Our deepest condolences go out to his family and friends, and to all those who had the privilege of working with him. Rest in peace, Amos. Your work will live on long after you are gone.
PROSITE documentation PDOC50807GCM domain profile
View entry in original PROSITE document format
View entry in raw text format (no links)
PURL: https://purl.expasy.org/prosite/documentation/PDOC50807
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.
-------------------------------------------------------------------------------
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 |
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.