PF01062: Bestrophin

Bestrophin, RFP-TM, chloride channel

Curation status: SEEDED
Seed status: EX DUF
Characterization: UNSCORED

Grounding

PF01062: Bestrophin, RFP-TM, chloride channel
IPR021134: integrated entry for Bestrophin, RFP-TM, chloride channel

Source description

This entry represents animal bestrophin homologues. 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 [InterPro reference PUB00011865]. 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 [InterPro reference PUB00011865]. 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 [InterPro reference PUB00011864]. The bestrophins are four-pass transmembrane chloride-channel proteins [InterPro reference PUB00096747], 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 [InterPro reference PUB00109156]. Interestingly, the RFP motif is not conserved evolutionarily back beyond Metazoa, neither is it in plant members.

Evidence and references

InterPro entry and its literature references. PUB identifiers are internal InterPro references, not PubMed identifiers. Unresolved citations link to the originating entry.
Frozen description source: InterPro/Pfam API

Source descriptions and links are provenance, not independent functional validation.

Evidence counts: not scored.

Curated functional assertions

No curated functional assertions supplied.

Protein sequence examples

8 verified sequence examples. FASTA

UniProt	Protein / organism	Sequence	Provenance
O76090	Bestrophin-1 Homo sapiens	585 aa; version 1 UniProt 2026_03	UNIPROT FETCH 13 sibling references ProteinTraitsMech: GO:0034707 ProteinTraitsMech: GO:0098857 ProteinTraitsMech: GO:0160133 ProteinTraitsMech: GO:0015106 ProteinTraitsMech: GO:0005254 ProteinTraitsMech: GO:0005229 ProteinTraitsMech: GO:0022834 ProteinTraitsMech: GO:1902476 ProteinTraitsMech: GO:0006821 ProteinTraitsMech: GO:0061534 ProteinTraitsMech: GO:0014047 ProteinTraitsMech: GO:0030321 ProteinTraitsMech: Pfam:PF01062
O88870	Bestrophin-1 Mus musculus	551 aa; version 3 UniProt 2026_03	UNIPROT FETCH 4 sibling references ProteinTraitsMech: GO:0098857 ProteinTraitsMech: GO:0160133 ProteinTraitsMech: GO:0005229 ProteinTraitsMech: GO:0030321
Q17528	Bestrophin homolog 1 Caenorhabditis elegans	450 aa; version 1 UniProt 2026_03	UNIPROT FETCH 8 sibling references ProteinTraitsMech: GO:0034707 ProteinTraitsMech: GO:0098857 ProteinTraitsMech: GO:0160133 ProteinTraitsMech: GO:0005254 ProteinTraitsMech: GO:0005229 ProteinTraitsMech: GO:0022834 ProteinTraitsMech: GO:0061534 ProteinTraitsMech: GO:0014047
Q6H1V1	Bestrophin-3 Mus musculus	669 aa; version 1 UniProt 2026_03	UNIPROT FETCH 3 sibling references ProteinTraitsMech: GO:0099095 ProteinTraitsMech: GO:0015698 ProteinTraitsMech: GO:0043271
Q8BGM5	Bestrophin-2 Mus musculus	508 aa; version 1 UniProt 2026_03	UNIPROT FETCH 4 sibling references ProteinTraitsMech: GO:0160133 ProteinTraitsMech: GO:0005217 ProteinTraitsMech: GO:0099095 ProteinTraitsMech: GO:0099094
Q8N1M1	Bestrophin-3 Homo sapiens	668 aa; version 1 UniProt 2026_03	UNIPROT FETCH 2 sibling references ProteinTraitsMech: GO:0099095 ProteinTraitsMech: Pfam:PF01062
Q8NFU0	Bestrophin-4 Homo sapiens	473 aa; version 1 UniProt 2026_03	UNIPROT FETCH 2 sibling references ProteinTraitsMech: GO:0160133 ProteinTraitsMech: Pfam:PF01062
Q8NFU1	Bestrophin-2a Homo sapiens	509 aa; version 1 UniProt 2026_03	UNIPROT FETCH 4 sibling references ProteinTraitsMech: GO:0160133 ProteinTraitsMech: GO:0005217 ProteinTraitsMech: GO:0099095 ProteinTraitsMech: GO:0099094

Pfam membership is not functional evidence. Whole-protein sequences do not establish domain boundaries. A coverage gap here is not absence from UniProt.

Sequences and metadata: UniProt Consortium, CC BY 4.0.

Domain matches

No residue-level domain match evidence is available in this build. Structure and AlphaFold counters do not supply coordinates or establish function.

Snapshot counters

proteins: 8,246
matches: 8,846
proteomes: 1,318
taxa: 4,218
structures: 45
alphafold models: 7,437
domain architectures: 106

Classification basis

pfam previous unknown name

No scoring reasons supplied.

Related Mech records

This family joined the worklist after the frozen cross-Mech scan, so other Mechs were not searched for it. Missing links here are not evidence that other Mechs lack it; rows shown come from mentions of a former DUF/UPF name.

No cross-Mech examples are present in the supplied snapshot.

Curation history and reviews

No retained curation events supplied.

No retained review supplied.

Record source

data/families/PF01062.yaml
Family YAML in this build

Download this family (JSON)

Status and evidence

Seed status: A name-based classification of frozen InterPro/Pfam metadata. UNKNOWN CANDIDATE means the metadata explicitly says the function is unknown. KNOWN HISTORICAL DUF means a DUF name matched without that wording; this heuristic is not proof of a known function and does not establish experimental characterization. EX DUF means Pfam renamed the family away from a DUF/UPF name, as recorded in Pfam's previous identifiers; a rename usually follows published work on some members but is naming history, not proof of function for every member. Some EX DUF families' current names or descriptions still say the function is unknown; their classification basis lists this, and scoring does not treat them as characterized. FALSE POSITIVE TEXT HIT means the naming rules did not match.
Characterization: A separate evidence-scoring result. UNSCORED means no score has been calculated; it is not evidence that the family lacks a known function. Missing scores are not negative evidence. PARTIALLY CHARACTERIZED has partial support; KNOWN HISTORICAL DUF can inherit the seed label or reflect a known-function signal. Neither label implies experimental validation.
Evidence counts: Source-specific signals, not unique proteins, publications, or confidence scores. Known counts Rhea reactions and experimentally supported GO molecular-function annotations. Partial counts functional/domain assignments. Context counts structural, environmental, orthology, interaction and neighborhood signals; context alone does not assign function. Repeated annotations may not be independent.
Curation status: Reported separately from seed classification and characterization. SNAPSHOT ONLY means no curated metadata was supplied for this build. SEEDED denotes a source-derived record, not an expert-reviewed functional claim.
Missing counts: Not available means the source did not supply that counter. A zero is a reported count. Not scored means evidence counts are unavailable.