class B family of seven-transmembrane G protein-coupled receptors; The class B of seven-transmembrane GPCRs is classified into three major subfamilies: subfamily B1 (secretin-like receptor family), B2 (adhesion family), and B3 (Methuselah-like family). The class B receptors have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi or prokaryotes. The B1 subfamily comprises receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the subfamily B1 receptors preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The subfamily B2 consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. Furthermore, the subfamily B3 includes Methuselah (Mth) protein, which was originally identified in Drosophila as a GPCR affecting stress resistance and aging, and its closely related proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125347372 101 NISNVNATDIWPATFCVGSAMWIQLLYSACFWWLFCYAVDVYLVIRRSAG---RSTILLYHIMAWGLAVLLCVEGAVMLY 177
Cdd:cd13952   54 FLIGQLLTSSDRPVLCKALAILLHYFLLASFFWMLVEAFDLYRTFVKVFGsseRRRFLKYSLYGWGLPLLIVIITAIVDF 133

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125347372 178 YPSVSRCERG-----LDHAIPHYVTTYLPLLLVLVANPILFhktVTSVASLLKGRKGVYTENERLMGAVIKTRFFKIMLV 252
Cdd:cd13952  134 SLYGPSPGYGgeycwLSNGNALLWAFYGPVLLILLVNLVFF---ILTVRILLRKLRETPKQSERKSDRKQLRAYLKLFPL 210

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 125347372 253 LIACWLSNIINEsllfylemqpdihggslkrIQNAARTTWFIMGILNPAQGLLLSLAF 310
Cdd:cd13952  211 MGLTWIFGILAP-------------------FVGGSLVFWYLFDILNSLQGFFIFLIF 249

class B family of seven-transmembrane G protein-coupled receptors; The class B of seven-transmembrane GPCRs is classified into three major subfamilies: subfamily B1 (secretin-like receptor family), B2 (adhesion family), and B3 (Methuselah-like family). The class B receptors have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi or prokaryotes. The B1 subfamily comprises receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the subfamily B1 receptors preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The subfamily B2 consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. Furthermore, the subfamily B3 includes Methuselah (Mth) protein, which was originally identified in Drosophila as a GPCR affecting stress resistance and aging, and its closely related proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125347372 101 NISNVNATDIWPATFCVGSAMWIQLLYSACFWWLFCYAVDVYLVIRRSAG---RSTILLYHIMAWGLAVLLCVEGAVMLY 177
Cdd:cd13952   54 FLIGQLLTSSDRPVLCKALAILLHYFLLASFFWMLVEAFDLYRTFVKVFGsseRRRFLKYSLYGWGLPLLIVIITAIVDF 133

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125347372 178 YPSVSRCERG-----LDHAIPHYVTTYLPLLLVLVANPILFhktVTSVASLLKGRKGVYTENERLMGAVIKTRFFKIMLV 252
Cdd:cd13952  134 SLYGPSPGYGgeycwLSNGNALLWAFYGPVLLILLVNLVFF---ILTVRILLRKLRETPKQSERKSDRKQLRAYLKLFPL 210

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 125347372 253 LIACWLSNIINEsllfylemqpdihggslkrIQNAARTTWFIMGILNPAQGLLLSLAF 310
Cdd:cd13952  211 MGLTWIFGILAP-------------------FVGGSLVFWYLFDILNSLQGFFIFLIF 249

slime mold cyclic AMP receptor, member of the class E family of seven-transmembrane G protein-coupled receptors; This family represents the class E of seven-transmembrane G-protein coupled receptors found in soil-living amoebas, commonly referred to as slime molds. The class E family includes cAMP receptors (cAR1-4) and cAMP receptors-like proteins (CrlA-C) from Dictyostelium discoideum, and their highly homologous cAMP receptors (TasA and TasB) from Polysphondylium pallidum. So far, four subtypes of cAMP receptors (cAR1-4) have been identified that play an essential role in the detection and transmit of the periodic extracellular cAMP waves that regulate chemotactic cell movement during Dictyostelium development, from the unicellular amoeba aggregate into many multicellular slugs and then differentiate into a sporocarp, a fruiting body with cells specialized for different functions. These four subtypes differ in their expression levels and patterns during development. cAR1 is high-affinity receptor that is the first one to be expressed highly during early aggregation and continues to be expressed at low levels during later developmental stages. cAR1 detects extracellular cAMP and is coupled to G-alpha2 protein. Cells lacking cAR1 fail to aggregate, demonstrating that cAR1 is responsible for aggregation. During later aggregation the high-affinity cAR3 receptor is expressed at low levels. Nonetheless, cells lacking cAR3 do not show an obviously altered pattern of development and are still able to aggregate into fruiting bodies. In contrast, cAR2 and cAR4 are low affinity receptors expressed predominantly after aggregation in pre-stalk cells. cAR2 is essential for normal tip formation and deletion of the receptor arrests development at the mound stage. On the other hand, CAR4 regulates axial patterning and cellular differentiation, and deletion of the receptor results in defects during culmination. Furthermore, three cAMP receptor-like proteins (CrlA-C) were identified in Dictyostelium that show limited sequence similarity to the cAMP receptors. Of these CrlA is thought to be required for normal cell growth and tip formation in developing aggregates.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125347372 116 CVGSAMWIQLLYSACFWWLFCYAVDVYLVIRRSAGRSTIL--LYHIMAWGLAVLLCVegaVML----YYPSVSRCERGLD 189
Cdd:cd14940   68 CYLYAIVITYGSLSCWLWTLCLAISIYLLIVKREPEPEKFekYYHFVCWGLPLISTI---IMLikhhYGPVGNWCWIGNQ 144

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125347372 190 HAIPHYVTTYLPLLLVLVANPILFhkTVTSVASLLKGRKGVYTENERLMGAVIKTRFFKImlVLIACWLSNIINesllfy 269
Cdd:cd14940  145 YTGYRFGLFYGPFFIIFGISAVLV--GLTSHYTYQVIHNWVSDNKDLHKTYQFKLVNYII--VFLLCWIFAVIN------ 214

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 125347372 270 lemqpdihggslkRIQNAARTTWFIMGIL----NPAQGLLLSLAF 310
Cdd:cd14940  215 -------------RIQNALNPFPFALNLLhtylSPSHGFYASVVF 246

adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G protein-coupled receptors; The B2 subfamily of class B GPCRs consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 125347372  98 FIENISN-VNATDIWPATFCVGSAMWIQLLYSACFWWLFCYAVDVYLVIRRSAGRST---ILLYHIMAWGLAVLLCVEGA 173
Cdd:cd15040   49 LLANLLFlFGINSTDNPVLCTAVAALLHYFLLASFMWMLVEALLLYLRLVKVFGTYPrhfILKYALIGWGLPLIIVIITL 128

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 125347372 174 VM---LYYPSVSRCerGLDHAIPHYVTTYLPLLLVLVANPILF 213
Cdd:cd15040  129 AVdpdSYGNSSGYC--WLSNGNGLYYAFLGPVLLIILVNLVIF 169