Eukaryotic transcriptional regulatory protein Lge1, periphilin, and similar proteins; This family includes transcriptional regulatory protein Lge1 found in fungi as well as periphilin-1, a component of the Human Silencing Hub (HUSH) complex, a multiprotein complex that mediates epigenetic repression. In yeasts, Lge1 is involved in the ubiquitination of histones H2A and H2B. This ubiquitination step is a vital one in the regulation of the transcriptional activity of RNA polymerase II. In Saccharomyces cerevisiae, Rad6 and Bre1 are present in a complex that contains Lge1; this complex is required for H2B ubiquitination. Bre1 is the H2B ubiquitin ligase that interacts with acidic activators, such as Gal4, and recruits Rad6 and its binding partner Lge1 to target promoters. In Schizosaccharomyces pombe, the equivalent protein to Lge1 appears to be Shf1. In human, periphilin acts a transcriptional co-repressor and regulates cell cycle progression. In human, periphilin-1 is involved in epithelial differentiation and contributes to epidermal integrity and barrier formation. It may act as transcriptional co-repressor involved in cell cycle progression. Chromosomal translocation of genes causing oncogenic fusion protein of Periphilin-1 and Fibroblast Growth Factor Receptor 2 (FGRF2) is associated with intrahepatic cholangiocarcinoma.

                        10        20
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gi 7020106  101 SQLTTRSKAIASKTKEIEQV 120
Cdd:cd22896   1 SLLDTRSKAIRAKKKEIEEA 20

Vertebrate periphilin-1 and similar proteins; This family contains periphilin (PPHLN1), a component of the Human Silencing Hub (HUSH) complex containing three proteins: periphilin, TASOR and MPP8 (also called MPHOSPH8) and mediates epigenetic repression. The HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3 (histone H3 lysine 9 trimethylation), as well as MORC2, a DNA-binding ATPase. The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed. In human, periphilin-1, the protein encoded by the gene PPHLN1, is involved in epithelial differentiation and contributes to epidermal integrity and barrier formation. It is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Oncogenic fusion protein of Fibroblast Growth Factor Receptor 2 (FGRF2) joined to periphilin 1, that occurs through a chromosomal translocation, is associated with intrahepatic cholangiocarcinoma; FGFR2-PPHLN1 activity requiring FGRF2-driven tyrosine kinase domain and PPHLN1 dimerization domain strongly drives cellular proliferation.

                        10        20
                ....*....|....*....|
gi 7020106  101 SQLTTRSKAIASKTKEIEQV 120
Cdd:cd22896   1 SLLDTRSKAIRAKKKEIEEA 20

Vertebrate periphilin-1 and similar proteins; This family contains periphilin (PPHLN1), a component of the Human Silencing Hub (HUSH) complex containing three proteins: periphilin, TASOR and MPP8 (also called MPHOSPH8) and mediates epigenetic repression. The HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3 (histone H3 lysine 9 trimethylation), as well as MORC2, a DNA-binding ATPase. The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed. In human, periphilin-1, the protein encoded by the gene PPHLN1, is involved in epithelial differentiation and contributes to epidermal integrity and barrier formation. It is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Oncogenic fusion protein of Fibroblast Growth Factor Receptor 2 (FGRF2) joined to periphilin 1, that occurs through a chromosomal translocation, is associated with intrahepatic cholangiocarcinoma; FGFR2-PPHLN1 activity requiring FGRF2-driven tyrosine kinase domain and PPHLN1 dimerization domain strongly drives cellular proliferation.

                        10        20
                ....*....|....*....|
gi 7020106  101 SQLTTRSKAIASKTKEIEQV 120
Cdd:cd22896   1 SLLDTRSKAIRAKKKEIEEA 20