Intersectin: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Michal Harel (talk | contribs) No edit summary |
Michal Harel (talk | contribs) No edit summary |
||
| (12 intermediate revisions by 2 users not shown) | |||
| Line 1: | Line 1: | ||
<StructureSection load='6gbu' size='340' side='right' caption=' | <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>. | '''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-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 == | ||
ITSN 1 is expressed in neuroblastoma tumors and tumor cell lines and is necessary for their tumorigenic properties<ref>PMID:22266851</ref>. | |||
ITSN 2 might be a potential biomarker for discrimination of severe acute pancreatitis to improve the prognosis of patients<ref>PMID:31880027</ref>. Overexpression of ITSN 1 is implicated for human neurodegenerative diseases such as Down's syndrome and Alzheimer's disease<ref>PMID:21876463</ref>. | ITSN 2 might be a potential biomarker for discrimination of severe acute pancreatitis to improve the prognosis of patients<ref>PMID:31880027</ref>. Overexpression of ITSN 1 is implicated for human neurodegenerative diseases such as Down's syndrome and Alzheimer's disease<ref>PMID:21876463</ref>. | ||
== Structural highlights == | == Structural highlights == | ||
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> | ||
| Line 22: | Line 30: | ||
{{#tree:id=OrganizedByTopic|openlevels=0| | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
*Intersectin 1 | *Intersectin 1 short isoform | ||
**[[3fia]] - hITSN1 EH domain 1-111<br /> | **[[3fia]] - hITSN1 EH domain 1-111<br /> | ||
| Line 30: | Line 38: | ||
**[[4iim]] - hITSN1 2nd SH3 domain + peptide<br /> | **[[4iim]] - hITSN1 2nd SH3 domain + peptide<br /> | ||
**[[6gbu]] - hITSN1 4th SH3 domain 1055-1133 + FCHSD2<br /> | **[[6gbu]] - hITSN1 4th SH3 domain 1055-1133 + FCHSD2<br /> | ||
**[[ | |||
*Intersectin 1 long isoform | |||
**[[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 /> | ||
*Intersectin 2 | *Intersectin 2 short isoform | ||
**[[1uff]] - hITSN2 1st SH3 domain 761-841 - NMR<br /> | **[[1uff]] - hITSN2 1st SH3 domain 761-841 - NMR<br /> | ||
| Line 42: | Line 55: | ||
**[[1ue9]] - hITSN2 4th SH3 domain 1055-1121 - NMR<br /> | **[[1ue9]] - hITSN2 4th SH3 domain 1055-1121 - NMR<br /> | ||
**[[1udl]] - hITSN2 5th SH3 domain 1102-1186 - NMR<br /> | **[[1udl]] - hITSN2 5th SH3 domain 1102-1186 - NMR<br /> | ||
*Intersectin 2 long isoform | |||
**[[3gf9]] - hITSN2 RhoGEF domain 1102-1378 <br /> | **[[3gf9]] - hITSN2 RhoGEF domain 1102-1378 <br /> | ||
**[[3jzy]] - hITSN2 C2 domain 1173-1664 <br /> | **[[3jzy]] - hITSN2 C2 domain 1173-1664 <br /> | ||
}} | |||
== References == | == References == | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
