FYVE-related domain found in synaptotagmin-like protein 3 (Slp3) and similar proteins
Slp3, also termed exophilin-6, functions as a Rab27A-specific effector in cytotoxic T lymphocytes. It binds to kinesin-1 motor through interaction with the tetratricopeptide repeat of the kinesin-1 light chain (KLC1). The kinesin-1/Slp3/Rab27a complex plays a role in mediating the terminal transport of lytic granules to the immune synapse. Slp3 contains an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains. The Slp homology domain (SHD) consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp3 are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. In addition, the Slp3 C2A domain showed Ca2+-dependent phospholipid binding activity. At this point, Slp3 is a Ca2+-dependent isoform in Slp proteins family.
Jiyao W et al.(2023). "The conserved domain database in 2023.",