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Gene Review

Scm  -  Sex comb on midleg

Drosophila melanogaster

Synonyms: CG9495, Dmel\CG9495, Polycomb protein Scm, SCM, Sex comb on midleg protein, ...
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Disease relevance of Scm

  • SCM contains two approximately 100-residue malignant brain tumor (MBT) repeats at the N terminus [1].

High impact information on Scm

  • A domain shared by the Polycomb group proteins Scm and ph mediates heterotypic and homotypic interactions [2].
  • In addition to in vitro studies, we show colocalization of the Scm and ph proteins at polytene chromosome sites in vivo [2].
  • Using the yeast two-hybrid system and in vitro protein-binding assays, we show that the SPM domain mediates direct interaction between Scm and ph [2].
  • Scm encodes a putative zinc finger protein of 877 amino acids [3].
  • Yeast two-hybrid and in vitro binding assays were used to isolate and characterize >30 missense mutations in the SPM domain of SCM [4].

Biological context of Scm

  • Expressed sequence tag (EST) databases were searched to recover putative mammalian Scm homologs, which were used to screen murine cDNA libraries [5].
  • We have identified a novel gene with homologies to the Drosophila Sex comb on midleg (Scm) gene from the short arm of the X chromosome [6].
  • The coding protein contained the SPM domain and mbt repeats, both of which are characteristic of the PcG proteins, and showed significant similarity in amino acid sequence to the Drosophila Sex comb on midleg (Scm) protein [7].
  • L3MBTL is highly homologous to the D-lethal(3) malignant brain tumor [D-l(3)mbt] gene, which is a putative tumor-suppressor gene (TSG) identified in Drosophila and which is closely related to the Drosophila sex combs on midleg (SCM) protein, a member of the Polycomb group (PcG) family of transcriptional repressors [8].
  • All tested sensitive cut mutations have a partially inactivated cut wing enhancer. e(y)3u1, Zv77h and Su(z)2(5) mutations enhance, while e(y)2u1, ZOp6, PSC1, Su(z)301, Su(z)302 and ScmD1 mutations suppress the ct mutant phenotype [9].

Associations of Scm with chemical compounds

  • The recovered cDNA encodes two mbt repeats and the SPM domain that characterize Scm, but lacks the cysteine clusters and the serine/threonine-rich region found at the amino terminus of Scm [5].

Other interactions of Scm

  • To investigate how SCM might link to PcG complexes, we analyzed the in vivo role of a conserved protein interaction module, the SPM domain [4].

Analytical, diagnostic and therapeutic context of Scm

  • However, gel filtration chromatography showed that the bulk of SCM is biochemically separable from PH in embryo nuclear extracts [4].
  • Sequence analysis of an Scm mutant allele suggests a functional requirement for the SPM domain [3].


  1. Crystal structure of the malignant brain tumor (MBT) repeats in Sex Comb on Midleg-like 2 (SCML2). Sathyamurthy, A., Allen, M.D., Murzin, A.G., Bycroft, M. J. Biol. Chem. (2003) [Pubmed]
  2. A domain shared by the Polycomb group proteins Scm and ph mediates heterotypic and homotypic interactions. Peterson, A.J., Kyba, M., Bornemann, D., Morgan, K., Brock, H.W., Simon, J. Mol. Cell. Biol. (1997) [Pubmed]
  3. The Drosophila Polycomb group gene Sex comb on midleg (Scm) encodes a zinc finger protein with similarity to polyhomeotic protein. Bornemann, D., Miller, E., Simon, J. Development (1996) [Pubmed]
  4. Requirement for sex comb on midleg protein interactions in Drosophila polycomb group repression. Peterson, A.J., Mallin, D.R., Francis, N.J., Ketel, C.S., Stamm, J., Voeller, R.K., Kingston, R.E., Simon, J.A. Genetics (2004) [Pubmed]
  5. A novel member of murine Polycomb-group proteins, Sex comb on midleg homolog protein, is highly conserved, and interacts with RAE28/mph1 in vitro. Tomotsune, D., Takihara, Y., Berger, J., Duhl, D., Joo, S., Kyba, M., Shirai, M., Ohta, H., Matsuda, Y., Honda, B.M., Simon, J., Shimada, K., Brock, H.W., Randazzo, F. Differentiation (1999) [Pubmed]
  6. Identification of SCML2, a second human gene homologous to the Drosophila sex comb on midleg (Scm): A new gene cluster on Xp22. Montini, E., Buchner, G., Spalluto, C., Andolfi, G., Caruso, A., den Dunnen, J.T., Trump, D., Rocchi, M., Ballabio, A., Franco, B. Genomics (1999) [Pubmed]
  7. Cloning of a novel murine gene Sfmbt, Scm-related gene containing four mbt domains, structurally belonging to the Polycomb group of genes. Usui, H., Ichikawa, T., Kobayashi, K., Kumanishi, T. Gene (2000) [Pubmed]
  8. Structural integrity and expression of the L3MBTL gene in normal and malignant hematopoietic cells. MacGrogan, D., Kalakonda, N., Alvarez, S., Scandura, J.M., Boccuni, P., Johansson, B., Nimer, S.D. Genes Chromosomes Cancer (2004) [Pubmed]
  9. Interactions between cut wing mutations and mutations in zeste, and the enhancer of yellow and Polycomb group genes of Drosophila melanogaster. Melnikova, L., Kulikov, A., Georgiev, P. Mol. Gen. Genet. (1996) [Pubmed]
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