{PDOC51113}
{PS51113; ZF_BTK}
{BEGIN}
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* Zinc finger Btk-type profile *
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The  Btk-type  zinc  finger  or  Btk motif (BM) is a domain of ~37 amino acids
present  in eukaryotic signalling proteins. The domain is named after Bruton's
tyrosine  kinase  (Btk), an enzyme which is essential for B cell maturation in
humans and mice [1,2]. Btk and other protein tyrosine kinases (PTK) of the Tec
family  contain  a  conserved  Tec homology (TH) region between the N-terminal
pleckstrin homology (PH) domain (see <PDOC50003>) and the Src homology 3 (SH3)
domain  (see <PDOC50002>). The Btk domain forms the N-terminal part of the Tec
homology  region  while  the  C-terminal portion of TH contains a proline-rich
region. The Btk domain occurs in some proteins outside the Tec family of PTKs,
where  it is also C-terminal to a PH domain. The Btk-type zinc finger seems to
be  involved  in  protein-protein  interactions,  and  it  can interact with G
proteins [3,4].

The  crystal  structures  of  Btk  show  that  the  Btk-type zinc finger has a
globular core, formed by a long loop which is held together by a zinc ion (see
<PDB:1BTK>).  The  zinc-binding  residues are a histidine and three cysteines,
which are fully conserved in the Btk motif [1-5].

Some proteins known to contain a Btk-type zinc finger:

 - Mammalian  Bruton's  tyrosine  kinase  (Btk),  a  protein  tyrosine  kinase
   involved  in  modulation of diverse cellular processes. Mutations affecting
   Btk  are  the  cause  of  X-linked  agammaglobulinemia  (XLA) in humans and
   X-linked immunodeficiency in mice.
 - Mammalian Tec, Bmx, and Itk proteins, which are tyrosine protein kinases of
   the Tec subfamily.
 - Drosophila  tyrosine-protein  kinase  Btk29A,  which  is  required  for the
   development  of  proper  ring canals and of male genitalia and required for
   adult survival.
 - Mammalian  Ras  GTPase-activating  proteins  (RasGAP),  which  regulate the
   activation of inactive GDP-bound Ras by converting GDP to GTP.

The profile we developed covers the entire Btk-type zinc finger.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: April 2005 / First entry.

[ 1] Vihinen M., Nilsson L., Smith C.I.E.
     "Tec homology (TH) adjacent to the PH domain."
     FEBS Lett. 350:263-265(1994).
     PubMed=8070576
[ 2] Lindvall J.M., Blomberg K.E.M., Valiaho J., Vargas L., Heinonen J.E.,
     Berglof A., Mohamed A.J., Nore B.F., Vihinen M., Smith C.I.E.
     "Bruton's tyrosine kinase: cell biology, sequence conservation,
     mutation spectrum, siRNA modifications, and expression profiling."
     Immunol. Rev. 203:200-215(2005).
     PubMed=15661031; DOI=10.1111/j.0105-2896.2005.00225.x
[ 3] Vihinen M., Nore B.F., Mattsson P.T., Backesjo C.M., Nars M.,
     Koutaniemi S., Watanabe C., Lester T., Jones A., Ochs H.D.,
     Smith C.I.E.
     "Missense mutations affecting a conserved cysteine pair in the TH
     domain of Btk."
     FEBS Lett. 413:205-210(1997).
     PubMed=9280283
[ 4] Jiang Y., Ma W., Wan Y., Kozasa T., Hattori S., Huang X.Y.
     "The G protein G alpha12 stimulates Bruton's tyrosine kinase and a
     rasGAP through a conserved PH/BM domain."
     Nature 395:808-813(1998).
     PubMed=9796816; DOI=10.1038/27454
[ 5] Hyvonen M., Saraste M.
     "Structure of the PH domain and Btk motif from Bruton's tyrosine
     kinase: molecular explanations for X-linked agammaglobulinaemia."
     EMBO J. 16:3396-3404(1997).
     PubMed=9218782; DOI=10.1093/emboj/16.12.3396

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