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 530360641  76 SWDCVLQGALSTFANTSSFFWTVAIALYLYLSIVRaaRGPRTDRLLWAFHVVSWGVPLVITVAAVALKKIGYdasdvSVG 155
Cdd:cd14940   65 GFLCYLYAIVITYGSLSCWLWTLCLAISIYLLIVK--REPEPEKFEKYYHFVCWGLPLISTIIMLIKHHYGP-----VGN 137

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530360641 156 WCWIdLEAKDHVLWMLLTGKLWEM--LAYVLLPLLYLLVRKHINRAEHRLLRHSSMADKKLVLIPLIFIGLRVWSTVRFV 233
Cdd:cd14940  138 WCWI-GNQYTGYRFGLFYGPFFIIfgISAVLVGLTSHYTYQVIHNWVSDNKDLHKTYQFKLVNYIIVFLLCWIFAVINRI 216

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 530360641 234 LTLCGSPavqTPVLVVLHGIGNTFQGGANCIMFVL 268
Cdd:cd14940  217 QNALNPF---PFALNLLHTYLSPSHGFYASVVFIY 248

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 530360641  76 SWDCVLQGALSTFANTSSFFWTVAIALYLYLSIVRaaRGPRTDRLLWAFHVVSWGVPLVITVAAVALKKIGYdasdvSVG 155
Cdd:cd14940   65 GFLCYLYAIVITYGSLSCWLWTLCLAISIYLLIVK--REPEPEKFEKYYHFVCWGLPLISTIIMLIKHHYGP-----VGN 137

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530360641 156 WCWIdLEAKDHVLWMLLTGKLWEM--LAYVLLPLLYLLVRKHINRAEHRLLRHSSMADKKLVLIPLIFIGLRVWSTVRFV 233
Cdd:cd14940  138 WCWI-GNQYTGYRFGLFYGPFFIIfgISAVLVGLTSHYTYQVIHNWVSDNKDLHKTYQFKLVNYIIVFLLCWIFAVINRI 216

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 530360641 234 LTLCGSPavqTPVLVVLHGIGNTFQGGANCIMFVL 268
Cdd:cd14940  217 QNALNPF---PFALNLLHTYLSPSHGFYASVVFIY 248

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 530360641  76 SWDCVLQGALSTFANTSSFFWTVAIALYLYLSIVRaaRGPRTDRLLWAFHVVSWGVPLVITVAAVALKKIGYdasdvSVG 155
Cdd:cd14940   65 GFLCYLYAIVITYGSLSCWLWTLCLAISIYLLIVK--REPEPEKFEKYYHFVCWGLPLISTIIMLIKHHYGP-----VGN 137

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530360641 156 WCWIdLEAKDHVLWMLLTGKLWEM--LAYVLLPLLYLLVRKHINRAEHRLLRHSSMADKKLVLIPLIFIGLRVWSTVRFV 233
Cdd:cd14940  138 WCWI-GNQYTGYRFGLFYGPFFIIfgISAVLVGLTSHYTYQVIHNWVSDNKDLHKTYQFKLVNYIIVFLLCWIFAVINRI 216

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 530360641 234 LTLCGSPavqTPVLVVLHGIGNTFQGGANCIMFVL 268
Cdd:cd14940  217 QNALNPF---PFALNLLHTYLSPSHGFYASVVFIY 248

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 530360641  65 FYGVLQNFAGPSWdCVLQGALSTFANTSSFFWTVAIALYLYLSIVRAaRGPRTDRLLWAFHVVSWGVPLVITVAAVALKK 144
Cdd:cd15040   55 FLFGINSTDNPVL-CTAVAALLHYFLLASFMWMLVEALLLYLRLVKV-FGTYPRHFILKYALIGWGLPLIIVIITLAVDP 132

                         90
                 ....*....|....*.
gi 530360641 145 IGYDASDvsvGWCWID 160
Cdd:cd15040  133 DSYGNSS---GYCWLS 145

7 transmembrane receptor (Secretin family); This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs). They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognized. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin, and brain-specific angiogenesis inhibitors amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteriztic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530360641   79 CVLQGALSTFANTSSFFWTVAIALYLYLSIVRAarGPRTDRLLWAFHVVSWGVPLVITVAAVALKKIGYDASDVsvgwCW 158
Cdd:pfam00002  75 CKVVAVFLHYFFLANFFWMLVEGLYLYTLLVEV--FFSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYGEDDG----CW 148

                          90
                  ....*....|.
gi 530360641  159 IDLEakDHVLW 169
Cdd:pfam00002 149 LSNE--NGLWW 157

The subfamily B1 of hormone receptors (secretin-like), member of the class B family seven-transmembrane G protein-coupled receptors; The B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, includes 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 this subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. Moreover, the B1 subfamily receptors play key roles in hormone homeostasis and are promising drug targets in various human diseases including diabetes, osteoporosis, obesity, neurodegenerative conditions (Alzheimer###s and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression). Furthermore, the subfamilies B2 and B3 consist of receptors that are capable of interacting with epidermal growth factors (EGF) and the Drosophila melanogaster Methuselah gene product (Mth), respectively. The class B GPCRs 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530360641  77 WDCVLQGALSTFANTSSFFWTVAIALYLYLSIVRAARGPrtDRLLWAFHVVSWGVPLVITVAAVALKKIGYDASdvsvgw 156
Cdd:cd15041   80 VGCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSE--PSSLKLYYAIGWGLPLVIVVIWAIVRALLSNES------ 151

                         90
                 ....*....|....*
gi 530360641 157 CWIDlEAKDHVLWML 171
Cdd:cd15041  152 CWIS-YNNGHYEWIL 165

Frizzled/Smoothened family membrane region; This family contains the membrane spanning region of frizzled and smoothened receptors. This membrane region is predicted to contain seven transmembrane alpha helices. Proteins related to Drosophila frizzled are receptors for Wnt (mediating the beta-catenin signalling pathway), but also the planar cell polarity (PCP) pathway and the Wnt/calcium pathway. The predominantly alpha-helical Cys-rich ligand-binding region (CRD) of Frizzled is both necessary and sufficient for Wnt binding. The smoothened receptor mediates hedgehog signalling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530360641   76 SWDCVLQGALSTFANTSSFFWTVAIALYLYLSIVRAARGPRTDRLLWAFHVVSWGVPLVITVAAVALKKIgyDASDVSvG 155
Cdd:pfam01534  91 NLSCTVVFLLLYYFGMAASIWWVILTLTWFLAAGLKWGSEAIEKKSSYFHLAAWGIPAVLTITVLALGKV--DGDELT-G 167

                          90
                  ....*....|....*..
gi 530360641  156 WCWIDLEAKDHVLWMLL 172
Cdd:pfam01534 168 ICFVGNQNSDALRGFVL 184

Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G protein-coupled receptors; The subfamily B3 of class B GPCRs consists of Methuselah (Mth) and its closely related proteins found in bilateria. Mth was originally identified in Drosophila as a GPCR affecting stress resistance and aging. In addition to the seven transmembrane helices, Mth contains an N-terminal extracellular domain involved in ligand binding, and a third intracellular loop (IC3) required for the specificity of G-protein coupling. Drosophila Mth mutants showed an increase in average lifespan by 35% and greater resistance to a variety of stress factors, including starvation, high temperature, and paraquat-induced oxidative toxicity. Moreover, mutations in two endogenous peptide ligands of Methuselah, Stunted A and B, showed an increased in lifespan and resistance to oxidative stress induced by dietary paraquat. These results strongly suggest that the Stunted-Methuselah system plays important roles in stress response and aging.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530360641  62 ASYFYGVLQNFAGPSWdCVLQGALSTFANTSSFFWTVAIALYLYLSIVRAARGPRTD---RLLWAFHVVSWGVPLVITVA 138
Cdd:cd15039   52 LLLLIGQLLSSGDSTL-CVALGILLHFFFLAAFFWLNVMSFDIWRTFRGKRSSSSRSkerKRFLRYSLYAWGVPLLLVAV 130

                         90       100
                 ....*....|....*....|....*.
gi 530360641 139 AVALKKIgYDASDVSVGW----CWID 160
Cdd:cd15039  131 TIIVDFS-PNTDSLRPGYgegsCWIS 155

corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, and parathyroid hormone (PTH). 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 B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530360641  79 CVLQGALSTFANTSSFFWTVAIALYLYLSIVRAARgprTDRLL-WAFHVVSWGVPLVITVAAvALKKIGYDASDvsvgwC 157
Cdd:cd15445   73 CRLVTAAYNYFHVTNFFWMFGEGCYLHTAIVLTYS---TDKLRkWMFICIGWCIPFPIIVAW-AIGKLYYDNEK-----C 143

                 .
gi 530360641 158 W 158
Cdd:cd15445  144 W 144

class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor superfamily; The class F G protein-coupled receptors includes the frizzled (FZD) family of seven-transmembrane proteins consisting of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. Also included in the class F family is the closely related smoothened (SMO), which is a transmembrane G protein-coupled receptor that acts as the transducer of the hedgehog (HH) signaling pathway. SMO is activated by the hedgehog (HH) family of proteins acting on the 12-transmembrane domain receptor patched (PTCH), which constitutively inhibits SMO. Thus, in the absence of HH proteins, PTCH inhibits SMO signaling. On the other hand, binding of HH to the PTCH receptor activates its internalization and degradation, thereby releasing the PTCH inhibition of SMO. This allows SMO to trigger intracellular signaling and the subsequent activation of the Gli family of zinc finger transcriptional factors and induction of HH target gene expression (PTCH, Gli1, cyclin, Bcl-2, etc). The WNT and HH signaling pathways play critical roles in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530360641  79 CVLQGALSTFANTSSFFWTVAIALYLYLSivraargprtDRLLWA----------FHVVSWGVPLVITVAAVALKKIgyD 148
Cdd:cd13951   94 CAIVFLLTYYFGMAASIWWVILTLTWFLS----------AGLKWSseaiekkssyFHLVAWGLPAVLTIAVLVLRKV--D 161

                         90       100
                 ....*....|....*....|....*
gi 530360641 149 ASDVSvGWCWIDLEAKDHVLWMLLT 173
Cdd:cd13951  162 GDELT-GICFVGNQNLDALRGFVLA 185

class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 3 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530360641  79 CVLQGALSTFANTSSFFWTVAIALYLYLSIVRAARGPRTDRLLWAFHVVSWGVPLVITVAAVALKKIgydASDVSVGWCW 158
Cdd:cd15033   95 CTMLFMVLYFFTMAGSVWWVILTITWFLAAVPKWGSEAIEKKALLFHASAWGIPGTLTIILLAMNKI---EGDNISGVCF 171

                         90
                 ....*....|....
gi 530360641 159 IDLEAKDHVLWMLL 172
Cdd:cd15033  172 VGLYDVDALRYFVL 185