Intersectin 1

Intersectin-1 is a protein that, in humans, is encoded by the ITSN1 gene.[5][6]

ITSN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1KI1, 2KGR, 2KHN, 3QBV, 4IIM
Identifiers
Aliases	ITSN1, ITSN, SH3D1A, SH3P17, intersectin 1
External IDs	OMIM: 602442 MGI: 1338069 HomoloGene: 2277 GeneCards: ITSN1
Gene location (Human) Chr. Chromosome 21 (human)[1] Band 21q22.11 Start 33,642,400 bp[1] End 33,899,861 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 C4 Start 91,729,281 bp[2] End 91,920,597 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • calcium ion binding • metal ion binding • GO:0001948 protein binding • kinase activator activity • GO:0032947 molecular adaptor activity • proline-rich region binding • guanyl-nucleotide exchange factor activity • Rho guanyl-nucleotide exchange factor activity Cellular component • cytosol • cell projection • membrane • cell membrane • endocytic vesicle • synapse • cell junction • neuron projection • clathrin-coated pit • endomembrane system • lamellipodium • calyx of Held • presynaptic endocytic zone • cell nucleus • nuclear envelope • cytoplasm • endosome • cytoplasmic vesicle • recycling endosome • neuronal cell body • dendritic spine • apical dendrite • intracellular vesicle • postsynaptic actin cytoskeleton • glutamatergic synapse Biological process • negative regulation of neuron apoptotic process • positive regulation of protein kinase B signaling • GO:0007243 intracellular signal transduction • endocytosis • ephrin receptor signaling pathway • synaptic vesicle endocytosis • positive regulation of apoptotic process • positive regulation of phosphorylation • regulation of Rho protein signal transduction • regulation of small GTPase mediated signal transduction • small GTPase mediated signal transduction • membrane organization • GO:0022415 viral process • G-protein coupled receptor signaling pathway • positive regulation of kinase activity • cellular protein localization • exocytosis • protein transport • brain development • positive regulation of growth hormone secretion • positive regulation of dendritic spine development • regulation of modification of postsynaptic actin cytoskeleton • positive regulation of caveolin-mediated endocytosis • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6453	16443
Ensembl	ENSG00000205726	ENSMUSG00000022957
UniProt	Q15811 Q6J334	Q9Z0R4
RefSeq (mRNA)	NM_001001132 NM_003024 NM_001331008 NM_001331009 NM_001331010 NM_001331011 NM_001331012	NM_001110275 NM_001110276 NM_010587
RefSeq (protein)	NP_001001132 NP_001317937 NP_001317938 NP_001317939 NP_001317940 NP_001317941 NP_003015	NP_001103745 NP_001103746 NP_034717
Location (UCSC)	Chr 21: 33.64 – 33.9 Mb	Chr 16: 91.73 – 91.92 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is a cytoplasmic membrane-associated protein that indirectly coordinates endocytic membrane traffic with the actin assembly machinery. In addition, the encoded protein may regulate the formation of clathrin-coated vesicles and could be involved in synaptic vesicle recycling. This protein has been shown to interact with dynamin, CDC42, SNAP23, SNAP25, SPIN90, EPS15, EPN1, EPN2, and STN2. Multiple transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been characterized so far.[7]

Interactions

ITSN1 has been shown to interact with:

• CDC42,[8][9]
• SCAMP1[10]
• SNAP-25,[11] and
• SOS1.[12]

References

1. GRCh38: Ensembl release 89: ENSG00000205726 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022957 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Guipponi M, Scott HS, Chen H, Schebesta A, Rossier C, Antonarakis SE (Nov 1998). "Two isoforms of a human intersectin (ITSN) protein are produced by brain-specific alternative splicing in a stop codon". Genomics. 53 (3): 369–76. doi:10.1006/geno.1998.5521. PMID 9799604.
6. Yamabhai M, Hoffman NG, Hardison NL, McPherson PS, Castagnoli L, Cesareni G, Kay BK (Nov 1998). "Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains". The Journal of Biological Chemistry. 273 (47): 31401–7. doi:10.1074/jbc.273.47.31401. PMID 9813051.
7. "Entrez Gene: ITSN1 intersectin 1 (SH3 domain protein)".
8. Hussain NK, Jenna S, Glogauer M, Quinn CC, Wasiak S, Guipponi M, Antonarakis SE, Kay BK, Stossel TP, Lamarche-Vane N, McPherson PS (Oct 2001). "Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP". Nature Cell Biology. 3 (10): 927–32. doi:10.1038/ncb1001-927. PMID 11584276.
9. Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J (Jun 2002). "Structural basis for the selective activation of Rho GTPases by Dbl exchange factors". Nature Structural Biology. 9 (6): 468–75. doi:10.1038/nsb796. PMID 12006984.
10. Fernández-Chacón R, Achiriloaie M, Janz R, Albanesi JP, Südhof TC (Apr 2000). "SCAMP1 function in endocytosis". The Journal of Biological Chemistry. 275 (17): 12752–6. doi:10.1074/jbc.275.17.12752. PMID 10777571.
11. Okamoto M, Schoch S, Südhof TC (Jun 1999). "EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25. A protein connection between exocytosis and endocytosis?". The Journal of Biological Chemistry. 274 (26): 18446–54. doi:10.1074/jbc.274.26.18446. PMID 10373452.
12. Tong XK, Hussain NK, de Heuvel E, Kurakin A, Abi-Jaoude E, Quinn CC, Olson MF, Marais R, Baranes D, Kay BK, McPherson PS (Mar 2000). "The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain". The EMBO Journal. 19 (6): 1263–71. doi:10.1093/emboj/19.6.1263. PMC 305667. PMID 10716926.

Further reading

• Keating DJ, Chen C, Pritchard MA (Nov 2006). "Alzheimer's disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1". Ageing Research Reviews. 5 (4): 388–401. doi:10.1016/j.arr.2005.11.001. PMID 16442855.
• Chen H, Antonarakis SE (1998). "The SH3D1A gene maps to human chromosome 21q22.1-->q22.2". Cytogenetics and Cell Genetics. 78 (3–4): 213–5. doi:10.1159/000134659. PMID 9465890.
• Sparks AB, Hoffman NG, McConnell SJ, Fowlkes DM, Kay BK (Jun 1996). "Cloning of ligand targets: systematic isolation of SH3 domain-containing proteins". Nature Biotechnology. 14 (6): 741–4. doi:10.1038/nbt0696-741. PMID 9630982.
• Sengar AS, Wang W, Bishay J, Cohen S, Egan SE (Mar 1999). "The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15". The EMBO Journal. 18 (5): 1159–71. doi:10.1093/emboj/18.5.1159. PMC 1171207. PMID 10064583.
• Guipponi M, Scott HS, Hattori M, Ishii K, Sakaki Y, Antonarakis SE (1999). "Genomic structure, sequence, and refined mapping of the human intersectin gene (ITSN), which encompasses 250 kb on chromosome 21q22.1-->q22.2". Cytogenetics and Cell Genetics. 83 (3–4): 218–20. doi:10.1159/000015182. PMID 10072581.
• Okamoto M, Schoch S, Südhof TC (Jun 1999). "EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25. A protein connection between exocytosis and endocytosis?". The Journal of Biological Chemistry. 274 (26): 18446–54. doi:10.1074/jbc.274.26.18446. PMID 10373452.
• Pucharcós C, Fuentes JJ, Casas C, de la Luna S, Alcántara S, Arbonés ML, Soriano E, Estivill X, Pritchard M (Sep 1999). "Alu-splice cloning of human Intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome". European Journal of Human Genetics. 7 (6): 704–12. doi:10.1038/sj.ejhg.5200356. PMID 10482960.
• Tong XK, Hussain NK, de Heuvel E, Kurakin A, Abi-Jaoude E, Quinn CC, Olson MF, Marais R, Baranes D, Kay BK, McPherson PS (Mar 2000). "The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain". The EMBO Journal. 19 (6): 1263–71. doi:10.1093/emboj/19.6.1263. PMC 305667. PMID 10716926.
• Fernández-Chacón R, Achiriloaie M, Janz R, Albanesi JP, Südhof TC (Apr 2000). "SCAMP1 function in endocytosis". The Journal of Biological Chemistry. 275 (17): 12752–6. doi:10.1074/jbc.275.17.12752. PMID 10777571.
• Pucharcos C, Estivill X, de la Luna S (Jul 2000). "Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis". FEBS Letters. 478 (1–2): 43–51. doi:10.1016/S0014-5793(00)01793-2. PMID 10922467.
• Martina JA, Bonangelino CJ, Aguilar RC, Bonifacino JS (May 2001). "Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery". The Journal of Cell Biology. 153 (5): 1111–20. doi:10.1083/jcb.153.5.1111. PMC 2174325. PMID 11381094.
• Hussain NK, Jenna S, Glogauer M, Quinn CC, Wasiak S, Guipponi M, Antonarakis SE, Kay BK, Stossel TP, Lamarche-Vane N, McPherson PS (Oct 2001). "Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP". Nature Cell Biology. 3 (10): 927–32. doi:10.1038/ncb1001-927. PMID 11584276.
• Pucharcos C, Casas C, Nadal M, Estivill X, de la Luna S (Oct 2001). "The human intersectin genes and their spliced variants are differentially expressed". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1521 (1–3): 1–11. doi:10.1016/s0167-4781(01)00276-7. PMID 11690630.
• Jenna S, Hussain NK, Danek EI, Triki I, Wasiak S, McPherson PS, Lamarche-Vane N (Feb 2002). "The activity of the GTPase-activating protein CdGAP is regulated by the endocytic protein intersectin". The Journal of Biological Chemistry. 277 (8): 6366–73. doi:10.1074/jbc.M105516200. PMID 11744688.
• Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J (Jun 2002). "Structural basis for the selective activation of Rho GTPases by Dbl exchange factors". Nature Structural Biology. 9 (6): 468–75. doi:10.1038/nsb796. PMID 12006984.
• Irie F, Yamaguchi Y (Nov 2002). "EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP". Nature Neuroscience. 5 (11): 1117–8. doi:10.1038/nn964. PMID 12389031.