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Symbol ITSN1 contributors: mct - updated : 13-11-2018
HGNC name intersectin 1 (SH3 domain protein)
HGNC id 6183
Corresponding disease
DEL21QD chromosome 21q deletion, including the APP-SOD1 region
Location 21q22.11      Physical location : 35.014.783 - 35.261.609
Synonym symbol(s) SH3D1A, ITSN, SH3P17, MGC134948, MGC134949
TYPE functioning gene
STRUCTURE 246.83 kb     40 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map cen - GART ,CRYZL1 - [D21S1976 - D21S219 - D21S216 - D21S235 ] - D21S325 - qter
Authors Chen (97), Guipponi (99)
Text [ITSN1 ]
TRANSCRIPTS type messenger
text identification of fifteen novel transcriptional isoforms of the human ITSN1 gene with full-length coding sequences that are the result of different combinations of the alternatively spliced exons 5, 6/6', 20, 23, 25, 26, 26a and 35 (PMID: 19777371)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
40 splicing 6439 195.3 1721 brain specific (neuron-specific isoform)(PMID: 19258322) 2010 19777371
  • involved in brain-specific synaptic vesicle recycling
  • long isoform ITSN1L
  • contains three additional domains, a Dbl homology (DH) domain, a Pleckstrin homology (PH) domain and a C2 domain
  • specific GEF for CDC42
  • may regulate multiple forms of endocytosis in mammalian neurons, including synaptic vesicle endocytosis
  • important regulator of constitutive endocytosis and neuronal development
  • may be more important for regulating neuronal differentiation versus oncogenic transformation (PMID: 22266851)
  • 30 splicing 5451 137.5 1220 ubiquitous; expressed in multiple tissues and cells, including glia, but excluded from neurons (PMID: 19258322) 2010 19777371
  • short isoform, ITSN1s
  • differing in the 3' UTR and coding region compared to variant 1
  • two Eps15 homology (EH) domains and five Src homology 3 (SH3) domains
  • multimodule scaffolding protein functioning in constitutive and regulated forms of endocytosis in non-neuronal cells and in synaptic vesicle
  • critical roles of ITSN1-S in malignant glioma proliferation (PMID: 25832561)
  • monoubiquitination is required for ITSN1-s stability (PMID: 29851086)
  • - - - - - - 2011 21712076
  • two EH domains, a coiled-coil region, an SH3A domain and a specific C-terminal domain (CTD) but lacks four SH3 domains in comparison with ITSN1s
  • binds via its CTD to the SH3 domain of the endocytic protein amphiphysin 1 and the SH3A domain of ITSN1
  • in contrast to ITSN1s did not interact with CBL
  • possesses a significantly altered domain structure and performs specific protein-protein interactions
  • undergoes a combination of mono- and oligoubiquitination (PMID: 29851086)
  • 28 - 5330 - 1149 - 2017 28161632
    29 - 5528 - 1215 - 2017 28161632
    39 - 6881 - 1716 - 2017 28161632
    27 - 5315 - 1144 - 2017 28161632
    29 - 5417 - 1178 - 2017 28161632
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
     vessel   moderately
    Hearing/Equilibriumearinnercochlea moderately
     nervecranial nerve  predominantly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cell lineage
    cell lines
    at STAGE
    physiological period fetal
    Text moderately in umbilical cord, proliferating and differentiating neurons
  • 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
    interspecies homolog to rattus Itsn1 (94.8 pc)
    homolog to murine Itsn1 (95 pc)
    CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
  • 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
    PHYSIOLOGICAL PROCESS endocytosis transport
  • synaptic vesicle endocytosis
    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
    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
    corresponding disease(s) DEL21QD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    overexpressed in brain from Down syndrome patients
    Variant & Polymorphism
    Candidate gene
    Therapy target
    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