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FLASH GENE

Symbol

PACSIN1

contributors: mct - updated : 25-09-2018

HGNC name	protein kinase C and casein kinase substrate in neurons 1
HGNC id	8570

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	6p21.31      Physical location : 34.433.904 - 34.502.998
Synonym name	syndapin I
Synonym symbol(s)	KIAA1379, PAC1, SDPI

DNA

TYPE	functioning gene
STRUCTURE	69.16 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_020804 10 - 5325 NP_065855 55 444 - 2009 19549836 NM_001199583 10 - 4332 NP_001186512 55 444 - 2009 19549836

EXPRESSION

Type	restricted

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 Digestive esophagus           liver         Lymphoid/Immune tonsils         Nervous brain       specific SELECTED Homo sapiens   nerve         Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	one FES/CIP4 homology domain at the N terminus, and N-terminal F-BAR domain implicated in sensing and/or inducing membrane curvature
	one central coiled coil region
	two NPF motifs (residues 364–366 and 376–378) to which the EH (Eps15 homology) protein domain binds
	a SH3 domain at the C terminus, SH3 domain-mediated autoregulation of the membrane-deforming activity of F-BAR domains that is of crucial importance for its function , binding to the proline-rich regions of several other proteins, endocytic proteins such as dynamin I and cytoskeletal proteins like WASL

conjugated

PhosphoP

HOMOLOGY

interspecies

homolog to murine Pacsin1

Homologene

FAMILY	pacsin family
	Fes-CIP4 homology BAR (F-BAR) subfamily

CATEGORY

adaptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,granule
	intracellular,cytoplasm,cytosolic,vesicle

basic FUNCTION	involved in vesicles formation and transport and in synaptic vesicle recycling
	in addition to a crucial role in endocytic internalization, complexes with EHDs play an important role in endocytic receptor recycling
	central component of the endocytic protein complex for synaptic vesicle endocytosis via stimulus-dependent recruitment to dynamin I and has a key role in synaptic transmission
	intracellular adapter protein involved in vesicle transport, membrane dynamics and actin reorganisation
	novel function for PACSIN1, PACSIN2, PACSIN3 in dynamic microtubuli nucleation
	participate in cellular membrane trafficking, in regulation of dynamin-mediated endocytotic processes and have been shown to generate membrane tubules
	implicated in neuronal transmission and the neuropathology of Huntington disease
	involved in synaptic vesicle endocytosis through the interaction of its SH3 domain with proline-rich domains of Dynamin I, Synapsin, Synaptojanin and WASL
	COBL and PACSIN1 work together in dendritic arbor development
	mediates neuronal morphogenesis via the membrane targeting, binding, and deformation properties of its F-BAR domain
	represents a plasmacytoid dendritic cells (pDCs)-specific adaptor molecule that plays a spcific role in the type I IFN signaling cascade
	is an important MAPT binding partner in regulating microtubule dynamics and forming axonal plasticity
	ciliated sensory hair cell formation and function require the F-BAR protein PACSIN1 and the WH2 domain-based actin nucleator COBL
	versatile role in sculpting cellular membranes that is likely dependent both on protein structure and membrane properties
	enriched at synapses and has been proposed to affect neuromorphogenesis and the formation and maturation of dendritic spines
	SHANK2 and PACSIN1 promote postsynapse formation and function
	PACSIN1 is a versatile membrane deformation protein that links the endocytic and recycling machineries essential for dynamic AMPAR trafficking in neurons
	PACSIN1 and PACSIN2 play an essential role in ciliogenesis, similar to their binding partner and membrane reorganizer EHD1

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	complexing with EHD1, EHD2
	components of the centrosome involved in microtubule dynamics

INTERACTION

DNA

RNA

small molecule

protein	HD (via the C terminal SH3 domain)
	critical for synaptic vesicle (SV) endocytosis, where it primarily acts through phospho-regulated binding to dynamin 1
	PACSIN1 is a CAMKK substrate (first non-kinase substrate for CAMKK1 and CAMKK2)
	directly interact with one another to regulate synaptic vesicle endocytosis and recycling
	wedge loop of PACSIN3 is more rigid as PACSIN1, PACSIN2, which influences the lateral interactions between assembled dimers
	SYNJ1 and PACSIN1 are potential substrates of PAK7
	interacts with MAPT in axon
	upon BDNF signaling PACSIN 1 is phosphorylated by CSNK2A2 which is essential for spine formation
	interaction between PICK1 and PACSIN1 is regulated by PACSIN1 phosphorylation within the variable region and is required for AMPAR endocytosis
	direct, SH3 domain-mediated associations and functional interactions of PACSIN1 with SHANK2
	interaction of GRIN3A with PACSIN1, which prevents the endocytosis of endogenous GRIN3A
	GDI1, PACSIN1, and DPYSL2 interact with not only phosphatidic acid (PA) but also with other phospholipids
	dual roles for PACSIN1 in controlling the internalization and recycling of GRIA2 after NMDAR activation
	the most abundant SLC12A5 interactor is a neuronal endocytic regulatory protein termed PACSIN1 (SYNDAPIN1)
	PACSIN1 is a novel and potent negative regulator of SLC12A5

cell & other

REGULATION

Phosphorylated by

PAK7 (phosphorylation promotes the interaction of SYNJ1 with PACSIN1, implicating PAK7 in synaptic vesicle trafficking)

Other

regulation by phospho-regulatory control over helix interactions affecting stability within a folded domain

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in Huntington disease synaptic vesicules

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS