PROSITE documentation PDOC51840
C2 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.


Technical section

PROSITE method (with tools and information) covered by this documentation:

C2_NT, PS51840; C2 NT-type domain profile  (MATRIX)


1AuthorsZhang D. Aravind L.
TitleIdentification of novel families and classification of the C2 domain superfamily elucidate the origin and evolution of membrane targeting activities in eukaryotes.
SourceGene 469:18-30(2010).
PubMed ID20713135

2AuthorsWang P. Liu H. Wang Y. Liu O. Zhang J. Gleason A. Yang Z. Wang H. Shi A. Grant B.D.
TitleRAB-10 Promotes EHBP-1 Bridging of Filamentous Actin and Tubular Recycling Endosomes.
SourcePLoS Genet. 12:E1006093-E1006093(2016).
PubMed ID27272733

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