Presenilin

Presenilin
Cryo-electron microscopy structure of the human presenilin-1 (orange) in complex with a fragment of one of its protein substrates, Notch (green). The two catalytic sites are shown in blue. Rendered from PDB: 6IDF​.[1]
Identifiers
Symbol	Presenilin
Pfam	PF01080
Pfam clan	CL0130
InterPro	IPR001108
MEROPS	A22
TCDB	1.A.54
OPM superfamily	244
OPM protein	4hyg
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset forms of familial Alzheimer's disease by Peter St George-Hyslop.^[2] Vertebrates have two presenilin genes, called PSEN1 (located on chromosome 14 in humans) that codes for presenilin 1 (PS-1) and PSEN2 (on chromosome 1 in humans) that codes for presenilin 2 (PS-2).^[3] Both genes show conservation between species, with little difference between rat and human presenilins. The nematode worm C. elegans has two genes that resemble the presenilins and appear to be functionally similar, sel-12 and hop-1.^[4]

Presenilins undergo cleavage in an alpha helical region of one of the cytoplasmic loops to produce a large N-terminal and a smaller C-terminal fragment that together form part of the functional protein.^[5] Cleavage of presenilin 1 can be prevented by a mutation that causes the loss of exon 9, and results in loss of function. Presenilins play a key role in the modulation of intracellular Ca²⁺ involved in presynaptic neurotransmitter release and long-term potentiation induction.^[6]