{PDOC50807}
{PS50807; GCM}
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* GCM domain profile *
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The GCM  domain  is  an  around  150  amino  acid residue region that has been
identified in  the  N-terminal  part of glial cell missing (GCM) transcription
factors, which  form  a  small  family  of metazoan transcriptional regulators
involved in  fundamental developmental processes. The GCM motif has been shown
to be  a  DNA-binding domain that recognizes preferentially the nonpalindromic
octamer 5'-ATGCGGGT-3' [1,2,3,4,5].

The GCM  motif  contains  many  conserved  basic  amino  acid  residues, seven
cysteine residues,  and  four  histidine residues [1]. The conserved cysteines
are involved in shaping the overall conformation of the domain, in the process
of DNA  binding and in the redox regulation of DNA binding [3]. The GCM domain
contains two  tetrahedrally  coordinated  zinc  ions.  The  resolution  of the
crystal structure  of  GCMa  has shown that the GCM domain consists of a large
and small  domain tethered together by one of the two zinc ions present in the
structure (see <PDB:1ODH>). The large and the small domains comprise five- and
three-stranded beta-sheets,  respectively,  with  three small helical segments
packed against  the same side of the two beta-sheets. The GCM domain exercises
a novel  mode  of  sequence-specific  DNA recognition, where the five-stranded
beta-pleated sheet  inserts  into  the  major  groove  of  the  DNA.  Residues
protruding from  the  edge  strand of the beta-pleated sheet and the following
loop and  strand contact the bases and backbone of both DNA strands, providing
specificity for its DNA target site [5].

Proteins known to contain a GCM motif are listed below:

 - Drosophila  glial  cell missing (GCM) protein. It functions as an important
   switch during early neurogenesis by committing cells to the glial cell fate
   [1,2].
 - Mammalian   GCMa   (or  GCM1)  protein.  GCMa  is  primarily  expressed  in
   trophoblasts of  the placenta and is possibly involved in the expression of
   multiple placenta-specific genes [4,6].
 - Mammalian  GCMb  (or  GCM2)  protein.  The function of this protein that is
   selectively detected in the forming parathyroid gland is not yet known [4].

The profile covers the entire GCM motif.

-Sequences known to belong to this class detected by the repeat profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: April 2003 / First entry.

[ 1] Akiyama Y., Hosoya T., Poole A.M., Hotta Y.
     "The gcm-motif: a novel DNA-binding motif conserved in Drosophila and
     mammals."
     Proc. Natl. Acad. Sci. U.S.A. 93:14912-14916(1996).
     PubMed=8962155
[ 2] Schreiber J., Sock E., Wegner M.
     "The regulator of early gliogenesis glial cells missing is a
     transcription factor with a novel type of DNA-binding domain."
     Proc. Natl. Acad. Sci. U.S.A. 94:4739-4744(1997).
     PubMed=9114061
[ 3] Schreiber J., Enderich J., Wegner M.
     "Structural requirements for DNA binding of GCM proteins."
     Nucleic Acids Res. 26:2337-2343(1998).
     PubMed=9580683
[ 4] Tuerk E.E., Schreiber J., Wegner M.
     "Protein stability and domain topology determine the transcriptional
     activity of the mammalian glial cells missing homolog, GCMb."
     J. Biol. Chem. 275:4774-4782(2000).
     PubMed=10671510
[ 5] Cohen S.X., Moulin M., Hashemolhosseini S., Kilian K., Wegner M.,
     Mueller C.W.
     "Structure of the GCM domain-DNA complex: a DNA-binding domain with a
     novel fold and mode of target site recognition."
     EMBO J. 22:1835-1845(2003).
     PubMed=12682016; DOI=10.1093/emboj/cdg182
[ 6] Yamada K., Ogawa H., Honda S., Harada N., Okazaki T.
     "A GCM motif protein is involved in placenta-specific expression of
     human aromatase gene."
     J. Biol. Chem. 274:32279-32286(1999).
     PubMed=10542267

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