Galactose/rhamnose-binding lectin domain; Galactose/rhamnose-binding lectin domain is formed from a four-stranded antiparallel beta-sheet which packs against an alpha-helix. It was originally described as galactose-binding lectin domain since it was found in a galactose-binding sea urchin egg lectin (SUEL). SUEL was first isolated as a D-galactoside binding lectin, it was later shown that it binds to L-rhamnose preferentially. Galactose/rhamnose-binding lectin domain is also found in many rhamnose-binding lectins, such as Oncorhynchus keta L-rhamnose-binding lectins (CSLs) and Silurus asotus rhamnose-binding lectin (SAL). In addition, the superfamily includes many SUEL/CSLs/SAL homologous proteins, such as plant beta-galactosidases, mammalian latrophilins, Caenorhabditis elegans protein EVA-1 and its homolog, human protein EVA-1 homolog C (also known as C21orf63). Due to the lack of galactose/rhamnose-binding key residues, some superfamily members may not form a binding pocket for galactose/rhamnose. Therefore, they are unlikely to act as galactose/rhamnose-binding lectins.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 386767537   1 MFPKSLSVLNSRCAHKQSCGVLAATSMFGDPCPGTHKYLEAHYQC 45
Cdd:cd22830   48 MSPRSLRVVQERCDGKRSCSIPASSSVFGDPCPGTPKYLEVHYQC 92

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
                 ....*....|....*....|....*....|...
gi 386767537 691 DGNMRIFIYISIGICVVFIVIALLTLKLFNGVF 723
Cdd:cd15441    1 VLLLKIVTYIGIGISLVLLVIAFLVLSCLRGLQ 33

galactose/rhamnose binding lectin domain found in Drosophila melanogaster Latrophilin Cirl and similar proteins; Latrophilin Cirl (calcium-independent receptor for latrotoxin) is an adhesion-type G-protein-coupled receptor (aGPCR) that acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response. It functions in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. The model corresponds to a galactose/rhamnose-binding lectin domain found at the N-terminus of Latrophilin Cirl.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 386767537   1 MFPKSLSVLNSRCAHKQSCGVLAATSMFGDPCPGTHKYLEAHYQC 45
Cdd:cd22830   48 MSPRSLRVVQERCDGKRSCSIPASSSVFGDPCPGTPKYLEVHYQC 92

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 386767537  635 PTCVFWNYIDH---AWSANGCSLESTNRTHSVCSCNHLTNFAIL 675
Cdd:pfam01825   1 PQCVFWDFTNSttgRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44

cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, 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. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. Celsr3 is expressed in both the developing and adult mouse brain. It has been functionally implicated in proper neuron migration and axon guidance in the CNS.

                         10        20        30
                 ....*....|....*....|....*....|...
gi 386767537 691 DGNMRIFIYISIGICVVFIVIALLTLKLFNGVF 723
Cdd:cd15441    1 VLLLKIVTYIGIGISLVLLVIAFLVLSCLRGLQ 33

galactose/rhamnose binding lectin domain found in Drosophila melanogaster Latrophilin Cirl and similar proteins; Latrophilin Cirl (calcium-independent receptor for latrotoxin) is an adhesion-type G-protein-coupled receptor (aGPCR) that acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response. It functions in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. The model corresponds to a galactose/rhamnose-binding lectin domain found at the N-terminus of Latrophilin Cirl.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 386767537   1 MFPKSLSVLNSRCAHKQSCGVLAATSMFGDPCPGTHKYLEAHYQC 45
Cdd:cd22830   48 MSPRSLRVVQERCDGKRSCSIPASSSVFGDPCPGTPKYLEVHYQC 92

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 386767537  635 PTCVFWNYIDH---AWSANGCSLESTNRTHSVCSCNHLTNFAIL 675
Cdd:pfam01825   1 PQCVFWDFTNSttgRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44

galactose/rhamnose binding lectin domain found in latrophilins; Latrophilins, also called lectomedins or latrotoxin receptors, belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: latrophilin-1 (LPHN1), Latrophilin-2 (LPHN2), and Latrophilin-3 (LPHN3). The LPHN1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. LPHN2 and LPHN3, although sharing strong sequence homology to LPHN1, do not bind alpha-latrotoxin. While LPHN3 is also brain specific, LPHN2, is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. All members in this family contain a galactose/rhamnose-binding lectin domain at N-terminus.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 386767537   2 FPKSLSVLNSRCAHKQSCGVLAATSMFGDPCPGTHKYLEAHYQC 45
Cdd:cd22826   49 LPDALAIVSQRCNNRTRCNVRADSSFFPDPCPGTFKYLEVIYEC 92

Galactose/rhamnose-binding lectin domain; Galactose/rhamnose-binding lectin domain is formed from a four-stranded antiparallel beta-sheet which packs against an alpha-helix. It was originally described as galactose-binding lectin domain since it was found in a galactose-binding sea urchin egg lectin (SUEL). SUEL was first isolated as a D-galactoside binding lectin, it was later shown that it binds to L-rhamnose preferentially. Galactose/rhamnose-binding lectin domain is also found in many rhamnose-binding lectins, such as Oncorhynchus keta L-rhamnose-binding lectins (CSLs) and Silurus asotus rhamnose-binding lectin (SAL). In addition, the superfamily includes many SUEL/CSLs/SAL homologous proteins, such as plant beta-galactosidases, mammalian latrophilins, Caenorhabditis elegans protein EVA-1 and its homolog, human protein EVA-1 homolog C (also known as C21orf63). Due to the lack of galactose/rhamnose-binding key residues, some superfamily members may not form a binding pocket for galactose/rhamnose. Therefore, they are unlikely to act as galactose/rhamnose-binding lectins.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 386767537   2 FPKSLSVLNSRCAHKQSCGVLAATSMFGDPCPGTHKYLEAHYQC 45
Cdd:cd22823   48 SPDVLDIVKELCDGKQSCSVPASNSVFGDPCPGTSKYLEVTYTC 91

second galactose/rhamnose binding lectin domain found in Scomberomorus niphonius L-rhamnose-binding lectin (SML) and similar proteins; SML is a rhamnose-binding lectin that also binds melibiose, raffinose, D-galactose, L-arabinose, D-fucose, maltose and D-glucose with decreasing affinity. It does not bind D-arabinose, L-fucose, lactose, xylose or 2-deoxy-D-galactose. SML shows strong hemagglutinating activity against rabbit erythrocytes. SML contains two tandem galactose/rhamnose-binding lectin domains. This model corresponds to the second one.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 386767537  12 RCAHKQSCGVLAATSMFGDPCPGTHKYLEAHYQC 45
Cdd:cd22835   59 RCNGKNSCSIKASNSVFGDPCVGTYKYLEVAYTC 92

third galactose/rhamnose binding lectin domain found in Silurus asotus rhamnose-binding lectin (RBL) and similar proteins; RBL, also known as Silurus asotus (catfish) roe lectin (SAL), is a lectin that binds L-rhamnose. It also binds monosaccharides possessing steric similarity to the hydroxyl group orientation at C2 and C4 of the pyranose ring structure of L-rhamnose, such as L-mannose and L-lyxose. RBL does not require a Ca2+ ion or free thiol group for its agglutination activity. RBL contains three galactose/rhamnose-binding lectin domains. This model corresponds to the third one.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 386767537   5 SLSVLNSRCAHKQSCGVLAATSMFGDPCPGTHKYLEAHYQC 45
Cdd:cd22837   47 TLAYIRALCQGKQTCTLQASNSVFGDPCPGTYKYLRITYSC 87

galactose/rhamnose binding lectin domain found in Strongylocentrotus purpuratus receptor for egg jelly 3 protein (REJ3) and similar proteins; REJ3 is a polycystin-1 protein (components of non-selective cation channels) that is cleaved at the GPS (G-protein-coupled receptor proteolytic site) domain and localizes to the acrosomal region of sea urchin sperm. REJ3 is a multidomain protein containing only one galactose/rhamnose-binding lectin domain at its N-terminus.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 386767537   8 VLNSRCAHKQSCGVLAATSMFGDPCPGTHKYLEAHYQC 45
Cdd:cd22841   55 ILSACCNGQSQCTVTATNSIFGDPCPGTYKYLNVTYTC 92

second galactose/rhamnose binding lectin domain found in Oncorhynchus keta CSL1 and similar proteins; The family includes a group of L-rhamnose-binding lectins, such as Oncorhynchus keta CSL1. CSL1 has hemagglutinating activity towards rabbit erythrocytes, but not human type B erythrocytes. Its hemagglutinating activity is inhibited by smooth-type lipopolysaccharide (LPS) from Klebsiella pneumoniae, Escherichia coli K-235, Shigella flexneri 1A, Aeromonas salmonicida and Salmonella minnesota and rough-type LPS from S. flexneri, but not by rough-type LPS from E. coli K12 and E. coli EH100. CSL1 agglutinates E. coli K12 and Bacillus subtilis. CSL1 contains two tandem galactose-binding lectin domains. This model corresponds to the second one.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 386767537   3 PKSLSVLNSRCAHKQSCGVLAaTSMFGDPCPGTHKYLEAHYQC 45
Cdd:cd22834   54 PETTKVMSERCNGKSLCDLLA-SNVVTDPCYGTYKYLEVSYSC 95

first and second galactose/rhamnose binding lectin domain found in Oncorhynchus keta L-rhamnose-binding lectin CSL3 and similar proteins; The family includes a group of L-rhamnose-binding lectins, such as Oncorhynchus keta CSL1-3. CSL1 has hemagglutinating activity towards rabbit erythrocytes, but not human type B erythrocytes. CSL2 has hemagglutinating activity towards rabbit erythrocytes and human type B erythrocytes. CSL3 has hemagglutinating activity towards rabbit erythrocytes, human type A erythrocytes, human type B erythrocytes, human type O erythrocytes, and sheep erythrocytes. Their hemagglutinating activities are inhibited by smooth-type lipopolysaccharide (LPS) from different bacterial species. Members in this family contain two tandem galactose-binding lectin domains. This model corresponds to the first and second galactose/rhamnose-binding lectin domains found in Oncorhynchus keta CSL3, as well as the second galactose/rhamnose-binding lectin domain found in Oncorhynchus keta CSL2.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 386767537   3 PKSLSVLNSRCAHKQSCGVLAATSMFGDPCPGTHKYLEAHYQC 45
Cdd:cd22832   52 QSTTSKMAERCDGKSQCIVPASNSVFGDPCVGTYKYLDVAYTC 94

second galactose/rhamnose binding lectin domain found in Caenorhabditis elegans protein EVA-1, human protein EVA-1 homolog C and similar proteins; The family includes Caenorhabditis elegans protein EVA-1 and its homologs, such as human protein EVA-1 homolog C (also known as C21orf63). EVA-1 functions as an UNC-40 coreceptor to enhance attraction to the MADD-4 guidance cue in C. elegans. It also acts as a receptor for slt-1 and is required for the guidance of the AVM pioneer axon to the ventral nerve cord. Human C21orf63 is a type-1 transmembrane heparin-binding protein. Members in this family contain two tandem galactose/rhamnose-binding lectin domains. This model corresponds to the second one. Due to the lack of rhamnose-binding key residues, the second galactose/rhamnose-binding domains of EVA-1 does not form a binding pocket for rhamnose.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 386767537   6 LSVLNSRCAHKQSCGVLAATSMFGDPC-PGTHKYLEAHYQCIS 47
Cdd:cd22829   57 LETVMKRCHGKRRCSLTADSETFGDPCpPGVRKYLKVVYTCVP 99

cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, 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. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. Celsr3 is expressed in both the developing and adult mouse brain. It has been functionally implicated in proper neuron migration and axon guidance in the CNS.

                         10        20        30
                 ....*....|....*....|....*....|...
gi 386767537 691 DGNMRIFIYISIGICVVFIVIALLTLKLFNGVF 723
Cdd:cd15441    1 VLLLKIVTYIGIGISLVLLVIAFLVLSCLRGLQ 33

galactose/rhamnose binding lectin domain found in Caenorhabditis elegans latrophilin-like protein 2 (LAT2) and similar proteins; LAT2 may have a role in pharyngeal pumping during feeding. It contains a galactose/rhamnose binding lectin domain at the N-terminal region. Due to the lack of rhamnose-binding key residues, the galactose/rhamnose-binding domains of LAT2 does not form a binding pocket for rhamnose. Therefore, LAT2 is unlikely to act as a rhamnose-binding lectin.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 386767537   3 PKSLSVLNSRCAHKQSCGVLAATSMF-GDPCPGTH-KYLEAHYQC 45
Cdd:cd22840   52 PNSLQTMRQRCQGRQSCEIRVLNSLFpNDPCPGTSkKYLEYRYRC 96

beta-galactosidase; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 386767537   4 KSLSVLNSRCAHKQSCGVLAATSMF-GDPCPGTHKYLEAHYQC 45
Cdd:PLN03059 797 KSYDAFERNCIGKQSCSVTVAPEVFgGDPCPDSMKKLSVEAVC 839