Bestrophin, RFP-TM, chloride channel; Bestrophin is a 68-kDa 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 characterized by a depressed light peak in the electrooculogram. VMD2 encodes a 585-amino acid protein with an approximate mass of 68 kDa 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, localized 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 chloride channels, indicating a direct role for bestrophin in generating the light peak. 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 RFP-TM domain implying important functional properties. The bestrophins are four-pass transmembrane chloride-channel proteins, and the RFP-TM or bestrophin domain extends from the N-terminus through approximately 350 amino acids and contains all of the TM domains as well as nearly all reported disease causing mutations. Interestingly, the RFP motif is not conserved evolutionarily back beyond Metazoa, neither is it in plant members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568967945    1 MLLISSSVHGSDQHGRLLRRTLMRYVNLTSLLIFRSVSTAVYKRFPTMDHVVEAGFmtADERKLFDHlksphlKYWVPFI 80
Cdd:pfam01062  83 ARSLARQVLGLDEEGRLARRTILRYLVLSLVAFFRALSAHLRKRFPTLDHLLPAGM--EEERKILEN------KYWVPIA 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568967945   81 WFGNLA---TKARNEGRIRDsvDLQSLMTEMNRYRSWCSLLFGYDWVGIPLVYTQVVTLAVYTFFFacLIGRQFLDptkg 157
Cdd:pfam01062 155 WLRRLAarlARLRREGRIRD--DQAQLDEELNAFRGVLGGCERIDWTPIPLAYTQLVHRAVYLYCL--LLPFTLLQ---- 226

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 568967945  158 yvghDLDLYVPIFTLLQFFFYAGWLKVAEQLINPFGEDDDDFETNWCIDR 207
Cdd:pfam01062 227 ----TLGWWTPLVVAIFAFFFFGWLKVAEELENPFGEDDDDLELNALIDR 272

Bestrophin, RFP-TM, chloride channel; Bestrophin is a 68-kDa 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 characterized by a depressed light peak in the electrooculogram. VMD2 encodes a 585-amino acid protein with an approximate mass of 68 kDa 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, localized 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 chloride channels, indicating a direct role for bestrophin in generating the light peak. 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 RFP-TM domain implying important functional properties. The bestrophins are four-pass transmembrane chloride-channel proteins, and the RFP-TM or bestrophin domain extends from the N-terminus through approximately 350 amino acids and contains all of the TM domains as well as nearly all reported disease causing mutations. Interestingly, the RFP motif is not conserved evolutionarily back beyond Metazoa, neither is it in plant members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568967945    1 MLLISSSVHGSDQHGRLLRRTLMRYVNLTSLLIFRSVSTAVYKRFPTMDHVVEAGFmtADERKLFDHlksphlKYWVPFI 80
Cdd:pfam01062  83 ARSLARQVLGLDEEGRLARRTILRYLVLSLVAFFRALSAHLRKRFPTLDHLLPAGM--EEERKILEN------KYWVPIA 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568967945   81 WFGNLA---TKARNEGRIRDsvDLQSLMTEMNRYRSWCSLLFGYDWVGIPLVYTQVVTLAVYTFFFacLIGRQFLDptkg 157
Cdd:pfam01062 155 WLRRLAarlARLRREGRIRD--DQAQLDEELNAFRGVLGGCERIDWTPIPLAYTQLVHRAVYLYCL--LLPFTLLQ---- 226

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 568967945  158 yvghDLDLYVPIFTLLQFFFYAGWLKVAEQLINPFGEDDDDFETNWCIDR 207
Cdd:pfam01062 227 ----TLGWWTPLVVAIFAFFFFGWLKVAEELENPFGEDDDDLELNALIDR 272

Bestrophin, RFP-TM, chloride channel; Bestrophin is a 68-kDa 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 characterized by a depressed light peak in the electrooculogram. VMD2 encodes a 585-amino acid protein with an approximate mass of 68 kDa 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, localized 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 chloride channels, indicating a direct role for bestrophin in generating the light peak. 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 RFP-TM domain implying important functional properties. The bestrophins are four-pass transmembrane chloride-channel proteins, and the RFP-TM or bestrophin domain extends from the N-terminus through approximately 350 amino acids and contains all of the TM domains as well as nearly all reported disease causing mutations. Interestingly, the RFP motif is not conserved evolutionarily back beyond Metazoa, neither is it in plant members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568967945    1 MLLISSSVHGSDQHGRLLRRTLMRYVNLTSLLIFRSVSTAVYKRFPTMDHVVEAGFmtADERKLFDHlksphlKYWVPFI 80
Cdd:pfam01062  83 ARSLARQVLGLDEEGRLARRTILRYLVLSLVAFFRALSAHLRKRFPTLDHLLPAGM--EEERKILEN------KYWVPIA 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568967945   81 WFGNLA---TKARNEGRIRDsvDLQSLMTEMNRYRSWCSLLFGYDWVGIPLVYTQVVTLAVYTFFFacLIGRQFLDptkg 157
Cdd:pfam01062 155 WLRRLAarlARLRREGRIRD--DQAQLDEELNAFRGVLGGCERIDWTPIPLAYTQLVHRAVYLYCL--LLPFTLLQ---- 226

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 568967945  158 yvghDLDLYVPIFTLLQFFFYAGWLKVAEQLINPFGEDDDDFETNWCIDR 207
Cdd:pfam01062 227 ----TLGWWTPLVVAIFAFFFFGWLKVAEELENPFGEDDDDLELNALIDR 272