USH1C

Protein identityUniProt · HPA

UniProt accession

Q9Y6N9

Gene

USH1C

Ensembl

ENSG00000006611

Chromosome

11

Canonical length

552 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

This gene encodes a scaffold protein that functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

Canonical amino-acid sequenceUniProt

552 residues, UniProt reviewed canonical sequence.

>Q9Y6N9|USH1C
     1  MDRKVAREFR HKVDFLIEND AEKDYLYDVL RMYHQTMDVA VLVGDLKLVI NEPSRLPLFD
    61  AIRPLIPLKH QVEYDQLTPR RSRKLKEVRL DRLHPEGLGL SVRGGLEFGC GLFISHLIKG
   121  GQADSVGLQV GDEIVRINGY SISSCTHEEV INLIRTKKTV SIKVRHIGLI PVKSSPDEPL
   181  TWQYVDQFVS ESGGVRGSLG SPGNRENKEK KVFISLVGSR GLGCSISSGP IQKPGIFISH
   241  VKPGSLSAEV GLEIGDQIVE VNGVDFSNLD HKEAVNVLKS SRSLTISIVA AAGRELFMTD
   301  RERLAEARQR ELQRQELLMQ KRLAMESNKI LQEQQEMERQ RRKEIAQKAA EENERYRKEM
   361  EQIVEEEEKF KKQWEEDWGS KEQLLLPKTI TAEVHPVPLR KPKYDQGVEP ELEPADDLDG
   421  GTEEQGEQDF RKYEEGFDPY SMFTPEQIMG KDVRLLRIKK EGSLDLALEG GVDSPIGKVV
   481  VSAVYERGAA ERHGGIVKGD EIMAINGKIV TDYTLAEAEA ALQKAWNQGG DWIDLVVAVC
   541  PPKEYDDELT FF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against USH1C can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.36

Highest tissue expression

92 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about USH1C.

Disease | AllUniProt

Conditions USH1C is implicated in, by any mechanism.

• Usher syndrome 1C (USH1C) MIM:276904
• Deafness, autosomal recessive, 18A (DFNB18A) MIM:602092

Disease | GeneticClinVar

200 pathogenic / likely-pathogenic of 1,520 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive nonsyndromic hearing loss 18A
• Usher syndrome type 1C
• Usher syndrome type 1
• USH1C-related disorder
• Retinal dystrophy

ReferencesPubMed · IEDB

Publications for USH1C from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.89

gnomAD pLI

0

gnomAD missense Z

-0.87

DepMap mean gene effect

0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• actin filament bundle assembly
• auditory receptor cell morphogenesis
• brush border assembly
• equilibrioception
• G2/M transition of mitotic cell cycle
• inner ear auditory receptor cell differentiation
• inner ear morphogenesis
• inner ear receptor cell stereocilium organization
• parallel actin filament bundle assembly
• photoreceptor cell maintenance
• protein localization to microvillus
• protein-containing complex assembly
• regulation of microvillus length
• retinal cone cell development
• sensory perception of light stimulus
• sensory perception of sound

Molecular functions

• spectrin binding

Cellular components

• apical part of cell
• brush border
• cilium
• cytoplasm
• cytoskeleton
• cytosol
• microvillus
• photoreceptor inner segment
• photoreceptor outer segment
• plasma membrane
• stereocilia ankle link complex
• stereocilium
• stereocilium tip
• synapse

Protein domainsUniProt · Pfam · InterPro

• PDZ domain
• PDZ superfamily
• Sensory Perception USH2 Complex Protein
• PDZ domain
• Harmonin, N-terminal
• Harmonin, N-terminal domain

KeywordsUniProt

• Cell projection
• Coiled coil
• Cytoplasm
• Cytoskeleton
• Deafness
• Differentiation
• Hearing
• Non-syndromic deafness
• Phosphoprotein
• Repeat
• Retinitis pigmentosa
• Usher syndrome

InteractionsUniProt · HPA

Protein binding partners of USH1C in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CDHR2
• CDHR5
• MYO7B
• SLC4A7
• USH1G
• USH2A
• DOCK4
• CDH23
• ANKS4B