Pathways & interactions
Ferlin, second C2 domain (IPR037720)
Short name: C2B_Ferlin
Overlapping homologous superfamilies
- C2 domain (IPR000008)
- Ferlin, second C2 domain (IPR037720)
Ferlins are involved in vesicle fusion events [PMID: 21838746]. Ferlins and other proteins, such as synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1).
Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF [PMID: 20667140].
C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: type I and type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins [PMID: 9632630, PMID: 8976547, PMID: 8771209].
This entry represents the second C2 repeat of ferlins, C2B, which has a type-II topology.
- cd04011 (C2B_Ferlin)