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 1958643172  29 IFSYLIFALTFVLGVLGNGLVIWVAGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVID 108
Cdd:cd14974     1 IVSLVLYALIFLLGLPGNGLVIWVAGFKMKRTVNTVWFLNLALADFLFCLFLPFLIVYIAMGHHWPFGSVLCKLNSFVIS 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958643172 109 INLFGSVFLIALIALDRCVCVLHPVWAQNHRTVTLA 144
Cdd:cd14974    81 LNMFASVFLLTAISLDRCLLVLHPVWAQNHRTVRLA 116

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 1958643172  29 IFSYLIFALTFVLGVLGNGLVIWVAGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVID 108
Cdd:cd14974     1 IVSLVLYALIFLLGLPGNGLVIWVAGFKMKRTVNTVWFLNLALADFLFCLFLPFLIVYIAMGHHWPFGSVLCKLNSFVIS 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958643172 109 INLFGSVFLIALIALDRCVCVLHPVWAQNHRTVTLA 144
Cdd:cd14974    81 LNMFASVFLLTAISLDRCLLVLHPVWAQNHRTVRLA 116

CC chemokine receptor-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  33 LIFALTFVLGVLGNGLVIWVAGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVmgGIWPFGWFMCKFIYTVIDINLF 112
Cdd:PHA02638  103 IFYIIIFILGLFGNAAIIMILFCKKIKTITDIYIFNLAISDLIFVIDFPFIIYNEF--DQWIFGDFMCKVISASYYIGFF 180

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1958643172 113 GSVFLIALIALDRCVCVLHPVWAQNHRTVTL 143
Cdd:PHA02638  181 SNMFLITLMSIDRYFAILYPISFQKYRTFNI 211

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 1958643172  29 IFSYLIFALTFVLGVLGNGLVIWVAGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVID 108
Cdd:cd14974     1 IVSLVLYALIFLLGLPGNGLVIWVAGFKMKRTVNTVWFLNLALADFLFCLFLPFLIVYIAMGHHWPFGSVLCKLNSFVIS 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958643172 109 INLFGSVFLIALIALDRCVCVLHPVWAQNHRTVTLA 144
Cdd:cd14974    81 LNMFASVFLLTAISLDRCLLVLHPVWAQNHRTVRLA 116

chemokine-like receptor 1, member of the class A family of seven-transmembrane G protein-coupled receptors; 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. CMKLR1 is prominently expressed in dendritic cells and macrophages.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  29 IFSYLIFALTFVLGVLGNGLVIWVAGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVID 108
Cdd:cd15116     1 ILSMVIYSVVFVLGVLGNGLVIFITGFKMKKTVNTVWFLNLAVADFLFTFFLPFSIAYTAMDFHWPFGRFMCKLNSFLLF 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958643172 109 INLFGSVFLIALIALDRCVCVLHPVWAQNHRTVTLAK 145
Cdd:cd15116    81 LNMFTSVFLLTVISIDRCISVVFPVWSQNHRSVRLAS 117

complement component 5a anaphylatoxin chemotactic receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The anaphylatoxin receptors are a group of G-protein coupled receptors which bind anaphylatoxins; members of this group include C3a receptors and C5a receptors. Anaphylatoxins are also known as complement peptides (C3a, C4a and C5a) that are produced from the activation of the complement system cascade. These complement anaphylatoxins can trigger degranulation of endothelial cells, mast cells, or phagocytes, which induce a local inflammatory response and stimulate smooth muscle cell contraction, histamine release, and increased vascular permeability. They are potent mediators involved in chemotaxis, inflammation, and generation of cytotoxic oxygen-derived free radicals. In humans, a single receptor for C3a (C3AR1) and two receptors for C5a (C5AR1 and C5AR2, also known as C5L2 or GPR77) have been identified, but there is no known receptor for C4a.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  29 IFSYLIFALTFVLGVLGNGLVIWVAGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVID 108
Cdd:cd15114     1 VVALVLYAVVFLVGVPGNALVAWVTGFEAKRSVNAVWFLNLAVADLLCCLSLPILAVPIAQDGHWPFGAAACKLLPSLIL 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958643172 109 INLFGSVFLIALIALDRCVCVLHPVWAQNHRTVTLA 144
Cdd:cd15114    81 LNMYASVLLLTAISADRCLLVLRPVWCQNHRRARLA 116

orphan receptor GPR33, member of the class A family of seven-transmembrane G protein-coupled receptors; G-protein coupled receptor GPR33, an orphan member of the chemokine-like receptor family, was originally identified as a pseudogene in humans as well as in several apes and rodent species. Although the intact GPR33 allele is still present in a small fraction of the human population, the human GPR33 contains a premature stop codon. The amino acid sequence of GPR33 shares a high degree of sequence identity with the members of the chemokine and chemoattractant receptors that control leukocyte chemotaxis. The human GPR33 is expressed in spleen, lung, heart, kidney, pancreas, thymus, gonads, and leukocytes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  33 LIFALTFVLGVLGNGLVIWVAGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVIDINLF 112
Cdd:cd15120     5 VALFVTFLVGLVVNGLYLWVLGFKMRRTVNTLWFLHLILSNLIFTLILPFMAVHVLMDNHWAFGTVLCKVLNSTLSVGMF 84

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1958643172 113 GSVFLIALIALDRCVCVLHPVWAQNHRTVTLAKK 146
Cdd:cd15120    85 TSVFLLTAISLDRYLLTLHPVWSRQHRTNRWASA 118

classical and atypical chemokine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; 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. In addition to these classical chemokine receptors, there exists a subfamily of atypical chemokine receptors (ACKRs) that are unable to couple to G-proteins and, instead, they preferentially mediate beta-arrestin dependent processes, such as receptor internalization, after ligand binding. The classical chemokine receptors contain a conserved DRYLAIV motif in the second intracellular loop, which is required for G-protein coupling. However, the ACKRs lack this conserved motif and fail to couple to G-proteins and induce classical GPCR signaling. Five receptors have been identified for the ACKR family, including CC-chemokine receptors like 1 and 2 (CCRL1 and CCRL2), CXCR7, Duffy antigen receptor for chemokine (DARC), and D6. Both ACKR1 (DARC) and ACKR3 (CXCR7) show low sequence homology to the classic chemokine receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  34 IFALTFVLGVLGNGLVIWVAGFRMK-RTVTTISYLNLAIADFCFTSTLPFYIVSLVMGgiWPFGWFMCKFIYTVIDINLF 112
Cdd:cd14984     6 LYSLVFLLGLVGNSLVLLVLLYYRKlRSMTDVYLLNLALADLLFVLTLPFWAVYAADG--WVFGSFLCKLVSALYTINFY 83

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1958643172 113 GSVFLIALIALDRCVCVLHPVWAQNHRTVTLAK 145
Cdd:cd14984    84 SGILFLACISIDRYLAIVHAVSALRARTLLHGK 116

somatostatin-like receptor for allatostatin C, 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. In Drosophila melanogaster and other insects, a 15-amino-acid peptide named allatostatin C(AstC) binds the somatostatin-like receptors. Two AstC receptors have been identified in Drosophila with strong sequence homology to human somatostatin and opioid receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  29 IFSYLIFALTFVLGVLGNGLVIWVA-GFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGiWPFGWFMCKFIYTVI 107
Cdd:cd15094     1 LISAVLYGLICIVGLVGNGLVIYVVlRYAKMKTVTNLYILNLAVADECFLIGLPFLIVTMILKY-WPFGAAMCKIYMVLT 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958643172 108 DINLFGSVFLIALIALDRCVCVLHPVWAQNHRTVTLAK 145
Cdd:cd15094    80 SINQFTSSFTLTVMSADRYLAVCHPIRSMRYRTPFIAK 117

type 1 angiotensin II receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; 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 AT2R, Ang II counteracts the vasoconstrictor action of AT1R and thereby induces vasodilation, sodium excretion, and reduction of blood pressure. Moreover, AT1R promotes cell proliferation, whereas AT2R inhibits proliferation and stimulates cell differentiation. The AT2R is highly expressed during fetal development, however it is scarcely present in adult tissues and is induced in pathological conditions. Generally, the AT1R mediates many actions of Ang II, while the AT2R is involved in the regulation of blood pressure and renal function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  34 IFALTFVLGVLGNGLVIWVAGFRMK-RTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVIDINLF 112
Cdd:cd15192     6 VYSIIFVVGIFGNSLVVIVIYCYMKlKTVANIFLLNLALADLCFLITLPLWAAYTAMEYHWPFGNFLCKIASALVSFNLY 85

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1958643172 113 GSVFLIALIALDRCVCVLHPVWAQNHRTVTLAK 145
Cdd:cd15192    86 ASVFLLTCLSIDRYLAIVHPMKSRLRRTLVVAR 118

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 1958643172  33 LIFALTFVLGVLGNGLVIWVAGF-RMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGgiWPFGWFMCKFIYTVIDINL 111
Cdd:cd15178     5 VIYVLVFLLSLPGNSLVVLVILYnRRSRSSTDVYLLHLAIADLLFALTLPFWAVSVVKG--WIFGTFMCKLVSLLQEANF 82

                          90       100
                  ....*....|....*....|....*...
gi 1958643172 112 FGSVFLIALIALDRCVCVLHPVWAQNHR 139
Cdd:cd15178    83 YSGILLLACISVDRYLAIVHATRALTQK 110

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 1958643172  33 LIFALTFVLGVLGNGLVIWVAGFRMK-RTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVIDINL 111
Cdd:cd14982     5 IVYSLIFILGLLGNILALWVFLRKMKkRSPTTIYMINLALADLLFVLTLPFRIYYYLNGGWWPFGDFLCRLTGLLFYINM 84

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1958643172 112 FGSVFLIALIALDRCVCVLHPVWAQNHRTVTLAKK 146
Cdd:cd14982    85 YGSILFLTCISVDRYLAVVHPLKSRRLRRKRYAVG 119

mas-related G protein-coupled receptors, 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. Also included in this family is Mas-related G-protein coupled receptor 1-like (MAS1L) which is only found in primates. The angiotensin-II metabolite angiotensin is an endogenous ligand for MAS1L.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  32 YLIFALTFVLGVLGNGLVIWVAGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGwFMCKFIYTVIDINL 111
Cdd:cd14973     4 FSLTVLLSLCGLVGNGLVLWLLGFRIKRNPFSVYILNLAAADFLFLSCQAIQSLEDLLGGSLPGF-ALCRLLATLMFFSY 82

                          90       100
                  ....*....|....*....|....*...
gi 1958643172 112 FGSVFLIALIALDRCVCVLHPVWAQNHR 139
Cdd:cd14973    83 TVGLSLLAAISTERCLSVLFPIWYRCHR 110

leukotriene B4 receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Leukotriene B4 (LTB4), a metabolite of arachidonic acid, is a powerful chemotactic activator for granulocytes and macrophages. Two receptors for LTB4 have been identified: a high-affinity receptor (LTB4R1 or BLT1) and a low-affinity receptor (TB4R2 or BLT2). Both BLT1 and BLT2 receptors belong to the rhodopsin-like G-protein coupled receptor superfamily and primarily couple to G(i) proteins, which lead to chemotaxis, calcium mobilization, and inhibition of adenylate cyclase. In some cells, they can also couple to the G(q)-like protein, G16, and activate phospholipase C. LTB4 is involved in mediating inflammatory processes, immune responses, and host defense against infection. Studies have shown that LTB4 stimulates leukocyte extravasation, neutrophil degranulation, lysozyme release, and reactive oxygen species generation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  34 IFALTFVLGVLGNGLVIWVAGFRMK-RTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGiWPFGWFMCKFIYTVIDINLF 112
Cdd:cd14975     6 LLSLAFAIGLPGNSFVIWSILIKVKqRSVTMLLVLNLALADLAVLLTLPVWIYFLATGT-WDFGLAACKGCVYVCAVSMY 84

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1958643172 113 GSVFLIALIALDRCVCVLHPVWAQNHRTVTLAKK 146
Cdd:cd14975    85 ASVFLITLMSLERFLAVSRPFVSQGWRAKALAHK 118

protease-activated receptor 4, member of the class A family of seven-transmembrane G protein-coupled receptors; Protease-acted receptors (PARs) are seven-transmembrane proteins that belong to the class A G-protein coupled receptor (GPCR) family. Four different types of the protease-activated receptors have been identified: PAR1, PAR2, PAR3, and PAR4. PARs are predominantly expressed in platelets and 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. 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 1958643172  34 IFALTFVLGVLGNGLVIWVAGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVIDINLFG 113
Cdd:cd15372     6 LYTLVFLVGLPANGLALWVLATQVKRLPSTIFLINLAVADLLLILVLPFKISYHFLGNNWPFGEGLCRVVTAFFYGNMYC 85

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1958643172 114 SVFLIALIALDRCVCVLHPVWAQNHRTVTLA 144
Cdd:cd15372    86 SVLLLMCISLDRYLAVVHPFFARTLRSRRFA 116

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  29 IFSYLIFALTFVLGVLGNGLVIWVAGFRMK-RTVTTISYLNLAIADFCFTSTLPFYIVSLVMGgiWPFGWFMCKFIYTVI 107
Cdd:cd15179     1 IFLPTVYSIIFLLGIVGNGLVILVMGYQKKsRTMTDKYRLHLSVADLLFVLTLPFWAVDAAAN--WYFGNFLCKAVHVIY 78

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1958643172 108 DINLFGSVFLIALIALDRCVCVLHPVWAQNHR 139
Cdd:cd15179    79 TVNLYSSVLILAFISLDRYLAIVHATNSQRPR 110

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 1958643172  33 LIFALTFVLGVLGNGLVIWVAGFRMK-RTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGiWPFGWFMCKFIYTVIDINL 111
Cdd:cd15093     5 CIYAVVCLVGLCGNSLVIYVVLRYAKmKTVTNIYILNLAIADELFMLGLPFLAASNALRH-WPFGSVLCRLVLSVDGINM 83

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1958643172 112 FGSVFLIALIALDRCVCVLHPVWAQNHRTVTLAK 145
Cdd:cd15093    84 FTSIFCLTVMSVDRYLAVVHPIKSARWRRPRVAK 117

P2Y purinoceptor 3-like proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; P2Y3-like proteins are an uncharacterized group that belongs to the G(i) class of a family of purinergic G-protein coupled receptors. The P2Y receptor family is composed of eight subtypes, which are activated by naturally occurring extracellular nucleotides such as ATP, ADP, UTP, UDP, and UDP-glucose. These eight receptors are ubiquitous in human tissues and can be further classified into two subfamilies based on sequence homology and second messenger coupling: a subfamily of five P2Y1-like receptors (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11Rs) that are coupled to G(q) protein to activate phospholipase C (PLC) and a second subfamily of three P2Y12-like receptors (P2Y12, P2YR13, and P2Y14Rs) that are coupled to G(i) protein to inhibit adenylate cyclase. Several cloned subtypes, such as P2Y3, P2Y5, and P2Y7-10, are not functional mammalian nucleotide receptors. The native agonists for P2Y receptors are: ATP (P2Y2, P2Y12), ADP (P2Y1, P2Y12, and P2Y13), UTP (P2Y2, P2Y4), UDP (P2Y6, P2Y14), and UDP-glucose (P2Y14).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  33 LIFALTFVLGVLGNGLVIWVAGFRMKR-TVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVIDINL 111
Cdd:cd16001     5 VTYSVVFVLGLPLNGTVLWLSWCRTKRwTCSTIYLVNLAVADLLYVCSLPLLIVNYAMRDRWPFGDFLCKLVRFLFYTNL 84

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1958643172 112 FGSVFLIALIALDRCVCVLHPVWAQNHRTVTLA 144
Cdd:cd16001    85 YGSILFLTCISVHRFLGVCYPIRSLAYRTRRLA 117

CC chemokine receptor type 9, member of the class A family of seven-transmembrane G protein-coupled receptors; CCR9 is a homeostatic receptor specific for CCL25 (formerly known as thymus expressed chemokine) and is highly expressed on both immature and mature thymocytes as well as on intestinal homing T Lymphocytes and mucosal Lymphocytes. In cutaneous melanoma, activation of CCR9-CCL25 has been shown to stimulate metastasis to the small intestine. 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. The CC chemokine receptors are all activating the G protein Gi.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  34 IFALTFVLGVLGNGLVIWV-AGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGgiWPFGWFMCKFIYTVIDINLF 112
Cdd:cd15174     6 LYWLIFLVGAVGNSLVVLIyTYYRRRKTMTDVYLLNLAIADLLFLCTLPFWATAASSG--WVFGTFLCKVVNSMYKINFY 83

                          90       100
                  ....*....|....*....|....*...
gi 1958643172 113 GSVFLIALIALDRCVCVLHPVWAQNHRT 140
Cdd:cd15174    84 SCMLLLTCISVDRYIAIVQATKAHNSKN 111

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  34 IFALTFVLGVLGNGLVIWVAgFRMK---RTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVIDIN 110
Cdd:cd15190    16 IYMLVFVLGLSGNGLVLWTV-FRSKrkrRRSADTFIANLALADLTFVVTLPLWAVYTALGYHWPFGSFLCKLSSYLVFVN 94

                          90       100
                  ....*....|....*....|...
gi 1958643172 111 LFGSVFLIALIALDRCVCVLHPV 133
Cdd:cd15190    95 MYASVFCLTGLSFDRYLAIVRSL 117

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 1958643172  34 IFALTFVLGVLGNGLVIWV-AGFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVIDINLF 112
Cdd:cd15088     6 VFGCICVVGLVGNGIVLYVlVRCSKLRTAPDIFIFNLAVADLLFMLGMPFLIHQFAIDGQWYFGEVMCKIITALDANNQF 85

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1958643172 113 GSVFLIALIALDRCVCVLHPVWAQNHRTVTLAK 145
Cdd:cd15088    86 TSTYILTAMSVDRYLAVVHPIRSTKYRTRFVAK 118

CC chemokine receptor type 3, member of the class A family of seven-transmembrane G protein-coupled receptors; CCR3 is a highly promiscuous receptor that binds a variety of inflammatory CC-type chemokines, including CCL11 (eotaxin-1), CCL3L1, CCL5 (regulated on activation, normal T cell expressed and secreted; RANTES), CCL7 (monocyte-specific chemokine 3 or MCP-3), CCL8 (MCP-2), CCL11, CCL13 (MCP-4), CCL15, CCL24 (eotaxin-2), CCL26 (eotaxin-3), and CCL28. Among these, the eosinophil chemotactic chemokines (CCL11, CCL24, and CCL26) are the most potent and specific ligands. In addition to eosinophil, CCR3 is expressed on cells involved in allergic responses, such as basophils, Th2 lymphocytes, and mast cells. 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 1958643172  34 IFALTFVLGVLGNGLVIWV-AGFRMKRTVTTISYLNLAIADFCFTSTLPFYIvSLVMGGIWPFGWFMCKFIYTVIDINLF 112
Cdd:cd15185     6 LYSLVFIVGLLGNVVVVVIlIKYRRLRIMTNIYLLNLAISDLLFLFTLPFWI-HYVRWNNWVFGHGMCKLLSGFYYLGLY 84

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1958643172 113 GSVFLIALIALDRCVCVLHPVWAQNHRTVTLA 144
Cdd:cd15185    85 SEIFFIILLTIDRYLAIVHAVFALRARTVTFG 116

opioid receptor subtype kappa, member of the class A family of seven-transmembrane G protein-coupled receptors; The kappa-opioid receptor binds the opioid peptide dynorphin as the primary endogenous ligand. The opioid receptor family is composed of four major subtypes: mu (MOP), delta (DOP), kappa (KOP) opioid receptors, and the nociceptin/orphanin FQ peptide receptor (NOP). They are distributed widely in the central nervous system and respond to classic alkaloid opiates, such as morphine and heroin, as well as to endogenous peptide ligands, which include dynorphins, enkephalins, endorphins, endomorphins, and nociceptin. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  34 IFALTFVLGVLGNGLVIWVA-GFRMKRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGiWPFGWFMCKFIYTVIDINLF 112
Cdd:cd15091     6 VYSVVFVVGLVGNSLVMFVIiRYTKMKTATNIYIFNLALADALVTTTMPFQSTVYLMNS-WPFGDVLCKIVISIDYYNMF 84

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1958643172 113 GSVFLIALIALDRCVCVLHPVWAQNHRTVTLAK 145
Cdd:cd15091    85 TSIFTLTMMSVDRYIAVCHPVKALDFRTPLKAK 117

type 2 angiotensin II receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; 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 AT2R, Ang II counteracts the vasoconstrictor action of AT1R and thereby induces vasodilation, sodium excretion, and reduction of blood pressure. Moreover, AT1R promotes cell proliferation, whereas AT2R inhibits proliferation and stimulates cell differentiation. The AT2R is highly expressed during fetal development, however it is scarcely present in adult tissues and is induced in pathological conditions. Generally, the AT1R mediates many actions of Ang II, while the AT2R is involved in the regulation of blood pressure and renal function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  34 IFALTFVLGVLGNGLVIWVAGFRM-KRTVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVIDINLF 112
Cdd:cd15191     6 LYSIIFILGFLGNSLVVCVFCHQSgPKTVASIYIFNLAVADLLFLATLPLWATYYSYGYNWLFGSVMCKICGSLLTLNLF 85

                          90       100
                  ....*....|....*....|....*..
gi 1958643172 113 GSVFLIALIALDRCVCVLHPVWAQNHR 139
Cdd:cd15191    86 ASIFFITCMSVDRYLAVVYPLRSQRRR 112

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 1958643172  29 IFSYLIFALTFVLGVLGNGLVIWVAGFR--MKRTVTTIsYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTV 106
Cdd:cd15193     1 IYIPILYLIIFFTGLLGNLFVIALMSKRstTKRLVDTF-VLNLAVADLVFVLTLPFWAASTALGGQWLFGEGLCKLSSFI 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958643172 107 IDINLFGSVFLIALIALDRCVCVL-----HPVWAQNHRTVT 142
Cdd:cd15193    80 IAVNRCSSILFLTGMSVDRYLAVVklldsRPLRTRRCALIT 120

bradykinin receptor B2, 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 1958643172  37 LTFVLGVLGNGLVIWVAGFRMKR-TVTTISYLNLAIADFCFTSTLPFYIVSLVMGGIWPFGWFMCKFIYTVIDINLFGSV 115
Cdd:cd15381     9 IIFVLGTIENAFVLIVFCLHKSScTVAEIYLGNLAAADLLLVCCLPFWAINISNGFNWPFGEFLCKSVNAVIYMNLYSSI 88

                          90       100       110
                  ....*....|....*....|....*....|
gi 1958643172 116 FLIALIALDRCVCVLHPVWAQNHRTVTLAK 145
Cdd:cd15381    89 YFLMMVSIDRYLALVKTMSSGRMRRPACAK 118

galanin receptor subtype 1, member of the class A family of seven-transmembrane G protein-coupled receptors; The G protein-coupled galanin receptors bind galanin, a neuropeptide that is widely expressed in the brain, peripheral tissues, and endocrine glands. Three receptors subtypes have been so far identified: GAL1, GAL2, and GAL3. The specific functions of each subtype remains mostly unknown, although galanin is thought to be involved in a variety of neuronal functions such as hormone release and food intake. Galanin is implicated in numerous neurological and psychiatric diseases including Alzheimer's disease, depression, eating disorders, epilepsy and stroke, among many others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  33 LIFALTFVLGVLGNGLVIWVAGfRMK----RTVTTISYLNLAIADFCF-TSTLPFYIVSLVMGGiWPFGWFMCKFIYTVI 107
Cdd:cd15098     5 VVFGLIFCLGVLGNSLVITVLA-RVKpgkrRSTTNVFILNLSIADLFFlLFCVPFQATIYSLPE-WVFGAFMCKFVHYFF 82

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958643172 108 DINLFGSVFLIALIALDRCVCVLHPVWAQNHRTVTLA 144
Cdd:cd15098    83 TVSMLVSIFTLVAMSVDRYIAVVHSRTSSSLRTRRNA 119

galanin receptor and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes G-protein coupled galanin receptors, kisspeptin receptor and allatostatin-A receptor (AstA-R) in insects. These receptors, which are members of the class A of seven transmembrane GPCRs, share a high degree of sequence homology among themselves. The galanin receptors bind galanin, a neuropeptide that is widely expressed in the brain, peripheral tissues, and endocrine glands. Galanin is implicated in numerous neurological and psychiatric diseases including Alzheimer's disease, eating disorders, and epilepsy, among many others. KiSS1-derived peptide receptor (also known as GPR54 or kisspeptin receptor) binds the peptide hormone kisspeptin (metastin), which encoded by the metastasis suppressor gene (KISS1) expressed in various endocrine and reproductive tissues. AstA-R is a G-protein coupled receptor that binds allatostatin A. Three distinct types of allatostatin have been identified in the insects and crustaceans: AstA, AstB, and AstC. They both inhibit the biosynthesis of juvenile hormone and exert an inhibitory influence on food intake. Therefore, allatostatins are considered as potential targets for insect control.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643172  33 LIFALTFVLGVLGNGLVIWV-AGFRMKRTVTTISYLNLAIADFCFT-STLPFYIVSLVMGGiWPFGWFMCKFIYTVIDIN 110
Cdd:cd14971     5 LFFALIFLLGLVGNSLVILVvARNKPMRSTTNLFILNLAVADLTFLlFCVPFTATIYPLPG-WVFGDFMCKFVHYFQQVS 83

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1958643172 111 LFGSVFLIALIALDRCVCVLHPVWAQNHRTVTLA 144
Cdd:cd14971    84 MHASIFTLVAMSLDRFLAVVYPLRSLHIRTPRNA 117