Intersectin

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<StructureSection load='6gbu' size='340' side='right' caption='Human intersectin 1 short isoform 4th SH3 domain (green, yellow, cyan, purple) complex with FCSHD2 SH3 2nd domain (grey, pink, light pink, orange) (PDB code [[6gbu]])' scene='84/842982/Cv/1'>
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<StructureSection load='6gbu' size='340' side='right' caption='Human intersectin 1 short isoform 4th SH3 domain (green, yellow, cyan, purple) complex with FCSHD2 SH3 2nd domain (deepskyblue, pink, light pink, orange) (PDB code [[6gbu]])' scene='84/842982/Cv/4'>
== Function ==
== Function ==
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'''Intersectin''' (ITSN) is an endocytic multidomain scaffold protein in neurons and is important regulator of synaptic vescicles replenishment at hippocampal synapses. The replenishment is needed in order to sustain neurotransmission during periods of elevated activity. ITSN interacts with synapsin I through its SH3 domains<ref>PMID:29229830</ref>. Alternative splicing of ITSN generates a short isoform with 2 EH (Eps15 homology) domains and 5 SH3 domains and a long isoform with additional DH, PH and C2 domains<ref>PMID:19037327</ref>,<ref>PMID:10922467</ref>.
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'''Intersectin''' (ITSN) is an endocytic multidomain scaffold protein in neurons and is important regulator of synaptic vescicles replenishment at hippocampal synapses. The replenishment is needed in order to sustain neurotransmission during periods of elevated activity. ITSN interacts with synapsin I through its SH3 domains<ref>PMID:29229830</ref>.
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'''ITSN 2''' is also involved in clathrin-mediated endocytosis and is very similar to '''ITSN 1'''.
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'''ITSN 2''' is also involved in clathrin-mediated endocytosis and is very similar to '''ITSN 1'''.
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ITSN-1 has two isoforms as a result of differential splicing:
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*'''ITSN-1 short form''' is 140kD and expressed in all tissues
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*'''ITSN-1 long form''' is 200kD and expressed in neutrons, eye, heart, blood cells and kidney<ref>PMID:32161523</ref>.
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*'''ITSN-2 short form''' contains 2 EH domains, a coiled-coil domain and 5 SH3 domains
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*'''ITSN-2 long form'''contains an extra carboxylate domain<ref>PMID:10922467</ref>.
== Relevance ==
== Relevance ==
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== Structural highlights ==
== Structural highlights ==
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The 3D structure of the complex between the SH3 domains of ITSN 1 and FCHSD2 shows extensive contact surface composed mainly of hydrophobic interactions<ref>PMID:29887380</ref>.
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The 3D structure of <scene name='84/842982/Cv/5'>the complex between the SH3 domains of ITSN 1 and FCHSD2</scene> shows extensive contact surface composed mainly of hydrophobic interactions<ref>PMID:29887380</ref>.
</StructureSection>
</StructureSection>

Current revision

Human intersectin 1 short isoform 4th SH3 domain (green, yellow, cyan, purple) complex with FCSHD2 SH3 2nd domain (deepskyblue, pink, light pink, orange) (PDB code 6gbu)

Drag the structure with the mouse to rotate

3D structures of intersectin

Updated on 07-July-2024

References

  1. ↑ . Correction for Gerth et al., Intersectin associates with synapsin and regulates its nanoscale localization and function. Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):E11060. doi:, 10.1073/pnas.1720226115. Epub 2017 Dec 11. PMID:29229830 doi:http://dx.doi.org/10.1073/pnas.1720226115
  2. ↑ Malakooti N, Pritchard MA, Chen F, Yu Y, Sgambelloni C, Adlard PA, Finkelstein DI. The Long Isoform of Intersectin-1 Has a Role in Learning and Memory. Front Behav Neurosci. 2020 Feb 25;14:24. PMID:32161523 doi:10.3389/fnbeh.2020.00024
  3. ↑ Pucharcos C, Estivill X, de la Luna S. Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis. FEBS Lett. 2000 Jul 28;478(1-2):43-51. doi: 10.1016/s0014-5793(00)01793-2. PMID:10922467 doi:http://dx.doi.org/10.1016/s0014-5793(00)01793-2
  4. ↑ Russo A, O'Bryan JP. Intersectin 1 is required for neuroblastoma tumorigenesis. Oncogene. 2012 Nov 15;31(46):4828-34. doi: 10.1038/onc.2011.643. Epub 2012 Jan, 23. PMID:22266851 doi:http://dx.doi.org/10.1038/onc.2011.643
  5. ↑ Li J, Bu X, Chen X, Xiong P, Chen Z, Yu L. Predictive value of long non-coding RNA intersectin 1-2 for occurrence and in-hospital mortality of severe acute pancreatitis. J Clin Lab Anal. 2019 Dec 27:e23170. doi: 10.1002/jcla.23170. PMID:31880027 doi:http://dx.doi.org/10.1002/jcla.23170
  6. ↑ Hunter MP, Nelson M, Kurzer M, Wang X, Kryscio RJ, Head E, Pinna G, O'Bryan JP. Intersectin 1 contributes to phenotypes in vivo: implications for Down's syndrome. Neuroreport. 2011 Oct 26;22(15):767-72. doi: 10.1097/WNR.0b013e32834ae348. PMID:21876463 doi:http://dx.doi.org/10.1097/WNR.0b013e32834ae348
  7. ↑ Almeida-Souza L, Frank RAW, Garcia-Nafria J, Colussi A, Gunawardana N, Johnson CM, Yu M, Howard G, Andrews B, Vallis Y, McMahon HT. A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits. Cell. 2018 Jun 4. pii: S0092-8674(18)30597-X. doi: 10.1016/j.cell.2018.05.020. PMID:29887380 doi:http://dx.doi.org/10.1016/j.cell.2018.05.020

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Michal Harel, Alexander Berchansky

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