Conserved Protein Domain Family
7tmB1_Secretin_R-like

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cd15930: 7tmB1_Secretin_R-like 
secretin receptor-like group of hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors
This group represents G protein-coupled receptors for structurally similar peptide hormones that include secretin, growth-hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal peptide (VIP). 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. Secretin, a polypeptide secreted by entero-endocrine S cells in the small intestine, is involved in maintaining body fluid balance. This polypeptide regulates the secretion of bile and bicarbonate into the duodenum from the pancreatic and biliary ducts, as well as regulates the duodenal pH by the control of gastric acid secretion. Studies with secretin receptor-null mice indicate that secretin plays a role in regulating renal water reabsorption. Secretin mediates its biological actions by elevating intracellular cAMP via G protein-coupled secretin receptors, which are expressed in the brain, pancreas, stomach, kidney, and liver. GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. 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. All B1 subfamily GPCRs are able to increase intracellular cAMP levels by coupling to adenylate cyclase via a stimulatory Gs protein. However, depending on its cellular location, some members of subfamily B1 are also capable of coupling to additional G proteins such as G(i/o) and/or G(q) proteins, thereby leading to activation of phospholipase C and intracellular calcium influx.
Statistics
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PSSM-Id: 320596
View PSSM: cd15930
Aligned: 6 rows
Threshold Bit Score: 439.559
Threshold Setting Gi: 71361879
Created: 3-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 974282    139 LLKLKVMYTVGYSSSLVMLLVALGILCAFRRlhctrNYIHMHLFVSFILRALSNFIKDAVLfssddvty---cdphragC 215
gi 392856272 137 FHTVKILYTCGYAASLTALVTAISIFSLFRKlhcprNFIHVNLFVSFILRGIAVFIKDAVLfadedvdh---ctmstvgC 213
gi 21264544  138 YGTVKTGYTIGHTLSLIALTAAMIILCLFRKlhctrNYIHMHLFMSFIMRAIAVFIKDVTLfesgepeh---cfvssvgC 214
gi 71361879  123 FSTIKIIYTVGYSLSITSLIIAVTVLMAFRRlrcprNYIHIQLFFTFILKAIAIFIKDSVLfqeedidh---csfstteC 199
gi 2506490   123 YILVKAIYTLGYSVSLMSLATGSIILCLFRKlhctrNYIHLNLFLSFILRAISVLVKDDVLysssgtlhcpdqpsswvgC 202
gi 2495066   150 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKlhctrNFIHMNLFVSFMLRAISVFIKDWILyaeqdssh---cfvstveC 226
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #      #                                                                      ##
gi 974282    216 KLVMVLFQYCIMANYSWLLVEGLYLHTLLAisffserKYLQGFVAFGWGSPAIFVALWAIARhfledvgCWDinaNASIW 295
gi 392856272 214 KAAVVFFQYSVLANFSWLLVEGMYLHTLLTltftyqrKYFWWYIVIGWGAPALTVSVWIKTRiqfdntgCWDd-yESIYW 292
gi 21264544  215 KAMMVFFQYCVMANFFWLLVEGLYLHTLLVisffserKYFWWYILIGWGAPSVFITAWTVVRiyffnvgCWEeiiESPIW 294
gi 71361879  200 KISVVFCHYFMMTNFIWLLVEALYLNCLLLsslshgrRYFWWLVLFGWGFPTLFTFIWILAKfyfedtaCWDinqDSPYW 279
gi 2506490   203 KLSLVFLQYCIMANFFWLLVEGLYLHTLLVaml-pprRCFLAYLLIGWGLPTVCIGAWTAARlyledtgCWDtndHSVPW 281
gi 2495066   227 KAVMVFFHYCVVSNYFWLFIEGLYLFTLLVetffperRYFYWYTIIGWGTPTVCVTVWAVLRlyfddagCWDmndSTALW 306
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         # #                                                                            
gi 974282    296 WIIRGPVILSILINFILFINILRILMRKLRtqetr----------------------------gnevsHYKRLARSTLLL 347
gi 392856272 293 WIIKTPILLAIFINFIIFLNVIRILIQKIRcpdis----------------------------knykqQYMRLAKSTLLL 344
gi 21264544  295 WIIKTPILVSILVNFILFICIIRILVQKLHspdvg----------------------------hnetsQYSRLAKSTLLL 346
gi 71361879  280 WLIKGPIIISVGVNFVLFINIIRILLKKLDprqin----------------------------fnnssQYRRLSRSTLLL 331
gi 2506490   282 WVIRIPILISIIVNFVLFISIIRILLQKLTspdvg----------------------------gndqsQYKRLAKSTLLL 333
gi 2495066   307 WVIKGPVVGSIMVNFVLFIGIIIILVQKLQspdmggnessiyfscvqkcyckpqraqqhsckmselstITLRLARSTLLL 386
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
Feature 1               #  #            #   #                               
gi 974282    348 IPLFGIHYIVFAFSPEd-aMEIQLFFELALGSFQGLVVAVLYCFLNgEVQLEVQKKWQQ 405
gi 392856272 345 IPLFGVHYVIFALFPEhigIWARMYFELVLGSNQGFIVALLYCFLNgEVQAEIQRHWGK 403
gi 21264544  347 IPLFGIHYIMFAFFPDnfkAQVKLVFELVVGSFQGFVVAVLYCFLNgEVQAELKRKWRR 405
gi 71361879  332 IPLFGTHYIVFNFLPEytsLGIRLYLELCIGSFQGFIVALLYCFLNqEVQTEIGRRWHG 390
gi 2506490   334 IPLFGVHYMVFAVFPIsisSKYQILFELCLGSFQGLVVAVLYCFLNsEVQCELKRKWRS 392
gi 2495066   387 IPLFGIHYTVFAFSPEnvsKRERLVFELGLGSFQGFVVAVLYCFLNgEVQAEIKRKWRS 445

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