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FLASH GENE

Symbol

ITSN1

contributors: mct - updated : 13-11-2018

HGNC name	intersectin 1 (SH3 domain protein)
HGNC id	6183

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

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 heart       moderately   vessel       moderately Digestive liver         Hearing/Equilibrium ear inner cochlea   moderately Nervous brain diencephalon amygdala       nerve cranial nerve     predominantly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Connective bone       Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	moderately in umbilical cord, proliferating and differentiating neurons

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two EH (Eps 15 homology) domains
	two EF-hand domains
	five SH3 (Src homolog 3) domains
	a DH (DBL-homology) domain
	a PH (pleckstrin homology)
	a C2 domains
	in the long form a GET (guanine nucleotide exchange factor)

secondary structure

a central alpha helix forming a coiled coil region

HOMOLOGY

interspecies	homolog to rattus Itsn1 (94.8 pc)
	homolog to murine Itsn1 (95 pc)

Homologene

FAMILY

CATEGORY

adaptor

SUBCELLULAR LOCALIZATION	plasma membrane,junction
	intracellular
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic,vesicle
text	colocalization of ITSN1 with the newly identified protein partners in clathrin-coated pits
	co-localization of ITSN1 and WIPF1 at sites of invadopodia formation and in clathrin-coated pits

basic FUNCTION	involved in membrane associated molecular trafficking and clathrin mediated endocytosis
	may provide indirect link between the endocytic membrane traffic and the actin assembly machinery
	may regulate the formation of clathrin-coated vesicles
	involved in receptor endocytosis regulation
	ITSN1 and ITSN2 are conserved proteins involved in clathrin-mediated endocytosis
	conserved adaptor protein implicated in endocytosis, regulation of actin cytoskeleton rearrangements and mitogenic signaling
	alternative splicing leads to the formation of two pools of ITSN1 with potentially different properties in neurons, affecting ITSN1 function as adaptor protein
	molecular link between INPPL1 and ITSN1 which are involved in receptor endocytosis regulation
	adaptor protein involved in clathrin-mediated endocytosis, cellular signaling and cytoskeleton rearrangement
	role of ITSN1 as a scaffolding molecule bringing together components of endocytic complexes
	functions as a scaffolding protein regulating many aspects of membrane traffic
	adaptor protein engaged in clathrin-mediated endocytosis, cell signaling and actin cytoskeleton rearrangements
	ITSN1 is an important component in the anchorage-independent growth of neuroblastoma (NB) cells
	is important for the tumorigenic potential of NB cells
	ITSN1 and ITSN2, are crucial for the initiation stage of clathrin-mediated endocytosis
	ITSN1, ITSN2 are scaffold proteins involved in the molecular mechanisms of invadopodia formation
	is a multidomain adapter protein implicated in endocytosis, exocytosis, and multiple signaling pathways

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

endocytosis transport

text	synaptic vesicle endocytosis

PATHWAY

metabolism

signaling

signal transduction

regulation of Rho protein signal transduction

a component	constituent of endocyte machinery
	ITSN1, ITSN2 form homomeric and heteromeric complexes with each other revealing an added level of complexity in the function of these evolutionarily conserved scaffolds
	WIPF1/ITSN1 complex is involved in the cellular vesicle trafficking and actin-dependent membrane processes

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	synaptogamin
	interacting with dynamin
	interacting with SNAP25
	interacting with SNAP23
	binding clathrin-associated proteins and other components of the endocytic machinery, such as SPIN90, EPS15, EPN1, EPN2 and STON2
	binding to INPPL1 via Src homology 3D, A, C, and E domains
	intersectin and EPS15 proteins function in the same genetic pathway, and appear to function synergistically with the clathrin-coat-associated sorting protein, Disabled, for viability
	SGIP1 and the signaling adaptor REPS1 interact with ITSN1
	intersectin-SH3D/ARHGAP31 interaction (interacts directly with a small region of ARHGAP31 highly enriched in basic residues and comprising a novel conserved xKx(K/R)K motif)
	binding partner of the SH2 domain containing inositol 5-phosphatase 2 (INPPL1)
	interaction between CDC42 and intersectin (ITSN1), a specific CDC42 guanine nucleotide exchange factor
	ITSN1 is an important general regulator of CDC42-, NCK1- and WASL-dependent actin polymerisation
	WIPF1 interacts with endocytic adaptor proteins of the intersectin (ITSN) family, ITSN1 and ITSN2
	ITSN1 is a component of RELN signaling that acts predominantly by facilitating the VLDLR-DAB1 axis to direct neuronal migration in the cortex and hippocampus and to augment synaptic plasticity
	ITSN1 and ITSN2 are podocytic guanine nucleotide exchange factors for CDC42
	ITCH contributes to the differential ubiquitination of isoforms of the endocytic scaffold protein intersectin1 (ITSN1)
	WIPF1 interaction with ITSN1 highly implicated in endo-/exocytosis, apoptosis, mitogenic signaling and cytoskeleton rearrangements

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DEL21QD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   overexpressed in brain from Down syndrome patients

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     ZCL278 is a small molecule that specifically targets CDC42–ITSN1 interaction and inhibits CDC42-mediated cellular processes, thus providing a tool for research of CDC42 subclass of Rho GTPases in pathogenesis, such as cancer and neurological disorders

ANIMAL & CELL MODELS