UniProt ID: Q5RH73 |
FUNCTION: G protein-coupled receptor which associates with the patched protein (ptch) to transduce Hedgehog protein signaling. Binding of sonic hedgehog (shh) to its receptor patched prevents inhibition of smoothened (smo) by patched. When active, smo binds to and sequesters protein kinase A catalytic subunit prkaca at the cell membrane, preventing prkaca-mediated phosphorylation of gli transcription factors which releases the gli proteins from prkaca-mediated inhibition and allows for transcriptional activation of Hedgehog signaling pathway target genes (By similarity). Required for the development of primary and secondary motoneurons but not for the specification of midbrain dopaminergic neurons or development of the medial floor plate (PubMed:11493557). Required for induction of lateral floor plate and posterior motoneurons, anterior neural plate patterning, dorsoventral forebrain patterning, dorsoventral retinal patterning, optic stalk development, and formation of the forebrain primary axonal scaffold (PubMed:11566855). Required to regulate the formation of a subset of cerebellar neurons by limiting wnt1 expression which controls cerebellar expression of transcription factor olig2 (PubMed:18423594). Required for development of the pancreas (PubMed:34087472). Required for muscle development (PubMed:16136078). Required for the formation of a single continuous intestinal lumen from multiple discontinuous lumens, probably by regulating remodeling through rab11a-mediated trafficking to facilitate lumen fusion (PubMed:24504339). Required for development of the adenohypophysis (PubMed:12606279, PubMed:11566855). Required for anteroposterior patterning of the otic vesicle (PubMed:12588855). Required for development of the anterior craniofacial skeleton (PubMed:16481351). Required for patterning of the caudal fin (PubMed:17597528). Required during gastrulation and early somitogenesis stages to promote cardiomyocyte formation by regulating the specification of myocardial progenitors (PubMed:18842815). Required for induction of arterial endothelial cell formation by repressing venous cell fate (PubMed:20193674). {ECO:0000250|UniProtKB:P56726, ECO:0000269|PubMed:11493557, ECO:0000269|PubMed:11566855, ECO:0000269|PubMed:12588855, ECO:0000269|PubMed:12606279, ECO:0000269|PubMed:16136078, ECO:0000269|PubMed:16481351, ECO:0000269|PubMed:17597528, ECO:0000269|PubMed:18423594, ECO:0000269|PubMed:18842815, ECO:0000269|PubMed:20193674, ECO:0000269|PubMed:24504339, ECO:0000269|PubMed:34087472, ECO:0000305}. SUBUNIT: Monomer. {ECO:0000269|PubMed:24171105}. SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P56726}; Multi-pass membrane protein {ECO:0000255}. Cell projection, cilium {ECO:0000250|UniProtKB:P56726}. Note=Cilium localization is promoted by shh and is required for activity. {ECO:0000250|UniProtKB:P56726}. DEVELOPMENTAL STAGE: Expressed from the beginning of embryogenesis and during gastrula stages with widespread expression during early gastrulation (PubMed:11493557, PubMed:11566855). As epiboly continues, a shallow dorsoventral gradient begins to appear around the embryonic shield stage at 5-6 hours post-fertilization (hpf) with higher levels seen in the future organizer region (PubMed:11493557). At the tail bud stage, expression is down-regulated in the non-neural ectoderm and is found only in the neural plate and axial mesoderm with higher levels seen in the future head and tail domains (PubMed:11493557). As somitogenesis proceeds, the expression domain on the dorsal side expands laterally to adaxial mesoderm and somites (PubMed:11493557). At 26 hpf, high levels of expression are found in the ventral diencephalon, epiphysis, tectum and pectoral fin buds (PubMed:11493557). Expressed at higher levels in the head than the rest of the body at the 18-somite stage and at 24 hpf (PubMed:11566855). By 2 days post-fertilization (dpf), expression in the head is confined to dorsal brain nuclei and jaw cartilages and expression is also seen in the pectoral fin (PubMed:11566855). Also expressed in cells of the caudal fin primordium during development (PubMed:17597528). {ECO:0000269|PubMed:11493557, ECO:0000269|PubMed:11566855, ECO:0000269|PubMed:17597528}. DOMAIN: The N-terminal extracellular domain mediates sterol-binding which is required for maximal activation of signaling (PubMed:24171105). Contains a second sterol-binding site within the seven-transmembrane pocket which is also required for activation (By similarity). The activating sterol is likely to be cholesterol (By similarity). The extracellular site is required for shh-induced activity while the site within the transmembrane pocket regulates basal signaling in the absence of shh (By similarity). {ECO:0000250|UniProtKB:P56726, ECO:0000269|PubMed:24171105}. DISRUPTION PHENOTYPE: Abnormalities in body size, abnormal development of the central nervous system, adaxial mesoderm, cartilage and pectoral fins, and reduced expression of ptc1 and foxa2/axial with most mutant embryos dying by the end of day 4 although some survive to day 6 (PubMed:11493557). Expansion of venous cells with a reciprocal loss of arterial cells (PubMed:20193674). {ECO:0000269|PubMed:11493557, ECO:0000269|PubMed:20193674}. SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family. {ECO:0000305}. SEQUENCE CAUTION: Sequence=AAK83380.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; |
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