PROSITE documentation PDOC50807
GCM domain profile


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 β-sheets, respectively, with three small helical segments packed against the same side of the two β-sheets. The GCM domain exercises a novel mode of sequence-specific DNA recognition, where the five-stranded β-pleated sheet inserts into the major groove of the DNA. Residues protruding from the edge strand of the β-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.

Last update:

April 2003 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

GCM, PS50807; GCM domain profile  (MATRIX)


1AuthorsAkiyama Y. Hosoya T. Poole A.M. Hotta Y.
TitleThe gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals.
SourceProc. Natl. Acad. Sci. U.S.A. 93:14912-14916(1996).
PubMed ID8962155

2AuthorsSchreiber J. Sock E. Wegner M.
TitleThe regulator of early gliogenesis glial cells missing is a transcription factor with a novel type of DNA-binding domain.
SourceProc. Natl. Acad. Sci. U.S.A. 94:4739-4744(1997).
PubMed ID9114061

3AuthorsSchreiber J. Enderich J. Wegner M.
TitleStructural requirements for DNA binding of GCM proteins.
SourceNucleic Acids Res. 26:2337-2343(1998).
PubMed ID9580683

4AuthorsTuerk E.E. Schreiber J. Wegner M.
TitleProtein stability and domain topology determine the transcriptional activity of the mammalian glial cells missing homolog, GCMb.
SourceJ. Biol. Chem. 275:4774-4782(2000).
PubMed ID10671510

5AuthorsCohen S.X. Moulin M. Hashemolhosseini S. Kilian K. Wegner M. Mueller C.W.
TitleStructure of the GCM domain-DNA complex: a DNA-binding domain with a novel fold and mode of target site recognition.
SourceEMBO J. 22:1835-1845(2003).
PubMed ID12682016

6AuthorsYamada K. Ogawa H. Honda S. Harada N. Okazaki T.
TitleA GCM motif protein is involved in placenta-specific expression of human aromatase gene.
SourceJ. Biol. Chem. 274:32279-32286(1999).
PubMed ID10542267

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