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Gene Review

ITSN1  -  intersectin 1 (SH3 domain protein)

Homo sapiens

Synonyms: ITSN, Intersectin-1, MGC134948, MGC134949, SH3 domain-containing protein 1A, ...
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Disease relevance of ITSN1


Psychiatry related information on ITSN1


High impact information on ITSN1

  • Two others, intersectin and syndapin, bind N-WASp, a potent activator of actin assembly via the Arp2/3 complex [3].
  • In particular, I discuss the relationship between actin and three components of the endocytic machinery--dynamin, HIPs (huntingtin-interacting proteins) and intersectin [4].
  • Using PC12 and chromaffin cells, we now show the presence of intersectin-1 at exocytotic sites [5].
  • Thus, we observed that intersectin, syndapin, and mAbp1, which are necessary for the uptake of transferrin (Tf), a marker of the clathrin route, are not required for gammac receptor endocytosis [6].
  • These results suggest that intersectin functions in cell signaling in addition to its role in endocytosis and may link these cellular processes [7].

Chemical compound and disease context of ITSN1


Biological context of ITSN1


Anatomical context of ITSN1


Associations of ITSN1 with chemical compounds

  • A biotin assay used to quantify caveolae internalization and extensive EM morphological analysis of ECs overexpressing wt-intersectin indicated a wide range of morphological changes (i.e., large caveolae clusters marginated at cell periphery and pleiomorphic caveolar necks) as well as impaired caveolae internalization [14].
  • We demonstrate herein by coimmunoprecipitation, velocity sedimentation on glycerol gradients, and cross-linking that intersectin is present in ECs in a membrane-associated protein complex containing dynamin and SNAP-23 [14].
  • More recently, we identified mammalian Sos, a guanine-nucleotide exchange factor for Ras, as an intersectin SH3 domain-binding partner [17].
  • And finally, intersectin cooperated with progesterone to accelerate maturation of Xenopus laevis oocytes [18].
  • Likewise, GEF activity afforded by DH/PH fragments of intersectin and Dbs are also not altered by phosphoinositide interactions [19].

Regulatory relationships of ITSN1


Other interactions of ITSN1

  • Here we report the characterization of a new human gene, ITSN2, highly similar to ITSN1 [9].
  • Moreover, their overexpression, as well as the corresponding ITSN1 protein forms, inhibits transferrin internalization [9].
  • We also showed that intersectin interaction with dynamin was important in regulating the fission and internalization of caveolae [14].
  • Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2 [15].
  • Here, analysis of 21q22.1-->q22.2 genomic sequence revealed that ITSN consists of 41 exons spanning approximately 250 kb and maps between GART and D21S325 [21].

Analytical, diagnostic and therapeutic context of ITSN1


  1. Alzheimer's disease and endocytic dysfunction: Clues from the Down syndrome-related proteins, DSCR1 and ITSN1. Keating, D.J., Chen, C., Pritchard, M.A. Ageing Res. Rev. (2006) [Pubmed]
  2. Safety of intrathecal sodium nitroprusside for the treatment and prevention of refractory cerebral vasospasm and ischemia in humans. Thomas, J.E., Rosenwasser, R.H., Armonda, R.A., Harrop, J., Mitchell, W., Galaria, I. Stroke (1999) [Pubmed]
  3. Coupling actin dynamics and membrane dynamics during endocytosis. Schafer, D.A. Curr. Opin. Cell Biol. (2002) [Pubmed]
  4. The endocytic machinery at an interface with the actin cytoskeleton: a dynamic, hip intersection. McPherson, P.S. Trends Cell Biol. (2002) [Pubmed]
  5. Intersectin-1L nucleotide exchange factor regulates secretory granule exocytosis by activating Cdc42. Malacombe, M., Ceridono, M., Calco, V., Chasserot-Golaz, S., McPherson, P.S., Bader, M.F., Gasman, S. EMBO J. (2006) [Pubmed]
  6. Cortactin and dynamin are required for the clathrin-independent endocytosis of gammac cytokine receptor. Sauvonnet, N., Dujeancourt, A., Dautry-Varsat, A. J. Cell Biol. (2005) [Pubmed]
  7. The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain. 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. EMBO J. (2000) [Pubmed]
  8. Application of Alu-splice PCR on chromosome 21: DSCR1 and Intersectin. Fuentes, J.J., Dierssen, M., Pucharcós, C., Fillat, C., Casas, C., Estivill, X., Pritchard, M. J. Neural Transm. Suppl. (1999) [Pubmed]
  9. Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis. Pucharcos, C., Estivill, X., de la Luna, S. FEBS Lett. (2000) [Pubmed]
  10. Alternative splicing of mammalian Intersectin 1: domain associations and tissue specificities. Tsyba, L., Skrypkina, I., Rynditch, A., Nikolaienko, O., Ferenets, G., Fortna, A., Gardiner, K. Genomics (2004) [Pubmed]
  11. Two isoforms of a human intersectin (ITSN) protein are produced by brain-specific alternative splicing in a stop codon. Guipponi, M., Scott, H.S., Chen, H., Schebesta, A., Rossier, C., Antonarakis, S.E. Genomics (1998) [Pubmed]
  12. Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains. Yamabhai, M., Hoffman, N.G., Hardison, N.L., McPherson, P.S., Castagnoli, L., Cesareni, G., Kay, B.K. J. Biol. Chem. (1998) [Pubmed]
  13. Intersectin activates Ras but stimulates transcription through an independent pathway involving JNK. Mohney, R.P., Das, M., Bivona, T.G., Hanes, R., Adams, A.G., Philips, M.R., O'Bryan, J.P. J. Biol. Chem. (2003) [Pubmed]
  14. Intersectin regulates fission and internalization of caveolae in endothelial cells. Predescu, S.A., Predescu, D.N., Timblin, B.K., Stan, R.V., Malik, A.B. Mol. Biol. Cell (2003) [Pubmed]
  15. Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2. Nishimura, T., Yamaguchi, T., Tokunaga, A., Hara, A., Hamaguchi, T., Kato, K., Iwamatsu, A., Okano, H., Kaibuchi, K. Mol. Biol. Cell (2006) [Pubmed]
  16. SCAMP1 function in endocytosis. Fernández-Chacón, R., Achiriloaie, M., Janz, R., Albanesi, J.P., Südhof, T.C. J. Biol. Chem. (2000) [Pubmed]
  17. Intersectin can regulate the Ras/MAP kinase pathway independent of its role in endocytosis. Tong, X.K., Hussain, N.K., Adams, A.G., O'Bryan, J.P., McPherson, P.S. J. Biol. Chem. (2000) [Pubmed]
  18. Intersectin, an adaptor protein involved in clathrin-mediated endocytosis, activates mitogenic signaling pathways. Adams, A., Thorn, J.M., Yamabhai, M., Kay, B.K., O'Bryan, J.P. J. Biol. Chem. (2000) [Pubmed]
  19. Quantitative analysis of the effect of phosphoinositide interactions on the function of Dbl family proteins. Snyder, J.T., Rossman, K.L., Baumeister, M.A., Pruitt, W.M., Siderovski, D.P., Der, C.J., Lemmon, M.A., Sondek, J. J. Biol. Chem. (2001) [Pubmed]
  20. Intersectin is a negative regulator of dynamin recruitment to the synaptic endocytic zone in the central synapse. Evergren, E., Gad, H., Walther, K., Sundborger, A., Tomilin, N., Shupliakov, O. J. Neurosci. (2007) [Pubmed]
  21. Genomic structure, sequence, and refined mapping of the human intersectin gene (ITSN), which encompasses 250 kb on chromosome 21q22.1-->q22.2. Guipponi, M., Scott, H.S., Hattori, M., Ishii, K., Sakaki, Y., Antonarakis, S.E. Cytogenet. Cell Genet. (1998) [Pubmed]
  22. Alu-splice cloning of human Intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome. Pucharcós, C., Fuentes, J.J., Casas, C., de la Luna, S., Alcántara, S., Arbonés, M.L., Soriano, E., Estivill, X., Pritchard, M. Eur. J. Hum. Genet. (1999) [Pubmed]
  23. Differential efficiency of the endocytic machinery in tonic and phasic synapses. Evergren, E., Zotova, E., Brodin, L., Shupliakov, O. Neuroscience (2006) [Pubmed]
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