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FLASH GENE
Symbol CLDN4 contributors: mct - updated : 21-01-2015
HGNC name claudin 4
HGNC id 2046
Location 7q11.23      Physical location : 73.245.192 - 73.247.014
Synonym name
  • clostridium perfringens enterotoxin receptor 4
  • Williams-Beuren syndrome chromosomal region 8 protein
  • Synonym symbol(s) CPETR1, CPE-R, WBSCR8, CPETR
    DNA
    TYPE functioning gene
    STRUCTURE 1.83 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • TWIST1 binds to an E-box site of the CLDN4 promoter
  • MAPPING cloned Y linked N status provisional
    regionally located situated in the Williams-Beuren critical region
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 1846 22 209 - 1999 10366445
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunethymus   highly Homo sapiens
    Reproductivemale systemmale genital tractepididymis   Homo sapiens
    Respiratorylung     Homo sapiens
    Urinarykidneytubulecollecting duct   Homo sapiens
     kidneynephronrenal capsule   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte Homo sapiens
    Respiratoryalveolar cell type 1 Homo sapiens
    Respiratoryepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period neonatal
    Text infant brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four putative transmembrane segments
  • a cytoplasmic region, which has important roles in the formation and function of tight junctions, but dispensable for the TCR costimulatory activity
  • mono polymer monomer
    HOMOLOGY
    Homologene
    FAMILY
  • claudin family
  • CATEGORY adhesion , structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
    text integral membrane protein
    basic FUNCTION
  • tight junction specific obliteration of the intercelular space
  • creating charge specific channels in the paracellular space
  • forms a paracellular chloride channel in the collecting duct
  • essential role in the formation and maintenance of tight junctions
  • integral membrane cell-junction protein
  • act as molecular mediator of embryo implantation
  • interaction with CLDN8 are required for the anion-selective paracellular channel in the collecting duct
  • forms a paracellular chloride channel in the collecting duct
  • with CLDN8 are required for paracellular reabsorption of Cl–, interacted in cell membranes
  • roles for CLDN3 and CLDN4 in alveolar epithelial barrier function
  • potentially promotes the recruitment of free CD4/LCK to the TCR proximity on antigen engagement directly or indirectly
  • both CLDN3 and CLDN4 mediate interactions with other cells that restrain growth and metastatic potential by sustaining expression of E-cadherin and limiting CTNNB1 signaling
  • plays an important role in maintaining the homeostatic integrity of normal urothelium
  • tight junction protein regulating the paracellular permeability of cell layers
  • CLDN4 and FUT4 are representative genes that participate in modulating trophoblast mobility
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • major structural components of tight junction (TJ) strands
  • CLDN4 and CLDN16 may participate not in homodimers but in obligate heterodimers with selected other claudins
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with LIF (are associated with assisted reproduction outcome)
  • in the collecting duct cells, the assembly of CLDN4 into tight junctions strands required its interaction with CLDN8
  • accumulates CLDN1 and CLDN3 in TJs to enhance cell-cell contact in renal tubular epithelial cells
  • GRHL2 regulates epithelial morphogenesis through transcriptional up-regulation of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at TJs
  • EGF controls the levels of CLDN2 and CLDN4 proteins and mRNAs through SRC and STAT3 activity
  • CLDN4 serves to restrain pro-oncogenic signaling from EPHA2 by limiting the activity of CTNNB1 and PI3K and preventing phosphorylation of EPHA2 on S897 by AKT1 0)
  • GRHL2/OVOL2 network controlling CLDN4 and RAB25 expression that facilitates lumen expansion and barrier formation in subtypes of renal epithelia
  • cell & other
    REGULATION
    induced by E-protein activity in the later stages of DP thymocytes before positive selection, suggesting that it increases the efficiency of positive selection through unique TCR costimulatory activity
    repressed by TWIST1 (up-regulation of TWIST1 decreased both gene and protein expression levels of endogenous CLDN4 and the suppression was mediated by direct binding of TWIST1 to the canonical E-box in the promoter region of CLDN4)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal cancer
    tumoral     --over  
    in ovarian carcinoma
    tumoral     --over  
    in intestinal-type gastric cancer ( lower in diffuse-type gasric cancer)
    tumoral     --over  
    in prostate cancer, highly expressed in lower grade lesions than in higher grade
    tumoral     --low  
    in highly aggressive esophageal cancer and the reduction of CLDN4 leads to the resultant disruption of tight junctions that may be associated with EMT
    constitutional     --over  
    in the placentas of diabetic mothers and in toxaemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • very useful marker for distinguishing mesothelioma and adenocarcinoma, even if histological specimens are small, as in biopsies that contain limited numbers of tumor cells
  • highly specific and sensitive immunohistochemical marker for assisting in distinguishing epithelioid mesotheliomas from metastatic carcinomas to the serosal membranes (pMID: 23596113)
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    anti-claudin-3 and -4 bispecific monoclonal antibody shows promise in the development of a diagnostic and therapeutic antibody for cancers
    cancerdigestivecolon
    potential markers and therapy target in colorectal cancer
    cancerreproductiveprostate
    useful as a potential marker and therapeutic target for prostate cancer metastases
    ANIMAL & CELL MODELS
  • progressive hydronephrosis in Cldn4(-/-) mice arises from urinary tract obstruction due to urothelial hyperplasia