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Q9ES64 (USH1C_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Harmonin
Alternative name(s):
PDZ domain-containing protein
Usher syndrome type-1C protein homolog
Gene names
Name:Ush1c
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length910 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for normal development and maintenance of cochlear hair cell bundles. Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal hearing. Ref.9

Subunit structure

Interacts with HARP. Interacts with USH1G/SANS, USH2A and SLC4A7. Part of a complex composed of USH1C, USH1G and MYO7A. Interacts (via the first PDZ domain) with the C-terminus of USHBP1. Interacts (via N-terminus and second PDZ domain) with CDH23. Interacts with F-actin. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Subcellular location

Cytoplasmcytosol By similarity. Cytoplasmcytoskeleton. Note: Detected at the tip of cochlear hair cell stereocilia. Colocalizes with F-actin. Ref.9

Tissue specificity

Detected in stereocilia of cochlear hair cells (at protein level). Isoform 1 is expressed in the eye, cochlea, vestibule, heart, kidney, small intestine and testis; it is barely visible in skeletal muscle, liver, and lung and is absent from the brain. Isoforms 2 and 3 are expressed in the cochlea and vestibule. Ref.1 Ref.9

Domain

The PDZ domain 1 mediates interactions with USH1G/SANS and SLC4A7.

The N-terminal region constitutes an independently folded domain that has structural similarity with the CCM2 C-terminus, despite very low sequence similarity By similarity.

Sequence similarities

Contains 3 PDZ (DHR) domains.

Ontologies

Keywords
   Biological processHearing
   Cellular componentCytoplasm
Cytoskeleton
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
Repeat
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin filament bundle assembly

Inferred from direct assay PubMed 12485990. Source: MGI

auditory receptor cell differentiation

Inferred from mutant phenotype PubMed 14519688. Source: MGI

inner ear morphogenesis

Inferred from mutant phenotype PubMed 14519688. Source: MGI

neuromuscular process controlling balance

Inferred from mutant phenotype PubMed 14519688. Source: MGI

parallel actin filament bundle assembly

Inferred from direct assay PubMed 12485990. Source: MGI

sensory perception of sound

Inferred from mutant phenotype PubMed 14519688. Source: MGI

   Cellular_componentcytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

photoreceptor inner segment

Inferred from direct assay PubMed 14578428. Source: MGI

photoreceptor outer segment

Inferred from direct assay PubMed 14578428. Source: MGI

plasma membrane

Inferred from direct assay Ref.6. Source: MGI

stereocilium

Inferred from direct assay PubMed 12485990PubMed 20016102. Source: MGI

synapse

Inferred from direct assay PubMed 14578428. Source: MGI

   Molecular_functionmyosin tail binding

Inferred from sequence orthology PubMed 23704327. Source: MGI

protein binding

Inferred from physical interaction PubMed 15590703PubMed 15928608PubMed 15590703PubMed 15928608. Source: IntAct

spectrin binding

Inferred from sequence orthology PubMed 23704327. Source: MGI

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms exist.
Isoform 3 (identifier: Q9ES64-1)

Also known as: b3;

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.
Isoform 2 (identifier: Q9ES64-2)

Also known as: b2;

The sequence of this isoform differs from the canonical sequence as follows:
     850-859: SSLPSSAAES → RKPPAGPKAA
     860-910: Missing.
Isoform 1 (identifier: Q9ES64-3)

Also known as: a1;

The sequence of this isoform differs from the canonical sequence as follows:
     404-423: SFGWFYRYDGKFPTIRKKAK → YDQGVEPADHLDGSTEEQRQ
     424-727: Missing.
     850-852: SSL → TFF

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 910910Harmonin
PRO_0000065728

Regions

Domain87 – 17185PDZ 1
Domain211 – 29585PDZ 2
Domain752 – 83988PDZ 3
Region1 – 8686N-terminal domain
Coiled coil299 – 37779 Potential
Coiled coil417 – 48266 Potential

Natural variations

Alternative sequence404 – 42320SFGWF…RKKAK → YDQGVEPADHLDGSTEEQRQ in isoform 1. Ref.1
VSP_050530
Alternative sequence424 – 727304Missing in isoform 1. Ref.1
VSP_050531
Alternative sequence850 – 85910SSLPSSAAES → RKPPAGPKAA in isoform 2.
VSP_050532
Alternative sequence850 – 8523SSL → TFF in isoform 1. Ref.1
VSP_050533
Alternative sequence860 – 91051Missing in isoform 2.
VSP_050534

Experimental info

Sequence conflict3751E → K in AAH10819. Ref.3
Sequence conflict7401Y → H in BAB25568. Ref.4

Secondary structure

................... 910
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 3 (b3) [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 427B97953BA5D941

FASTA910102,285
        10         20         30         40         50         60 
MDRKVAREFR HKVDFLIEND AEKDYLYDVL RMYHQTMDVA VLVGDLKLVI NEPNRLPLFD 

        70         80         90        100        110        120 
AIRPLIPLKH QVEYDQLTPR RSRKLKEVRL DRLHPEGLGL SVRGGLEFGC GLFISHLIKG 

       130        140        150        160        170        180 
GQADSVGLQV GDEIVRINGY SISSCTHEEV INLIRTKKTV SIKVRHIGLI PVKSSPEESL 

       190        200        210        220        230        240 
KWQYVDQFVS ESGGVRGGLG SPGNRTTKEK KVFISLVGSR GLGCSISSGP IQKPGIFVSH 

       250        260        270        280        290        300 
VKPGSLSAEV GLETGDQIVE VNGIDFTNLD HKEAVNVLKS SRSLTISIVA GAGRELFMTD 

       310        320        330        340        350        360 
RERLEEARQR ELQRQELLMQ KRLAMESNKI LQEQQEMERQ RRKEIAQKAA EENERYRKEM 

       370        380        390        400        410        420 
EQISEEEEKF KKQWEEDWGS KEQLILPKTI TAEVHPVPLR KPKSFGWFYR YDGKFPTIRK 

       430        440        450        460        470        480 
KAKEKKKAKY DSLQDLRKNK KELEFEQKLY KEKEEMLEKE KQLKINRLAQ EVSETEREDL 

       490        500        510        520        530        540 
EESEKTQYWV ERLCQTRLEQ ISSAENEIPE MTTGPPPPPP SVSPLAPPLR RFAGGIHLHT 

       550        560        570        580        590        600 
TDLDDIPLDM FYYPPKTPSA LPVMPHPPSV NSPSKVPAPP VLPSSGHVSS SSSPWVQRTP 

       610        620        630        640        650        660 
PPIPIPPPPS IPTQDLTPTR PLPSALEEAL GNHPFRTGDP GHPADDWEAN THSGKPSSSP 

       670        680        690        700        710        720 
TTERSFPPAP KTFCPSPQPP RGPGVSTISK PVMVHQEHNF VYRPAVKSEV LPQEMLKRMV 

       730        740        750        760        770        780 
VYQTAFRQDF RKYEEGFDPY SMFSPEQIAG KDVRLLRIKK EGSLDLALEG GVDSPVGKVV 

       790        800        810        820        830        840 
VSAVYEGGAA ERHGGVVKGD EIMAINGKIV TDYTLAEAEA ALQKAWNQGG DWIDLVVAVC 

       850        860        870        880        890        900 
PPKEYDDELS SLPSSAAESP QLARKQLEAY EPVCRHGFFL QLEPTNLLLK SRERNQTDPS 

       910 
WRPASSAPSP 

« Hide

Isoform 2 (b2) [UniParc].

Checksum: 80041ACF7FE5F3D2
Show »

FASTA85996,498
Isoform 1 (a1) [UniParc].

Checksum: 59A90F640A915A36
Show »

FASTA60668,185

References

« Hide 'large scale' references
[1]"A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C."
Verpy E., Leibovici M., Zwaenepoel I., Liu X.-Z., Gal A., Salem N., Mansour A., Blanchard S., Kobayashi I., Keats B.J.B., Slim R., Petit C.
Nat. Genet. 26:51-55(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
Tissue: Inner ear.
[2]Verpy E., Leibovici M., Zwaenepoel I., Blanchard S., Petit C.
Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 740-852 (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Small intestine.
[5]"Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin."
Weil D., El-Amraoui A., Masmoudi S., Mustapha M., Kikkawa Y., Laine S., Delmaghani S., Adato A., Nadifi S., Zina Z.B., Hamel C., Gal A., Ayadi H., Yonekawa H., Petit C.
Hum. Mol. Genet. 12:463-471(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HARP.
[6]"Harp (harmonin-interacting, ankyrin repeat-containing protein), a novel protein that interacts with harmonin in epithelial tissues."
Johnston A.M., Naselli G., Niwa H., Brodnicki T., Harrison L.C., Gonez L.J.
Genes Cells 9:967-982(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HARP.
[7]"Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2."
Reiners J., van Wijk E., Maerker T., Zimmermann U., Juergens K., te Brinke H., Overlack N., Roepman R., Knipper M., Kremer H., Wolfrum U.
Hum. Mol. Genet. 14:3933-3943(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC4A7.
[8]"Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells."
Adato A., Lefevre G., Delprat B., Michel V., Michalski N., Chardenoux S., Weil D., El-Amraoui A., Petit C.
Hum. Mol. Genet. 14:3921-3932(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH USH2A.
[9]"Harmonin mutations cause mechanotransduction defects in cochlear hair cells."
Grillet N., Xiong W., Reynolds A., Kazmierczak P., Sato T., Lillo C., Dumont R.A., Hintermann E., Sczaniecka A., Schwander M., Williams D., Kachar B., Gillespie P.G., Muller U.
Neuron 62:375-387(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH CDH23 AND WITH F-ACTIN, SUBCELLULAR LOCATION.
[10]"Solution structure of the third PDZ domain of mouse harmonin."
RIKEN structural genomics initiative (RSGI)
Submitted (MAY-2004) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 742-849.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF228925 mRNA. Translation: AAG12458.1.
AF228924 mRNA. Translation: AAG12457.1.
AY103465 mRNA. Translation: AAM44072.1.
BC010819 mRNA. Translation: AAH10819.1.
AK008274 mRNA. Translation: BAB25568.2.
CCDSCCDS21276.1. [Q9ES64-1]
RefSeqNP_001157205.1. NM_001163733.1.
NP_076138.2. NM_023649.2.
NP_710143.2. NM_153677.2.
UniGeneMm.119709.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1V6BNMR-A742-849[»]
ProteinModelPortalQ9ES64.
SMRQ9ES64. Positions 1-299, 741-850.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid215143. 5 interactions.
IntActQ9ES64. 5 interactions.
MINTMINT-1895746.

PTM databases

PhosphoSiteQ9ES64.

Proteomic databases

MaxQBQ9ES64.
PaxDbQ9ES64.
PRIDEQ9ES64.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000078680; ENSMUSP00000077747; ENSMUSG00000030838.
GeneID72088.
KEGGmmu:72088.

Organism-specific databases

CTD10083.
MGIMGI:1919338. Ush1c.

Phylogenomic databases

eggNOGNOG255885.
GeneTreeENSGT00530000063178.
HOGENOMHOG000126890.
HOVERGENHBG057181.
InParanoidQ9ES64.
OrthoDBEOG75MVW2.
PhylomeDBQ9ES64.

Gene expression databases

ArrayExpressQ9ES64.
BgeeQ9ES64.
CleanExMM_USH1C.
GenevestigatorQ9ES64.

Family and domain databases

Gene3D2.30.42.10. 3 hits.
InterProIPR001478. PDZ.
[Graphical view]
PfamPF00595. PDZ. 3 hits.
[Graphical view]
SMARTSM00228. PDZ. 3 hits.
[Graphical view]
SUPFAMSSF50156. SSF50156. 3 hits.
PROSITEPS50106. PDZ. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9ES64.
NextBio335406.
PROQ9ES64.
SOURCESearch...

Entry information

Entry nameUSH1C_MOUSE
AccessionPrimary (citable) accession number: Q9ES64
Secondary accession number(s): Q91XD1, Q9CVG7, Q9ES65
Entry history
Integrated into UniProtKB/Swiss-Prot: May 16, 2003
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot