GLI1 (glioma-associated oncogene homologue 1) is a central effector of the Hedgehog (HH) pathway, a pathway that governs many developmental processes []. It is a member of the GLI family of transcription factors, which also includes GLI2 and GLI3 []. GLI1 is an obligatory activator, whereas GLI2 and GLI3 carry activator and repressor functions []. GLI1 is amplified in a subset of human tumours []. It contains five repeats of a zinc finger DNA-binding motif and binds DNA in a sequence-specific fashion [, ].
GLI3 is a member of the GLI family of transcription factors, which also includes GLI1 and GLI2. They are central effectors of the Hedgehog (Hh) pathway in vertebrates [, ]. GLI1 is an obligatory activator, whereas GLI2 and GLI3 carry activator and repressor functions []. The full-length GLI3 form, after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while its C-terminally truncated form acts as a repressor (GLI3R). GLI3 participates in the patterning and growth of many organs, including the central nervous system (CNS) and limbs [, , , , ].
This entry includes a group of zinc finger transcription regulators, including GLI1-3 and GLIS1/3 from humans.GLI1-3 are central effectors of the Hedgehog (Hh) pathway in vertebrates [, ]. GLI1 is an obligatory activator, whereas GLI2 and GLI3 carry activator and repressor functions []. The full-length GLI3 form, after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while its C-terminally truncated form acts as a repressor (GLI3R). GLI3 participates in the patterning and growth of many organs, including the central nervous system (CNS) and limbs [, , , , ].GLIS1/3 play key roles in the regulation of a number of physiological processes and have been implicated in several pathologies. Glis1-3 share a highly homologous zinc finger domain (ZFD) containing five Cys2-His2-type zinc finger (ZF) motifs with members of the Gli and Zic family [].
Sufu, encoding the human ortholog of Drosophila suppressor of fused, appears to have a conserved role in the repression of Hedgehog signalling []. It is a repressor of the Gli and Ci transcription factors of the Hedgehog signalling cascade [], and functions by binding these proteins and preventing their translocation to the nucleus. Sufu has been found to be a tumour-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signalling pathway []. Homologues of Sufu have been found in bacteria, though their function is not currently known.Sufu contains at least two distinct domains: a highly conserved carboxy-terminal region required for binding to the amino-terminal ends of the Gli proteins and a unique amino-terminal domain that binds the carboxy-terminal tail of Gli1 []. This entry represents the N-terminal domain of Sufu. Its structure has an unusual fold composed of bifurcated β-sheet with left-handed β-α-β unit.
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [, , ].Computational methods, including percent identity plots, hydropathy profiles and BLAST, have been used to analyse a gene-rich cluster at human chromosome 12p13 and to compare it with its syntenic region in mouse chromosome 6 [, , ]. Of 6 genes identified, a number were novel receptors, including GPR153 (also known as PGR1) and GPR162 (also known as GRCA) []. GPR153 is a cerebellar target of the Gli1 transcription factor, which is involved in the maintenance and proliferation of grabule neuron precursor cells in the cerebellum, and like GPR162 has a noted role in food uptake and decision making processes [].This entry represents G-protein coupled receptor 153 and G-protein coupled receptor 162.
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [, , ].Computational methods, including percent identity plots, hydropathy profiles and BLAST, have been used to analyse a gene-rich cluster at human chromosome 12p13 and to compare it with its syntenic region in mouse chromosome 6 [, , ]. Of 6 genes identified, a number were novel receptors, including GPR153 (also known as PGR1) and GPR162 (also known as GRCA) []. GPR153 is a cerebellar target of the Gli1 transcription factor, which is involved in the maintenance and proliferation of grabule neuron precursor cells in the cerebellum, and like GPR162 has a noted role in food uptake and decision making processes [].This entry represents G-protein coupled receptor 162.
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [, , ].Computational methods, including percent identity plots, hydropathy profiles and BLAST, have been used to analyse a gene-rich cluster at human chromosome 12p13 and to compare it with its syntenic region in mouse chromosome 6 [, , ]. Of 6 genes identified, a number were novel receptors, including GPR153 (also known as PGR1) and GPR162 (also known as GRCA) []. GPR153 is a cerebellar target of the Gli1 transcription factor, which is involved in the maintenance and proliferation of grabule neuron precursor cells in the cerebellum, and like GPR162 has a noted role in food uptake and decision making processes [].This entry represents G-protein coupled receptor 153, identified by conserved sections along the length of the protein that characterise GP153 and distinguish itfrom closely related GP162 proteins.
