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FLASH GENE
Symbol CLIC4 contributors: mct/npt - updated : 30-09-2015
HGNC name chloride intracellular channel 4
HGNC id 13518
Location 1p36.11      Physical location : 25.071.759 - 25.170.815
Synonym name intracellular chloride ion channel protein p64H1
Synonym symbol(s) H1, huH1, P64H1, CLIC4L, FLJ38640, MTCLIC, DKFZP566G223
DNA
TYPE functioning gene
SPECIAL FEATURE head to head
STRUCTURE 99.56 kb     6 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 4452 28.8 253 - Singh (2007)
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunelymph node   highly
Reproductivefemale systembreast   
 female systemuterus  highly
Respiratoryrespiratory tracttrachea  highly
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Connectivebone  highly
Muscularstriatumskeletal  
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunemacrophage Mus musculusFetal
Skin/Tegumentkeratinocyte
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to murine Clic4
Homologene
FAMILY
  • CLIC family of chloride channel
  • CATEGORY chaperone/stress , regulatory , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus
    intracellular,nuclear envelope
    text
  • trans-golgi network vesicles
  • nuclear CLIC4, possibly by altering the Cl(-) and pH of the nucleus, contributes to cell cycle arrest and the specific gene expression program associated with keratinocyte terminal differentiation (Suh 2007)
  • in keratinocytes, resides in the mitochondria and cytoplasm (Suh 2007)
  • nuclear translocation of cytosolic CLIC4 is an essential feature of its proapoptotic and prodifferentiation functions
  • localizes to mitochondria, endoplasmic reticulum (ER), nucleus and cytoplasm, and participates in the apoptotic response to stress
  • basic FUNCTION
  • involved in cell membrane remodelling, control of cell shape, anion channel activity
  • actin-regulated membrane protein that could modify solute transport at key stages during cellular events such as apoptosis, cell and organelle division and fusion, cell-volume regulation, and cell movement
  • mediates and is required for Ca2+-induced keratinocyte differentiation
  • may play a role in maintaining apical-basolateral membrane polarity during mitosis and cytokinesis, and may be important for regulating cytoskeletal organization during the cell cycle
  • chaperon component of a GPCR trafficking machinery that operates at some location along the exocytic pathway where heterotrimeric G protein assembly takes place
  • functions to promote endothelial cell proliferation and to regulate endothelial morphogenesis
  • a multifunctional protein that traffics between the cytoplasm and nucleus
  • plays an important role in RPE-photoreceptor adhesion, perhaps by modulating the activity of cell surface channels/transportersv
  • is a bacterial lipopolysaccharide (LPS)-induced product that can serve as a positive regulator of LPS signaling
  • role for CLIC4 in innate immunity
  • importance of nuclear CLIC4 for deactivation of proinflammatory macrophages
  • CLIC4 nuclear translocation is an integral part of the cellular response to starvation
  • regulates vasculogenesis through endothelial tube formation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • dynamin 1, alpha-tubulin, beta-actin
  • interacting with AKAP9 (CLIC4 and AKAP9 colocalize at the centrosome)
  • interacts with HIVEP2 (HIVEP2 and CLIC4 are modifiers of TGF-beta signalling through their stabilization of p-Smad2 and 3 in the nucleus)
  • overexpression of nuclear-targeted CLIC4 down-regulates IL1B in stimulated macrophages
  • CLIC4 is a regulator of RAB35 activity and serum- and LPA-dependent integrin trafficking
  • cell & other
    REGULATION
    induced by induced concurrently with inducible nitric oxide synthase (iNOS) and S-nitrosylated in proinflammatory peritoneal macrophages
    Other regulated by RHOA to be targeted to the plasma membrane, where it may function not as an inducible chloride channel but rather by displaying Cys-dependent transferase activity toward a yet unknown substrate
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in tumor stromal cells stimulates tumor growth (Suh 2007)
    constitutional     --other  
    aberrant CLIC4 expression may contribute to the vascular pathology of pulmonary arterial hypertension
    constitutional     --over  
    is an early manifestation and mediator of endothelial dysfunction in pulmonary hypertension
    constitutional     --low  
    enhances autophagy and contributes to mitochondrial and ER stress-induced apoptosis under starvation
    tumoral     --over  
    of CLIC3, CLIC4 in malignant pleural mesothelioma (MPM) as compared to controls
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target participates in normal and pathological processes and may serve as a useful target for therapies in disturbances of homeostasis and neoplastic transformation (Suh 2007)
    ANIMAL & CELL MODELS