seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share 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. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  33 DTKYEKDNRCLASNFFTAACLIFLFVVLCLSSLALLVRLFCGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWIK 112
Cdd:cd15105   141 DTKYENDSVCLASNFFTAAYLMFLFVVLCLSSLALLARLFCGAGQMKLTRLYVTIMLTVLVFLLCGLPFGIYWFLLFWIK 220

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958642666 113 IDYGKFAYGLYLAALVLTAVNSCANPIIYFFVGSFRHQ-KHQTLKMVLQRALQDTP 167
Cdd:cd15105   221 DDFHVLDYGLYLASVVLTAVNSCANPIIYFFVGSFRHRlKHQTLKMVLQSALQDTP 276

mas-related G protein-coupled receptor subtype A, member of the class A family of seven-transmembrane G protein-coupled receptors; The Mas-related G-protein coupled receptor (Mrgpr) family constitutes a group of orphan receptors exclusively expressed in nociceptive primary sensory neurons and mast cells in the skin. Members of the Mrgpr family have been implicated in the modulation of nociception, pruritus (itching), and mast cell degranulation. The Mrgpr family in rodents and humans contains more than 50 members that can be grouped into 9 distinct subfamilies: MrgprA, B, C (MrgprX1), D, E, F, G, H (GPR90), and the primate-specific MrgprX subfamily. Some Mrgprs can be activated by endogenous ligands such as beta-alanine, adenine (a cell metabolite and potential transmitter), RF-amide related peptides, or salusin-beta (a bioactive peptide). However, the effects of these agonists are not clearly understood, and the physiological role of the individual receptor family members remains to be determined.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  33 DTKYEKDNRCLASNFFTAACLIFLFVVLCLSSLALLVRLFCGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWIK 112
Cdd:cd15105   141 DTKYENDSVCLASNFFTAAYLMFLFVVLCLSSLALLARLFCGAGQMKLTRLYVTIMLTVLVFLLCGLPFGIYWFLLFWIK 220

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958642666 113 IDYGKFAYGLYLAALVLTAVNSCANPIIYFFVGSFRHQ-KHQTLKMVLQRALQDTP 167
Cdd:cd15105   221 DDFHVLDYGLYLASVVLTAVNSCANPIIYFFVGSFRHRlKHQTLKMVLQSALQDTP 276

G protein-coupled chemokine receptor-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  57 FVVLCLSSLALLVRLFCGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFL----LIWIK---IDYGKFAYGLYlAALVL 129
Cdd:PHA03087  216 LTILLYCYSKILITLKGINKSKKNKKAIKLVLIIVILFVIFWLPFNVSVFVyslhILHFKsgcKAVKYIQYALH-VTEII 294

                          90
                  ....*....|....*...
gi 1958642666 130 TAVNSCANPIIYFFVGSF 147
Cdd:PHA03087  295 SLSHCCINPLIYAFVSEF 312

mas-related G protein-coupled receptor subtype A, member of the class A family of seven-transmembrane G protein-coupled receptors; The Mas-related G-protein coupled receptor (Mrgpr) family constitutes a group of orphan receptors exclusively expressed in nociceptive primary sensory neurons and mast cells in the skin. Members of the Mrgpr family have been implicated in the modulation of nociception, pruritus (itching), and mast cell degranulation. The Mrgpr family in rodents and humans contains more than 50 members that can be grouped into 9 distinct subfamilies: MrgprA, B, C (MrgprX1), D, E, F, G, H (GPR90), and the primate-specific MrgprX subfamily. Some Mrgprs can be activated by endogenous ligands such as beta-alanine, adenine (a cell metabolite and potential transmitter), RF-amide related peptides, or salusin-beta (a bioactive peptide). However, the effects of these agonists are not clearly understood, and the physiological role of the individual receptor family members remains to be determined.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  33 DTKYEKDNRCLASNFFTAACLIFLFVVLCLSSLALLVRLFCGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWIK 112
Cdd:cd15105   141 DTKYENDSVCLASNFFTAAYLMFLFVVLCLSSLALLARLFCGAGQMKLTRLYVTIMLTVLVFLLCGLPFGIYWFLLFWIK 220

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958642666 113 IDYGKFAYGLYLAALVLTAVNSCANPIIYFFVGSFRHQ-KHQTLKMVLQRALQDTP 167
Cdd:cd15105   221 DDFHVLDYGLYLASVVLTAVNSCANPIIYFFVGSFRHRlKHQTLKMVLQSALQDTP 276

mas-related G protein-coupled receptor subtype B, member of the class A family of seven-transmembrane G protein-coupled receptors; The Mas-related G-protein coupled receptor (Mrgpr) family constitutes a group of orphan receptors exclusively expressed in nociceptive primary sensory neurons and mast cells in the skin. Members of the Mrgpr family have been implicated in the modulation of nociception, pruritus (itching), and mast cell degranulation. The Mrgpr family in rodents and humans contains more than 50 members that can be grouped into 9 distinct subfamilies: MrgprA, B, C (MrgprX1), D, E, F, G, H (GPR90), and the primate-specific MrgprX subfamily. Some Mrgprs can be activated by endogenous ligands such as beta-alanine, adenine (a cell metabolite and potential transmitter), RF-amide related peptides, or salusin-beta (a bioactive peptide). However, the effects of these agonists are not clearly understood, and the physiological role of the individual receptor family members remains to be determined.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  42 CLASNFFTAACLIFLFVVLCLSSLALLVRLFCGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWIKIDYGKFAYG 121
Cdd:cd15107   149 CWTLDLITTAWLIVLFVVLSGSSLALLVRIFCGSHRIPVTRLYVTIALTVLVFLIFGLPFGIYWFLLKWIEEFYIVPCCG 228

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958642666 122 LYLAALVLTAVNSCANPIIYFFVGSFRHQKHQ--TLKMVLQRALQDTP 167
Cdd:cd15107   229 FYEVILFLSCVNSCANPIIYFLVGSIRHHRFQrkTLKLLLQRAMQDTP 276

mas-related G protein-coupled receptor subtype E, member of the class A family of seven-transmembrane G protein-coupled receptors; The Mas-related G-protein coupled receptor (Mrgpr) family constitutes a group of orphan receptors exclusively expressed in nociceptive primary sensory neurons and mast cells in the skin. Members of the Mrgpr family have been implicated in the modulation of nociception, pruritus (itching), and mast cell degranulation. The Mrgpr family in rodents and humans contains more than 50 members that can be grouped into 9 distinct subfamilies: MrgprA, B, C (MrgprX1), D, E, F, G, H (GPR90), and the primate-specific MrgprX subfamily. Some Mrgprs can be activated by endogenous ligands such as beta-alanine, adenine (a cell metabolite and potential transmitter), RF-amide related peptides, or salusin-beta (a bioactive peptide). However, the effects of these agonists are not clearly understood, and the physiological role of the individual receptor family members remains to be determined.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  50 AACLIFLFVVLCLSSLALLVRLFCGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWIkidyGKFAYGLYLAALVL 129
Cdd:cd15112   158 AVLLALLCCTMCVSSLVLLLRVERGPPRQRPRGFPALVLLTVLLFLFCGLPFGIYWLSLNLL----WRIPHYFYHFSFLM 233

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958642666 130 TAVNSCANPIIYFFVGSFRHQK-HQTLKMVLQRALQD 165
Cdd:cd15112   234 AAVHSAAKPPIYFCLGSLRGGRfREPLRLVLQRALGD 270

mas-related G protein-coupled receptor 1-like (MAS1L), member of the class A family of seven-transmembrane G protein-coupled receptors; MAS1L is also called MAS1 oncogene-like (MAS1-like) or mas-related G-protein coupled receptor MRG. MAS1L is a G protein-coupled receptor that only found in primates. The angiotensin-II metabolite angiotensin is an endogenous ligand for MAS1L. The Mas-related G-protein coupled receptor (Mrgpr) family constitutes a group of orphan receptors exclusively expressed in nociceptive primary sensory neurons and mast cells in the skin. Members of the Mrgpr family have been implicated in the modulation of nociception, pruritus (itching), and mast cell degranulation. The Mrgpr family in rodents and humans contains more than 50 members that can be grouped into 9 distinct subfamilies: MrgprA, B, C (MrgprX1), D, E, F, G, H (GPR90), and the primate-specific MrgprX subfamily. Some Mrgprs can be activated by endogenous ligands such as beta-alanine, adenine (a cell metabolite and potential transmitter), RF-amide related peptides, or salusin-beta (a bioactive peptide). However, the effects of these agonists are not clearly understood, and the physiological role of the individual receptor family members remains to be determined.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  43 LASNFFTAACLIF---LFVVLCLSSLALLVRLFCGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLliwikIDYGKFA 119
Cdd:cd15113   143 LACDIFHKGFGIFhalISLVMCVSSLTLTIRSLCCSQQCSATRIYHVVRISAIMFLLWGLPLVVAPLL-----PDFEYLT 217

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1958642666 120 YGLYLAALvLTAVNSCANPIIYFFVGSFRHQKH-QTLKMVLQRALQDTP 167
Cdd:cd15113   218 TTFDLLLL-LSIIVSSANPIIYFLVGSLRRKRLkESLKVILQRALADKM 265

mas-related G protein-coupled receptor subtype F, member of the class A family of seven-transmembrane G protein-coupled receptors; The Mas-related G-protein coupled receptor (Mrgpr) family constitutes a group of orphan receptors exclusively expressed in nociceptive primary sensory neurons and mast cells in the skin. Members of the Mrgpr family have been implicated in the modulation of nociception, pruritus (itching), and mast cell degranulation. The Mrgpr family in rodents and humans contains more than 50 members that can be grouped into 9 distinct subfamilies: MrgprA, B, C (MrgprX1), D, E, F, G, H (GPR90), and the primate-specific MrgprX subfamily. Some Mrgprs can be activated by endogenous ligands such as beta-alanine, adenine (a cell metabolite and potential transmitter), RF-amide related peptides, or salusin-beta (a bioactive peptide). However, the effects of these agonists are not clearly understood, and the physiological role of the individual receptor family members remains to be determined.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  54 IFLFVVLC----LSSLALLVRLFCGAGR-MKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWIKIdygKFAYGLYLAALV 128
Cdd:cd15109   159 ILLFLLFCplmvLPCLALILHVECRARRrQRSAKLNHVILAMVSVFLVSSIYLGIDWFLFWVFQI---PAPFPEYVTDLC 235

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958642666 129 LtAVNSCANPIIYFFVGSFRHQK-HQTLKMVLQRALQD 165
Cdd:cd15109   236 I-CINSSAKPIVYFLAGRDKSQRlWEPLRVVFQRALRD 272

opioid receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes opioid receptors, somatostatin receptors, melanin-concentrating hormone receptors (MCHRs), and neuropeptides B/W receptors. Together they constitute the opioid receptor-like family, members of the class A G-protein coupled receptors. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and are involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others. G protein-coupled somatostatin receptors (SSTRs), which display strong sequence similarity with opioid receptors, binds somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. MCHR binds melanin concentrating hormone and is presumably involved in the neuronal regulation of food intake. Despite strong homology with somatostatin receptors, MCHR does not appear to bind somatostatin. Neuropeptides B/W receptors are primarily expressed in the CNS and stimulate the cortisol secretion by activating the adenylate cyclase- and the phospholipase C-dependent signaling pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  45 SNFFTAACLIFLFV----VLCLSSLALLVRLFC------------GAGRMKLTRLYATImltVLVFLLCGLPFGIHWFLL 108
Cdd:cd14970   162 GRVFTIYTFVLGFAvpllVITVCYSLIIRRLRSsrnlstsgarekRRARRKVTRLVLVV---VAVFVVCWLPFHVFQIVR 238

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958642666 109 IWIKIDYGKFAYGLYLAALVLTAVNSCANPIIYFFVG-SFR 148
Cdd:cd14970   239 LLIDPPETLTVVGVFLFCIALSYANSCLNPILYAFLDeNFR 279

somatostatin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled somatostatin receptors (SSTRs) are composed of five distinct subtypes (SSTR1-5) that display strong sequence similarity with opioid receptors. All five receptor subtypes bind the natural somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. They share common signaling cascades such as inhibition of adenylyl cyclase, activation of phosphotyrosine phosphatase activity, and G-protein-dependent regulation of MAPKs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  49 TAACLIFLFVVLCLSSLALlvRLFCGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWIKIDYGKFAYGLYLAALV 128
Cdd:cd15093   179 LIICLCYLLIVIKVKSAGL--RAGWQQRKRSERKVTRMVVMVVVVFVICWLPFYVLQLVNVFVQLPETPALVGVYHFVVI 256

                          90
                  ....*....|....*.
gi 1958642666 129 LTAVNSCANPIIYFFV 144
Cdd:cd15093   257 LSYANSCANPILYGFL 272

KiSS1-derived peptide (kisspeptin) receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The G protein-coupled KiSS1-derived peptide receptor (GPR54 or kisspeptin receptor) binds the peptide hormone kisspeptin (previously known as metastin), which encoded by the metastasis suppressor gene (KISS1) expressed in various endocrine and reproductive tissues. The KiSS1 receptor is coupled to G proteins of the G(q/11) family, which lead to activation of phospholipase C and increase of intracellular calcium. This signaling cascade plays an important role in reproduction by regulating the secretion of gonadotropin-releasing hormone.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  74 GAGRMKLTRLYATImltVLVFLLCGLPfgIHWFLLiWIKIDYG----KFAYGLYLAALVLTAVNSCANPIIYFFVG-SFR 148
Cdd:cd15095   212 LRQKRKVTRMVIVV---VVLFAICWLP--NHVLNL-WQRFDPNfpetYATYALKIAALCLSYANSAVNPFVYAFMGeNFR 285

purinoceptor and its related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; Members of this subfamily include lysophosphatidic acid receptor, P2 purinoceptor, protease-activated receptor, platelet-activating factor receptor, Epstein-Barr virus induced gene 2, proton-sensing G protein-coupled receptors, GPR35, and GPR55, among others. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  47 FFTAACLIFLFVVLCLSSL---ALLVRLFCGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWIKIDYGK------ 117
Cdd:cd14982   169 ALVVGFLIPLLIILVCYSLiirALRRRSKQSQKSVRKRKALRMILIVLAVFLVCFLPYHVTRILYLLVRLSFIAdcsarn 248

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1958642666 118 FAYGLYLAALVLTAVNSCANPIIYFFVGS-FRHQ 150
Cdd:cd14982   249 SLYKAYRITLCLASLNSCLDPLIYYFLSKtFRKR 282

somatostatin receptor type 2, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled somatostatin receptors (SSTRs), which display strong sequence similarity with opioid receptors, binds somatostatin, a polypeptide hormone that regulates a wide variety of physiological such as neurotransmission, endocrine secretion, cell proliferation, and smooth muscle contractility. SSTRs are composed of five distinct subtypes (SSTR1-5) which are encoded by separate genes on different chromosomes. SSTR2 plays critical roles in growth hormone secretion, glucagon secretion, and immune responses. SSTR2 is expressed in the normal human pituitary and in nearly all pituitary growth hormone adenomas.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  48 FTAACLIFLFVVLCLSSLALLVrlfcGAGRMKLTRLYATIMLT--VLVFLLCGLPFGIHWFLLIWIKIDYGKFAYGLYLA 125
Cdd:cd15971   177 LTIICLCYLFIIIKVKSSGIRV----GSSKRKKSEKKVTRMVSivVAVFVFCWLPFYIFNVSSVSVSISPTPGLKGMFDF 252

                          90
                  ....*....|....*....
gi 1958642666 126 ALVLTAVNSCANPIIYFFV 144
Cdd:cd15971   253 VVVLSYANSCANPILYAFL 271

bradykinin receptor B1, member of the class A family of seven-transmembrane G protein-coupled receptors; The bradykinin receptor family is a group of the seven transmembrane G-protein coupled receptors, whose endogenous ligand is the pro-inflammatory nonapeptide bradykinin that mediates various vascular and pain responses. Two major bradykinin receptor subtypes, B1 and B2, have been identified based on their pharmacological properties. The B1 receptor is rapidly induced by tissue injury and inflammation, whereas the B2 receptor is ubiquitously expressed on many tissue types. Both receptors contain three consensus sites for N-linked glycosylation in extracellular domains and couple to G(q) protein to activate phospholipase C, leading to phosphoinositide hydrolysis and intracellular calcium mobilization. They can also interact with G(i) protein to inhibit adenylate cyclase and activate the MAPK (mitogen-activated protein kinase) pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  76 GRMKLTRLYATIMLTVLVFLLCGLPFGIHWFL--LIWIKIDYGKF-----AYGLYLAALvLTAVNSCANPIIYFFVGSFR 148
Cdd:cd15380   204 GGLKDTKATRLILTLVLMFLVCWTPYHFFAFLdfLFQVEVIQGCFweefiDLGLQLANF-FAFANSCLNPVIYVFAGKLF 282

                  ...
gi 1958642666 149 HQK 151
Cdd:cd15380   283 RTK 285

anaphylatoxin receptors and related G protein-coupled chemokine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily of G-protein coupled receptors includes anaphylatoxin receptors, formyl peptide receptors (FPR), prostaglandin D2 receptor 2, GPR1, and related chemokine receptors. The anaphylatoxin receptors are a group of G-protein coupled receptors that bind anaphylatoxins. The members of this group include C3a and C5a receptors. The formyl peptide receptors (FPRs) are chemoattractant GPCRs that involved in mediating immune responses to infection. They are expressed mainly on polymorphonuclear and mononuclear phagocytes and bind N-formyl-methionyl peptides (FMLP), which are derived from the mitochondrial proteins of ruptured host cells or invading pathogens. Chemokine receptor-like 1 (also known as chemerin receptor 23) is a GPCR for the chemoattractant adipokine chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), and for the omega-3 fatty acid derived molecule resolvin E1. Interaction with chemerin induces activation of the MAPK and PI3K signaling pathways leading to downstream functional effects, such as a decrease in immune responses, stimulation of adipogenesis, and angiogenesis. On the other hand, resolvin E1 negatively regulates the cytokine production in macrophages by reducing the activation of MAPK1/3 and NF-kB pathways. Prostaglandin D2 receptor, also known as CRTH2, is a chemoattractant G-protein coupled receptor expressed on T helper type 2 cells that binds prostaglandin D2 (PGD2). PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses and also causes vasodilation. PGD2 exerts its inflammatory effects by binding to two G-protein coupled receptors, the D-type prostanoid receptor (DP) and PD2R2 (CRTH2). PD2R2 couples to the G protein G(i/o) type which leads to a reduction in intracellular cAMP levels and an increase in intracellular calcium. GPR1 is an orphan receptor that can be activated by the leukocyte chemoattractant chemerin, thereby suggesting that some of the anti-inflammatory actions of chemerin may be mediated through GPR1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  55 FLFVVLCLSSLALLVRlfcGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWIKIDYGKFAYGLYLAALVLTAVNS 134
Cdd:cd14974   180 LLIIAICYSVIAVKLR---RKRLAKSSKPLRVLLAVVVAFFLCWLPYHVFALLELVAAAGLPEVVLLGLPLATGLAYFNS 256

                          90
                  ....*....|.
gi 1958642666 135 CANPIIYFFVG 145
Cdd:cd14974   257 CLNPILYVFMG 267

melanin concentrating hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Melanin-concentrating hormone receptor (MCHR) binds melanin concentrating hormone and is presumably involved in the neuronal regulation of food intake and energy homeostasis. Despite strong homology with somatostatin receptors, MCHR does not appear to bind somatostatin. Two MCHRs have been characterized in vertebrates, MCHR1 and MCHR2. MCHR1 is expressed in all mammals, whereas MCHR2 is only expressed in the higher order mammals, such as humans, primates, and dogs, and is not found in rodents. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  52 CLIFLF--VVLCLSSLALLVRLFC-------GAGRMKLTRLYATIMLTVLVFLLCGLPFgiHWFLLIWIKIDYGKFAYG- 121
Cdd:cd15088   170 ILGFAVplVVITVCYILILHRLARgvapgnqSHGSSRTKRVTKMVILIVVVFIVCWLPF--HVVQLVNLAMNRPTLAFEv 247

                          90       100
                  ....*....|....*....|....*...
gi 1958642666 122 LYLAALVLTAVNSCANPIIYFFVGS-FR 148
Cdd:cd15088   248 AYFLSICLGYANSCLNPFVYILVSEnFR 275

N-formyl peptide receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The formyl peptide receptors (FPRs) are chemoattractant GPCRs that involved in mediating immune responses to infection. They are expressed at elevated levels on polymorphonuclear and mononuclear phagocytes. FPRs bind N-formyl peptides, which are derived from the mitochondrial proteins of ruptured host cells or invading pathogens. Activation of FPRs by N-formyl peptides such as N-formyl-Met-Leu-Phe (FMLP) triggers a signaling cascade that stimulates neutrophil accumulation, phagocytosis and superoxide production. These responses are mediated through a pertussis toxin-sensitive G(i) protein that activates a PLC-IP3-calcium signaling pathway. While FPRs are involved in host defense responses to bacterial infection, they can also suppress the immune system under certain conditions. Yet, the physiological role of the FPR family is not fully understood.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  73 CGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWI----KIDYGKFAYGLYLAALVLTAVNSCANPIIYFFVG-SF 147
Cdd:cd15117   205 WREGWVHSSRPFRVLTAVVAAFFLCWFPFHLVSLLELVVilnqKEDLNPLLILLLPLSSSLACVNSCLNPLLYVFVGrDF 284

                  ...
gi 1958642666 148 RHQ 150
Cdd:cd15117   285 RER 287

somatostatin receptor type 5, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled somatostatin receptors (SSTRs) are composed of five distinct subtypes (SSTR1-5) that display strong sequence similarity with opioid receptors. All five receptor subtypes bind the natural somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. SSTR5 is coupled to inward rectifying K channels and phospholipase C, and plays critical roles in growth hormone and insulin secretion. SSTR5 acts as a negative regulator of PDX-1 (pancreatic and duodenal homeobox-1) expression, which is a conserved homeodomain-containing beta cell-specific transcription factor essentially involved in pancreatic development, among many other functions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  52 CLIFLFVVLCLSSLALLVrlfcGAGRMKLTRLYATIM--LTVLVFLLCGLPFGIHWFLLIWIKIDYGKFAYGLYLAALVL 129
Cdd:cd15974   179 CLCYLLIVIKVKSSGLRV----GSTKRRKSERKVTRMvvIIVVVFVFCWLPFYMLNIVNLIVILPEEPAFVGVYFFVVVL 254

                          90
                  ....*....|....*
gi 1958642666 130 TAVNSCANPIIYFFV 144
Cdd:cd15974   255 SYANSCANPILYGFL 269

angiotesin receptor family and its related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the angiotensin receptors, the bradykinin receptors, apelin receptor as well as putative G-protein coupled receptors (GPR15 and GPR25). Angiotensin II (Ang II), the main effector in the renin-angiotensin system, plays a crucial role in the regulation of cardiovascular homeostasis through its type 1 (AT1) and type 2 (AT2) receptors. Ang II contributes to cardiovascular diseases such as hypertension and atherosclerosis via AT1R activation. Ang II increases blood pressure through Gq-mediated activation of phospholipase C, resulting in phosphoinositide (PI) hydrolysis and increased intracellular calcium levels. Through the AT2 receptor, Ang II counteracts the vasoconstrictor action of AT1R and thereby induces vasodilation, sodium excretion, and reduction of blood pressure. Bradykinins (BK) are pro-inflammatory peptides that mediate various vascular and pain responses to tissue injury through its B1 and B2 receptors. Apelin (APJ) receptor binds the endogenous peptide ligands, apelin and Toddler/Elabela. APJ is an adipocyte-derived hormone that is ubiquitously expressed throughout the human body, and Toddler/Elabela is a short secretory peptide that is required for normal cardiac development in zebrafish. Activation of APJ receptor plays key roles in diverse physiological processes including vasoconstriction and vasodilation, cardiac muscle contractility, angiogenesis, and regulation of water balance and food intake. Orphan receptors, GPR15 and GPR25, share strong sequence homology to the angiotensin II type AT1 and AT2 receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  74 GAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFL--LIWIKIDYG-KFAYGLYLA---ALVLTAVNSCANPIIYFFVGSF 147
Cdd:cd14985   200 GKNGRKRRKSLKIIFALVVAFLVCWLPFHFFKFLdfLAQLGAIRPcFWELFLDLGlpiATCLAFTNSCLNPFIYVFVDRR 279

                  ....
gi 1958642666 148 RHQK 151
Cdd:cd14985   280 FRQK 283

neuropeptide Y receptor-like found in insect and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes a novel G protein-coupled receptor (also known as PR4 receptor) from Drosophila melanogaster, which can be activated by the members of the neuropeptide Y (NPY) family, including NPY, peptide YY (PYY) and pancreatic polypeptide (PP), when expressed in Xenopus oocytes. These homologous peptides of 36-amino acids in length contain a hairpin-like structural motif, which referred to as the pancreatic polypeptide fold, and function as gastrointestinal hormones and neurotransmitters. The PR4 receptor also shares strong sequence homology to the mammalian tachykinin receptors (NK1R, NK2R, and NK3R), whose endogenous ligands are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), respectively. The tachykinins function as excitatory transmitters on neurons and cells in the gastrointestinal tract.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958642666  75 AGRMKLTRLYATImltVLVFLLCGLPFGIhwfLLIWIKIDYGKFAYG----LYLAALVLTAVNSCANPIIYFFVGS-FR 148
Cdd:cd15392   212 ESKRKLVKMMITV---VAIFALCWLPLNI---LNLVGDHDESIYSWPyipyLWLAAHWLAMSHCCYNPFIYCWMNAkFR 284

G protein-coupled receptor 25, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR25 is an orphan G-protein coupled receptor that shares strong sequence homology to GPR15 and the angiotensin II receptors. These closely related receptors form a group within the class A G-protein coupled receptors (GPCRs). GPR15 controls homing of T cells, especially FOXP3(+) regulatory T cells, to the large intestine mucosa and thereby mediates local immune homeostasis. Moreover, GRP15-deficient mice were shown to be prone to develop more severe large intestine inflammation. Angiotensin II (Ang II), the main effector in the renin-angiotensin system, plays a crucial role in the regulation of cardiovascular homeostasis through its type 1 (AT1) and type 2 (AT2) receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  43 LASNFFTAAcLIFLFVVLCLSSLALLVRLFCGAGRMKLTRLYAT---IMLTVLVFLLCGLPFGIHWFLLIWIKIDYGKFA 119
Cdd:cd15193   161 LATLFLTFV-LPLIVILFCYCSILVRLRRHFHGAKRTGRRRRNSlriVFAIVTAFVLSWLPFNTLKAVRLLLELGGGVLP 239

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1958642666 120 YGLYLA---ALVLTA----VNSCANPIIYFFV-GSFRHQ 150
Cdd:cd15193   240 CHTTVAirqGLTITAclafVNSCVNPLIYSLLdRHFRRR 278

bombesin receptor subfamily, member of the class A family of seven-transmembrane G protein-coupled receptors; This bombesin subfamily of G-protein coupled receptors consists of neuromedin B receptor (NMBR), gastrin-releasing peptide receptor (GRPR), and bombesin receptor subtype 3 (BRS-3). Bombesin is a tetradecapeptide, originally isolated from frog skin. Mammalian bombesin-related peptides are widely distributed in the gastrointestinal and central nervous systems. The bombesin family receptors couple mainly to the G proteins of G(q/11) family. NMBR functions as the receptor for the neuropeptide neuromedin B, a potent mitogen and growth factor for normal and cancerous lung and for gastrointestinal epithelial tissues. Gastrin-releasing peptide is an endogenous ligand for GRPR and shares high sequence homology with NMB in the C-terminal region. Both NMB and GRP possess bombesin-like biochemical properties. BRS-3 is classified as an orphan receptor and suggested to play a role in sperm cell division and maturation. BRS-3 interacts with known naturally-occurring bombesin-related peptides with low affinity; however, no endogenous high-affinity ligand to the receptor has been identified. The bombesin receptor family belongs to the seven transmembrane rhodopsin-like G-protein coupled receptors (class A GPCRs), which perceive extracellular signals and transduce them to guanine nucleotide-binding (G) proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  86 TIMLTVLVFLLCGLPfgIHWFLLiWI------KIDYGKFAYGLYLAALVLTAVNSCANPI-IYFFVGSFR 148
Cdd:cd15927   225 TVLAFVVLFAVCWLP--RHVFML-WFhfapngLVDYNAFWHVLKIVGFCLSFINSCVNPVaLYLLSGSFR 291

endothelial differentiation gene family, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents the endothelial differentiation gene (Edg) family of G-protein coupled receptors, melanocortin/ACTH receptors, and cannabinoid receptors as well as their closely related receptors. The Edg GPCRs bind blood borne lysophospholipids including sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), which are involved in the regulation of cell proliferation, survival, migration, invasion, endothelial cell shape change and cytoskeletal remodeling. The Edg receptors are classified into two subfamilies: the lysophosphatidic acid subfamily that includes LPA1 (Edg2), LPA2 (Edg4), and LPA3 (Edg7); and the S1P subfamily that includes S1P1 (Edg1), S1P2 (Edg5), S1P3 (Edg3), S1P4 (Edg6), and S1P5 (Edg8). Melanocortin receptors bind a group of pituitary peptide hormones known as melanocortins, which include adrenocorticotropic hormone (ACTH) and the different isoforms of melanocyte-stimulating hormones. Two types of cannabinoid receptors, CB1 and CB2, are activated by naturally occurring endocannabinoids, cannabis plant-derived cannabinoids such as tetrahydrocannabinol, or synthetic cannabinoids. The CB receptors are involved in the various physiological processes such as appetite, mood, memory, and pain sensation. CB1 receptor is expressed predominantly in central and peripheral neurons, while CB2 receptor is found mainly in the immune system.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958642666  86 TIMLTVLVFLLCGLPFGIHWFLLIWIKIDYGKFAYGLYlaALVLTAVNSCANPIIYffvgSFRHQK 151
Cdd:cd14972   211 TVVIVLGVFLVCWLPLLILLVLDVLCPSVCDIQAVFYY--FLVLALLNSAINPIIY----AFRLKE 270

apelin receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Apelin (APJ) receptor is a G protein-coupled receptor that binds the endogenous peptide ligands, apelin and Toddler/Elabela. APJ is an adipocyte-derived hormone that is ubiquitously expressed throughout the human body and Toddler/Elabela is a short secretory peptide that is required for normal cardiac development in zebrafish. Activation of APJ receptor plays key roles in diverse physiological processes including vasoconstriction and vasodilation, cardiac muscle contractility, angiogenesis, and regulation of water balance and food intake.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958642666  82 RLYATIMLTVLVFLLCGLPFGI--HWFLLIWIKI-----DYGKFAYGLYLAALVLTAVNSCANPIIY-FFVGSFRHQ 150
Cdd:cd15190   227 RLLKIIITLVVTFALCWLPFHLvkTLYALMYLGIlpfscGFDLFLMNAHPYATCLAYVNSCLNPFLYaFFDPRFRQQ 303

CXC chemokine receptor types 1 and 2, member of the class A family of seven-transmembrane G protein-coupled receptors; CXCR1 and CXCR2 are closely related chemotactic receptors for a group of CXC chemokines distinguished by the presence of the amino acid motif ELR immediately adjacent to their CXC motif. Expression of CXCR1 and CXCR2 is strictly controlled in neutrophils by external stimuli such as lipopolysaccharide (LPS), tumor necrosis factor (TNF)-alpha, Toll-like receptor agonists, and nitric oxide. CXCL8 (formerly known as interleukin-8) binds with high-affinity and activates both receptors. CXCR1 also binds CXCL7 (neutrophil-activating protein-2), whereas CXCR2 non-selectively binds to all seven ELR-positive chemokines (CXCL1-7). 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  65 LALLVRLFCGAGRMKltRLYAT-----------IMLTVLVFLLCGLPFGIHWF--LLIWIK-IDYGKFAYGLYLAALVLT 130
Cdd:cd15178   176 LPLVVMLFCYGFTIK--TLLQTrsfqkhramrvIFAVVLAFLLCWLPYNVTVLidTLMRTKlITETCELRNHVDVALYVT 253

                          90       100
                  ....*....|....*....|....*
gi 1958642666 131 AV----NSCANPIIYFFVG-SFRHQ 150
Cdd:cd15178   254 QIlgflHSCINPVLYAFIGqKFRNN 278

neurokinin receptors (or tachykinin receptors), member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents G-protein coupled receptors for a variety of neuropeptides of the tachykinin (TK) family. The tachykinins are widely distributed throughout the mammalian central and peripheral nervous systems and act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. SP is a high-affinity endogenous ligand for NK1R, which interacts with the Gq protein and activates phospholipase C, leading to elevation of intracellular calcium. NK2R is a high-affinity receptor for NKA, the tachykinin neuropeptide substance K. SP and NKA are found in the enteric nervous system and mediate in the regulation of gastrointestinal motility, secretion, vascular permeability, and pain perception. NK3R is activated by its high-affinity ligand, NKB, which is primarily involved in the central nervous system and plays a critical role in the regulation of gonadotropin hormone release and the onset of puberty.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958642666  87 IMLTVLVFLLCGLPFGIhWFLLIWIK--IDYGKFAYGLYLAALVLTAVNSCANPIIYFFVGS-FRH 149
Cdd:cd15390   223 MIVVVVIFAICWLPYHL-YFILTYLYpdINSWKYIQQIYLAIYWLAMSNSMYNPIIYCWMNKrFRY 287

G protein-coupled receptor 17, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR17 is a Forkhead box protein O1 (FOXO1) target and abundantly expressed in agouti-related peptide (AGRP) neurons. FOXO1 is a transcription factor that plays key roles in regulation of gluconeogenesis and glycogenolysis by insulin signaling. For instance, food intake and body weight increase when hypothalamic FOXO1 is activated, whereas they both decrease when FOXO1 is inhibited. However, a recent study has been reported that GPR17 deficiency in mice did not affect food intake or glucose homeostasis. Thus, GPR17 may not play a role in the control of food intake, body weight, or glycemic control. GPR17 is phylogenetically closely related to purinergic P2Y and cysteinyl-leukotriene receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  49 TAACLIFLFVVLCLSSLALLVRLFCGAGRMKLTRLYA--TIMLTVLVFLLCGLPFGIHWFLLIWIKIDYG---KFAYGLY 123
Cdd:cd15161   166 LAVAFTIPFVTTVTCYLLIIRSLRTGKREEKPLKDKAikMIILVLTIFLICFVPYHISRYIYILSHNGAGascSSRRGLA 245

                          90       100       110
                  ....*....|....*....|....*....|
gi 1958642666 124 LAALV---LTAVNSCANPIIYFFVG-SFRH 149
Cdd:cd15161   246 LANRItscLTCLNGALDPVMYFFVAeKFRE 275

proton-sensing G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Proton/pH-sensing G-protein coupled receptors sense pH of 7.6 to 6.0. They mediate a variety of biological activities in neutral and mildly acidic pH conditions, whereas the acid-sensing ionotropic ion channels typically sense strong acidic pH. The proton/pH-sensing receptor family includes the G2 accumulation receptor (G2A, also known as GPR132), the T cell death associated gene-8 (TDAG8, GPR65) receptor, ovarian cancer G-protein receptor 1 (OGR-1, GPR68), and G-protein-coupled receptor 4 (GPR4).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958642666  82 RLYATIMLTVLVFLLCGLPFGI------HWFLLIWIKIDYGKFAYGLYLAALVLTAVNSCANPIIYFFV 144
Cdd:cd15160   204 KIIGLLLSIVVIFLLCFLPYHVvllvrsVIELVQNGLCGFEKRVFTAYQISLCLTSLNCVADPILYIFV 272

purinergic receptor P2Y8, member of the class A family of seven-transmembrane G protein-coupled receptors; P2Y8 (or P2RY8) expression is often increased in leukemia patients, and it plays a role in the pathogenesis of acute leukemia. P2Y8 is phylogenetically closely related to the protease-activated receptors (PARs), which are activated by serine proteases such as thrombin, trypsin, and tryptase. These proteases cleave the extracellular domain of the receptor to form a new N-terminus, which in turn functions as a tethered ligand. The newly-formed tethered ligand binds intramolecularly to activate the receptor and triggers G-protein binding and intracellular signaling. Four different types of the protease-activated receptors have been identified (PAR1-4) and are predominantly expressed in platelets. PAR1, PA3, and PAR4 are activated by thrombin, whereas PAR2 is activated by trypsin. The PARs are known to couple with several G-proteins including Gi (cAMP inhibitory), G12/13 (Rho and Ras activation), and Gq (calcium signaling) to activate downstream signaling messengers which induces numerous cellular and physiological effects.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958642666  55 FLFVVLCLSSLAL-LVRLFCGAGRMKLTRLYATIMLTVLVFLLCGLPFGIHWFLLIWIKIDYGKFAYGLYLAALVLTAVN 133
Cdd:cd15368   183 FIITVYCYVLIILkLVQTSERYGREQKRRAIYLALIVLLVFITCFAPNNFILLAHMVSRLFYGKSLYHAYKLTLSLSCLN 262

                          90
                  ....*....|
gi 1958642666 134 SCANPIIYFF 143
Cdd:cd15368   263 SCLDPFIYYF 272

neuromedin-K receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The neuromedin-K receptor (NKR), also known as tachykinin receptor 3 (TACR3) or neurokinin B receptor or NK3R, is a G-protein coupled receptor that specifically binds to neurokinin B. The tachykinins (TKs) act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. NK3R is activated by its high-affinity ligand, NKB, which is primarily involved in the central nervous system and plays a critical role in the regulation of gonadotropin hormone release and the onset of puberty.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958642666  76 GRMKLTRLYATIML-TVLVFLLCGLPFGIHWFLL-IWIKIDYGKFAYGLYLAALVLTAVNSCANPIIY 141
Cdd:cd16003   204 EQLRAKRKVVKMMIiVVLTFAICWLPYHIYFIVTgLYQQLNRWKYIQQVYLASFWLAMSSTMYNPIIY 271