Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Harmonin

Gene

USH1C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 development and maintenance of cochlear hair cell bundles (By similarity). As part of the intermicrovillar adhesion complex/IMAC plays a role in brush border differentiation, controlling microvilli organization and length. Probably plays a central regulatory role in the assembly of the complex, recruiting CDHR2, CDHR5 and MYO7B to the microvilli tips (PubMed:24725409, PubMed:26812018).By similarity2 Publications

GO - Molecular functioni

  • actin filament binding Source: InterPro
  • spectrin binding Source: MGI

GO - Biological processi

Keywordsi

Biological processDifferentiation, Hearing

Names & Taxonomyi

Protein namesi
Recommended name:
Harmonin
Alternative name(s):
Antigen NY-CO-38/NY-CO-37
Autoimmune enteropathy-related antigen AIE-75
Protein PDZ-73
Renal carcinoma antigen NY-REN-3
Usher syndrome type-1C protein
Gene namesi
Name:USH1C
Synonyms:AIE75
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000006611.15
HGNCiHGNC:12597 USH1C
MIMi605242 gene
neXtProtiNX_Q9Y6N9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Usher syndrome 1C (USH1C)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionUSH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.
See also OMIM:276904
Deafness, autosomal recessive, 18A (DFNB18A)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:602092

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi103R → H: Strongly reduced affinity for USH1G. 1 Publication1

Keywords - Diseasei

Deafness, Non-syndromic deafness, Retinitis pigmentosa, Usher syndrome

Organism-specific databases

DisGeNETi10083
GeneReviewsiUSH1C
MalaCardsiUSH1C
MIMi276900 phenotype
276904 phenotype
602092 phenotype
OpenTargetsiENSG00000006611
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
231169 Usher syndrome type 1
PharmGKBiPA37226

Polymorphism and mutation databases

BioMutaiUSH1C
DMDMi160113087

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000657271 – 552HarmoninAdd BLAST552

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei219PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9Y6N9
PeptideAtlasiQ9Y6N9
PRIDEiQ9Y6N9
ProteomicsDBi86750
86751 [Q9Y6N9-2]
86752 [Q9Y6N9-3]
86753 [Q9Y6N9-4]
86754 [Q9Y6N9-5]

PTM databases

iPTMnetiQ9Y6N9
PhosphoSitePlusiQ9Y6N9

Expressioni

Tissue specificityi

Expressed in small intestine, colon, kidney, eye and weakly in pancreas. Expressed also in vestibule of the inner ear.1 Publication

Gene expression databases

BgeeiENSG00000006611 Expressed in 138 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_USH1C
ExpressionAtlasiQ9Y6N9 baseline and differential
GenevisibleiQ9Y6N9 HS

Organism-specific databases

HPAiCAB013690
HPA027398
HPA027492
HPA028033

Interactioni

Subunit structurei

Part of the IMAC/intermicrovillar adhesion complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, USH1C, CDHR2 and CDHR5 (Probable). Part of a complex composed of USH1C, USH1G and MYO7A (PubMed:21709241). Interacts with F-actin (By similarity). Interacts with USH2A (PubMed:16301216). Interacts with SLC4A7 (PubMed:16301216). Interacts (via PDZ1 domain) with the C-terminus of USHBP1 (PubMed:11311560). Interacts (via N-terminus and PDZ 2 domain) with CDH23 (PubMed:19297620). Interacts with USH1G (PubMed:12588794, PubMed:20142502). Interacts with MYO7B (PubMed:24725409, PubMed:26812017). Interacts with CDHR2 and CDHR5; may mediate their interaction with MYO7B at the microvilli tip (PubMed:24725409, PubMed:26812017). Interacts (via PDZ 1 domain) with ANKS4B (PubMed:26812018, PubMed:26812017).By similarity2 Publications9 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115392, 23 interactors
CORUMiQ9Y6N9
DIPiDIP-41473N
ELMiQ9Y6N9
IntActiQ9Y6N9, 28 interactors
MINTiQ9Y6N9
STRINGi9606.ENSP00000005226

Structurei

Secondary structure

1552
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Y6N9
SMRiQ9Y6N9
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y6N9

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini87 – 169PDZ 1PROSITE-ProRule annotationAdd BLAST83
Domaini211 – 293PDZ 2PROSITE-ProRule annotationAdd BLAST83
Domaini452 – 537PDZ 3PROSITE-ProRule annotationAdd BLAST86

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 86N-terminal domain1 PublicationAdd BLAST86
Regioni194 – 552Mediates interaction with MYO7B2 PublicationsAdd BLAST359

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili310 – 377Sequence analysisAdd BLAST68

Domaini

The PDZ 1 domain mediates interaction with ANKS4B, USHBP1, USH1G, SLC4A7.5 Publications
The N-terminal region constitutes an independently folded domain that has structural similarity with the CCM2 C-terminus, despite very low sequence similarity.1 Publication

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG3528 Eukaryota
ENOG4110362 LUCA
GeneTreeiENSGT00530000063178
HOGENOMiHOG000126890
HOVERGENiHBG057181
InParanoidiQ9Y6N9
KOiK21877
OMAiKRLAMES
OrthoDBiEOG091G073L
PhylomeDBiQ9Y6N9
TreeFamiTF325033

Family and domain databases

InterProiView protein in InterPro
IPR030237 Harmonin
IPR001478 PDZ
IPR036034 PDZ_sf
PANTHERiPTHR23116:SF36 PTHR23116:SF36, 2 hits
PfamiView protein in Pfam
PF00595 PDZ, 3 hits
SMARTiView protein in SMART
SM00228 PDZ, 3 hits
SUPFAMiSSF50156 SSF50156, 3 hits
PROSITEiView protein in PROSITE
PS50106 PDZ, 3 hits

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9Y6N9-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MDRKVAREFR HKVDFLIEND AEKDYLYDVL RMYHQTMDVA VLVGDLKLVI
60 70 80 90 100
NEPSRLPLFD AIRPLIPLKH QVEYDQLTPR RSRKLKEVRL DRLHPEGLGL
110 120 130 140 150
SVRGGLEFGC GLFISHLIKG GQADSVGLQV GDEIVRINGY SISSCTHEEV
160 170 180 190 200
INLIRTKKTV SIKVRHIGLI PVKSSPDEPL TWQYVDQFVS ESGGVRGSLG
210 220 230 240 250
SPGNRENKEK KVFISLVGSR GLGCSISSGP IQKPGIFISH VKPGSLSAEV
260 270 280 290 300
GLEIGDQIVE VNGVDFSNLD HKEAVNVLKS SRSLTISIVA AAGRELFMTD
310 320 330 340 350
RERLAEARQR ELQRQELLMQ KRLAMESNKI LQEQQEMERQ RRKEIAQKAA
360 370 380 390 400
EENERYRKEM EQIVEEEEKF KKQWEEDWGS KEQLLLPKTI TAEVHPVPLR
410 420 430 440 450
KPKYDQGVEP ELEPADDLDG GTEEQGEQDF RKYEEGFDPY SMFTPEQIMG
460 470 480 490 500
KDVRLLRIKK EGSLDLALEG GVDSPIGKVV VSAVYERGAA ERHGGIVKGD
510 520 530 540 550
EIMAINGKIV TDYTLAEAEA ALQKAWNQGG DWIDLVVAVC PPKEYDDELT

FF
Length:552
Mass (Da):62,211
Last modified:November 13, 2007 - v3
Checksum:i7E75CEE873C57F41
GO
Isoform 2 (identifier: Q9Y6N9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: Missing.

Show »
Length:521
Mass (Da):58,343
Checksum:iA303D7D48D91A847
GO
Isoform 3 (identifier: Q9Y6N9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     404-552: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:403
Mass (Da):45,812
Checksum:iAB350B62ED2C44FD
GO
Isoform 4 (identifier: Q9Y6N9-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     274-292: Missing.

Note: No experimental confirmation available.
Show »
Length:533
Mass (Da):60,329
Checksum:iA9D7E121B11E2FBD
GO
Isoform 5 (identifier: Q9Y6N9-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     404-427: YDQGVEPELEPADDLDGGTEEQGE → SFGWFYRYDG...RMVVYQTAFR
     550-552: TFF → ASLPSSVAESPQPVRKLLEDRAAVHRHGFLLQLEPTDLLLKSKRGNQIHR

Note: No experimental confirmation available.
Show »
Length:899
Mass (Da):101,344
Checksum:i6DA49F7674BFA920
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PNW1E9PNW1_HUMAN
Harmonin
USH1C
317Annotation score:

Sequence cautioni

The sequence AAC18049 differs from that shown. Reason: Frameshift at position 552.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti103R → S in BAA81739 (PubMed:10500064).Curated1
Sequence conflicti280S → N in AAC18049 (PubMed:9610721).Curated1
Sequence conflicti280S → N in AAC18048 (PubMed:9610721).Curated1
Sequence conflicti305A → T in BAA81739 (PubMed:10500064).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012320519E → D3 PublicationsCorresponds to variant dbSNP:rs1064074Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0037891 – 31Missing in isoform 2. 1 PublicationAdd BLAST31
Alternative sequenceiVSP_007422274 – 292Missing in isoform 4. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_003790404 – 552Missing in isoform 3. 1 PublicationAdd BLAST149
Alternative sequenceiVSP_043520404 – 427YDQGV…EEQGE → SFGWFYRYDGKFPTIRKKGK DKKKAKYGSLQDLRKNKKEL EFEQKLYKEKEEMLEKEKQL KINRLAQEVSETEREDLEES EKIQYWVERLCQTRLEQISS ADNEISEMTTGPPPPPPSVS PLAPPLRRFAGGLHLHTTDL DDIPLDMFYYPPKTPSALPV MPHPPPSNPPHKVPAPPVLP LSGHVSASSSPWVQRTPPPI PIPPPPSVPTQDLTPTRPLP SALEEALSNHPFRTGDTGNP VEDWEAKNHSGKPTNSPVPE QSFPPTPKTFCPSPQPPRGP GVSTISKPVMVHQEPNFIYR PAVKSEVLPQEMLKRMVVYQ TAFR in isoform 5. CuratedAdd BLAST24
Alternative sequenceiVSP_043521550 – 552TFF → ASLPSSVAESPQPVRKLLED RAAVHRHGFLLQLEPTDLLL KSKRGNQIHR in isoform 5. Curated3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF039700 mRNA Translation: AAC18049.1 Frameshift.
AF039699 mRNA Translation: AAC18048.1
AB006955 mRNA Translation: BAA81739.1
AB018687 mRNA Translation: BAA81740.1
AK290788 mRNA Translation: BAF83477.1
AC124799 Genomic DNA No translation available.
BC016057 mRNA Translation: AAH16057.1
CH471064 Genomic DNA Translation: EAW68432.1
BK000147 mRNA Translation: DAA00086.1
CCDSiCCDS31438.1 [Q9Y6N9-1]
CCDS73265.1 [Q9Y6N9-4]
CCDS7825.1 [Q9Y6N9-5]
RefSeqiNP_001284693.1, NM_001297764.1 [Q9Y6N9-4]
NP_005700.2, NM_005709.3 [Q9Y6N9-1]
NP_710142.1, NM_153676.3 [Q9Y6N9-5]
UniGeneiHs.502072

Genome annotation databases

EnsembliENST00000005226; ENSP00000005226; ENSG00000006611 [Q9Y6N9-5]
ENST00000318024; ENSP00000317018; ENSG00000006611 [Q9Y6N9-1]
ENST00000526313; ENSP00000432236; ENSG00000006611 [Q9Y6N9-3]
ENST00000527020; ENSP00000436934; ENSG00000006611 [Q9Y6N9-4]
ENST00000527720; ENSP00000432944; ENSG00000006611 [Q9Y6N9-2]
GeneIDi10083
KEGGihsa:10083
UCSCiuc001mne.4 human [Q9Y6N9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Mutations of the USH1C gene

Retina International's Scientific Newsletter

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF039700 mRNA Translation: AAC18049.1 Frameshift.
AF039699 mRNA Translation: AAC18048.1
AB006955 mRNA Translation: BAA81739.1
AB018687 mRNA Translation: BAA81740.1
AK290788 mRNA Translation: BAF83477.1
AC124799 Genomic DNA No translation available.
BC016057 mRNA Translation: AAH16057.1
CH471064 Genomic DNA Translation: EAW68432.1
BK000147 mRNA Translation: DAA00086.1
CCDSiCCDS31438.1 [Q9Y6N9-1]
CCDS73265.1 [Q9Y6N9-4]
CCDS7825.1 [Q9Y6N9-5]
RefSeqiNP_001284693.1, NM_001297764.1 [Q9Y6N9-4]
NP_005700.2, NM_005709.3 [Q9Y6N9-1]
NP_710142.1, NM_153676.3 [Q9Y6N9-5]
UniGeneiHs.502072

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X5NNMR-A201-301[»]
2KBQNMR-A1-80[»]
2KBRNMR-A1-80[»]
2KBSNMR-A208-299[»]
2LSRNMR-A1-80[»]
3K1RX-ray2.30A1-192[»]
5F3XX-ray2.65A/C1-194[»]
5MV8X-ray1.88B428-552[»]
5MV9X-ray2.60B428-552[»]
5XBFX-ray1.80B428-552[»]
ProteinModelPortaliQ9Y6N9
SMRiQ9Y6N9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115392, 23 interactors
CORUMiQ9Y6N9
DIPiDIP-41473N
ELMiQ9Y6N9
IntActiQ9Y6N9, 28 interactors
MINTiQ9Y6N9
STRINGi9606.ENSP00000005226

PTM databases

iPTMnetiQ9Y6N9
PhosphoSitePlusiQ9Y6N9

Polymorphism and mutation databases

BioMutaiUSH1C
DMDMi160113087

Proteomic databases

PaxDbiQ9Y6N9
PeptideAtlasiQ9Y6N9
PRIDEiQ9Y6N9
ProteomicsDBi86750
86751 [Q9Y6N9-2]
86752 [Q9Y6N9-3]
86753 [Q9Y6N9-4]
86754 [Q9Y6N9-5]

Protocols and materials databases

DNASUi10083
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000005226; ENSP00000005226; ENSG00000006611 [Q9Y6N9-5]
ENST00000318024; ENSP00000317018; ENSG00000006611 [Q9Y6N9-1]
ENST00000526313; ENSP00000432236; ENSG00000006611 [Q9Y6N9-3]
ENST00000527020; ENSP00000436934; ENSG00000006611 [Q9Y6N9-4]
ENST00000527720; ENSP00000432944; ENSG00000006611 [Q9Y6N9-2]
GeneIDi10083
KEGGihsa:10083
UCSCiuc001mne.4 human [Q9Y6N9-1]

Organism-specific databases

CTDi10083
DisGeNETi10083
EuPathDBiHostDB:ENSG00000006611.15
GeneCardsiUSH1C
GeneReviewsiUSH1C
H-InvDBiHIX0009478
HGNCiHGNC:12597 USH1C
HPAiCAB013690
HPA027398
HPA027492
HPA028033
MalaCardsiUSH1C
MIMi276900 phenotype
276904 phenotype
602092 phenotype
605242 gene
neXtProtiNX_Q9Y6N9
OpenTargetsiENSG00000006611
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
231169 Usher syndrome type 1
PharmGKBiPA37226
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3528 Eukaryota
ENOG4110362 LUCA
GeneTreeiENSGT00530000063178
HOGENOMiHOG000126890
HOVERGENiHBG057181
InParanoidiQ9Y6N9
KOiK21877
OMAiKRLAMES
OrthoDBiEOG091G073L
PhylomeDBiQ9Y6N9
TreeFamiTF325033

Miscellaneous databases

ChiTaRSiUSH1C human
EvolutionaryTraceiQ9Y6N9
GeneWikiiUSH1C
GenomeRNAii10083
PROiPR:Q9Y6N9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000006611 Expressed in 138 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_USH1C
ExpressionAtlasiQ9Y6N9 baseline and differential
GenevisibleiQ9Y6N9 HS

Family and domain databases

InterProiView protein in InterPro
IPR030237 Harmonin
IPR001478 PDZ
IPR036034 PDZ_sf
PANTHERiPTHR23116:SF36 PTHR23116:SF36, 2 hits
PfamiView protein in Pfam
PF00595 PDZ, 3 hits
SMARTiView protein in SMART
SM00228 PDZ, 3 hits
SUPFAMiSSF50156 SSF50156, 3 hits
PROSITEiView protein in PROSITE
PS50106 PDZ, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiUSH1C_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6N9
Secondary accession number(s): A8K423
, Q7RTU8, Q96B29, Q9UM04, Q9UM17, Q9UPC3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: November 13, 2007
Last modified: September 12, 2018
This is version 171 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again