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FLASH GENE

Symbol

SYNJ1

contributors: mct/npt - updated : 04-01-2015

HGNC name	synaptojanin 1
HGNC id	11503

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	EIEE53 epileptic encephalopathy, early infantile, 53 PARK20 Parkinson disease 20, early-onset
Location	21q22.11      Physical location : 34.001.068 - 34.100.351
Synonym name	inositol 5'-phosphatase (synaptojanin 1)
	synaptojanin-1, polyphosphoinositide phosphatase
Synonym symbol(s)	INPP5G, KIAA0910, SJ1
EC.number	3.1.3.36

DNA

TYPE	functioning gene
STRUCTURE	103.08 kb     32 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Physical map

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003895 32 splicing 7075 NP_003886 173.1 1570 nonneuronal ubiquitously expressed 2006 17158794 present at all stages of clathrin-coated pit formation NM_203446 32 splicing 7099 NP_982271 144.86 1311 predominant isoform expressed in the brain 2006 17158794 rapidly recruited as a "burst," together with endophilin, at a late stage of clathrin-coated pits formation NM_001160306 28 - 6942 NP_001153778 - 1526 - 2006 17158794 NM_001160302 32 - 7059 NP_001153774 1432.25 1295 - 2006 17158794

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 Endocrine neuroendocrine pituitary     predominantly Nervous brain       highly   nerve cranial nerve     moderately Reproductive female system placenta     highly   male system prostate       Visual eye retina       Danio rerio

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Connective bone       Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Visual cone photoreceptor Danio rerio

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	developing brain, placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal Sac1 phosphatase domain
	a central 5- phosphatase domain
	a C-terminal proline-rich domain with catalytic activity required for normal synaptic vesicle internalization and reavailability (Mani 2007)
	a SAC1 like phosphatase domain
	one RNA recognition motif (RRM)
	a C terminal proline-rich region

HOMOLOGY

interspecies	homolog to rattus Synj1 (90.4 pc)
	homolog to murine Synj1 (90.4 pc)

Homologene

FAMILY

inositol-1, 4, 5-triphosphate 5-phosphatase family

CATEGORY

enzyme , transport

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic,vesicle
text	secretory vesicles
	mostly expressed in the synaptic terminals of neurons (Herrera 2009)

basic FUNCTION	polyphosphoinositide phosphatase, key factor controlling the level of PtdIns(4,5)P2 required for proper neurotransmission
	playing an essential role in synaptic vesicle recycling
	acting as a negative regulator of clathrin coats
	playing a role in neurological manifestations in Down syndrome
	also required for normal vesicle endocytosis (Mani 2007)
	playing a critical role for retrieval of membrane in order to maintain the quantity, timing of fusion, and spontaneous release properties of synaptic vesicles at hair-cell ribbon synapses
	major regulators of inositol metabolism and signaling in the brain and involved in astrogliogenesis
	may have a possible role for astrocytes or astrogliogenesis in Doiwn syndrome
	polyphosphoinositide phosphatase involved in clathrin-mediated endocytosis in conventional synapses
	acts with membrane curvature generators/sensors, such as the BAR protein endophilin, to preferentially remove PI(4,5)P2 from curved membranes as opposed to relatively flat ones
	key regulator of the signalling phospholipid phosphatidylinositol-4,5-biphosphate that regulate clathrin-mediated endocytosis
	involvement of SYNJ1 in endosomal abnormalities is consistent with the finding that the 145 kDa isoform interacts with endocytic SH3 domain-containing proteins, such as endophilin, amphiphysin and intersectin

CELLULAR PROCESS

protein

PHYSIOLOGICAL PROCESS

endocytosis transport

text	synaptic vesicle endocytosis

PATHWAY

metabolism

other

signaling

phosphate metabolism

a component

INTERACTION

DNA

RNA

binding

small molecule

nucleotide,

protein	binding to EPS15 (a clathrin coat-associated protein) via a C-terminal domain containing three Asn-Pro-Phe (NPF) repeats
	binding to a variety of SH3 domain-containing proteins including AMPH, SH3GL1, SH3GL2, SH3GL3 and GRB2 via the C-terminal proline-rich region
	intersection (ITSN)
	Sh3p4
	GRB2
	directly interact with one another to regulate synaptic vesicle endocytosis and recycling
	EPS15 (a clathrin coat-associated protein)
	interacting with DYRK1A (involved in regulating the recruitment activity but not the phosphatase activity of SYNJ1)
	SYNJ1 and PACSIN1 are potential substrates of PAK7

cell & other

REGULATION

inhibited by

cyclin-dependent kinase 5 (Cdk5) phosphorylation

Phosphorylated by

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

ASSOCIATED DISORDERS

corresponding disease(s)

PARK20 , EIEE53

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   may affect a variety of synaptic processes, particularly in brain regions normally exhibiting the highest levels of expression, such as the hippocampus constitutional     --over   contribution of SYNJ1 overexpression to the endosomal changes observed in Down syndrome

Susceptibility

Variant & Polymorphism

Candidate gene	for bipolar disorder
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer SYNJ1 reduction ameliorates Alzheimer disease -associated behavioral and synaptic deficits, providing evidence that SYNJ1 and, more generally, phosphoinositide metabolism may be promising therapeutic targets mental retardation trisomy   attractive new target for rescuing endocytic dysfunction and lipid metabolism in Down syndrome neurology neurodegenerative alzheimer attractive new target for rescuing endocytic dysfunction and lipid metabolism in AD

ANIMAL & CELL MODELS

	Synj1-/- mice display elevated steady-state levels of PIP2 with an accumulation of clathrin-coated vesicles in nerve terminals, and these animals die shortly after birth
	presence of enlarged endosomes in the cortex of transgenic mice overexpressing Synj1