Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol PCDH15 contributors: mct/shn - updated : 12-12-2017
HGNC name protocadherin-related 15
HGNC id 14674
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminus contains polar amino acids (Elledge 2010)
  • a signal peptide
  • 11 extracellular cadherin (EC) repeats, with canonical EC4-5 linker binding three Ca2+ ions, and non-canonical EC3-4 linker binding only two Ca2+ ions
  • a transmembrane segment encoded by a large unique exon
  • a cytoplasmic domain containing two proline-rich regions
  • a polyadenylation signal
  • conjugated GlycoP
    isoforms Precursor
    HOMOLOGY
    interspecies ortholog to Pcdh15, Mus musculus
    ortholog to Pcdh15, Rattus norvegicus
    ortholog to PCDH15, Pan troglodytes
    intraspecies homolog to cadherin
    homolog to PCDH23
    homolog to CDH23
    Homologene
    FAMILY
  • cadherin superfamily of calcium dependent cell-cell adhesion glycoproteins
  • protocadherin subfamily
  • CATEGORY adhesion , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,nuclear envelope,int
    text
  • integral plasma membrane,localized at the synaptic junction
  • expressed in photoreceptor cells of the mammalian retina, where it is colocalized with harmonin, myosin VIIa, and cadherin 23 at the synaptic terminal
  • basic FUNCTION
  • maintaining normal function of inner ear and retina
  • mediating adhesion in synaptic junctions through lack-in process
  • playing an essential role in maintaining the normal organization of the stereocilia bundle
  • CDH23, PCDH15 and ADGRV1 have been implicated in the development of cochlear hair cell stereocilia, while CLRN1 has been suggested to also play a role in synaptogenesis
  • USH1G, MYO7A, USH1C, CDH23, PCDH15 form an adhesion belt around the basolateral region of the photoreceptor outer segment, and defects in this structure cause the retinal degeneration in USH1 patients
  • PCDH15 and LHFPL5 facilitate each other’s cell surface transport
  • is a central component of the mechanotransduction complex in auditory and vestibular hair cells
  • is a core component of hair cell tip-links and crucial for proper function of inner ear hair cells
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction , sensory transduction/hearing
    cell-cell signaling
    a component
  • TMIE forms a ternary complex with the tip-link component PCDH15 and its binding partner LHFPL5
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • interacted with harmonin USH1C (probably play a role in disk morphogenesis)
  • interact CDH23 to form a filament with structural similarity to tip links, in sensory hair cells
  • CDH23 and PCDH15 interact to form tip links, which gate mechanotransduction channels in hair cells of the inner ear (Elledge 2010)
  • cytoplasmic N-terminus of HCN1 binds the cytoplasmic C-terminus of stereociliary tip-link protein PCDH15
  • is an integral component of the hair cells mechanotransduction machinery that functionally couples PCDH15 to the transduction channel
  • CDH23, PCDH15 bind tip-to-tip in a "handshake" mode that involves the EC1 and EC2 repeats ofCDH23, PCDH15
  • PCDH15 interacts with transmembrane channel-like proteins TMC1 and TMC2
  • both LHFPL5 and TMC1 were shown to interact with PCDH15, a component of the tip link, which applies force to the mechanotransducer (MT) channel
  • interaction of MYO3A with the cytosolic tail of the integral tip-link protein protocadherin 15 (PCDH15), a core component of MET complex
  • GOPC, a Golgi-associated, PDZ domain-containing protein, interacts with PCDH15
  • CDH23 and PCDH15, interact in a Ca2+-dependent manner to form tip links
  • cell & other
  • cell cell homophilic interaction
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) USH1F , DFNB23
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in cytotoxic tumor-derived T- and NK-cell lines as well as in biopsies of nasal NK/T-cell lymphomas
    Susceptibility
  • to familial combined hyperlipidemia
  • to Noise-induced hearing loss (NIHL)
  • Variant & Polymorphism SNP
  • nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia (Huertas-Vazquez 2010)
  • genetic variations in PCDH15 modify the susceptibility to NIHL development
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Ames waltzer a recessive mutation in mice causes deafness and a balance disorder associated with the degeneration of inner ear neuroepithelia
  • Digenic heterozygotes mice for cadherin 23 and protocadherin 15 display a significant levels of hearing loss, cytoarchitectural defects in the cochlea, degeneration of the stereocilia and a base-apex loss of hair cells and spiral ganglion cells
  • Pcdh15-CD2-deficient mice are deaf, lack kinociliary links and have abnormally polarized hair bundles
  • noddy homozygotes lack inner ear function, and noddy mutant mice harbor an isoleucine-to-asparagine (I108N) mutation in the EC1 repeat of Pcdh15