Conserved Protein Domain Family
7tmA_GPR149

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cd15011: 7tmA_GPR149 
G protein-coupled receptor 149, member of the class A family of seven-transmembrane G protein-coupled receptors
GPR149 is predominantly expressed in the ovary and is present at low levels in the brain and the digestive tract (stomach and small intestine). GPR149-null mice are viable and have normal maturation of the ovarian follicle, but show enhanced fertility and ovulation. Additionally, the null mice showed increased expression levels of growth differentiation factor 9 (Gdf9) in oocytes, and upregulated expression of cyclin D2, a downstream target of FSH (follicle-stimulating hormone) receptor signaling pathways that promotes granulosa cell proliferation. GPR149 is an orphan receptor with no known endogenous ligand as yet identified. Although categorized as a member of the class A GPCRs, GPR149 lacks the first two charged amino acids of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of class A receptors which is important for efficient G protein-coupled signal transduction. Moreover, the transmembrane domains and carboxyl terminus of GPR149 show low similarities to other GPCRs. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.
Statistics
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PSSM-Id: 320139
View PSSM: cd15011
Aligned: 6 rows
Threshold Bit Score: 306.303
Threshold Setting Gi: 632935037
Created: 12-Dec-2013
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative ligand binding pocket [chemical binding site]
Evidence:
  • Comment:based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
  • Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracelllular surface of its receptor.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                              #  ##           ###### ## 
gi 84029267   35 YLFCLTCLMTFAALVGSIYSLISLLKMQNrtvVSMLVASWSVDDLMSVLSVTIFMFLQWpnevpgyfqflCTTSALMYLC 114
gi 82246973   35 FLFCSTFIIAFTVLLGSIYSLVSLLKLQNkstISMIVTSLSIDDLISIVPVIIFMLTQWssdal--pqplCTTSALIYLF 112
gi 512841229  34 LLFSLTLIITLTVFLGSIISLVSLLKMKSkstLSLLVTSLSVDDLVSVVPASIFMLHQWtthal--pqplCSAAAFLYLF 111
gi 556979214  35 ILFCVTFIIALLTLSGSVYSLISLQKMRNktpISVIVVSLSLDDLLSVVAVSIFLFMQLesgev--ssplCSTAAVLYLL 112
gi 632935037  34 VLFSLTLSLCLLTLPGSLYSLLRLLRAPRt-cLTVLVASISLDDALSLVPCSMFLAMQWdrrgl--paslCQASALLYAL 110
gi 410909914  36 LLFGLCVTIAAATFAGGVYSLLSLLRMRRktsLCLIVASMSVDDLLSVVPLSLFMLLQWetdgregsaslCTLSGLLYVF 115
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         #                                              # #####                         
gi 84029267  115 QGLSSNLKATLLVSYNFYTMHRGVgsqta-srrsgQVLGVVLTVWAASLLLSALPLCGWgafvrtpwgclvdcsssyvlf 193
gi 82246973  113 QGISSNLKGSLIVSYNFYSINKTEtmncsaskrrvSMVWAILSIWIVSLLICILPLCGWgkyipttwgcftdhassyilf 192
gi 512841229 112 QGISSNLKASSIICYNFYTVNKLGsyett--kisvKIFCAVATIWVISILISAIPFFGWgrfhttswgcftdctssyilf 189
gi 556979214 113 QGMASNLKASLIASYNYYTTKKLGlfktt--kqkqRIIWAIVTIWIGSLSVSILPLFGWgayvptswgcladymssyvlf 190
gi 632935037 111 QALANVLKSTLLLLYHQGVWAWAGw---------hWAPKLVLLSWVASLALSLLPLCGWgsfvptpwgclvnpqssytll 181
gi 410909914 116 QGVSSNMKACLIAAYTFYVTKRFGvlqsi--rrplRVMWAIAGVWAVSLTVSVLPLCGWgsfapaslgcfpksdsfyill 193
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #  ### ### ##                                                                   
gi 84029267  194 LSIVYALAFGLLVGLSVPLTHRLLCSEEpprlhsnyqeisrgasipgtpptagrvvslspedapgpslrrsggcspssdt 273
gi 82246973  193 LFIVYSLCFCLLTVLSVPLTYQLLCSDEqqllhvnyqeisrgyitpgtpagcstatpclspvdpvdk---tlkhfqnacl 269
gi 512841229 190 LFGLYSLCFCILVILSAPLTHQLLCSDDhqhinykdiskgyltpttplgsnasslspdnpvgktlk------nsnekyvs 263
gi 556979214 191 LFALYSLCVCILTVFSVPLTYQLLCSDDqqqcfypsyqkiarrhlsdrtvtagnssplspedpv----------dktfrt 260
gi 632935037 182 LVSVYALCLCALVLCSVPLTYRLLCSEEqerhlypayyrvsesvslaagpstsedpvektlk-------------slqgg 248
gi 410909914 194 LFSLYSLCFCGLLFFFIPLTYQLLCSREpqrtllypsylqmagglggsspfcdlqsfsrdslnksf------gaynelsp 267
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                         #  ## ##  #      ## ###  #  ## 
gi 84029267  274 vfgpgapaaagaeacrrenrgtlygtrsfTVSVAQKRFALILALTKVVLWLPMMMHMVVQnvvgfqSLPLETFSFLLTLL 353
gi 82246973  270 sskavfrkgvaessgleprcmnnaksrsfTVGFAQKRFSLILALTKVILWLPMMIQMVVQhitgyqSFSFETLSFLLTLL 349
gi 512841229 264 peavfkrsvaetsgdvqhssnsvrggrniTVLYAQKRFSLILALTKVILWLPIMIQMVVQhivafqSLSFETLSFILSLL 343
gi 556979214 261 igerstssevvfknnksqsqnnihsakcsTAVFAQKRFSLILAMVKITLWLPMMIQMVVFhvagfmNTSVERLTFVLSLL 340
gi 632935037 249 gqagslsqladtgvsgrphspeasvsptnKVSFTQKRFSLILAVSKIVLWLPMMIQLLVHhvtrlqSVSIDSLSFMLTLL 328
gi 410909914 268 ssfgtevrepeggcvspvngqgaaavedtPVVFAQKRFSMILAIVRVILWMPLMTLVLLRhvlnasSSSLETLSFFLTLL 347
                        330       340
                 ....*....|....*....|.
Feature 1                             
gi 84029267  354 ATTVTPVFVLSKRwTHLPCGC 374
gi 82246973  350 AATVTPVFVLSEHwIHLPCGC 370
gi 512841229 344 SAAATPLFVLSERwRHLPCGC 364
gi 556979214 341 AAVITPLFVFSERwIHLPCGC 361
gi 632935037 329 ATAVTPIFVLSEHwLQLPCGC 349
gi 410909914 348 APAVTPLFVLSERwIHMPCGC 368

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