bestrophin family protein is a member of a family of Ca2+-regulated homo-tetrameric anion channels; similar to Escherichia coli voltage-dependent anion channel-forming protein YneE
Bestrophin, RFP-TM, chloride channel; Bestrophin is a 68-kDa basolateral plasma membrane ...
10-267
3.32e-51
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.
Pssm-ID: 460047 Cd Length: 272 Bit Score: 169.27 E-value: 3.32e-51
Bestrophin, RFP-TM, chloride channel; Bestrophin is a 68-kDa basolateral plasma membrane ...
10-267
3.32e-51
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.
Pssm-ID: 460047 Cd Length: 272 Bit Score: 169.27 E-value: 3.32e-51
Database: CDSEARCH/cdd Low complexity filter: no Composition Based Adjustment: yes E-value threshold: 0.01
References:
Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
of the residues that compose this conserved feature have been mapped to the query sequence.
Click on the triangle to view details about the feature, including a multiple sequence alignment
of your query sequence and the protein sequences used to curate the domain model,
where hash marks (#) above the aligned sequences show the location of the conserved feature residues.
The thumbnail image, if present, provides an approximate view of the feature's location in 3 dimensions.
Click on the triangle for interactive 3D structure viewing options.
Functional characterization of the conserved domain architecture found on the query.
Click here to see more details.
This image shows a graphical summary of conserved domains identified on the query sequence.
The Show Concise/Full Display button at the top of the page can be used to select the desired level of detail: only top scoring hits
(labeled illustration) or all hits
(labeled illustration).
Domains are color coded according to superfamilies
to which they have been assigned. Hits with scores that pass a domain-specific threshold
(specific hits) are drawn in bright colors.
Others (non-specific hits) and
superfamily placeholders are drawn in pastel colors.
if a domain or superfamily has been annotated with functional sites (conserved features),
they are mapped to the query sequence and indicated through sets of triangles
with the same color and shade of the domain or superfamily that provides the annotation. Mouse over the colored bars or triangles to see descriptions of the domains and features.
click on the bars or triangles to view your query sequence embedded in a multiple sequence alignment of the proteins used to develop the corresponding domain model.
The table lists conserved domains identified on the query sequence. Click on the plus sign (+) on the left to display full descriptions, alignments, and scores.
Click on the domain model's accession number to view the multiple sequence alignment of the proteins used to develop the corresponding domain model.
To view your query sequence embedded in that multiple sequence alignment, click on the colored bars in the Graphical Summary portion of the search results page,
or click on the triangles, if present, that represent functional sites (conserved features)
mapped to the query sequence.
Concise Display shows only the best scoring domain model, in each hit category listed below except non-specific hits, for each region on the query sequence.
(labeled illustration) Standard Display shows only the best scoring domain model from each source, in each hit category listed below for each region on the query sequence.
(labeled illustration) Full Display shows all domain models, in each hit category below, that meet or exceed the RPS-BLAST threshold for statistical significance.
(labeled illustration) Four types of hits can be shown, as available,
for each region on the query sequence:
specific hits meet or exceed a domain-specific e-value threshold
(illustrated example)
and represent a very high confidence that the query sequence belongs to the same protein family as the sequences use to create the domain model
non-specific hits
meet or exceed the RPS-BLAST threshold for statistical significance (default E-value cutoff of 0.01, or an E-value selected by user via the
advanced search options)
the domain superfamily to which the specific and non-specific hits belong
multi-domain models that were computationally detected and are likely to contain multiple single domains
Retrieve proteins that contain one or more of the domains present in the query sequence, using the Conserved Domain Architecture Retrieval Tool
(CDART).
Modify your query to search against a different database and/or use advanced search options
