PROSITE documentation PDOC51840C2 NT-type domain profile
The C2 domain is one of the most prevalent eukaryotic lipid-binding domains deployed in diverse functional contexts (see <PDOC00380>). 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 β-sandwich composed of two four-stranded β sheets with highly variable inter-strand regions that might contain one or more α-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 <PDOC51126>). It is also coupled with the Calponin homology (CH) domain (see <PDOC50021>) in EHBP1 proteins, Filamin/ABP280 repeats (see <PDOC50194>) 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.
Last update:August 2017 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Zhang D. Aravind L. |
| Title | Identification of novel families and classification of the C2 domain superfamily elucidate the origin and evolution of membrane targeting activities in eukaryotes. | |
| Source | Gene 469:18-30(2010). | |
| PubMed ID | 20713135 | |
| DOI | 10.1016/j.gene.2010.08.006 |
| 2 | Authors | Wang P. Liu H. Wang Y. Liu O. Zhang J. Gleason A. Yang Z. Wang H. Shi A. Grant B.D. |
| Title | RAB-10 Promotes EHBP-1 Bridging of Filamentous Actin and Tubular Recycling Endosomes. | |
| Source | PLoS Genet. 12:E1006093-E1006093(2016). | |
| PubMed ID | 27272733 | |
| DOI | 10.1371/journal.pgen.1006093 |
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