{PDOC51489}
{PS51489; BUB1_N}
{BEGIN}
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* BUB1 N-terminal domain profile *
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The missegregation  of sister chromatids during mitosis results in the loss or
gain of chromosomes in daughter cells (aneuploidy). This disastrous outcome is
avoided by  the  mitotic checkpoint for spindle assembly (SAC), which monitors
the proper  assembly  of  the mitotic spindle and blocks the onset of anaphase
until the  kinetochores  of  all  chromosomes  receive a bipolar attachment to
spindle microtubules.  BUB1  and  BUB1R (BUB1-related kinase, known as MAD3 in
the yeast)  are  multidomain proteins that play central roles in this process,
working together with other kinetochore-bound components including MAD2, BUB3,
CDC20, and  MPS1. BUB1 acts as an upstream component of the mitotic checkpoint
pathway, while  BUBR1  is  a downstream component that inhibits the regulatory
protein CDC20.  BUB1  and BUBR1 are highly conserved in eukaryotes and share a
common architecture:  a  conserved  N-terminal region, a central non-conserved
region that   contains   the  bonding  region  for  other  mitotic  checkpoint
components such  as BUB3, and a C-terminal serine/threonine kinase domain (see
<PDOC00100>). The  BUB1  N-terminal  domain  mediates  the binding of BUB1 and
BUBR1 to the mitotic kinetochore protein Blinkin [1,2,3,4].

The BUB1  N-terminal  domain is composed of eight alpha-helices arranged in an
anti-parallel fashion  reminiscent  of  a  TPR  domain  (see <PDOC50005>). The
central six  alpha-helices  fold  into three sequential helix-loop-helix units
(TPR1-3), with  their  alpha-helices  forming concave inner and outer surfaces
(see <PDB:2WVI>).  Each  of the helix-loop-helix units ressembles a single TPR
repeat. The  three  TPR  units are packed together such that "A" alpha-helices
form the  inner  surface and "B" alpha-helices form the outer surface, and the
entire structure  has  a  subtle  right-handed  super-helical  twist. The BUB1
structure also  contains  a short N-terminal alpha-helix connected by a kinked
loop and  an  extended  C-terminal alpha-helix that mimics an A-type helix but
protrudes greater than 20 Angstroms from the molecule. These alpha-helices are
unlikely to  form  additional  TPR motifs in the full-length protein given the
hydrophilic nature  of  their outer edges. The extended C-terminal alpha-helix
ressembles a caping alpha-helix as observed in numerous TPR domains [3,4].

The profile we developed covers the entire BUB1 N-terminal domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2010 / First entry.

[ 1] Bolanos-Garcia V.M., Beaufils S., Renault A., Grossmann J.G.,
     Brewerton S., Lee M., Venkitaraman A., Blundell T.L.
     "The conserved N-terminal region of the mitotic checkpoint protein
     BUBR1: a putative TPR motif of high surface activity."
     Biophys. J. 89:2640-2649(2005).
     PubMed=16040755; DOI=10.1529/biophysj.105.063511
[ 2] Beaufils S., Grossmann J.G., Renault A., Bolanos-Garcia V.M.
     "Characterization of the tetratricopeptide-containing domain of BUB1,
     BUBR1, and PP5 proves that domain amphiphilicity over amino acid
     sequence specificity governs protein adsorption and interfacial
     activity."
     J. Phys. Chem. B 112:7984-7991(2008).
     PubMed=18547097; DOI=10.1021/jp711222s
[ 3] Bolanos-Garcia V.M., Kiyomitsu T., D'Arcy S., Chirgadze D.Y.,
     Grossmann J.G., Matak-Vinkovic D., Venkitaraman A.R., Yanagida M.,
     Robinson C.V., Blundell T.L.
     "The crystal structure of the N-terminal region of BUB1 provides
     insight into the mechanism of BUB1 recruitment to kinetochores."
     Structure 17:105-116(2009).
     PubMed=19141287; DOI=10.1016/j.str.2008.10.015
[ 4] D'Arcy S., Davies O.R., Blundell T.L., Bolanos-Garcia V.M.
     "Defining the molecular basis of BubR1 kinetochore interactions and
     APC/C-CDC20 inhibition."
     J. Biol. Chem. 285:14764-14776(2010).
     PubMed=20220147; DOI=10.1074/jbc.M109.082016

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