Synaptotagmin-like protein 4 (SYTL4, Slp4), also known as granuphilin or exophilin-2, belongs to the synaptotagmin-like protein family (Slp), which is a group of putative membrane trafficking proteins []. The characteristic feature of the Slp family is the N-terminal Slp homology domain (SHD), which functions as a Rab27-binding domain and C-terminal tandem C2 domains (known as the C2A domain and C2B domain), putative Ca2+-binding motifs [, ]. SHD consists of two conserved regions, designated SHD1 and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp4 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.There are several alternatively spliced isoform of Slp4. Slp4-a (granuphilin-a) has two C2 domains, whereas Slp4-b (granuphilin-b) contains only the first C2 domain. Expression of Slp4-a inhibits regulated secretion in endocrine cells. Slp4-a binds to both the GTP- and GDP-bound forms of Rab27A and inhibits a specific GTP/GDP exchange cycle required for dense-core vesicle exocytosis []. Slp4 has been detected inthe pancreatic islet, in particular in insulin-positive beta cells, and in pituitary [].
