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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1488403123  55 FLTYFLNLSIADFGVLIGLSCDNPYVYEYAYICSSLNSTINPLIYFLVGRDKSRTSRMKIKVIFGKVFKEE 125
Cdd:cd14973   201 FLLCGLPLGIYWFLLLWFSNYLFHTFHPISDLLSCVNSSANPIIYFFVGSLRGRRLREPLRVVLQRALRDE 271

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1488403123  55 FLTYFLNLSIADFGVLIGLSCDNPYVYEYAYICSSLNSTINPLIYFLVGRDKSRTSRMKIKVIFGKVFKEE 125
Cdd:cd14973   201 FLLCGLPLGIYWFLLLWFSNYLFHTFHPISDLLSCVNSSANPIIYFFVGSLRGRRLREPLRVVLQRALRDE 271

mas-related G protein-coupled receptor subtype H, 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.

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                  ....*....|....*....|....*....|....*....|....*...
gi 1488403123  24 MITITLLICLWGLVGNGGTISLLGVRIKRNNFLTYFLNLSIADFGVLI 71
Cdd:cd15110     3 EVWVSLIICLLGLVGNGIVLWFLGFRIRRNPFTVYILHLAIADFTFLL 50

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.

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                  ....*....|....*....|....*....|....*....|....*...
gi 1488403123  23 LMITITLLICLWGLVGNGGTISLLGVRIKRNNFLTYFLNLSIADFGVL 70
Cdd:cd15109     2 VMNYIFLLLCLCGLVGNGLVLWFFGFSIKRNPFSIYFLHLASADVGYL 49

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1488403123  24 MITITLLICLWGLVGNGGTISLLGVRIKRNNFLTYFLNLSIADFGVL---IGLSCDNPYVYEYAYICSSLNSTINPLIYF 100
Cdd:cd15107     3 MNFLSIIIALVGLAGNAIVLWLLGFHMHRNAFSVYILNLAGADFLFLctqIVFSLEIVLQFHSIDIHIPLFLLTVTMFAY 82

                  ...
gi 1488403123 101 LVG 103
Cdd:cd15107    83 LAG 85

mas-related G protein-coupled receptor subtype H, 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.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1488403123  79 YVYEYAYICSSLNSTINPLIYFLVGRDKSRTSRMKIKVIFGKVFKEE 125
Cdd:cd15110   227 FSNPVPFLLSTVNSSINPIVYFLVGSLRRKRIKKSLKVALQRVFEDK 273

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.

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                  ....*....|....*....|....*....|....*....|....*
gi 1488403123  23 LMITITLLIclwGLVGNGGTISLLGVRIKRNNFLTYFLNLSIADF 67
Cdd:cd15105     5 LMIIIFGLV---GLTGNAIVFWLLGFRLHRNAFSVYILNLALADF 46

mas-related G protein-coupled receptor subtype D, 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1488403123  55 FLTYFLNLSIADFgVLIGLSCDNPYVYEYAYIC---SSLNSTINPLIYFLVGRDKSRTSRMKIKVIFGKVFKEE 125
Cdd:cd15108   203 FLACALPLGIYWF-LLYWLDLPQEVKTLFSCLSrlsSSVSSSANPVIYFLVGSRGSRRLREPLGAVLQRALREE 275

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
                  ....*....|....*....|....*....|....*...
gi 1488403123  30 LICLWGLVGNGGTISLLGVRIKRNNFLTYFLNLSIADF 67
Cdd:cd14974     9 LIFLLGLPGNGLVIWVAGFKMKRTVNTVWFLNLALADF 46

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.

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                  ....*....|....*....|....*....|....*....|....*....
gi 1488403123  27 ITLLICLWGLVGNGGTISLLGVRIKRNNFLTYFLNLSIADfgvLIGLSC 75
Cdd:cd15113     6 LAVLVSLCGLVGNGVVFWLLCCGVRSNPYMVYILNLAAAD---VINLSC 51