ID   S26A5_MERUN             Reviewed;         744 AA.
AC   Q9JKQ2;
DT   27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   13-SEP-2023, entry version 100.
DE   RecName: Full=Prestin {ECO:0000303|PubMed:10821263};
DE   AltName: Full=Solute carrier family 26 member 5;
GN   Name=SLC26A5 {ECO:0000250|UniProtKB:P58743}; Synonyms=PRES;
OS   Meriones unguiculatus (Mongolian jird) (Gerbillus unguiculatus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Gerbillinae; Meriones.
OX   NCBI_TaxID=10047;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP   STAGE.
RC   TISSUE=Organ of Corti;
RX   PubMed=10821263; DOI=10.1038/35012009;
RA   Zheng J., Shen W., He D.Z.Z., Long K.B., Madison L.D., Dallos P.;
RT   "Prestin is the motor protein of cochlear outer hair cells.";
RL   Nature 405:149-155(2000).
RN   [2]
RP   TOPOLOGY, AND SUBCELLULAR LOCATION.
RX   PubMed=11435925; DOI=10.1097/00001756-200107030-00032;
RA   Zheng J., Long K.B., Shen W., Madison L.D., Dallos P.;
RT   "Prestin topology: localization of protein epitopes in relation to the
RT   plasma membrane.";
RL   NeuroReport 12:1929-1935(2001).
RN   [3]
RP   FUNCTION, AND MOTIF.
RX   PubMed=22399806; DOI=10.1242/jcs.097337;
RA   Tan X., Pecka J.L., Tang J., Lovas S., Beisel K.W., He D.Z.;
RT   "A motif of eleven amino acids is a structural adaptation that facilitates
RT   motor capability of eutherian prestin.";
RL   J. Cell Sci. 125:1039-1047(2012).
RN   [4] {ECO:0007744|PDB:7SUN}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) IN COMPLEX, TOPOLOGY,
RP   SUBUNIT, MUTAGENESIS OF SER-398 AND ARG-399, DOMAIN, AND FUNCTION.
RX   PubMed=35022426; DOI=10.1038/s41467-021-27915-z;
RA   Butan C., Song Q., Bai J.P., Tan W.J.T., Navaratnam D., Santos-Sacchi J.;
RT   "Single particle cryo-EM structure of the outer hair cell motor protein
RT   prestin.";
RL   Nat. Commun. 13:290-290(2022).
CC   -!- FUNCTION: Voltage-sensitive motor protein that drives outer hair cell
CC       (OHC) electromotility (eM) and participates in sound amplification in
CC       the hearing organ (PubMed:10821263, PubMed:22399806). Converts changes
CC       in the transmembrane electric potential into mechanical displacements
CC       resulting in the coupling of its expansion to movement of a charged
CC       voltage sensor across the lipid membrane (PubMed:10821263,
CC       PubMed:22399806). The nature of the voltage sensor is not completely
CC       clear, and two models compete. In the first model, acts as an
CC       incomplete transporter where intracellular chloride anion acts as
CC       extrinsic voltage sensor that drives conformational change in the
CC       protein which is sufficient to produce a length change in the plane of
CC       the membrane and hence in the length of the OHC (By similarity). The
CC       second model in which multiple charged amino acid residues are
CC       distributed at the intracellular and extracellular membrane interfaces
CC       that form an intrinsic voltage sensor, whose movement produces the non-
CC       linear capacitance (NLC) (PubMed:35022426). However, the effective
CC       voltage sensor may be the result of a hybrid voltage sensor assembled
CC       from intrinsic charge (charged residues) and extrinsic charge (bound
CC       anion) (By similarity). Notably, binding of anions to the anion-binding
CC       pocket partially neutralizes the intrinsic positive charge rather than
CC       to form an electrically negative sensor, therefore remaining charge may
CC       serve as voltage sensor that, after depolarization, moves from down
CC       (expanded state) to up (contracted) conformation, which is accompanied
CC       by an eccentric contraction of the intermembrane cross-sectional area
CC       of the protein as well as a major increase in the hydrophobic thickness
CC       of the protein having as consequences the plasma membrane thickening
CC       and the cell contraction after membrane depolarization (By similarity).
CC       The anion-binding pocket transits from the inward-open (Down) state,
CC       where it is exposed toward the intracellular solvent in the absence of
CC       anion, to the occluded (Up) state upon anion binding (By similarity).
CC       Salicylate competes for the anion-binding site and inhibits the
CC       voltage-sensor movement, and therefore inhibits the charge transfer and
CC       electromotility by displacing Cl(-) from the anion-binding site and by
CC       preventing the structural transitions to the contracted state
CC       (PubMed:35022426). In addition, can act as a weak Cl(-)/HCO3 (-)
CC       antiporter across the cell membrane and so regulate the intracellular
CC       pH of the outer hair cells (OHCs), while firstly found as being unable
CC       to mediate electrogenic anion transport (By similarity). Moreover,
CC       supports a role in cardiac mechanical amplification serving as an
CC       elastic element to enhance the actomyosin- based sarcomere contraction
CC       system (By similarity). {ECO:0000250|UniProtKB:D7PC76,
CC       ECO:0000250|UniProtKB:P58743, ECO:0000250|UniProtKB:Q99NH7,
CC       ECO:0000250|UniProtKB:Q9EPH0, ECO:0000269|PubMed:10821263,
CC       ECO:0000269|PubMed:22399806, ECO:0000269|PubMed:35022426}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + 2 hydrogencarbonate(in) = chloride(in) + 2
CC         hydrogencarbonate(out); Xref=Rhea:RHEA:72207, ChEBI:CHEBI:17544,
CC         ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:Q9EPH0};
CC   -!- SUBUNIT: Homodimer (PubMed:35022426). Interacts (via STAS domain) with
CC       CALM; this interaction is calcium-dependent and the STAS domain
CC       interacts with only one lobe of CALM which is an elongated conformation
CC       (By similarity). {ECO:0000250|UniProtKB:A0FKN5,
CC       ECO:0000250|UniProtKB:Q9EPH0, ECO:0000269|PubMed:35022426}.
CC   -!- SUBCELLULAR LOCATION: Lateral cell membrane
CC       {ECO:0000269|PubMed:11435925}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:35022426}. Note=Lateral cell membrane of outer hair
CC       cells (PubMed:11435925). Alters profoundly the shape of its surrounding
CC       lipid bilayer (By similarity). {ECO:0000250|UniProtKB:P58743,
CC       ECO:0000269|PubMed:11435925}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in mature outer hair cells, but
CC       not in inner hair cells or other cells of the basilar membrane and the
CC       organ of Corti. {ECO:0000269|PubMed:10821263}.
CC   -!- DEVELOPMENTAL STAGE: Detected in the organ of Corti as early as 6 days
CC       after birth; levels increase up to day 20, concomitant with the
CC       development of high sensitivity hearing. {ECO:0000269|PubMed:10821263}.
CC   -!- DOMAIN: The STAS domain mediates dimerization, with both STAS domains
CC       latched onto each other in a domain-swapped manner (PubMed:35022426).
CC       The N-terminus domain is involved in dimerization such that each N-
CC       terminus domain embraces both STAS domains (PubMed:35022426). The STAS
CC       domain harbors a unique anion-binding site important for the fine
CC       regulation of the high-frequency electromotile properties (By
CC       similarity). The transmembrane domain consists of 14 transmembrane
CC       segments organized a 7(+)7 inverted repeat architecture that can be
CC       divided into two main helix bundles, the ''core'' domain and the
CC       ''gate'' domain (PubMed:35022426). The transmembrane regions are
CC       domain-swapped with the STAS domain containing N- and C-terminal
CC       cytoplasmic domains (By similarity). The STAS domain mediates CALM
CC       binding CALM (By similarity). {ECO:0000250|UniProtKB:D7PC76,
CC       ECO:0000250|UniProtKB:Q9EPH0, ECO:0000269|PubMed:35022426}.
CC   -!- SIMILARITY: Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Pump up the volume - Issue
CC       22 of May 2002;
CC       URL="https://web.expasy.org/spotlight/back_issues/022";
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DR   EMBL; AF230376; AAF71715.1; -; mRNA.
DR   PDB; 7SUN; EM; 3.60 A; A/B=1-744.
DR   PDBsum; 7SUN; -.
DR   AlphaFoldDB; Q9JKQ2; -.
DR   SMR; Q9JKQ2; -.
DR   GlyCosmos; Q9JKQ2; 2 sites, No reported glycans.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR   GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB.
DR   GO; GO:0140900; F:chloride:bicarbonate antiporter activity; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0008271; F:secondary active sulfate transmembrane transporter activity; IEA:InterPro.
DR   GO; GO:0015701; P:bicarbonate transport; ISS:UniProtKB.
DR   GO; GO:0006821; P:chloride transport; ISS:UniProtKB.
DR   GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR   GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR   CDD; cd07042; STAS_SulP_like_sulfate_transporter; 1.
DR   Gene3D; 3.30.750.24; STAS domain; 1.
DR   InterPro; IPR018045; S04_transporter_CS.
DR   InterPro; IPR011547; SLC26A/SulP_dom.
DR   InterPro; IPR001902; SLC26A/SulP_fam.
DR   InterPro; IPR002645; STAS_dom.
DR   InterPro; IPR036513; STAS_dom_sf.
DR   NCBIfam; TIGR00815; sulP; 1.
DR   PANTHER; PTHR11814:SF32; PRESTIN; 1.
DR   PANTHER; PTHR11814; SULFATE TRANSPORTER; 1.
DR   Pfam; PF01740; STAS; 1.
DR   Pfam; PF00916; Sulfate_transp; 1.
DR   SUPFAM; SSF52091; SpoIIaa-like; 1.
DR   PROSITE; PS01130; SLC26A; 1.
DR   PROSITE; PS50801; STAS; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Cell shape; Glycoprotein; Hearing; Membrane;
KW   Motor protein; Transmembrane; Transmembrane helix.
FT   CHAIN           1..744
FT                   /note="Prestin"
FT                   /id="PRO_0000080168"
FT   TOPO_DOM        1..79
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        80..105
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        106..109
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        110..125
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        126..137
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        138..147
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        148..178
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        179..196
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        197..208
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        209..230
FT                   /note="Helical; Name=5a"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        231..243
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        244..252
FT                   /note="Helical; Name=5b"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        253..258
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        259..282
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        283..291
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        292..304
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        305..337
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        338..361
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        362..370
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        371..388
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        389..396
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        397..406
FT                   /note="Helical; Name=10"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        407..410
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        411..429
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        430..436
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        437..455
FT                   /note="Helical; Name=12"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        456..469
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        470..484
FT                   /note="Helical; Name=13"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        485
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        486..497
FT                   /note="Helical; Name=14"
FT                   /evidence="ECO:0000269|PubMed:35022426,
FT                   ECO:0007744|PDB:7SUN"
FT   TOPO_DOM        498..744
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          525..713
FT                   /note="STAS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00198"
FT   REGION          505..718
FT                   /note="Extended region for STAS domain"
FT                   /evidence="ECO:0000250|UniProtKB:Q9EPH0"
FT   REGION          717..744
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           158..168
FT                   /note="Involved in motor function"
FT                   /evidence="ECO:0000269|PubMed:22399806"
FT   BINDING         398
FT                   /ligand="salicylate"
FT                   /ligand_id="ChEBI:CHEBI:30762"
FT                   /ligand_note="antagonist"
FT                   /evidence="ECO:0000250|UniProtKB:P58743"
FT   SITE            398
FT                   /note="Controls the electromotile activity"
FT                   /evidence="ECO:0000250|UniProtKB:A0FKN5,
FT                   ECO:0000250|UniProtKB:Q9EPH0"
FT   SITE            399
FT                   /note="Contributes to anion binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q9EPH0"
FT   CARBOHYD        163
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        166
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         398
FT                   /note="S->E: Removes salicylate competition with anions.
FT                   Retains the displacement currents."
FT                   /evidence="ECO:0000269|PubMed:35022426"
FT   MUTAGEN         399
FT                   /note="R->E: Removes salicylate competition with anions.
FT                   Retains the displacement currents."
FT                   /evidence="ECO:0000269|PubMed:35022426"
SQ   SEQUENCE   744 AA;  81419 MW;  1CDF66589DAACBBC CRC64;
     MDHAEENEIP VATQKYHVER PIFSHPVLQE RLHVKDKVSE SIGDKLKQAF TCTPKKIRNI
     IYMFLPITKW LPAYKFKEYV LGDLVSGIST GVLQLPQGLA FAMLAAVPPV FGLYSSFYPV
     IMYCFFGTSR HISIGPFAVI SLMIGGVAVR LVPDDIVIPG GVNATNGTEA RDALRVKVAM
     SVTLLSGIIQ FCLGVCRFGF VAIYLTEPLV RGFTTAAAVH VFTSMLKYLF GVKTKRYSGI
     FSVVYSTVAV LQNVKNLNVC SLGVGLMVFG LLLGGKEFNE RFKEKLPAPI PLEFFAVVMG
     TGISAGFNLH ESYSVDVVGT LPLGLLPPAN PDTSLFHLVY VDAIAIAIVG FSVTISMAKT
     LANKHGYQVD GNQELIALGI CNSIGSLFQT FSISCSLSRS LVQEGTGGKT QLAGCLASLM
     ILLVILATGF LFESLPQAVL SAIVIVNLKG MFMQFSDLPF FWRTSKIELT IWLTTFVSSL
     FLGLDYGLIT AVIIALLTVI YRTQSPSYKV LGQLPDTDVY IDIDAYEEVK EIPGIKIFQI
     NAPIYYANSD LYSNALKRKT GVNPALIMGA RRKAMRKYAK EVGNANIANA AVVKVDGEVD
     GENATKPEEE DDEVKYPPIV IKTTFPEELQ RFMPQTENVH TIILDFTQVN FIDSVGVKTL
     AVMVKEYGDV GIYVYLAGCS PQVVNDLTRN RFFENPALKE LLFHSIHDAV LGSHVREAMA
     EQEASAPPPQ DDMEPNATPT TPEA
//