Intersectin-1 (ITSN1)
The protein contains 1721 amino acids for an estimated molecular weight of 195422 Da.
Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery (PubMed:11584276, PubMed:29887380). Acts as guanine nucleotide exchange factor (GEF) for CDC42, and thereby stimulates actin nucleation mediated by WASL and the ARP2/3 complex (PubMed:11584276). Plays a role in the assembly and maturation of clathrin-coated vesicles (By similarity). Recruits FCHSD2 to clathrin-coated pits (PubMed:29887380). Involved in endocytosis of activated EGFR, and probably also other growth factor receptors (By similarity). Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2 (PubMed:22648170). Promotes ubiquitination and subsequent degradation of EGFR, and thereby contributes to the down-regulation of EGFR-dependent signaling pathways. In chromaffin cells, required for normal exocytosis of catecholamines. Required for rapid replenishment of release-ready synaptic vesicles at presynaptic active zones (By similarity). Inhibits ARHGAP31 activity toward RAC1 (PubMed:11744688).', 'Plays a role in synaptic vesicle endocytosis in brain neurons. (updated: Dec. 11, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs187895245 |
Biological Process
Apoptotic signaling pathway
Axon guidance
Brain development
Cellular protein localization
Clathrin-dependent synaptic vesicle endocytosis
Endocytosis
Endosomal transport
Ephrin receptor signaling pathway
Exocytosis
G protein-coupled receptor signaling pathway
Intracellular signal transduction
Membrane organization
Negative regulation of neuron apoptotic process
Neurotrophin TRK receptor signaling pathway
Positive regulation of apoptotic process
Positive regulation of caveolin-mediated endocytosis
Positive regulation of dendritic spine development
Positive regulation of growth hormone secretion
Positive regulation of GTPase activity
Positive regulation of protein kinase B signaling
Protein transport
Regulation of modification of postsynaptic actin cytoskeleton
Regulation of Rho protein signal transduction
Regulation of small GTPase mediated signal transduction
Small GTPase mediated signal transduction
Synaptic vesicle endocytosis
Viral process
Cellular Component
Apical dendrite
Calyx of Held
Cell junction
Clathrin-coated pit
Cytoplasm
Cytosol
Dendritic spine
Endocytic vesicle
Glutamatergic synapse
Lamellipodium
Neuron projection
Neuronal cell body
Nuclear envelope
Plasma membrane
Postsynaptic actin cytoskeleton
Presynapse
Presynaptic endocytic zone
Recycling endosome
Synapse
The reference OMIM entry for this protein is 602442
Intersectin 1; itsn1
Itsn
Sh3 domain protein 1a; sh3d1a
Src homology 3 domain-containing protein
Sh3p17
DESCRIPTION
Intersectin-1 is an evolutionarily conserved, multidomain protein that functions in clathrin-associated endocytosis and as a mediator of MAPK signaling pathways (Tsyba et al., 2004).CLONING
Chen and Antonarakis (1997) used exon trapping to identify portions of genes on human chromosome 21. A BLAST search of databases revealed that 1 trapped sequence was identical to a region of the GenBank entry for the Src homology 3 (SH3) domain-containing gene SH3D1A, formerly called SH3P17 by Sparks et al. (1996). By Alu-splice PCR, Pucharcos et al. (1999) trapped 2 exons and subsequently identified the full-length cDNA of the ITSN gene. The gene has the potential to code for at least 2 different protein isoforms by alternative splicing (ITSN-L and ITSN-S). Intersectin exists with a high degree of similarity in flies, frogs, and mammals, suggesting a conserved role in higher eukaryotes. ITSN mRNAs were detected in all adult and fetal tissues tested in human and mouse, with the longer isoform present in the brain. In situ hybridization studies in the developing mouse brain showed ITSN expression in both proliferating and differentiating neurons. Pucharcos et al. (1999) determined the genomic structure of ITSN using chromosome 21 sequences deposited in the public databases. The protein contains several known motifs which implicate ITSN in clathrin-mediated endocytosis and synaptic vesicle recycling. The expression pattern of intersectin in mouse brain, its presumed function, and its overexpression in brains from Down syndrome patients, suggested intersectin may contribute in a gene dosage-dependent manner to some of the abnormalities of Down syndrome. Pucharcos et al. (2000) determined by Western blot analysis that the short and long isoforms of ITSN1 encode 138- and 195-kD proteins, respectively, as predicted. Immunofluorescence microscopy demonstrated sparse punctate expression throughout the cytoplasm for both ITSN1 and ITSN2 (604464), with ITSN1 having a more marked perinuclear pattern and a concentration in Golgi-like structures. Tsyba et al. (2004) noted that ITSN1 has a complex domain structure. Both ITSN1 isoforms have 2 N-terminal Eps15 (600051) homology (EH) domains, followed by a coiled-coil domain and 5 Src (190090) homology-3 (SH3) domains. In addition, the long isoform has a C-terminal extension containing a Dbl (311030) homology (DH), or RhoGEF (see 601855), domain, a pleckstrin (173570) homology (PH) domain, and a putative calcium-interaction domain. Tsyba et al. (2004) identified 8 additional alternative splicing events that affect mouse and human ITSN1 transcripts. These splicing events decrease the EH domain spacing, introduce an insertion in the first SH3 domain, delete the DH domain, or create frameshifts that truncate the open reading frames at several points. Tsyba et al. (2004) concluded that alternative splicing contributes to the regulation of ITSN1 protein functions by creating diversity in domain composition among protein isoforms.GENE FUNCTION
Pucharcos et al. (2000) found that overexpression of either of the ITSN2 isoforms or ITSN1 resulted in the inhibition of transferrin uptake and the blockage of clathrin-mediated endocytosis. Morphologic changes in neuronal dendritic spines are believed to be caused by dynamic regulation of actin polymerization. Irie and Yamaguchi (2002) found that the EphB2 receptor tyrosine kinase (600997) physically associates with intersectin-1 in coo ... More on the omim web site
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602442 was added.