Function: Component of the THO subcomplex of the TREX complex. The TREX complex specifically associates with spliced mRNA and not with unspliced pre-mRNA. It is recruited to spliced mRNAs by a transcription-independent mechanism. Binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export. The recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. DDX39B functions as a bridge between ALYREF/THOC4 and the THO complex. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. The recruitment of the TREX complex to the intronless viral mRNA occurs via an interaction between KSHV ORF57 protein and ALYREF/THOC4. Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17Regulates transcriptional elongation of a subset of genes. Participates in an apoptotic pathway which is characterized by activation of caspase-6, increases in the expression of BAK1 and BCL2L1 and activation of NF-kappa-B. This pathway does not require p53/TP53, nor does the presence of p53/TP53 affect the efficiency of cell killing. Activates a G2/M cell cycle checkpoint prior to the onset of apoptosis. Apoptosis is inhibited by association with RB1. Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17
Subunit structure: Component of the THO complex, which is composed of THOC1, THOC2, THOC5, THOC6 and THOC7. Together with THOC3, ALYREF/THOC4 and DDX39B, THO forms the transcription/export (TREX) complex. Binds to the hypophosphorylated form of RB1. Interacts with THOC2, DDX39B and RNA polymerase II. Ref.1 Ref.10 Ref.12 Ref.13 Ref.14
Subcellular location: Isoform 1: Nucleus speckle. Nucleus › nucleoplasm. Nucleus matrix. Cytoplasm Ref.1 Ref.2 Ref.11. Note: Can shuttle between the nucleus and cytoplasm. Nuclear localization is required for induction of apoptotic cell death. Translocates to the cytoplasm during the early phase of apoptosis execution. Ref.1 Ref.2 Ref.11Isoform 2: Cytoplasm Ref.1 Ref.2 Ref.11.
Tissue specificity: Ubiquitous. Expressed in various cancer cell lines. Expressed at very low levels in normal breast epithelial cells and highly expressed in breast tumors. Expression is strongly associated with an aggressive phenotype of breast tumors and expression correlates with tumor size and the metastatic state of the tumor progression. Ref.2 Ref.12
Induction: Up-regulated during cell proliferation. Ref.2
Domain: An intact death domain is needed for apoptosis. Ref.7
Post-translational modification: Expression is altered specifically during apoptosis and is accompanied by the appearance of novel forms with smaller apparent molecular mass.
Sequence similarities: Contains 1 death domain.
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