SLC26A5
Domain
The STAS domain mediates dimerization, with both STAS domains latched onto each other in a domain-swapped manner (PubMed:34390643). The N-terminus domain is involved in dimerization such that each N-terminus domain embraces both STAS domains (PubMed:34390643). The STAS domain harbors a unique anion-binding site important for the fine regulation of the high-frequency electromotile properties (By similarity). The transmembrane domain consists of 14 transmembrane segments organized in a 7(+)7 inverted repeat architecture that can be divided into two main helix bundles, the ''core'' domain and the ''gate'' domain (PubMed:34390643). The transmembrane regions are domain-swapped with the STAS domain containing N- and C-terminal cytoplasmic domains (By similarity). The STAS domain mediates CALM binding CALM (By similarity).
Function
Voltage-sensitive motor protein that drives outer hair cell (OHC) electromotility (eM) and participates in sound amplification in the hearing organ (By similarity). Converts changes in the transmembrane electric potential into mechanical displacements resulting in the coupling of its expansion to movement of a charged voltage sensor across the lipid membrane (By similarity). The nature of the voltage sensor is not completely clear, and two models compete. In the first model, acts as an incomplete transporter where intracellular chloride anion acts as extrinsic voltage sensor that drives conformational change in the protein which is sufficient to produce a length change in the plane of the membrane and hence in the length of the OHC (By similarity). The second model in which multiple charged amino acid residues are distributed at the intracellular and extracellular membrane interfaces that form an intrinsic voltage sensor, whose movement produces the non-linear capacitance (NLC) (PubMed:34390643). However, the effective voltage sensor may be the result of a hybrid voltage sensor, assembled from intrinsic charge (charged residues) and extrinsic charge (bound anion) (By similarity). Notably, binding of anions to the anion-binding pocket partially neutralizes the intrinsic positive charge rather than to form an electrically negative sensor, therefore remaining charge may serve as voltage sensor that, after depolarization, moves from down (expanded state) to up (contracted) conformation, which is accompanied by an eccentric contraction of the intermembrane cross-sectional area of the protein as well as a major increase in the hydrophobic thickness of the protein having as consequences the plasma membrane thickening and the cell contraction after membrane depolarization (PubMed:34390643). The anion-binding pocket transits from the inward-open (Down) state, where it is exposed toward the intracellular solvent in the absence of anion, to the occluded (Up) state upon anion binding (PubMed:34390643). Salicylate competes for the anion-binding site and inhibits the voltage-sensor movement, and therefore inhibits the charge transfer and electromotility by displacing Cl(-) from the anion-binding site and by preventing the structural transitions to the contracted state (PubMed:34390643). In addition, can act as a weak Cl(-)/HCO3(-) antiporter across the cell membrane and so regulate the intracellular pH of the outer hair cells (OHCs), while firstly found as being unable to mediate electrogenic anion transport (By similarity). Moreover, supports a role in cardiac mechanical amplification serving as an elastic element to enhance the actomyosin- based sarcomere contraction system (By similarity).
Involvement in disease
Deafness, autosomal recessive, 61
DFNB61
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.
Cellular localization
- Lateral cell membrane
- Multi-pass membrane protein
- Localized at the lateral cell membrane of outer hair cells (By similarity). Alters profoundly the shape of its surrounding lipid bilayer (PubMed:34390643).
Alternative names
PRES, SLC26A5, Prestin, Solute carrier family 26 member 5