Peropsin is a visual pigment-like protein found in ocular tissues.The protein has been localised to the apical face of the retinal pigmentepithelium (RPE), most prominently to the microvilli that surround thephotoreceptor outer segments. It is believed that peropsin may play arole in RPE physiology, either by detecting light directly, or by monitoringthe concentration of retinoids or other photoreceptor-derived compounds [].
The TOBE domain [](Transport-associated OB) always occurs as a dimer as the C-terminal strand of each domain is supplied by the partner. Probably involved in the recognition of small ligands such as molybdenum (e.g. ) and sulphate (). Found in ABC transporters immediately after the ATPase domain. A strong RPE motif is found at the presumed N terminus of the domain.
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as nerve growth factor receptor (NGFR) or p75 neurotrophin receptor (p75NTR or p75), CD271, or Gp80-LNGFR, is a common receptor for both neurotrophins and proneurotrophins, and plays a diverse role in many tissues, including the nervous system. It has been shown to be expressed in various types of stem cells and has been used to prospectively isolate stem cells with different degrees of potency []. p75NTR owes its signaling to the recruitment of intracellular binding proteins, leading to the activation of different signaling pathways []. It binds nerve growth factor (NGF) and the complex can initiate a signaling cascade which has been associated with both neuronal apoptosis and neuronal survival of discrete populations of neurons, depending on the presence or absence of intracellular signaling molecules downstream of p75NTR (e.g. NF-kB, JNK, or p75NTR intracellular death domain). p75NTR can also bind NGF in concert with the neurotrophic tyrosine kinase receptor type 1 (TrkA) protein where it is thought to modulate the formation of the high-affinity neurotrophin binding complex [].In melanoma cells, p75NTR is an immunosuppressive factor, induced by interferon (IFN)-gamma, and mediates down-regulation of melanoma antigens []. It can interact with the aggregated form of amyloid beta (Abeta) peptides, and plays an important role in etiopathogenesis of Alzheimer's disease by influencing protein tau hyper-phosphorylation []. p75NTR is involved in the formation and progression of retina diseases; its expression is induced in retinal pigment epithelium (RPE) cells and its knockdown rescues RPE cell proliferation activity and inhibits RPE apoptosis induced by hypoxia []. It can therefore be a potential therapeutic target for RPE hypoxia or oxidative stress diseases.This entry represents the N-terminal domain of TNFRSF16. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family [, , ].
Bestrophin is a 68kDa basolateral plasma membrane protein expressed in retinal pigment epithelial cells (RPE). It is encoded by the VMD2 gene, which is mutated in Best macular dystrophy, a disease characterised by a depressed light peak in the electrooculogram []. VMD2 encodes a 585-amino acid protein with an approximate mass of 68kDa which has been designated bestrophin. Bestrophin shares homology with the Caenorhabditis elegans RFP gene family, named for the presence of a conserved arginine (R), phenylalanine (F), proline (P), amino acid sequence motif. Bestrophin is a plasma membrane protein, localised to the basolateral surface of RPE cells consistent with a role for bestrophin in the generation or regulation of the EOG light peak. Bestrophin and other RFP family members represent a new class of calcium-activated chloride channels (CaCC) [], indicating a direct role for bestrophin in generating the light peak [, , ]. Bestrophins are also permeable to other monovalent anions including bicarbonate, bromine, iodine, thiocyanate an nitrate [, ]. Structural analysis revealed thatN-terminal region of the proteins is highly conserved and sufficient for its CaCC activity. The C-terminal region has low sequence identity. The VMD2 gene underlying Best disease was shown to represent the first human member of the RFP-TM protein family. More than 97% of the disease-causing mutations are located in the N-terminal domain altering the electrophysiological properties of the channel [, ].
Bestrophin is a 68kDa basolateral plasma membrane protein expressed in retinal pigment epithelial cells (RPE). It is encoded by the VMD2 gene, which is mutated in Best macular dystrophy, a disease characterised by a depressed light peak in the electrooculogram []. VMD2 encodes a 585-amino acid protein with an approximate mass of 68kDa which has been designated bestrophin. Bestrophin shares homology with the Caenorhabditis elegans RFP gene family, named for the presence of a conserved arginine (R), phenylalanine (F), proline (P), amino acid sequence motif. Bestrophin is a plasma membrane protein, localised to the basolateral surface of RPE cells consistent with a role for bestrophin in the generation or regulation of the EOG light peak. Bestrophin and other RFP family members represent a new class of calcium-activated chloride channels (CaCC) [], indicating a direct role for bestrophin in generating the light peak [, , ]. Bestrophins are also permeable to other monovalent anions including bicarbonate, bromine, iodine, thiocyanate an nitrate [, ]. Structural analysis revealed that N-terminal region of the proteins is highly conserved and sufficient for its CaCC activity. The C-terminal region has low sequence identity. The VMD2 gene underlying Best disease was shown to represent the first human member of the RFP-TM protein family. More than 97% of the disease-causing mutations are located in the N-terminal domain altering the electrophysiological properties of the channel [, ].This entry also includes uncharacterised proteins belonging to protein family UPF0187.
