Alternative titles; symbols
HGNC Approved Gene Symbol: UACA
Cytogenetic location: 15q23 Genomic coordinates (GRCh38) : 15:70,654,554-70,778,903 (from NCBI)
By sequencing clones obtained from a size-fractionated human fetal brain cDNA library, Nagase et al. (2000) cloned KIAA1561. RT-PCR ELISA detected ubiquitous expression, with highest levels in skeletal muscle.
By immunoscreening of a bovine uveal cDNA expression library with serum samples obtained from patients with Vogt-Koyanagi-Harada (VKH) disease, Yamada et al. (2001) identified a novel autoantigen, which they designated UACA. Using a human sequence homologous to the bovine UACA sequence to screen a Jurkat cell cDNA library, they isolated the human homolog, which was found have the same sequence as KIAA1561. Human UACA encodes a deduced 1,449-amino acid protein with a predicted molecular mass of approximately 166 kD. It contains 6 ankyrin repeats, a leucine zipper motif, and coiled-coil domains. The bovine and human proteins share 86% sequence homology. Northern blot analysis demonstrated expression at various levels in all tissues analyzed, with highest expression in skeletal muscle.
Using a subtractive cloning strategy, Sakai et al. (2003) cloned the mouse homolog of UACA, which they called Nucling, that was expressed selectively by embryonal carcinoma cells. They found that the mouse and human proteins share 79% sequence identity. Northern blot analysis revealed predominant expression in heart, liver, kidney, and testis. Immunofluorescence microscopy showed that Nucling was expressed in clusters around the nuclear membrane and was also expressed diffusely in cytoplasm.
By sequence analysis, Yamada et al. (2001) mapped the UACA gene to chromosome 15q24.
Yamada et al. (2001) found that the prevalence of IgG anti-UACA autoantibodies in patients with panuveitis (VKH disease, Behcet disease (109650), sarcoidosis (see 181000)) was significantly higher than that in healthy controls (19.6-28.1% vs 0%, p less than 0.05), indicating that autoimmunity directed against UACA is a common phenomenon in these diseases.
Sakai et al. (2003) demonstrated that the mouse Uaca transcript increases progressively during the early developmental stages, and specifically at cardiomuscular differentiation.
Liu et al. (2004) demonstrated that mouse Uaca downregulated expression of the antiapoptotic molecule galectin-3 (153619) through interference with nuclear factor kappa-B (164011) signaling.
Sakai et al. (2004) showed that Uaca was upregulated by proapoptotic stimuli and was important for the induction of apoptosis after cytotoxic stress. Overexpression of Uaca induced apoptosis in mammalian cells. In Uaca-deficient cells, the expression levels of Apaf1 (602233) and cytochrome c (123970), major components of the apoptosome complex, were both downregulated under cellular stress. A deficiency of Uaca also conferred resistance to apoptotic stress on the cells. After UV irradiation, Uaca was shown to reside in an Apaf1/procaspase-9 (CASP9; 602234) complex, suggesting that Uaca may be important for the formation and maintenance of this complex. Uaca induced translocation of Apaf1 to the nucleus, thereby distributing the Uaca/Apaf2/Casp9 complex to the nuclear fraction. Sakai et al. (2004) suggested that Uaca recruits and transports the apoptosome complex during stress-induced apoptosis.
Using yeast 2-hybrid assays, Mori et al. (2013) identified mouse Uaca as a Rab39a (619558)- and Rab39b (300774)-binding protein, with the C-terminal coiled-coil domain of Uaca functioning as the binding domain. Immunofluorescence analysis showed that Uaca colocalized with Rab39a or Rab39b in dot-like structures outside of the Golgi when coexpressed in COS-7 cells. Knockdown of Rab39a or Uaca in Neuro2A mouse neuroblastoma cells changed the retinoic acid (RA)-induced neurite morphology from multipolar to bipolar morphology, whereas knockdown of Rab39b had no effect. The authors concluded that Uaca functions as a Rab39a effector in RA-induced differentiation of Neuro2A cells.
Liu, L., Sakai, T., Sano, N., Fukui, K. Nucling mediates apoptosis by inhibiting expression of galectin-3 through interference with nuclear factor kappa-B signalling. Biochem. J. 380: 31-41, 2004. [PubMed: 14961764] [Full Text: https://doi.org/10.1042/BJ20031300]
Mori, Y., Matsui, T., Omote, D., Fukuda, M. Small GTPase Rab39A interacts with UACA and regulates the retinoic acid-induced neurite morphology of Neuro2A cells. Biochem. Biophys. Res. Commun. 435: 113-119, 2013. [PubMed: 23624502] [Full Text: https://doi.org/10.1016/j.bbrc.2013.04.051]
Nagase, T., Kikuno, R., Nakayama, M., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 273-281, 2000. [PubMed: 10997877] [Full Text: https://doi.org/10.1093/dnares/7.4.271]
Sakai, T., Liu, L., Shishido, Y., Fukui, K. Identification of a novel, embryonal carcinoma cell-associated molecule, nucling, that is up-regulated during cardiac muscle differentiation. J. Biochem. 133: 429-436, 2003. [PubMed: 12761289] [Full Text: https://doi.org/10.1093/jb/mvg056]
Sakai, T., Liu, L., Teng, X., Mukai-Sakai, R., Shimada, H., Kaji, R., Mitani, T., Matsumoto, M., Toida, K., Ishimura, K., Shishido, Y., Mak, T. W., Fukui, K. Nucling recruits Apaf-1/Pro-caspase-9 complex for the induction of stress-induced apoptosis. J. Biol. Chem. 279: 41131-41140, 2004. [PubMed: 15271982] [Full Text: https://doi.org/10.1074/jbc.M402902200]
Yamada, K., Senju, S., Nakatsura, T., Murata, Y., Ishihara, M., Nakamura, S., Ohno, S., Negi, A., Nishimura, Y. Identification of a novel autoantigen UACA in patients with panuveitis. Biochem. Biophys. Res. Commun. 280: 1169-1176, 2001. [PubMed: 11162650] [Full Text: https://doi.org/10.1006/bbrc.2001.4189]