Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol PICALM contributors: mct - updated : 23-05-2014
HGNC name phosphatidylinositol binding clathrin assembly protein
HGNC id 15514
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • AP180 N-terminal homology (ANTH) domain required for its effect on VAMP2 trafficking, and the ANTH domain itself acts as a dominant-negative mutant
  • a NAP domain
  • two DLL motifs within the clathrin-binding domain exclusively involved in clathrin binding
  • a CATS interaction domain mapped to AA 221-335, contained in the CALM/MLLT10 fusion protein
  • C-terminal PICALM AAs are critical for its association with clathrin and for the inhibitory effect of PICALM overexpression on TFRC internalization
  • HOMOLOGY
    interspecies homolog to murine clathrin assembly protein Ap3
    homolog to C.elegans UNC11
    intraspecies homolog to SNAP91
    Homologene
    FAMILY
    CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus
    text
  • coated pits
  • robustly expressed in brain microvessels
  • basic FUNCTION
  • SNAP91 and PICALM function as endocytic accessory proteins at synapses, but each may regulate distinct clathrin pathways
  • involved in the coated pits internalization machinery and in the regulation of clathrin recruitment to the membrane and/or formation of the coated pit
  • regulates the formation of clathrin-coated vesicles
  • playing a role in directing VAMP2 trafficking during endocytosis
  • PICALM/MLLT10 might interfere with normal Ikaros (IKZF1)function, and thereby block lymphoid differentiation in PICALM/MLLT10 positive leukemias
  • SNAP91 and PICALM play critical roles in establishing the polarity and controlling the growth of axons and dendrites in embryonic hippocampal neurons
  • having functions in intracellular trafficking that are essential in the growth of neurons
  • SNAP91 and PICALM, while similar in their domain structures and biochemical properties, are in fact dedicated to separate trafficking pathways in neurons
  • PICALM-mediated trafficking could function as a component of a dedicated system for controlling postsynaptic abundance of GRIA2
  • SNAP91 and PICALM are cargo-specific adaptors for synaptobrevin endocytosis, in the central nervous system
  • SNAP91 and PICALM not only regulate the assembly of the endocytic machinery but also act as sorters for a subset of SNAREs, the vesicle-associated membrane proteins (VAMPs), most notably VAMP/synaptobrevin 2 at synapses
  • SNAP91 and PICALM regulate the assembly of clathrin-coated vesicles (CCVs), which mediate diverse intracellular trafficking processes, including synaptic vesicle (SV) recycling at the synapse
  • SNAP91 and PICALM in the presynaptic terminals of hippocampal neurons, have a similar role in regulating synaptic vesicles
  • plays a critical role in iron homeostasis
  • cytoplasmic adaptor protein that also plays a critical role in clathrin-mediated endocytosis (PMISD: 24067654)
  • crucial role of PICALM in APP metabolism (PMISD: 24067654)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • binding to clathrin heavy chain
  • component of coated pits and Golgi
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • clathrin heavy chain binding
  • interacting with auxilin to compete for binding to the alpha-ear domain of AP-2
  • controls the level of the synaptic vesicle protein VAMP2 at the plasma membrane by regulating VAMP2 endocytosis
  • link between SMAP2 and PICALM/STX2 in clathrin-coated vesicle formation from the TGN and subsequent acrosome formation
  • although AP2 and PICALM bind to MAP1LC3A, they do not seem to be direct substrates of autophagy
  • interaction between MAP1LC3A and AP2M1 as well as PICALM showed a significant increase triggered by starvation
  • is able to sort VAMP4 and VAMP7, even though they have sorting signals for other clathrin adaptors
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with MLLT10 in acute lymphoblastic,myeloblastic leukemia with translocation t(10;11)(p13;q14) and t(10;11) (p13;q21) and in megakaryoblastic leukemia
    Susceptibility to Alzheimer disease
    Variant & Polymorphism other
  • polymorphisms increasing the risk of Alzheimer disease
  • SNPs in PICALM, in association with APOE epsilon4 homozygotes associated to familial late-onset Alzheimer disease
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS