{PDOC51230}
{PS51230; EB1_C}
{BEGIN}
**********************************************
* EB1-like C-terminal (EB1-C) domain profile *
**********************************************

A group  of  microtubule-associated  proteins  called +TIPs (plus end tracking
proteins), including  EB1  (end-binding  protein  1)  family  proteins,  label
growing microtubules ends specifically in diverse organisms and are implicated
in spindle dynamics, chromosome segregation, and directing microtubules toward
cortical sites.  EB1  members  have a bipartite composition: the N-terminal CH
domain (see  <PDOC50021>)  mediates microtubule plus end localization and a C-
terminal cargo   binding   domain   (EB1-C)   that   captures   cell  polarity
determinants. The EB1-C domain comprises a unique EB1-like sequence motif that
acts as  a binding site for other +TIP proteins. It interacts with the carboxy
terminus of  the  adenomatous  polyposis  coli  (APC) tumor suppressor, a well
conserved +TIP   phosphoprotein   with   a  pivotal  function  in  cell  cycle
regulation. Another  binding partner of the EB1-C domain is the well conserved
+TIP  protein dynactin,  a  component of the large cytoplasmic dynein/dynactin
complex [1-3].

The ~80-residue  EB1-C  domain  starts  with  a  long  smoothly  curved  helix
(alpha1), which  is followed by a hairpin connection leading to a short second
helix (alpha2)  running  antiparallel  to  alpha1  (see  <PDB:1WU9>).  The two
parallel alpha1  helices of the EB1-C domain dimer wrap around each other in a
slightly left-handed  supercoil.  The  two  alpha2 helices run antiparallel to
helices alpha1 and form a similar fork in the opposite orientation and rotated
by 90°.  As a result, two helical segments from each monomer form a four-helix
bundle. The  side chain forming the hydrophobic core of this bundle are highly
conserved [2-4].

Some protein known to contain a EB1-C domain are listed below:

 - Yeast protein BIM1.
 - Fission yeast microtubule integrity protein mal3.
 - Vertebrate microtubule-associated protein RP/EB family member 1 (EB1).
 - Vertebrate  microtubule-associated  protein  RP/EB  family member 2 (EB2 or
   RP1).
 - Vertebrate microtubule-associated protein RP/EB family member 3 (EBF3).

The profile we developed covers the entire EB1-C domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: July 2006 / First entry.

[ 1] Mathur J., Mathur N., Kernebeck B., Srinivas B.P., Huelskamp M.
     "A novel localization pattern for an EB1-like protein links
     microtubule dynamics to endomembrane organization."
     Curr. Biol. 13:1991-1997(2003).
     PubMed=14614826
[ 2] Slep K.C., Rogers S.L., Elliott S.L., Ohkura H., Kolodziej P.A.,
     Vale R.D.
     "Structural determinants for EB1-mediated recruitment of APC and
     spectraplakins to the microtubule plus end."
     J. Cell Biol. 168:587-598(2005).
     PubMed=15699215; DOI=10.1083/jcb.200410114
[ 3] Honnappa S., John C.M., Kostrewa D., Winkler F.K., Steinmetz M.O.
     "Structural insights into the EB1-APC interaction."
     EMBO J. 24:261-269(2005).
     PubMed=15616574; DOI=10.1038/sj.emboj.7600529
[ 4] Hayashi I., Wilde A., Mal T.K., Ikura M.
     "Structural basis for the activation of microtubule assembly by the
     EB1 and p150Glued complex."
     Mol. Cell 19:449-460(2005).
     PubMed=16109370; DOI=10.1016/j.molcel.2005.06.034

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}