Toll-interacting protein, C2 domain (IPR037301)

Short name: Tollip_C2

Overlapping homologous superfamilies

Domain relationships

  • C2 domain (IPR000008)
    • Toll-interacting protein, C2 domain (IPR037301)


Tollip is a part of the Interleukin-1 receptor (IL-1R) signaling pathway. Tollip is proposed to link serine/threonine kinase IRAK to IL-1Rs as well as inhibiting phosphorylation of IRAK [PMID: 11751856]. The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates [PMID: 25042851]. There is a single C2 domain present in Tollip.

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 phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions [PMID: 9632630, PMID: 8976547, PMID: 8771209, PMID: 8662510, PMID: 7791877, PMID: 7697723, PMID: 1589771, PMID: 2333096].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.