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FLASH GENE
Symbol CLDN4 contributors: mct - updated : 21-01-2015
HGNC name claudin 4
HGNC id 2046
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