 126 YTVMKTLYTLGHSLSLIALITGSTILCLFRKLHCTRNYIHLNLFFSFILRAIAVLVKDAILFSHengect--vqpslMGC 203
gi 573893636 128 YLVVKTLYTLGYSASFIALTTGSAILCLFRKLHCTRNYIHLNLFFSFIVKTVSVFVKDEILYSSssltqc-tedlslIGC 206
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #      #                                                                     ## 
gi 2506490   203 KLSLVFLQYCIMANFFWLLVEGLYLHTLLVamlpprRCFLAYLLIGWGLPTVCIGAWTAARLYleDTGCWDtndHSVPWW 282
gi 62461590  205 KAILVFFQYGVMANFYWLLVEGLYLHILLVlifspnRHFTVYLLIGWGIPTIFIITWTVTRIIleDTGCWDtneHGGPWW 284
gi 187607730 200 KVILVLMQYCVMANFYWLLVEGLYLQTLLVviftshKLFIVYLLIGWGIPTIFIIIWIVSRVYldDTECWDtndHSVPWW 279
gi 161878876 204 KVSLVILNYFIMANFYWLLVEGLYLHTLLMvifsenRHFIIYLLIGWGFPTVFVTPWIVCRIYleDTGCWEridNPIPWR 283
gi 573893636 207 KASLVIFQYCAMANYFWLLVEGLYLHTLLVaifsenRHFKVYLLIGWGIPAVFVIAWIVARIYleDTGCWDmtdKDTPKW 286
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        # #                                                       #  #              #   
gi 2506490   283 VIRIPILISIIVNFVLFISIIRILLQKLTSPDVGgndqsQYKRLAKSTLLLIPLFGVHYMVFAVFPISi--sSKYQILFE 360
gi 62461590  285 VIRIPILISIIVNFILFISIIRILLQKLRSPDVGgndqsQYKRLAKSTLLLIPLFGVHYTVFALFPDRs--sNNYKIIFE 362
gi 187607730 280 IIRIPIIISITLNFCLFINIIRILLQKLLSPDVGgndqsQFKRLAKSTLLLIPLFGVHYMVFVGFPMPs--fSDCQIWFE 357
gi 161878876 284 VINWPIMASVILNFILFISIIRILVQKLRCPDVGgndqsQYRRLAKSTLLLIPLFGVHYIVFVYIIDGngerENYKIFFD 363
gi 573893636 287 IINSPIIISIVLNFLLFISIIRILVQKLMCPDVGgndqsQYKRLAKSTLLLIPLFGVHYIVFVSQTLS----PEYQVSFE 362
                        250       260       270
                 ....*....|....*....|....*....|..
Feature 1        #                               
gi 2506490   361 LCLGSFQGLVVAVLYCFLNSEVQCELKRKWRS 392
gi 62461590  363 LCLGSFQGLIVAVLYCFLNSEVQGELKRKWRS 394
gi 187607730 358 LCVGSFQGLVVAILYCFLNTEVQGELKRKWRS 389
gi 161878876 364 LGLGSFQGLVVAILYCFLNSEVQSELKRKWRS 395
gi 573893636 363 LAIGSFQGLVVAILYCFLNSEVQGELKRKWRS 394

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