This entry represents smoothened (SMO) and its homologues, which are related to the frizzled protein family. Smoothened is a G protein-coupled receptor that is involved in the hedgehog signalling pathway. Smoothened probably associates with the patched protein to transduce the hedgehog's proteins signal []. Mutated smoothened can function as an oncogene [].
The cysteine-rich domain (CRD) is part of the smoothened receptor (Smo), an integral membrane protein and one of the key players in the Hedgehog (Hh) signaling pathway, critical for development, cell growth and migration, as well as stem cell maintenance. The CRD of Smo is conserved in vertebrates and can also be identified in invertebrates. The precise function of the CRD in Smo is unknown []. Mutations in the Drosophila CRD disrupt Smo activity in vivo, while deletion of the CRD in mammalian cells does not seem to affect the activity of overexpressed Smo [].
MOSMO, also known as Atthog (attenuator of hedgehog) in mouse, acts as a negative regulator of hedgehog (Hh) signaling, probably by promoting internalization and subsequent degradation of Smoothened (SMO). SMO is an oncoprotein that transduces the Hh signal across the membrane. In the absence of Atthog, SMO was stabilized at the cell surface and concentrated in the ciliary membrane [].
Smoothened (SMO) 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) []. SMO is closely related to the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate family of G-protein coupled receptors [, ].
This entry includes fatty acid and carotene hydroxylases and sterol desaturases. Beta-carotene hydroxylase is involved in zeaxanthin synthesis by hydroxylating beta-carotene, but the enzyme may be involved in other pathways []. This family includes C-5 sterol desaturase []and C-4 sterol methyl oxidase (SMO) [, ]. Members of this family are involved in cholesterol biosynthesis and biosynthesis a plant cuticular wax. These enzymes contain two copies of a HXHH motif, involved in coordination of two iron atoms in the catalytic centre. Members of this family are ER integral membrane proteins with a mushroom-like structure consisting of four transmembrane helices (TM1-TM4) that anchor them to the membrane, capped by a cytosolic domain containing the unique histidine-coordinating di metal centre [].The plant SMO amino acid sequences possess three histidine-rich motifs (HX3H, HX2HH and HX2HH), characteristic of the small family of membrane-bound non-haem iron oxygenases that are involved in lipid oxidation [].
