Intersectin: Difference between revisions

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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'>
<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 ==


'''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>.  
'''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>.  


'''ITSN 2''' is also involved in clathrin-mediated endocytosis and is very similar to '''ITSN 1'''.  
'''ITSN 2''' is also involved in clathrin-mediated endocytosis and is very similar to '''ITSN 1'''.  
 
ITSN-1 has two isoforms as a result of differential splicing:
*'''ITSN-1 short form''' is 140kD and expressed in all tissues
*'''ITSN-1 long form''' is 200kD and expressed in neutrons, eye, heart, blood cells and kidney<ref>PMID:32161523</ref>.
*'''ITSN-2 short form''' contains 2 EH domains, a coiled-coil domain and 5 SH3 domains
*'''ITSN-2 long form'''contains an extra carboxylate domain<ref>PMID:10922467</ref>.


== Relevance ==
== Relevance ==
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== Structural highlights ==
== Structural highlights ==


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>.
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>
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*Intersectin 1 long isoform
*Intersectin 1 long isoform


**[[1ki1]] - hITSN1 DBL+PH domains 1229-1580 + Cdc42<br />
**[[5hzj]] - hITSN1 DBL+PH domains 1229-1580 <br />
**[[5hzi]] - hITSN1 DBL+PH domains (mutant)<br />
**[[1ki1]], [[5hzk]] - hITSN1 DBL+PH domains  + Cdc42<br />
**[[3qbv]] - hITSN1 DBL+PH domains (mutant) + Cdc42<br />
**[[3qbv]] - hITSN1 DBL+PH domains (mutant) + Cdc42<br />
**[[3jv3]] - mITSN1 5th SH3+DH domains 1151-1431 <br />
**[[3jv3]] - mITSN1 5th SH3+DH domains 1151-1431 <br />