{PDOC52051} {PS52051; CXC_MSL2} {BEGIN} ******************************** * CXC MSL2-type domain profile * ******************************** Organisms with different numbers of sex chromosomes between males and females face the problem of an unequal dosage of genes from sex chromosomes. In humans and fruit flies, two X chromosomes define the female sex, whereas males have only one X in addition to the Y chromosome. This unbalanced situation diminishes the vitality of the organism and therefore generated an evolutionary pressure to compensate for the reduced dosage of X chromosomal genes. In mammals and fruit flies, this is achieved by selective transcriptional activation of X chromosomal genes through histone acetylation. Whereas in Drosophila melanogaster, the X chromosome is only boosted in males, in mammals, all X chromosomes in both sexes are activated followed by the selective inactivation of one X in females. In drosophilid species, the process of dosage compensation involves a general modification of the chromatin structure of the X chromosome in males. This dosage compensation process is mediated, for most X chromosome genes, by the dosage compensation complex (DCC) or male-specific lethal (MSL) complex, which contains at least five proteins MSL1, MSL2, MSL3, males absent on the first (MOF) and maleless (MLE) and two non-coding RNAs roX1 and roX2. A module consisting of only MSL2 and MSL1 recognizes a small number of primary targeting elements on the X that are called the 'chromosomal entry sites' (CES), or 'high-affinity sites' (HAS). MSL2 is characterized by several domains: a RING finger mediates the interaction with MSL1, a conserved cysteine-rich domain similar to the CXC domain of Enhancer of Zeste (E[Z]) proteins (see ) and a basic, proline-rich patch (Pro/Bas patch). The MSL2-type CXC dpmain has a DNA binding function as it can mediate the DNA binding of the MSL2-MSL1 heteromer [1,2,3,4]. The MSL2-type CXC domain is remarkable by having 9 invariant Cys within about 50 residue region. The pattern of conserved residues characteristic of the MSL2-type CXC domain can be generalized as C-X-C-X(10-11)-C-X(4)-C-X-C-X(6)-C- X(2)-C-X-C-X(2)-C. Each MSL2-type CXC domain is composed of several loops and a short alpha helix that encircle three Zn ions by two rounds in a right- handed manner. The three Zn ions are coordinated by six terminal and three bridging cysteines (see ) [3,4]. Mammals contain a similar MSL complex that is composed of orthologs of MSL1, MSL2, MSL3, and MOF and conducts H4K16 acetylation of all chromosomes [4]. The profile we developed covers the entire MSL2-type CXC domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: September 2024 / First entry. [ 1] Marin I. "Evolution of chromatin-remodeling complexes: comparative genomics reveals the ancient origin of 'novel' compensasome genes." J. Mol. Evol. 56:527-539(2003). PubMed=12698291; DOI=10.1007/s00239-002-2422-1 [ 2] Fauth T., Muller-Planitz F., Konig C., Straub T., Becker P.B. "The DNA binding CXC domain of MSL2 is required for faithful targeting the Dosage Compensation Complex to the X chromosome." Nucleic. Acids. Res. 38:3209-3221(2010). PubMed=20139418; DOI=10.1093/nar/gkq026 [ 3] Zheng S., Wang J., Feng Y., Wang J., Ye K. "Solution structure of MSL2 CXC domain reveals an unusual Zn3Cys9 cluster and similarity to pre-SET domains of histone lysine methyltransferases." PLoS One. 7:E45437-E45437(2012). PubMed=23029009; DOI=10.1371/journal.pone.0045437 [ 4] Zheng S., Villa R., Wang J., Feng Y., Wang J., Becker P.B., Ye K. "Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation." Genes. Dev. 28:2652-2662(2014). PubMed=25452275; DOI=10.1101/gad.250936.114 -------------------------------------------------------------------------------- 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 https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}