This entry includes Sec8 from fungi and EXOC4 from animals. Sec8 is a component of the exocyst complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane []. In fission yeasts, the exocyst complex is also required for polarized cell growth and division septum assembly []. EXOC4 has been shown to regulate N-cadherin expression by controlling Smad3 and Smad4 expression through CREB binding protein, thereby mediating the epithelial-mesenchymal transition and early embryonic development [].
Ski family transcriptional corepressor 1 (SKOR1), also known as ladybird homeobox corepressor 1 or fussel-15 homologue, belongs to Ski family. Like the other members, it is characterised by a Ski homologue domain and a SAND domain - a domain found in some nuclear proteins involved in chromatin-dependent transcriptional regulation. Fussel-15 is mainly expressed in the central nervous system (CNS). The Ski family of nuclear oncoproteins is known to repress transforming growth factor-beta (TGF-beta) signalling through inhibition of transcriptional activity of Smad proteins. Fussel-15 interacts with Smad1, Smad2 and Smad3 molecules and suppresses mainly BMP signalling pathway, but it has only minor effects on TGF-beta signalling [].
This entry represents the RNA recognition motif 1 (RRM1) of Man1, an integral protein of the inner nuclear membrane that binds to nuclear lamins and emerin, thus playing a role in nuclear organization []. It is part of a protein complex essential for chromatin organization and cell division. It also functions as an important negative regulator for the transforming growth factor (TGF) beta/activin/Nodal signaling pathway by directly interacting with chromatin-associated proteins and transcriptional regulators, including the R-Smads, Smad1, Smad2, and Smad3 [, ]. Moreover, Man1 is a unique type of left-right (LR) signaling regulator that acts on the inner nuclear membrane. Man1 plays a crucial role in angiogenesis. The vascular remodeling can be regulated at the inner nuclear membrane through the interaction between Man1 and Smads []. Man1 contains an N-terminal LEM domain, two putative transmembrane domains, a MAN1-Src1p C-terminal (MSC) domain, and a C-terminal RNA recognition motif (RRM) []. The LEM domain interacts with the DNA and chromatin-binding protein Barrier-to-Autointegration Factor, and is also necessary for efficient localization of MAN1 in the inner nuclear membrane []. Research has indicated that C-terminal nucleoplasmic region of Man1 exhibits a DNA binding winged helix domain and is responsible for both DNA- and Smad-binding [].Mutations in the Man1 gene cause Buschke-Ollendorf syndrome (BOS), an uncommon syndrome characterised by osteopoikilosis and other bone abnormalities [].
This entry represents the inner nuclear membrane proteins Man1 (also known as LEM domain-containing protein 3). Man1 is an integral protein of the inner nuclear membrane that binds to nuclear lamins and emerin, thus playing a role in nuclear organization []. It is part of a protein complex essential for chromatin organization and cell division. It also functions as an important negative regulator for the transforming growth factor (TGF) beta/activin/Nodal signaling pathway by directly interacting with chromatin-associated proteins and transcriptional regulators, including the R-Smads, Smad1, Smad2, and Smad3 [, ]. Moreover, Man1 is a unique type of left-right (LR) signaling regulator that acts on the inner nuclear membrane. Man1 plays a crucial role in angiogenesis. The vascular remodeling can be regulated at the inner nuclear membrane through the interaction between Man1 and Smads []. Man1 contains an N-terminal LEM domain, two putative transmembrane domains, a MAN1-Src1p C-terminal (MSC) domain, and a C-terminal RNA recognition motif (RRM) []. The LEM domain interacts with the DNA and chromatin-binding protein Barrier-to-Autointegration Factor, and is also necessary for efficient localization of MAN1 in the inner nuclear membrane []. Research has indicated that C-terminal nucleoplasmic region of Man1 exhibits a DNA binding winged helix domain and is responsible for both DNA- and Smad-binding [].Mutations in the Man1 gene cause Buschke-Ollendorf syndrome (BOS), an uncommon syndrome characterised by osteopoikilosis and other bone abnormalities [].
Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth []. The dwarfin family also includes the Drosophila protein MAD that is required for the function of decapentaplegic (DPP) and may play a role in DPP signalling. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Dpp []. This domain is also found in nuclear factor I (NF-I) or CCAAT box-binding transcription factor (CTF).This entry represents the MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue beta hairpin is used to bind the DNA consensus sequence GNCN in the major groove, shown to be vital for the transcriptional activation of target genes. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. A basic helix (H2) in MH1 with the nuclear localisation signal KKLKK has been shown to be essential for Smad3 nuclear import. Smads also use the MH1 domain to interact with transcription factors such as Jun, TFE3, Sp1, and Runx [, , ].
