P58743 · S26A5_HUMAN
- ProteinPrestin
- GeneSLC26A5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids744 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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).
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).
Catalytic activity
- chloride(out) + 2 hydrogencarbonate(in) = chloride(in) + 2 hydrogencarbonate(out)chloride (out)CHEBI:17996
+ 2 hydrogencarbonate (in)CHEBI:17544= chloride (in)CHEBI:17996+ 2 hydrogencarbonate (out)CHEBI:17544
Features
Showing features for binding site, site.
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended namePrestin
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP58743
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Lateral cell membrane ; Multi-pass membrane protein
Note: Localized at the lateral cell membrane of outer hair cells (By similarity).
Alters profoundly the shape of its surrounding lipid bilayer (PubMed:34390643).
Alters profoundly the shape of its surrounding lipid bilayer (PubMed:34390643).
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-75 | Cytoplasmic | ||||
Sequence: MDHAEENEILAATQRYYVERPIFSHPVLQERLHTKDKVPDSIADKLKQAFTCTPKKIRNIIYMFLPITKWLPAYK | ||||||
Transmembrane | 76-105 | Helical; Name=1 | ||||
Sequence: FKEYVLGDLVSGISTGVLQLPQGLAFAMLA | ||||||
Topological domain | 106-108 | Extracellular | ||||
Sequence: AVP | ||||||
Transmembrane | 109-126 | Helical; Name=2 | ||||
Sequence: PIFGLYSSFYPVIMYCFL | ||||||
Topological domain | 127-137 | Cytoplasmic | ||||
Sequence: GTSRHISIGPF | ||||||
Transmembrane | 138-151 | Helical; Name=3 | ||||
Sequence: AVISLMIGGVAVRL | ||||||
Topological domain | 152-168 | Extracellular | ||||
Sequence: VPDDIVIPGGVNATNGT | ||||||
Transmembrane | 169-196 | Helical; Name=4 | ||||
Sequence: EARDALRVKVAMSVTLLSGIIQFCLGVC | ||||||
Topological domain | 197-206 | Cytoplasmic | ||||
Sequence: RFGFVAIYLT | ||||||
Transmembrane | 207-230 | Helical; Name=5a | ||||
Sequence: EPLVRGFTTAAAVHVFTSMLKYLF | ||||||
Topological domain | 231-241 | Extracellular | ||||
Sequence: GVKTKRYSGIF | ||||||
Intramembrane | 242-253 | Helical; Name=5b | ||||
Sequence: SVVYSTVAVLQN | ||||||
Topological domain | 254-258 | Extracellular | ||||
Sequence: VKNLN | ||||||
Transmembrane | 259-282 | Helical; Name=6 | ||||
Sequence: VCSLGVGLMVFGLLLGGKEFNERF | ||||||
Topological domain | 283-291 | Cytoplasmic | ||||
Sequence: KEKLPAPIP | ||||||
Transmembrane | 292-307 | Helical; Name=7 | ||||
Sequence: LEFFAVVMGTGISAGF | ||||||
Topological domain | 308-332 | Extracellular | ||||
Sequence: NLKESYNVDVVGTLPLGLLPPANPD | ||||||
Transmembrane | 333-367 | Helical; Name=8 | ||||
Sequence: TSLFHLVYVDAIAIAIVGFSVTISMAKTLANKHGY | ||||||
Topological domain | 368-370 | Cytoplasmic | ||||
Sequence: QVD | ||||||
Transmembrane | 371-388 | Helical; Name=9 | ||||
Sequence: GNQELIALGLCNSIGSLF | ||||||
Topological domain | 389-396 | Extracellular | ||||
Sequence: QTFSISCS | ||||||
Transmembrane | 397-406 | Helical; Name=10 | ||||
Sequence: LSRSLVQEGT | ||||||
Topological domain | 407-410 | Cytoplasmic | ||||
Sequence: GGKT | ||||||
Transmembrane | 411-432 | Helical; Name=11 | ||||
Sequence: QLAGCLASLMILLVILATGFLF | ||||||
Topological domain | 433-436 | Extracellular | ||||
Sequence: ESLP | ||||||
Transmembrane | 437-464 | Helical; Name=12 | ||||
Sequence: QAVLSAIVIVNLKGMFMQFSDLPFFWRT | ||||||
Topological domain | 465 | Cytoplasmic | ||||
Sequence: S | ||||||
Transmembrane | 466-481 | Helical; Name=13 | ||||
Sequence: KIELTIWLTTFVSSLF | ||||||
Topological domain | 482-483 | Extracellular | ||||
Sequence: LG | ||||||
Transmembrane | 484-504 | Helical; Name=14 | ||||
Sequence: LDYGLITAVIIALLTVIYRTQ | ||||||
Topological domain | 505-744 | Cytoplasmic | ||||
Sequence: SPSYKVLGKLPETDVYIDIDAYEEVKEIPGIKIFQINAPIYYANSDLYSNALKRKTGVNPAVIMGARRKAMRKYAKEVGNANMANATVVKADAEVDGEDATKPEEEDGEVKYPPIVIKSTFPEEMQRFMPPGDNVHTVILDFTQVNFIDSVGVKTLAGIVKEYGDVGIYVYLAGCSAQVVNDLTRNRFFENPALWELLFHSIHDAVLGSQLREALAEQEASAPPSQEDLEPNATPATPEA |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Deafness, autosomal recessive, 61 (DFNB61)
- Note
- DescriptionA 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.
- See alsoMIM:613865
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 101 | Decreases salicylate inhibition. | ||||
Sequence: F → Y |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 803 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000080167 | 1-744 | Prestin | |||
Sequence: MDHAEENEILAATQRYYVERPIFSHPVLQERLHTKDKVPDSIADKLKQAFTCTPKKIRNIIYMFLPITKWLPAYKFKEYVLGDLVSGISTGVLQLPQGLAFAMLAAVPPIFGLYSSFYPVIMYCFLGTSRHISIGPFAVISLMIGGVAVRLVPDDIVIPGGVNATNGTEARDALRVKVAMSVTLLSGIIQFCLGVCRFGFVAIYLTEPLVRGFTTAAAVHVFTSMLKYLFGVKTKRYSGIFSVVYSTVAVLQNVKNLNVCSLGVGLMVFGLLLGGKEFNERFKEKLPAPIPLEFFAVVMGTGISAGFNLKESYNVDVVGTLPLGLLPPANPDTSLFHLVYVDAIAIAIVGFSVTISMAKTLANKHGYQVDGNQELIALGLCNSIGSLFQTFSISCSLSRSLVQEGTGGKTQLAGCLASLMILLVILATGFLFESLPQAVLSAIVIVNLKGMFMQFSDLPFFWRTSKIELTIWLTTFVSSLFLGLDYGLITAVIIALLTVIYRTQSPSYKVLGKLPETDVYIDIDAYEEVKEIPGIKIFQINAPIYYANSDLYSNALKRKTGVNPAVIMGARRKAMRKYAKEVGNANMANATVVKADAEVDGEDATKPEEEDGEVKYPPIVIKSTFPEEMQRFMPPGDNVHTVILDFTQVNFIDSVGVKTLAGIVKEYGDVGIYVYLAGCSAQVVNDLTRNRFFENPALWELLFHSIHDAVLGSQLREALAEQEASAPPSQEDLEPNATPATPEA | ||||||
Glycosylation | 163 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 166 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homodimer (PubMed:34390643).
Interacts (via STAS domain) with CALM; this interaction is calcium-dependent and the STAS domain interacts with only one lobe of CALM which is an elongated conformation (By similarity).
Interacts (via STAS domain) with CALM; this interaction is calcium-dependent and the STAS domain interacts with only one lobe of CALM which is an elongated conformation (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P58743-6 | UBE2J1 Q9Y385 | 3 | EBI-18029942, EBI-988826 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 158-168 | Involved in motor function | ||||
Sequence: IPGGVNATNGT | ||||||
Region | 505-718 | Extended region for STAS domain | ||||
Sequence: SPSYKVLGKLPETDVYIDIDAYEEVKEIPGIKIFQINAPIYYANSDLYSNALKRKTGVNPAVIMGARRKAMRKYAKEVGNANMANATVVKADAEVDGEDATKPEEEDGEVKYPPIVIKSTFPEEMQRFMPPGDNVHTVILDFTQVNFIDSVGVKTLAGIVKEYGDVGIYVYLAGCSAQVVNDLTRNRFFENPALWELLFHSIHDAVLGSQLREA | ||||||
Domain | 525-713 | STAS | ||||
Sequence: AYEEVKEIPGIKIFQINAPIYYANSDLYSNALKRKTGVNPAVIMGARRKAMRKYAKEVGNANMANATVVKADAEVDGEDATKPEEEDGEVKYPPIVIKSTFPEEMQRFMPPGDNVHTVILDFTQVNFIDSVGVKTLAGIVKEYGDVGIYVYLAGCSAQVVNDLTRNRFFENPALWELLFHSIHDAVLGS | ||||||
Region | 718-744 | Disordered | ||||
Sequence: ALAEQEASAPPSQEDLEPNATPATPEA |
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).
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).
Sequence similarities
Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 6 isoforms produced by Alternative splicing.
P58743-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsSLC26A5a
- Length744
- Mass (Da)81,264
- Last updated2002-03-27 v1
- Checksum9E64BE6DB2DC065E
P58743-2
- Name2
- SynonymsSLC26A5b
P58743-3
- Name3
- SynonymsSLC26A5c
P58743-4
- Name4
- SynonymsSLC26A5d
P58743-5
- Name5
- Differences from canonical
- 438-469: Missing
P58743-6
- Name6
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_010190 | 325-335 | in isoform 4 | |||
Sequence: LLPPANPDTSL → FHTEMTRRWRP | ||||||
Alternative sequence | VSP_010191 | 336-744 | in isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_043153 | 438-469 | in isoform 5 and isoform 6 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_010192 | 506-516 | in isoform 3 | |||
Sequence: PSYKVLGKLPE → FHTEMTRRWRP | ||||||
Alternative sequence | VSP_010193 | 517-744 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_047640 | 595 | in isoform 6 | |||
Sequence: A → ATQ | ||||||
Alternative sequence | VSP_010194 | 682-685 | in isoform 2 | |||
Sequence: QVVN → FIQR | ||||||
Alternative sequence | VSP_010195 | 686-744 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF523354 EMBL· GenBank· DDBJ | AAP31417.1 EMBL· GenBank· DDBJ | mRNA | ||
AY256823 EMBL· GenBank· DDBJ | AAP31532.1 EMBL· GenBank· DDBJ | mRNA | ||
AY256824 EMBL· GenBank· DDBJ | AAP31533.1 EMBL· GenBank· DDBJ | mRNA | ||
AY256825 EMBL· GenBank· DDBJ | AAP31534.1 EMBL· GenBank· DDBJ | mRNA | ||
AY289134 EMBL· GenBank· DDBJ | AAP43686.1 EMBL· GenBank· DDBJ | mRNA | ||
AC004668 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC005064 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC093701 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC100833 EMBL· GenBank· DDBJ | AAI00834.1 EMBL· GenBank· DDBJ | mRNA |