{PDOC51840} {PS51840; C2_NT} {BEGIN} ***************************** * C2 NT-type domain profile * ***************************** The C2 domain is one of the most prevalent eukaryotic lipid-binding domains deployed in diverse functional contexts (see ). Many C2 domains bind directly to membrane lipids and display a wide range of lipid selectivity, with preference for anionic phosphatidylserine (PS) and phosphatidylinositol-phosphates (PIPs). Despite their limited sequence similarity, all C2 domains contain at their core a compact beta-sandwich composed of two four-stranded beta sheets with highly variable inter-strand regions that might contain one or more alpha- helices. The NT-type C2 domain is a distinct C2-like domain found in: - Vertebrate early estrogen-induced gene 1 protein (EEIG1) or protein FAM102A. - Drosophila ortholog of EEIG1 (CG8671), required for uptake of dsRNA via the endocytic machinery to induce RNAi silencing. - Caenorhabditis elegans ortholog SYnthetic lethal with Mec-3 (sym-3). - Mammalian EH domain-binding protein 1 (EHBP1), regulates endocytic recycling. - Plant PLASTID MOVEMENT IMPAIRED 1 (PMI1) protein, essential for intracellular movement of chloroplasts in response to blue light. - Arabidopsis thaliana SYNC1 protein. - Medicago truncatula RPG, regulates Rhizobium-directed polar growth. The NT-type C2 domain shows a diverse range of domain architectures but it is nearly always found at the N-termini of proteins that contain it. Hence, it has been named the N-terminal C2 (NT-C2) family. It is typically coupled with a coiled-coil domain, that could mediate di/oligo-merization and the DIL (Dilute) domain (see ). It is also coupled with the Calponin homology (CH) domain (see ) in EHBP1 proteins, Filamin/ABP280 repeats (see ) and Mg2+ transporter MgtE N-terminal domain in proteins from chlorophyte algae such as Micromonas and Ostreococcus tauri. Thus, a common theme across the NT-type C2 domain proteins is the combination to several different domains with microfilament-binding or actin-related roles (i.e. such as CH, DIL, and Filamin). Other conserved groups of the NT-type C2 proteins prototyped by EEIG1, PMI1, and SYNC1 have their own distinct C- terminal conserved extensions that are restricted to these groups and might mediate specific interactions. The primary function of the NT-type C2 domain appears to be the linking of actin/microfilament-binding adaptors to the membrane and to act as a link that tethers endosomal vesicles to the cytoskeleton in course of their intracellular trafficking [1,2]. The profile we developed covers the entire NT-type C2 domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: August 2017 / First entry. [ 1] Zhang D., Aravind L. "Identification of novel families and classification of the C2 domain superfamily elucidate the origin and evolution of membrane targeting activities in eukaryotes." Gene 469:18-30(2010). PubMed=20713135; DOI=10.1016/j.gene.2010.08.006 [ 2] Wang P., Liu H., Wang Y., Liu O., Zhang J., Gleason A., Yang Z., Wang H., Shi A., Grant B.D. "RAB-10 Promotes EHBP-1 Bridging of Filamentous Actin and Tubular Recycling Endosomes." PLoS Genet. 12:E1006093-E1006093(2016). PubMed=27272733; DOI=10.1371/journal.pgen.1006093 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}