InterPro domain: IPR043970

This entry represents the third Longin domain of FUZ, MON1 and HPS1 proteins.

Longin domains are evolutionarily conserved regions widely distributed among eukaryotes, involved in membrane dynamic regulation and exhibit similarities in primary sequence and secondary structure. Longin-like domains are found in FUZ and related proteins, such as the MON1 and HPS1 proteins [ 1 , 2 , 3 ]. The MON1/CCZ1 complex (MC1) is the GDP/GTP exchange factor (GEF) for the Rab GTPase Ypt7/Rab7 during vesicular trafficking [ 4 ]. The HPS1/HPS4 complex (BLOC-3) is a Rab32 and Rab38 GEF and is required for biogenesis of melanosomes and platelet dense granules [ 5 ]. Inturned (INTU) and Fuzzy (FUZ) proteins interact as members of the ciliogenesis and planar polarity effector (CPLANE) complex that controls recruitment of intraflagellar transport machinery to the basal body of primary cilia [ 5 , 6 ]. Structurally, these domains are composed of an alpha/beta fold which contains five anti-parallel beta-strands organised as a central beta-sheet and around it, two alpha-helices [ 7 ].

1. Longin-like folds identified in CHiPS and DUF254 proteins: vesicle trafficking complexes conserved in eukaryotic evolution. Protein Sci. 15, 2669-74
2. BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor. Curr. Biol. 22, 2135-9
3. Hexa-Longin domain scaffolds for inter-Rab signalling. Bioinformatics 36, 990-993
4. Architecture and mechanism of the late endosomal Rab7-like Ypt7 guanine nucleotide exchange factor complex Mon1-Ccz1. Nat Commun 8, 14034
5. The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis and mouse embryonic development. Nat. Cell Biol. 11, 1225-32
6. The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery. Nat. Genet. 48, 648-56