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FLASH GENE

Symbol

PICALM

contributors: mct - updated : 23-05-2014

HGNC name	phosphatidylinositol binding clathrin assembly protein
HGNC id	15514

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel capillary       Homo sapiens Nervous brain         Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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