ITSN1

Intersectin 1 (SH3 domain protein)

PDB rendering based on 1ki1.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1KI1, 2KGR, 2KHN, 3FIA, 3QBV, 4IIM

Identifiers

Symbols

ITSN1 ; ITSN; SH3D1A; SH3P17

External IDs

OMIM: 602442 MGI: 1338069 HomoloGene: 2277 GeneCards: ITSN1 Gene

Gene ontology
Molecular function	• guanyl-nucleotide exchange factor activity • Rho guanyl-nucleotide exchange factor activity • calcium ion binding • protein binding • kinase activator activity • protein complex scaffold • proline-rich region binding
Cellular component	• cytosol • plasma membrane • coated pit • lamellipodium • cell junction • endocytic vesicle • neuron projection • synapse
Biological process	• small GTPase mediated signal transduction • positive regulation of Rho GTPase activity • positive regulation of phosphorylation • positive regulation of apoptotic process • negative regulation of neuron apoptotic process • positive regulation of GTPase activity • neurotrophin TRK receptor signaling pathway • synaptic vesicle endocytosis • regulation of small GTPase mediated signal transduction • positive regulation of protein kinase B signaling • apoptotic signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 21:
35.01 – 35.27 Mb

Chr 16:
91.73 – 91.92 Mb

PubMed search

Intersectin-1 is a protein that, in humans, is encoded by the ITSN1 gene.^[1]^[2]

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.^[3]

Interactions

ITSN1 has been shown to interact with SNAP-25,^[4] SOS1,^[5] SCAMP1^[6] and CDC42.^[7]^[8]

References

↑ Guipponi M, Scott HS, Chen H, Schebesta A, Rossier C, Antonarakis SE (December 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.
↑ Yamabhai M, Hoffman NG, Hardison NL, McPherson PS, Castagnoli L, Cesareni G, Kay BK (December 1998). "Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains". J Biol Chem 273 (47): 31401–7. doi:10.1074/jbc.273.47.31401. PMID 9813051.
↑ "Entrez Gene: ITSN1 intersectin 1 (SH3 domain protein)".
↑ Okamoto, M; Schoch S; Südhof T C (June 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?". J. Biol. Chem. (UNITED STATES) 274 (26): 18446–54. doi:10.1074/jbc.274.26.18446. ISSN 0021-9258. PMID 10373452.
↑ Tong, X K; Hussain N K, de Heuvel E, Kurakin A, Abi-Jaoude E, Quinn C C, Olson M F, Marais R, Baranes D, Kay B K, McPherson P S (March 2000). "The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain". EMBO J. (ENGLAND) 19 (6): 1263–71. doi:10.1093/emboj/19.6.1263. ISSN 0261-4189. PMC 305667. PMID 10716926.
↑ Fernández-Chacón, R; Achiriloaie M; Janz R; Albanesi J P; Südhof T C (April 2000). "SCAMP1 function in endocytosis". J. Biol. Chem. (UNITED STATES) 275 (17): 12752–6. doi:10.1074/jbc.275.17.12752. ISSN 0021-9258. PMID 10777571.
↑ Hussain, N K; Jenna S, Glogauer M, Quinn C C, Wasiak S, Guipponi M, Antonarakis S E, Kay B K, Stossel T P, Lamarche-Vane N, McPherson P S (October 2001). "Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP". Nat. Cell Biol. (England) 3 (10): 927–32. doi:10.1038/ncb1001-927. ISSN 1465-7392. PMID 11584276.
↑ Snyder, Jason T; Worthylake David K; Rossman Kent L; Betts Laurie; Pruitt Wendy M; Siderovski David P; Der Channing J; Sondek John (June 2002). "Structural basis for the selective activation of Rho GTPases by Dbl exchange factors". Nat. Struct. Biol. (United States) 9 (6): 468–75. doi:10.1038/nsb796. ISSN 1072-8368. PMID 12006984.

Keating DJ, Chen C, Pritchard MA (2006). "Alzheimer's disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1". Ageing Res. Rev. 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". Cytogenet. Cell Genet. 78 (3–4): 213–5. doi:10.1159/000134659. PMID 9465890.
Sparks AB; Hoffman NG; McConnell SJ et al. (1998). "Cloning of ligand targets: systematic isolation of SH3 domain-containing proteins". Nat. Biotechnol. 14 (6): 741–4. doi:10.1038/nbt0696-741. PMID 9630982.
Sengar AS; Wang W; Bishay J et al. (1999). "The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15". EMBO J. 18 (5): 1159–71. doi:10.1093/emboj/18.5.1159. PMC 1171207. PMID 10064583.
Guipponi M; Scott HS; Hattori M et al. (1999). "Genomic structure, sequence, and refined mapping of the human intersectin gene (ITSN), which encompasses 250 kb on chromosome 21q22.1→q22.2". Cytogenet. Cell Genet. 83 (3–4): 218–20. doi:10.1159/000015182. PMID 10072581.
Okamoto M, Schoch S, Südhof TC (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?". J. Biol. Chem. 274 (26): 18446–54. doi:10.1074/jbc.274.26.18446. PMID 10373452.
Pucharcós C; Fuentes JJ; Casas C et al. (1999). "Alu-splice cloning of human Intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome". Eur. J. Hum. Genet. 7 (6): 704–12. doi:10.1038/sj.ejhg.5200356. PMID 10482960.
Tong XK; Hussain NK; de Heuvel E et al. (2000). "The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain". EMBO J. 19 (6): 1263–71. doi:10.1093/emboj/19.6.1263. PMC 305667. PMID 10716926.
Fernández-Chacón R; Achiriloaie M; Janz R et al. (2000). "SCAMP1 function in endocytosis". J. Biol. Chem. 275 (17): 12752–6. doi:10.1074/jbc.275.17.12752. PMID 10777571.
Hattori M; Fujiyama A; Taylor TD et al. (2000). "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.
Pucharcos C, Estivill X, de la Luna S (2000). "Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis". FEBS Lett. 478 (1–2): 43–51. doi:10.1016/S0014-5793(00)01793-2. PMID 10922467.
Martina JA, Bonangelino CJ, Aguilar RC, Bonifacino JS (2001). "Stonin 2: An Adaptor-like Protein That Interacts with Components of the Endocytic Machinery". J. Cell Biol. 153 (5): 1111–20. doi:10.1083/jcb.153.5.1111. PMC 2174325. PMID 11381094.
Hussain NK; Jenna S; Glogauer M et al. (2001). "Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP". Nat. Cell Biol. 3 (10): 927–32. doi:10.1038/ncb1001-927. PMID 11584276.
Pucharcos C; Casas C; Nadal M et al. (2001). "The human intersectin genes and their spliced variants are differentially expressed". Biochim. Biophys. Acta 1521 (1–3): 1–11. doi:10.1016/s0167-4781(01)00276-7. PMID 11690630.
Jenna S; Hussain NK; Danek EI et al. (2002). "The activity of the GTPase-activating protein CdGAP is regulated by the endocytic protein intersectin". J. Biol. Chem. 277 (8): 6366–73. doi:10.1074/jbc.M105516200. PMID 11744688.
Snyder JT; Worthylake DK; Rossman KL et al. (2002). "Structural basis for the selective activation of Rho GTPases by Dbl exchange factors". Nat. Struct. Biol. 9 (6): 468–75. doi:10.1038/nsb796. PMID 12006984.
Irie F, Yamaguchi Y (2002). "EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP". Nat. Neurosci. 5 (11): 1117–8. doi:10.1038/nn964. PMID 12389031.
Strausberg RL; Feingold EA; Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.

PDB gallery

1ki1: Guanine Nucleotide Exchange Region of Intersectin in Complex with Cdc42

ITSN1

Interactions

References

Further reading