Extended synaptotagmin-1 (E-Syt1)

Extended synaptotagmin-1 (E-Syt1) is an evolutionarily conserved lipid transfer and membrane tethering protein localized to the endoplasmic reticulum (ER), where it plays a pivotal role in tethering the ER to the plasma membrane (PM) at membrane contact sites. E-Syt1 contains an N-terminal ER anchoring segment, a central synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain that mediates non-vesicular lipid transfer, and five C-terminal C2 domains which interact with acidic phospholipids at the PM in a calcium-dependent manner[5][8][1][3][2]. E-Syt1 is critical for regulating local lipid composition (such as diacylglycerol and phosphoinositides) and maintaining structural and signaling integrity at ER–PM contacts. Although E-Syt1 is not directly implicated as a conventional drug target, its central role in membrane biology and cell signaling—particularly in T cell function and neural tissue integrity—highlights its importance in fundamental cell physiology and as a potential target for modulation in diseases related to cell signaling defects and membrane dynamics[5][7][8][6].

Other names

ESYT1E-Syt1Extended synaptotagmin Itricalbin-1 (in yeast orthologs)dEsyt (in Drosophila)

Not directly targeted by drugs; hypothetical mechanisms would target lipid transfer, ER–PM tethering, or calcium-regulated activity at membrane contact sites