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FLASH GENE

Symbol

PCLO

contributors: mct/npt/pgu - updated : 07-03-2016

HGNC name	piccolo (presynaptic cytomatrix protein)
HGNC id	13406

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal glutamine-rich sequence,
	two pairs of Cys(4) zinc fingers, apolyproline tract
	a PDZ domain
	a C-terminal PDZ-domain, and two C-terminal C2-domains (referred to as the C2A- and C2B-domain) that are absent from bassoon

HOMOLOGY

Homologene

FAMILY

CATEGORY

chaperone/stress , secretory , structural protein

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytoskeleton
text	presynaptic plasma membrane, synaptic junction

basic FUNCTION	synaptic vesicle trafficking
	core active zone protein, putative anchoring synaptic vesicles to the presynaptic plasma membrane
	involved in the molecular organization of synaptic active zones
	presynaptic cytomatrix protein that functions as a Ca(2+) sensor that may be involved in insulin secretion and/or insulin action
	piccolo, RIMS2, RIMS3, are involved in the neurobiology of schizophrenia
	with BSN play a redundant role in synaptic vesicle clustering in nerve terminals without directly participating in neurotransmitter release
	function as tethering proteins that mediate efficient synaptic vesicle clustering, but that neither piccolo nor bassoon has a direct role in either synapse formation or neurotransmitter release
	multidomain protein of the active zone cytomatrix, is a key regulator of presynaptic F-actin assembly
	regulates neurotransmitter release by facilitating activity-dependent F-actin assembly and the dynamic recruitment of key signaling molecules into presynaptic boutons
	novel role for BSN and PCLO as critical regulators of presynaptic ubiquitination and proteostasis

CELLULAR PROCESS

cell organization/biogenesis

PHYSIOLOGICAL PROCESS

cellular trafficking transport

text	cytoskeleton organization, vesicular trafficking

PATHWAY

metabolism

signaling

a component

major component of the presynaptic active zones of neurons in the central nervous system, and component of neuromuscular junction synapses in the peripheral nervous system

INTERACTION

DNA

RNA

small molecule

protein	profilin binding
	dual prenylated RAB3A and VAMP2/synaptobrevin receptor PRA1
	CTBP1 is targeted and/or anchored to presynapses by direct interaction with the active zone scaffolding proteins BSN and PCLO
	interact with the C-terminal PBH 9/10 domains of PCLO and BSN via its own N-terminal Spectrin repeats, a domain that is also critical for its localization to the cytoskeletal matrix assembled at the presynaptic active zone (AZ) (CAZ)
	expression of Piccolo constrained KIF11 function in synaptic transmission

cell & other

Ca2+ dependent phospholipid binding

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CLAM

Susceptibility

to type 2 diabetes (minor role) to depressive disorders to bipolar disorder

Variant & Polymorphism SNP	association between SNP rs2522833 and depressive disorders
	one SNP (rs13438494), in an intron of the piccolo (PCLO) gene, was significantly associated with bipolar disorder

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS