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FLASH GENE
Symbol CLTC contributors: mct/npt/pgu - updated : 25-06-2017
HGNC name clathrin, heavy polypeptide (Hc)
HGNC id 2092
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal globular domain
  • seven clathrin propeller repeats
  • light chain binding domain
  • HOMOLOGY
    interspecies homolog to Drosophila Chc
    homolog to C.elegans T20G5.1
    intraspecies homolog to CLTCL1
    Homologene
    FAMILY
  • clathrin heavy chain family
  • CATEGORY transport
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    text
  • translocated to plasma membrane through AP2 binding
  • synaptic vesicles
  • exists not only in cytosol but also in nuclei
  • TP53 co-localized with CLTC at the plasma membrane in response to EGF stimulation
  • is detected in lamellipodia in the absence of the adaptor and accessory proteins of endocytosis
  • localizes to the mitotic spindle
  • basic FUNCTION
  • involved in the intracellular trafficking of receptors and endocytosis of a variety of macromolecules
  • functions as a vesicle transporter
  • nuclear form is required for the transactivation of TP53 target genes and plays a distinct role from clathrin-mediated endocytosis
  • play a role in receptor-mediated endocytosis
  • endogenous CLTCL1 and CLTC function independently in nonmuscle and muscle cells
  • functions as a built-in molecular brake that ensures a tight control of basal NFKB1 activation and gene expression in unstimulated cells
  • required for Golgi reassembly following disruption with pharmacological agents and for mitotic chromosome congression
  • involved in endocytosis, intracellular trafficking, and synaptic recycling
  • in addition to its classical role in membrane trafficking, brings the Scar/Wave complex to the plasma membrane, thereby controlling lamellipodium formation
  • has a well-characterized role in endocytosis and sorting at the trans-Golgi network and endosomes
  • plays likely a role in centrosome function that could directly or indirectly influence later mitotic events
  • does not play a direct role in centriole duplication but may affect centrosome number through another pathway
  • centrosome maturation requires CLTC and CLTCL1 influences the cell cycle independently, further establishing that functions of both clathrins are required for normal cell division
  • DNM2, CLTC and lipid rafts mediate SLC12A1 endocytosis and maintain steady-state apical surface SLC12A1 in native renal thick ascending limb (THAL)
  • plays a role in the processes of tumorigenesis and angiogenesis
  • SNX9 and clathrin heavy chain (CLTC) each have roles in mitosis during metaphase
  • SNX9 and CLTC function in the same molecular pathway for chromosome alignment and segregation, which is dependent on their direct association
  • CKAP5 is likely important in oocyte maturation and early embryo development, and CKAP5 might work together with CLTC in oocyte maturation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS endocytosis transport , cellular trafficking transport
    PATHWAY
    metabolism
    signaling
    a component
  • major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits
  • basic subunit of the clathrin coat composed of three heavy chains and three light chains
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • catalytic domain of FKBP6 binds to clathrin heavy chain (CLTC) of clathrin
  • GAK and CLTC function cooperatively not only in endocytosis, but also in mitotic progression
  • cytosolic protein regulating endocytosis, present in nuclei and binding to TP53 to promote TP53-mediated transcription
  • binding GABARAP
  • CLTC binds specifically to phosphorylated TACC3 and recruits it to spindle poles for proper spindle assembly and chromosome alignment
  • MAP1B, a microtubule stabilizing protein, and CLTC, the major component of the clathrin triskelion, are interaction partners for DST
  • one of the key functions of CLTC was to bind HIF1A protein, increasing the stability of this protein and facilitating its nuclear translocation, thereby regulating the expression of VEGFA
  • CLTC physically interacts with ESR1 in the cytoplasm of breast cancer cells and regulates E2-induced cell proliferation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MRD56
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    to ALK in anaplastic large cell lymphoma
    tumoral fusion      
    to TFE3 in t(X;17)(p11.2;q23)in renal adenocarcinoma
    tumoral fusion      
    with CLTC in t(2;17)(p23;q23)in inflammatory myofibroblastic tumors
    Susceptibility to Developmental and epileptic encephalopathy (DEE)
    Variant & Polymorphism other
  • de novo frameshift in CLTC (c.2737_2738dupGA [p.Asp913Glufs&
  • 8727;59]) was reported in a subject with DEE
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS