PROSITE documentation PDOC50807GCM 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.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Akiyama Y. Hosoya T. Poole A.M. Hotta Y. |
| Title | The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 93:14912-14916(1996). | |
| PubMed ID | 8962155 |
| 2 | Authors | Schreiber J. Sock E. Wegner M. |
| Title | The regulator of early gliogenesis glial cells missing is a transcription factor with a novel type of DNA-binding domain. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 94:4739-4744(1997). | |
| PubMed ID | 9114061 |
| 3 | Authors | Schreiber J. Enderich J. Wegner M. |
| Title | Structural requirements for DNA binding of GCM proteins. | |
| Source | Nucleic Acids Res. 26:2337-2343(1998). | |
| PubMed ID | 9580683 |
| 4 | Authors | Tuerk E.E. Schreiber J. Wegner M. |
| Title | Protein stability and domain topology determine the transcriptional activity of the mammalian glial cells missing homolog, GCMb. | |
| Source | J. Biol. Chem. 275:4774-4782(2000). | |
| PubMed ID | 10671510 |
| 5 | Authors | Cohen S.X. Moulin M. Hashemolhosseini S. Kilian K. Wegner M. Mueller C.W. |
| Title | Structure of the GCM domain-DNA complex: a DNA-binding domain with a novel fold and mode of target site recognition. | |
| Source | EMBO J. 22:1835-1845(2003). | |
| PubMed ID | 12682016 | |
| DOI | 10.1093/emboj/cdg182 |
| 6 | Authors | Yamada K. Ogawa H. Honda S. Harada N. Okazaki T. |
| Title | A GCM motif protein is involved in placenta-specific expression of human aromatase gene. | |
| Source | J. Biol. Chem. 274:32279-32286(1999). | |
| PubMed ID | 10542267 |
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