PROSITE documentation PDOC51381
C2 B9-type domain profile


The C2 domain, usually containing ~130 residues, is one of the most prevalent eukaryotic lipid-binding domains deployed in diverse functional contexts. Distinct versions of the C2 domain have been recognized, the classical C2 (see <PDOC00380>), the PI3K-type (see <PDOC51547>), the tensin-type (see <PDOC51181>), the B9-type, the DOCK-type (see <PDOC51650>), the NT-type (see <PDOC51840>) and the Aida-type (see <PDOC51911>). 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. One feature that is highly conserved in the C2 domains is the pair of hydrophobic residues on the upper part of the β sheet, which are involved in imparting a curvature of the sheet that allows formation of a concave ligand-binding area. However, beyond the use of the β sheet in forming this concavity, the C2 domains are extremely divergent suggesting that different families might have optimized their interactions with membrane through divergent means. C2 domains have been shown to mediate specific associations with anionic phospholipids, in a Ca(2+)-dependent or Ca(2+)-independent manner, thereby participating in a variety of cellular processes, including cell signaling and vesicle trafficking. C2 domains interact with lipids primarily through two separate binding sites: the Ca(2+)-binding loops and the cationic β-groove. Calcium ion(s) binds to a cluster of aspartates located in three Ca(2+)-binding loops (CBR1, CBR2, and CBR3), which confer a positive charge on the C2 domain and therefore effectively mediate the interaction with phospholipids. Some other C2 domains present a cationic β-groove, the basic patch in the concave face of the β-sandwich, which is also involved in binding with anionic lipids, either, albeit with lower specificity [1].

The B9-type C2 domain is found in ciliary basal body associated proteins. B9-type C2 domain proteins show a very simple architecture with nearly all members being composed of just the C2 domain [1,2,3,4].

Some proteins known to contain a B9-type C2 domain are listed below:

  • Mammalian Meckel syndrome 1 (MKS1) protein, which may be related to the ciliary basal body.
  • Mammalian protein B9D1 and B9D2.
  • Caenorhabditis elegans X-box promoter element regulated protein 7 (xbx-7). It corresponds to mammalian MKS1.
  • Caenorhabditis elegans ciliary transition zone associate protein 1 (tza-1). It corresponds to mammalian B9D2.
  • Caenorhabditis elegans ciliary transition zone associate protein 2 (tza-2). It corresponds to mammalian B9D1.
  • Paramecium tetraurelia ICIS-1 (Involved in Cilia Stability-1), the B9D2 homolog.

The profile we developed covers the entire B9-type C2 domain.

Last update:

January 2020 / Text revised.


Technical section

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

C2_B9, PS51381; C2 B9-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

2AuthorsKyttaelae M. Tallila J. Salonen R. Kopra O. Kohlschmidt N. Paavola-Sakki P. Peltonen L. Kestilae M.
TitleMKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.
SourceNat. Genet. 38:155-157(2006).
PubMed ID16415886

3AuthorsPonsard C. Skowron-Zwarg M. Seltzer V. Perret E. Gallinger J. Fisch C. Dupuis-Williams P. Caruso N. Middendorp S. Tournier F.
TitleIdentification of ICIS-1, a new protein involved in cilia stability.
SourceFront. Biosci. 12:1661-1669(2007).
PubMed ID17127412

4AuthorsWilliams C.L. Winkelbauer M.E. Schafer J.C. Michaud E.J. Yoder B.K.
TitleFunctional redundancy of the B9 proteins and nephrocystins in Caenorhabditis elegans ciliogenesis.
SourceMol. Biol. Cell. 19:2154-2168(2008).
PubMed ID18337471

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