PROSITE documentation PDOC50021

Calponin homology (CH) domain profile

A number of actin-binding proteins, including spectrin, α-actinin and fimbrin, contain a 250 amino acid stretch called the actin binding domain (ABD). The ABD has probably arisen from duplication of a domain which is also found in a single copy in a number of other proteins like calponin or the vav proto-oncogene and has been called calponin homology (CH) domain [1,2].

A detailed analysis of the CH domain-containing proteins has shown that they can be divided in three groups [1]:

• The fimbrin family of monomeric actin cross-linking molecules containing two ABDs
• Dimeric cross-linking proteins (α-actinin, β-spectrin, filamin, etc.) and monomeric F-actin binding proteins (dystrophin, utrophin) each containing one ABD
• Proteins containing only a single amino terminal CH domain.

Each single ABD, comprising two CH domains, is able to bind one actin monomer in the filament. The amino terminal CH domain has the intrinsic ability to bind actin, albeit with lower affinity than the complete ABD, whereas the carboxy terminal CH bind actin extremely weakly or not at all. Nevertheless both CH domains are required for a fully functional ABD; the C-terminal CH domain contributing to the overall stability of the complete ABD through inter-domain helix-helix interactions [1]. Some of the proteins containing a single CH domain also bind to actin, although this has not been shown to be via the single CH domain alone [2]. In addition, the CH domain occurs also in a number of proteins not known to bind actin, a notable example being the vav proto-oncogene.

The resolution of the 3D structure of various CH domains has shown that the conserved core consist of four major α-helices [2].

Some proteins known to contain a CH-domain are listed below:

• α-actinins. F-actin cross-linking proteins which are thought to anchor actin to a variety of intracellular structures.
• Calponins (see <PDOC00808>). Thin filament-associated proteins which are implicated in the regulation and modulation of smooth muscle contraction.
• Human dystrophin. This protein is defective in Duchenne muscular dystrophy and Becker muscular dystrophy. It may play a role in anchoring the cytoskeleton to the plasma membrane.
• Mammalian vav proto-oncogene. It could be an exchange factor for a small ras-like GTP-binding protein.
• Animal testis-specific proteins Spef1 and Spef2 [3].
• Animal Spermatogenesis-associated protein 4 (SPATA4), involved in regulating cell proliferation, differentiation and apoptosis [4].
• Metazoan Hook proteins, a class of dynein-associated-cargo adaptor proteins. Drosophila and fungi have a single Hook gene, whereas mammals have three Hook genes. They contain an N-terminal CH domain necessary for interaction with dynein and dynactin [5].
• Human ras GTPase activating-like protein IQGAP1.
• Spectrin β chain. Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane.
• Transgelins. There are actin cross-linking/gelling proteins involved in calcium interactions and contractile properties of the cell that may contribute to replicative senescence.
• T-plastin, an actin-bundling protein found in intestinal microvilli, hair cell stereocilia, and fibroblast filopodia.
• Drosophila muscle-specific protein 20. It might be the calcium-binding protein of synchronous muscle.
• Yeast fimbrin. It binds to actin.
• Slime mold gelation factor. It is a F-actin cross-linking protein.