The LDOC1 gene includes only one exon.

A longer wild type 1376-bp transcript (Nagasaki et al., 1999), and a much shorter 165-bp splice variant LDOC1S (Duzakale et al. 2014) are reported. The cDNA sequence of wild type LDOC1 contains a 104-bp 5 untranslated region (5-UTR), a 438-bp open reading frame (ORF), and a 834-bp 3 untranslated region (3-UTR) including a consensus polyadenylation signal (Nagasaki et al., 1999).

Not reported.

The wild type LDOC1 is a 17 kDa protein containing 146 amino acids, with a leucine-zipper like motif at the N-terminal and a proline-rich region that similarity to an Src homolog 3 (SH3)-binding domain (Nagasaki et al., 1999). A shorter 165-bp splice variant is predicted to translate into a truncated protein of 44 amino acids that contains only the leucine-zipper region of wide type protein (Duzakale et al. 2014).

LDOC1 is expressed in a wide variety of normal tissues including heart, brain, lung, skeletal muscles, kidney, pancreas, spleen, thymus, prostate, testis, ovary, stomach, small intestine, colon, adrenal medulla, thyroid, adrenal cortex, thymus (Nagasaki et al., 1999). Down-regulation of LDOC1 have been reported in various kinds of human cancer tissues, including oral cancer (Lee et al., 2013), hepatocellular carcinoma (Riordan and Dupuy, 2013), Chronic lymphocytic leukemia (Duzakale et al., 2014), prostate cancer (Camões et al., 2012), as well as in a variety of human cancer cell lines, including pancreatic cancer cell line, gastric cancer cell lines, some breast cancer cell lines (Nagasaki et al., 1999), ovarian cancer cell lines (Buchholtz et al., 2014), cervical cancer cell lines (Buchholtz et al., 2013) and oral cancer cell lines (Lee et al., 2013). Epigenetic silencing by promoter hypermethylation was shown to be an important cause of LDOC1 down-regulation in oral cancer (Lee et al., 2013), cervical cancer (Buchholtz et al., 2013), and ovarian cancer cells (Buchholtz et al., 2014).

LDOC1 localizes predominantly in the nucleus (Nagasaki et al., 1999). It may also be retained in cytoplasm through interaction with WAVE3 (Mizutani et al., 2005).

Most reports demonstrated that the biological function of LDOC1 is closely related to modulation of apoptosis. Forced expression of LDOC1 induced apoptosis in Jurkat lymphoma cells, K562 leukemia cells (Inoue et al., 2015), Hela cervical cancer cells (Buchholtz et al., 2013) and oral cancer cells (Lee et al., 2013). Expression of LDOC1 also enhanced TNF-? or phorbol 12-myristate 13-acetate (PMA)-induced anti-proliferative effects in pancreatic cancer cells (Nagasaki et al., 2003). A hematopoietic transcriptional factor (MZF-1) important in regulating myeloid cell differentiation and proliferation may interact with LDOC1 and enhance it apoptosis-inducing function in K562 leukemia cells (Inoue et al., 2015). LDOC1 also induced apoptosis and inhibited degradation of p53, resulting in p53 accumulation in MDCK cells. WAVE3 could interact with LDOC1 with its C-terminal verprolin homolog domain and act as a negative regulator of LDOC1. Forced expression of WAVE3 retained LDOC1 in cytoplasm and attenuated the apoptosis-inducing effect of LDOC1 (Mizutani et al., 2005). Expression of LDOC1 also significantly inhibited the NF-?B reporter activity in LDOC1-negative BxPC-3 pancreatic cancer cells (Nagasaki et al., 2003) and suppressed TNF-? induced activation of NF-?B (Lee et al., 2013). LDOC1 may also interact with CCAAT-enhancer binding protein-? (C/EBP?) (Chih et al., 2004). However, in human intrahepatic biliary epithelial cells, over expression LDOC1 increased the expression of NF-?B (p65), promoted IL-2 and TNF-? secretion and inhibited apoptosis (Song et al., 2013). LDOC1 has recently been reported as a eutherian-specific acquired gene that regulates placental endocrine function (Naruse et al., 2014).

HomoloGene:32153