Q9EPH0 (S26A5_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prestin

Alternative name(s):
Solute carrier family 26 member 5

Gene names

Name:	Slc26a5
Synonyms:	Pres

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	744 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Motor protein that converts auditory stimuli to length changes in outer hair cells and mediates sound amplification in the mammalian hearing organ. Prestin is a bidirectional voltage-to-force converter, it can operate at microsecond rates. It uses cytoplasmic anions as extrinsic voltage sensors, probably chloride and bicarbonate. After binding to a site with millimolar affinity, these anions are translocated across the membrane in response to changes in the transmembrane voltage. They move towards the extracellular surface following hyperpolarization, and towards the cytoplasmic side in response to depolarization. As a consequence, this translocation triggers conformational changes in the protein that ultimately alter its surface area in the plane of the plasma membrane. The area decreases when the anion is near the cytoplasmic face of the membrane (short state), and increases when the ion has crossed the membrane to the outer surface (long state). So, it acts as an incomplete transporter. It swings anions across the membrane, but does not allow these anions to dissociate and escape to the extracellular space. Salicylate, an inhibitor of outer hair cell motility, acts as competitive antagonist at the prestin anion-binding site By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein. Note: Lateral wall of outer hair cells.
Tissue specificity	Specifically expressed in outer hair cells. Not detected in other cells of the organ of Corti. Ref.4
Developmental stage	Low levels are present in newborn rats and up to day 6. Subsequently, levels increase strongly. Adult levels are detected starting from day 9 in the basal turn of the cochlea, from day 10-11 in the middle turn, and from day 12 in the apical turn.
Sequence similarities	Belongs to the SLC26A/SulP transporter (TC 2.A.53) family. [View classification] Contains 1 STAS domain.

Ontologies

Keywords
Biological process	Cell shape Hearing
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	Motor protein
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of cell shape Inferred from electronic annotation. Source: UniProtKB-KW regulation of membrane potential Inferred from electronic annotation. Source: Compara sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW sulfate transport Inferred from electronic annotation. Source: InterPro
Cellular_component	basolateral plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lateral plasma membrane Inferred from direct assay PubMed 11867734. Source: RGD
Molecular_function	motor activity Traceable author statement PubMed 11867734. Source: RGD secondary active sulfate transmembrane transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 744

744

Prestin

PRO_0000080170

Regions

Topological domain

1 – 79

79

Cytoplasmic Potential

Transmembrane

80 – 100

21

Helical; Name=1; Potential

Topological domain

101 – 102

2

Extracellular Potential

Transmembrane

103 – 123

21

Helical; Name=2; Potential

Topological domain

124 – 131

8

Cytoplasmic Potential

Transmembrane

132 – 152

21

Helical; Name=3; Potential

Topological domain

153 – 183

31

Extracellular Potential

Transmembrane

184 – 204

21

Helical; Name=4; Potential

Topological domain

205 – 211

7

Cytoplasmic Potential

Transmembrane

212 – 232

21

Helical; Name=5; Potential

Topological domain

233 – 253

21

Extracellular Potential

Transmembrane

254 – 274

21

Helical; Name=6; Potential

Topological domain

275 – 286

12

Cytoplasmic Potential

Transmembrane

287 – 307

21

Helical; Name=7; Potential

Topological domain

308 – 334

27

Extracellular Potential

Transmembrane

335 – 355

21

Helical; Name=8; Potential

Topological domain

356 – 374

19

Cytoplasmic Potential

Transmembrane

375 – 395

21

Helical; Name=9; Potential

Topological domain

396 – 411

16

Extracellular Potential

Transmembrane

412 – 432

21

Helical; Name=10; Potential

Topological domain

433 – 441

9

Cytoplasmic Potential

Transmembrane

442 – 462

21

Helical; Name=11; Potential

Topological domain

463 – 479

17

Extracellular Potential

Transmembrane

480 – 500

21

Helical; Name=12; Potential

Topological domain

501 – 744

244

Cytoplasmic Potential

Domain

525 – 713

189

STAS

Amino acid modifications

Glycosylation

163

1

N-linked (GlcNAc...) Potential

Glycosylation

166

1

N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis

154

1

D → N: Shifts the voltage-sensitivity to more negative values. Ref.5

Mutagenesis

155

1

D → N: Shifts the voltage-sensitivity to more negative values. Ref.5

Mutagenesis

169

1

E → Q: No effect. Ref.5

Mutagenesis

177

1

K → Q: No effect. Ref.5

Mutagenesis

197

1

R → Q: Shifts the voltage-sensitivity to more negative values. Ref.5

Mutagenesis

233

1

K → Q: Shifts the voltage-sensitivity to more negative values; when associated with Q-235 and Q-236. Ref.5

Mutagenesis

235

1

K → Q: Shifts the voltage-sensitivity to more negative values; when associated with Q-233 and Q-236. Ref.5

Mutagenesis

236

1

R → Q: Shifts the voltage-sensitivity to more negative values; when associated with Q-233 and Q-235. Ref.5

Mutagenesis

277

1

E → Q: Shifts the voltage-sensitivity to slightly more positive values. Ref.5

Mutagenesis

281

1

R → Q: No effect; when associated with Q-283 and Q-285. Ref.5

Mutagenesis

283

1

K → Q: No effect; when associated with Q-218 and Q-285. Ref.5

Mutagenesis

285

1

K → Q: No effect; when associated with Q-281 and Q-283. Ref.5

Mutagenesis

332

1

D → Q: No effect. Ref.5

Mutagenesis

342

1

D → Q: Shifts the voltage-sensitivity to more positive values. Ref.5

Mutagenesis

409

1

K → Q: No effect. Ref.5

Mutagenesis

557

1

K → Q: No effect; when associated with Q-558 and Q-559. Ref.5

Mutagenesis

558

1

R → Q: No effect; when associated with Q-557 and Q-559. Ref.5

Mutagenesis

559

1

K → Q: No effect; when associated with Q-557 and Q-558. Ref.5

Mutagenesis

571

1

R → Q: Shifts the voltage-sensitivity to slightly more positive values; when associated with Q-572 and Q-577. Ref.5

Mutagenesis

572

1

R → Q: Shifts the voltage-sensitivity to slightly more positive values; when associated with Q-571 and Q-577. Ref.5

Mutagenesis

577

1

K → Q: Shifts the voltage-sensitivity to slightly more positive values; when associated with Q-571 and Q-572. Ref.5

Sequence conflict

251

1

L → V in AAG30297. Ref.2

Sequence conflict

567

1

I → M in AAG30297. Ref.2

Sequence conflict

572

1

R → S in AAG30297. Ref.2

Sequence conflict

612

1

D → G in AAG30297. Ref.2

Sequence conflict

662 – 663

2

GI → VM in AAG30297. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

744

Helix Strand Turn

Details...

Beta strand

507 – 513

7

Beta strand

520 – 522

3

Turn

523 – 525

3

Beta strand

535 – 540

6

Helix

544 – 554

11

Beta strand

640 – 645

6

Helix

654 – 668

15

Turn

669 – 671

3

Beta strand

673 – 678

6

Helix

681 – 689

9

Turn

690 – 693

4

Helix

696 – 701

6

Beta strand

702 – 705

4

Helix

706 – 712

7

Sequences

	Sequence		Length	Mass (Da)
	Q9EPH0 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: E49E842CF7A3CD58	FASTA	744	81,279
	10 20 30 40 50 60 MDHAEENEIP AETQKYLVER PIFSHPVLQE RLHVKDKVTD SIGDKLKQAF TCTPKKVRNI 70 80 90 100 110 120 IYMFLPITKW LPAYKFKEYV LGDLVSGIST GVLQLPQGLA FAMLAAVPPV FGLYSSFYPV 130 140 150 160 170 180 IMYCFFGTSR HISIGPFAVI SLMIGGVAVR LVPDDIVIPG GVNATNGTEA RDALRVKVAM 190 200 210 220 230 240 SVTLLSGIIQ FCLGVCRFGF VAIYLTEPLV RGFTTAAAVH VFTSMLKYLF GVKTKRYSGI 250 260 270 280 290 300 FSVVYSTVAV LQNVKNLNVC SLGVGLMVFG LLLGGKEFNE RFKEKLPAPI PLEFFAVVMG 310 320 330 340 350 360 TGISAGFNLH ESYSVDVVGT LPLGLLPPAN PDTSLFHLVY VDAIAIAIVG FSVTISMAKT 370 380 390 400 410 420 LANKHGYQVD GNQELIALGI CNSIGSLFQT FSISCSLSRS LVQEGTGGKT QLAGCLASLM 430 440 450 460 470 480 ILLVILATGF LFESLPQAVL SAIVIVNLKG MFMQFSDLPF FWRTSKIELT IWLTTFVSSL 490 500 510 520 530 540 FLGLDYGLIT AVIIALLTVI YRTQSPSYTV LGQLPDTDVY IDIDAYEEVK EIPGIKIFQI 550 560 570 580 590 600 NAPIYYANSD LYSSALKRKT GVNPAIIMGA RRKAMRKYAK EVGNANIANA TVVKVDAEVD 610 620 630 640 650 660 GENATKPEEE DDEVKFPPIV IKTTFPEELQ RFLPQGENIH TVILDFTQVN FMDSVGVKTL 670 680 690 700 710 720 AGIVKEYGDV GIYVYLAGCS AQVVNDLTSN RFFENPALKE LLFHSIHDAV LGSQVREAMA 730 740 EQETTVLPPQ EDMEPNATPT TPEA

References

[1]	"Reciprocal electromechanical properties of rat prestin: the motor molecule from rat outer hair cells." Ludwig J., Oliver D., Frank G., Kloecker N., Gummer A.W., Fakler B. Proc. Natl. Acad. Sci. U.S.A. 98:4178-4183(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TOPOLOGY. Tissue: Cochlea.
[2]	"Dynamic developmental expression of cochlear hair cell genes: prestin and otoferlin." Beisel K.W., Nelson N.C., Beisel C.L., Delimont D.C., He D.Z.Z., Fritzsch B. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 249-668. Strain: Sprague-Dawley.
[3]	"Thyroid horomone is a critical determinant for the regulation of the cochlear motor protein prestin." Weber T., Zimmermann U., Winter H., Mack A., Koepschall I., Rohbock K., Zenner H.P., Knipper M. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 1-20. Strain: Sprague-Dawley.
[4]	"Expression and localization of prestin and the sugar transporter GLUT-5 during development of electromotility in cochlear outer hair cells." Belyantseva I.A., Adler H.J., Curi R., Frolenkov G.I., Kachar B. J. Neurosci. 20:RC116-RC116(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein." Oliver D., He D.Z.Z., Kloecker N., Ludwig J., Schulte U., Waldegger S., Ruppersberg J.P., Dallos P., Fakler B. Science 292:2340-2343(2001) [PubMed] [Europe PMC] [Abstract] Cited for: MODE OF ACTION, MUTAGENESIS OF ASP-154; ASP-155; GLU-169; LYS-177; ARG-197; LYS-233; LYS-235; ARG-236; GLU-277; ARG-281; LYS-283; LYS-285; ASP-332; ASP-342; LYS-409; LYS-557; ARG-558; LYS-559; ARG-571; ARG-572 AND LYS-577.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Pump up the volume - Issue 22 of May 2002

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ303372 mRNA. Translation: CAC21555.1.
AF315652 mRNA. Translation: AAG30297.1.
AJ428404 Genomic DNA. Translation: CAD21439.1.

IPI

IPI00189056.

RefSeq

NP_110467.1. NM_030840.1.

UniGene

Rn.64631.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LLO	X-ray	1.57	A	505-718	[»]

ProteinModelPortal

Q9EPH0.

ModBase

Search...

Protein-protein interaction databases

STRING

10116.ENSRNOP00000015733.

Proteomic databases

PaxDb

Q9EPH0.

PRIDE

Q9EPH0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000015733; ENSRNOP00000015733; ENSRNOG00000011616.

GeneID

83819.

KEGG

rno:83819.

Organism-specific databases

CTD

375611.

RGD

69334. Slc26a5.

Phylogenomic databases

eggNOG

COG0659.

GeneTree

ENSGT00670000097702.

HOGENOM

HOG000006546.

HOVERGEN

HBG000639.

InParanoid

Q9EPH0.

KO

K14703.

OMA

IILDFTQ.

OrthoDB

EOG44MXRJ.

Gene expression databases

ArrayExpress

Q9EPH0.

Genevestigator

Q9EPH0.

GermOnline

ENSRNOG00000011616. Rattus norvegicus.

Family and domain databases

Gene3D

3.30.750.24. 2 hits.

InterPro

IPR018045. S04_transporter_CS.
IPR002645. STAS_dom.
IPR001902. SulP_transpt.
IPR011547. Sulph_transpt.
[Graphical view]

Pfam

PF01740. STAS. 1 hit.
PF00916. Sulfate_transp. 1 hit.
[Graphical view]

SUPFAM

SSF52091. STAS. 1 hit.

TIGRFAMs

TIGR00815. sulP. 1 hit.

PROSITE

PS01130. SLC26A. 1 hit.
PS50801. STAS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9EPH0.

NextBio

616430.

Entry information

Entry name

S26A5_RAT

Accession

Primary (citable) accession number: Q9EPH0
Secondary accession number(s): Q9ERC6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	March 1, 2001
Last modified:	April 3, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program