SPPL2C
Domain
The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP.
Function
Sperm-specific intramembrane-cleaving aspartic protease (I-CLiP) that cleaves distinct tail-anchored proteins and SNARE proteins (PubMed:30733281). In elongated spermatids, modulates intracellular Ca(2+) homeostasis by controlling PLN abundance through proteolytic cleavage (By similarity). During spermatogenesis, processes SNARE proteins and impacts vesicular trafficking which supports compartmental reorganization in maturating spermatids and may play a role in formation of the acrosome (PubMed:30733281).
In round spermatids, acts as a scaffold protein supporting FREY1 in IZUMO1 recruitment at the endoplasmic reticulum membrane and coordination of IZUMO1 complex assembly. Stabilizes FREY1 at the endoplasmic reticulum membrane through interaction. May recruit IZUMO1 interaction partners.
Post-translational modifications
Glycosylated.
Sequence Similarities
Belongs to the peptidase A22B family.
Tissue Specificity
Highly expressed in testis where it is primarily localised in spermatids (at protein level).
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Lumenal side
Alternative names
IMP5, SPPL2C, Signal peptide peptidase-like 2C, SPP-like 2C, SPPL2c, Intramembrane protease 5, IMP-5