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0  structures 1111  species 0  interactions 2221  sequences 18  architectures

Family: Bestrophin (PF01062)

Summary: Bestrophin, RFP-TM, chloride channel

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Bestrophin, RFP-TM, chloride channel Provide feedback

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 characterised by a depressed light peak in the electrooculogram [1]. 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, 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 chloride channels, indicating a direct role for bestrophin in generating the light peak [1]. 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 [2]. The bestrophins are four-pass transmembrane chloride-channel proteins [3] 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 [4]. Interestingly, the RFP motif is not conserved evolutionarily back beyond Metazoa, neither is it in plant members.

Literature references

  1. Marmorstein LY, McLaughlin PJ, Stanton JB, Yan L, Crabb JW, Marmorstein AD; , J Biol Chem 2002;277:30591-30597.: Bestrophin interacts physically and functionally with protein phosphatase 2A. PUBMED:12058047 EPMC:12058047

  2. Stohr H, Marquardt A, Nanda I, Schmid M, Weber BH; , Eur J Hum Genet 2002;10:281-284.: Three novel human VMD2-like genes are members of the evolutionary highly conserved RFP-TM family. PUBMED:12032738 EPMC:12032738

  3. Tsunenari T, Sun H, Williams J, Cahill H, Smallwood P, Yau KW, Nathans J;, J Biol Chem. 2003;278:41114-41125.: Structure-function analysis of the bestrophin family of anion channels. PUBMED:12907679 EPMC:12907679

  4. Marmorstein AD, Cross HE, Peachey NS;, Prog Retin Eye Res. 2009;28:206-226.: Functional roles of bestrophins in ocular epithelia. PUBMED:19398034 EPMC:19398034


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR021134

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 [PUBMED:12032738]. 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, 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 chloride channels, indicating a direct role for bestrophin in generating the light peak [PUBMED:12032738]. 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 [PUBMED:12058047].

This entry also includes a number of hypothetical proteins belonging to protein family UPF0187.

Domain organisation

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Alignments

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

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(123)
Full
(2221)
Representative proteomes NCBI
(1855)
Meta
(146)
RP15
(469)
RP35
(658)
RP55
(954)
RP75
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Format an alignment

  Seed
(123)
Full
(2221)
Representative proteomes NCBI
(1855)
Meta
(146)
RP15
(469)
RP35
(658)
RP55
(954)
RP75
(1116)
Alignment:
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  Seed
(123)
Full
(2221)
Representative proteomes NCBI
(1855)
Meta
(146)
RP15
(469)
RP35
(658)
RP55
(954)
RP75
(1116)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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Curation and family details

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Curation View help on the curation process

Seed source: [1]
Previous IDs: Worm_family_8;DUF289;
Type: Family
Author: Bateman A, Moxon SJ
Number in seed: 123
Number in full: 2221
Average length of the domain: 255.60 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 74.64 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.2 23.4
Trusted cut-off 24.6 23.6
Noise cut-off 22.8 23.3
Model length: 293
Family (HMM) version: 16
Download: download the raw HMM for this family

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