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FLASH GENE
Symbol PCDH8 contributors: mct - updated : 20-11-2019
HGNC name protocadherin 8
HGNC id 8660
Location 13q14.3      Physical location : 53.418.110 - 53.422.774
Synonym name
  • arcadlin
  • Paraxial protocadherin
    • Synonym symbol(s) PAPC, ARCADLIN
    DNA
    TYPE functioning gene
    STRUCTURE 4.67 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D13S300 - D13S137 - PCDH8 - D13S155 - D13S59 - PCDH9 - D13S288 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 4076 113 1070 - 1998 9787079
    3 - 3785 100 973 - 1998 9787079
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal peptide
  • six extracellular cadherin repeats
  • a transmembrane domain encoded by a large unique exon and a distinct cytoplasmic tail specifically interacting with tyrosine kinases, with two conserved motifs
    • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Pcdh8 protocadherin 8
    homolog to rattus norvegicus Pcdh8 protocadherin 8
    homolog to zebrafish Danio rerio pcdh8 protocadherin 8
    intraspecies homolog to cadherin
    Homologene
    FAMILY
  • cadherin superfamily of calcium dependent cell-cell adhesion glycoproteins
  • protocadherin subfamily
    • CATEGORY adhesion , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
    text integral plasma membrane localized at the synaptic junction
    basic FUNCTION
  • cadherin-related neuronal receptor, putatively involved in the specificity of neuronal connections
  • may play specific roles in the establishment of selective synaptic connections of specific modality of cerebral cortex with other communicating brain regions such as the thalamus
  • loss of PCDH8 promotes oncogenesis in epithelial human cancers by disrupting cell-cell communication dedicated to tissue organization and repression of mitogenic signaling
  • functions as a molecular "governor" to maintain FLRT3 activity at the optimal level for physiological regulation of C-cadherin adhesion, cell sorting, and morphogenesis)
  • play likely roles in the wiring of neural circuit formation and maintenance through its adhesive and regulatory mechanism
  • PCDH8, PCDH9, PCDH17 and PCDH20 genes are located around 13q21.1 and might be broadly involved in tumor suppression in a variety of tumors
  • PCDH8 signaling via RHOA and WNT5a/ROR2 activity are required to keep cells aligned in apical-basal orientation during invagination of the ear placode
  • plays an important role in signaling pathways of cell adhesion, proliferation, and migration
  • tumor suppressor involved in tumorigenesis in cancers
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development , nervous system
    text putative role in cell-cellinteractions critical in the development of the central nervous system, mediating adhesion in synaptic junctions through lack-in process
    PATHWAY
    metabolism
    signaling signal transduction
    cell-cell signaling
    a component
  • PCDH8 and FLRT3 form a functional complex with cadherins
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
    • protein
  • WNT-11/FZD7 controls cell adhesion by forming separate adhesion-modulating complexes (AMCs) with the paraxial protocadherin PCDH8 and C-cadherin via distinct FZD7 interaction domains
  • periodic expression of PCDH8 in the anterior presomitic mesoderm (PSM) triggers rhythmic endocytosis of CDH2, allowing for segmental de-adhesion and individualization of somites
    • cell & other
  • cells expressing in the same protocadherin
    • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    by promoter region methylation in primary renal cell carcinoma
    tumoral       loss of function
    through either mutation or epigenetic silencing in a high fraction of breast carcinomas
    tumoral       loss of function
    by tumor-suppressive function of PCDH8 and epigenetic inactivation due to promoter methylation in hypopharyngeal carcinoma
    tumoral       loss of function
    often inactivated by promoter methylation in liver cancer
    tumoral       loss of function
    PCDH8 methylation may be associated with tumor progression and poor prognosis in non-muscle invasive bladder cancer (NMIBC)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • candidate tumor suppressor and play a crucial role in the progression of Ovarian carcinoma
    • Marker
  • may serve as a useful prognostic biomarker for hypopharyngeal carcinoma patients
  • PCDH8 methylation can serve as a valuable diagnostic biomarker for early detection of liver cancer and might be useful to predict an unfavorable clinical feature
    • Therapy target
    SystemTypeDisorderPubmed
    cancerhead and neck 
    potential therapeutic target for hypopharyngeal carcinoma patients
    ANIMAL & CELL MODELS