View source for Synaptotagmin

<StructureSection load='4npk' size='340' side='right' caption='Synaptostagmin-2 C2A and C2B domains complex with Ca+2 ions (green) (PDB code [[4npk]])' scene='80/802718/Cv/1'>
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== Function ==

'''Synaptotagmin''' (SYT) are calcium-binding proteins which are conserved from nematodes to humans.  Fifteen SYTs have been identified in mammals<ref>PMID:18468511</ref>. '''Synaptotagmin-1''' (SYT1) is a synaptic vesicle membrane protein and is a sensor which induces release in neurons upon binding of Ca+2 ions<ref>PMID:19412166</ref>.  The C2A domain of SYT binds phospholipids in Ca+2-dependent manner<ref>PMID:9730811</ref>.  The C2B domain of SYT promotes binding to other C2B domains and to accessory proteins.  Ca+2 binding causes intramolecular association of domains C2A and C2B.  The synaptic fusion apparatus includes the affinity between SYT and [[Syntaxin]]-1,  This affinity increases by ca. 2 orders of magnitude upon binding of Ca+2<ref>PMID:7559535</ref>. 

*'''Synaptotagmin-2''' is a Ca+2 sensor for fast neurotransmitter release in caudal brain regions<ref>PMID:17192432</ref>.
*'''Synaptotagmin-3''' is a Ca+2 sensor for fast neurotransmitter release in presynapses<ref>PMID:36261524</ref>.
*'''Synaptotagmin-4''' regulates membrane traffic in neurons<ref>PMID:31743468</ref>.
*'''Synaptotagmin-5''' is dense-core vesicle-specific controlling Ca+2-regulated secretion<ref>PMID:12006594</ref>.
*'''Synaptotagmin-7''' is a plasma membrane Ca+2 sensor in synaptic exocytosis<ref>PMID:11395007</ref>.
*'''Synaptotagmin-13''' is a Ca+2-independent regulator of endocrine cell aggression and islet formation<ref>PMID:35927244</ref>.
*'''Synaptotagmin-like proteins''' (SYTL) are required in a generation of a single apical surface per cell<ref>PMID:22820376</ref>.
*'''Synaptotagmin-like protein 4''' (SYTL4) is involved in intracellular membrane trafficking.

== Relevance ==

'''Synaptotagmin-4''' is up-regulated by chronic depolarization and seizures. '''Synaptotagmin-1''' is a promising biomarker to monitor dysfunction and degeneration in Alzheimer disease<ref>PMID:27716408</ref>. 

== Structural highlights ==

SYT-2 structure contains the SMP (synaptotagmin-like-mitochondrial-lipid binding) domain, followed by the <scene name='80/802718/Cv/12'>C2A Ca+2-binding, C2B</scene>, spacer and C2C domains. At the cup-shaped cavity at the of SYT C2A domain there are three tightly clustered Ca+2 binding sites formed by canonical 5 aspartates<ref>PMID:24373768</ref>.
*<scene name='80/802718/Cv/8'>1st Ca+2 binding site</scene>. Water molecules are shown as red spheres.
*<scene name='80/802718/Cv/9'>2nd Ca+2 binding site</scene>.
*<scene name='80/802718/Cv/10'>3th Ca+2 binding site</scene>.
*<scene name='80/802718/Cv/11'>All Ca+2 binding sites</scene>.

==3D structures of synaptotagmin==
[[Synaptotagmin 3D structures]]

</StructureSection>

== References ==
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