{PDOC50021}
{PS50021; CH}
{BEGIN}
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* Calponin homology (CH) domain profile *
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A number  of  actin-binding  proteins,   including spectrin, alpha-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  (alpha-actinin,  beta-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 alpha-helices [2].

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

 - Alpha-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  beta 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: August 2017 / Profile and text revised.

[ 1] Stradal T., Kranewitter W., Winder S.J., Gimona M.
     "CH domains revisited."
     FEBS Lett. 431:134-137(1998).
     PubMed=9708889
[ 2] Keep N.H., Norwood F.L., Moores C.A., Winder S.J., Kendrick-Jones J.
     "The 2.0 A structure of the second calponin homology domain from the
     actin-binding region of the dystrophin homologue utrophin."
     J. Mol. Biol. 285:1257-1264(1999).
     PubMed=9887274
[ 3] Chan S.W., Fowler K.J., Choo K.H.A., Kalitsis P.
     "Spef1, a conserved novel testis protein found in mouse sperm
     flagella."
     Gene 353:189-199(2005).
     PubMed=15979255; DOI=10.1016/j.gene.2005.04.025
[ 4] Wang X., Harimoto K., Liu J., Guo J., Hinshaw S., Chang Z., Wang Z.
     "Spata4 promotes osteoblast differentiation through Erk-activated
     Runx2 pathway."
     J. Bone Miner. Res. 26:1964-1973(2011).
     PubMed=21445983; DOI=10.1002/jbmr.394
[ 5] Schroeder C.M., Vale R.D.
     "Assembly and activation of dynein-dynactin by the cargo adaptor
     protein Hook3."
     J. Cell Biol. 214:309-318(2016).
     PubMed=27482052; DOI=10.1083/jcb.201604002

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