The BCLAF1 gene is composed of 13 exons and spans 32989 bases.

Two transcripts 5 kb and 3 kb in length are predominantly detected, however additional variant transcripts have been described with alternative promoters, cassette exons and polyadenylation sites.

None identified.

At least 4 isoforms are generated by alternative splicing. Two predominant BCLAF1 forms were initially described: a longer isoform 920 amino acids in length with a predicted molecular mass of 106 kDa, and a smaller isoform missing 49 amino acids (residues 797-846) with a predicted molecular mass of 101 kDa (Kasof et al., 1999). Residues 110-126 exhibit 88% homology to the bZIP DNA binding domain (Kasof et al., 1999). Residues 522-531 exhibit 80% homology to the Myb DNA binding domain (Kasof et al., 1999). Functional evidence for both of these domains remains to be shown. The N-terminal region (residues 3-161) of BCLAF1 is arginine- and serine-rich (RS domain). The C-terminal region (residues 512-913) is 59% similar to the C-terminal region of thyroid hormone receptor associated protein 3 (THRAP3/TRAP150).

BCLAF1 is ubiquitously expressed, with high steady-state mRNA levels in skeletal muscle, haematopoietic cells, and various other cell lineages (Kasof et al., 1999; McPherson et al., 2009). Steady-state levels of BCLAF1 protein fluctuate in a temporal and cell-lineage dependent fashion during development (McPherson et al., 2009).

Bclaf1 is concentrated in punctate foci interspersed through the nucleus. In the presence of E19K and conditions which trigger apoptosis, the nuclear distribution of Bclaf1 appears to concentrate at the nuclear periphery or envelope (Kasof et al., 1999; Haraguchi et al., 2004).
Bclaf1 was identified as a protein component of interchromatin granular clusters, subnuclear structures that appear to serve as repositories for pre-mRNA splicing factors (Misteli and Spector, 1998; Sutherland et al., 2001; Saitoh et al., 2004).

The exact molecular function of BCLAF1 remains to be defined. BCLAF1 was originally identified as having properties of a death-inducing transcriptional repressor (Kasof et al., 1999). Several subsequent studies have expanded on the link between BCLAF1, transcription and apoptosis. Depletion of BCLAF1 was reported to render cells resistant to ceramide-induced apoptosis (Renert et al., 2009). Protein kinase C delta-mediated transactivation of p53 transcription has been shown to occur through the stimulation of BCLAF1 to co-occupy a core promoter element in the TP53 promoter (Liu et al., 2007). A role for Bclaf1 in lung development and T cell homeostasis was demonstrated in Bclaf1-deficient mice (McPherson et al., 2009). Bclaf1 was shown to be required for the proper spatial and temporal organization of smooth muscle lineage cells during the saccular stage of lung development. Bclaf1 was also shown to be critical for T cell activation. The phenotype of these mice could not be explained by a defect in apoptosis, furthermore Bclaf1-deficient cells displayed no defect in cell death following exposure to various apoptotic stimuli.
Recent studies have implicated BCLAF1 in processes linked to RNA metabolism. BCLAF1 contains an RS domain, a feature of many factors that facilitate pre-mRNA splicing and mRNA processing. BCLAF1 was found to be a component of ribonucleoprotein complexes (Merz et al., 2007; Sarras et al., 2010). Bclaf1-deficient cells were found to exhibit altered preferences for alternative splicing of a model substrate (Sarras et al., 2010). BCLAF1 was found associated with SkIP, TRAP150 and Pinin in a complex known as SNIP1. SNIP1 was found to regulate cyclin D1 mRNA processing by facilitating the recruitment of the RNA processing factor U2AF65 to cyclin D1 mRNA (Bracken et al., 2008).
BCLAF1 has been shown to complex with the RNA export factor TAP/NXF1 (Sarras et al., 2010). This property has also recently been reported for TRAP150, a protein showing structural similarity to BCLAF1 that also is found in ribonucleoprotein complexes (Lee et al., 2010). TRAP150 has been shown to promote pre-mRNA splicing of reporter substrates and promotes mRNA decay in a manner that is independent of nonsense-mediated decay of mRNA (Lee et al., 2010).

Regulation
Sirt1 has been shown to exert transcriptional control of BCLAF1 at the promoter level (Kong et al., 2011). Sirt1 was found to form a complex with the histone acetyltransferase p300 and NF-kB transcription factor Rel-A, bind the BCLAF1 promoter and suppress BCLAF1 transcription via H3K56 deacetylation (Kong et al., 2011).
BCLAF1 protein levels fluctuate according to cell cycle position, with levels highest during the G1 phase, but lower during S and G2 phases (Bracken et al., 2008). BCLAF1 protein levels also fluctuate in a cell-lineage and temporal manner during differentiation of certain tissues and organs (McPherson et al., 2009).
Several studies have determined that Bclaf1 is extensively phosphorylated, although the functional significance of this modification is unclear. BCLAF1 has been proposed as a substrate of GSK-3 kinase (Linding et al., 2007). Vasopressin action in kidney cells has been reported to simulate BCLAF1 phosphorylation (Hoffert et al., 2006).
BCLAF1 has been shown to be one of the cellular targets for microRNAs (miRNAs) encoded by Kaposis sarcoma-associated herpesvirus (KSHV). KSHV triggers certain acquired immune deficiency syndrome-related malignancies such as Kaposis sarcoma, primary effusion lymphoma and variants of multicentric Castleman disease. A miRNA cluster within the KSHV genome is expressed during viral latency. During induction of lytic KSHV growth, inhibition of miRNAs was associated with increased BCLAF1 expression and decreased KSHV virion production (Ziegelbauer et al., 2009).

Interactions
E1B 19K. By yeast two-hybrid analysis, BCLAF1 was shown to directly interact with adenoviral E1B 19K via a BH3 domain and another region immediately adjacent to BH3 in E1B 19K (Kasof et al., 1999). In vitro binding assays reported BCLAF1 associates with BCL-2 and BCL2L1.
emerin. By yeast-two hybrid analysis and microtiter well binding assays, BCLAF1 was shown to directly interact with emerin, a nuclear membrane protein. Mutations that result in a loss of functional emerin cause X-linked recessive Emery-Dreifuss muscular dystrophy. The residues of emerin required for binding to BCLAF1 mapped to two regions that flank its lamin-binding domain. Two disease-causing mutations in emerin, S54F and Delta95-99, disrupted binding to BCLAF1. BCLAF1 and emerin were observed to co-localize in the vicinity of the nuclear envelope following induction of apoptosis by Fas antibody (Haraguchi et al., 2004).
MAN1. The C-terminal domain of MAN1, a nuclear inner membrane protein that inhibits Smad signaling downstream of transforming growth factor beta, was observed to bind BCLAF1, as well as the transcriptional regulators GCL, and barrier-to-autointegration factor (BAF) (Mansharamani and Wilson, 2005).
Factors that participate in RNA metabolism. BCLAF1 and TRAP150 have been identified to be protein components of ribonucleoprotein complexes that participate in pre-mRNA splicing and other mRNA processing events (Merz et al., 2007; Sarras et al., 2010; Lee et al., 2010). Both BCLAF1 and TRAP150 have been reported to reside in protein complexes that contain the mRNA export factor NXF1/TAP (Sarras et al., 2010; Lee et al., 2010). Both BCLAF1 and TRAP150, together with Pinin and SkIP, have been found in a protein complex that regulates cyclin D1 mRNA stability.

BCLAF1 shares amino acid similarity (48% overall identity) with TRAP150 in their C-terminal domains. Both proteins also contain RS-rich tracts within their N-termini (Lee et al., 2010).

BCLAF1 is located at chromosome 6q23 , a region that has been reported to exhibit a high frequency of deletions in tumours, such as lymphomas and leukemias. BCLAF1 has observed to be absent in Raji cells, derived from Burkitts lymphoma, which has deletions in 6q (Kasof et al., 1999). A role for the loss of BCLAF1 in neoplastic transformation remains to be determined and may be coincidental.