Alternative titles; symbols
HGNC Approved Gene Symbol: SP140
Cytogenetic location: 2q37.1 Genomic coordinates (GRCh38) : 2:230,186,151-230,316,571 (from NCBI)
By subtractive hybridization for cDNAs enriched in a Raji Burkitt lymphoma (113970) cell line cDNA library, followed by screening Raji and HeLa cell cDNA libraries, Dent et al. (1996) cloned splice variants of SP140, which they designated LYSP100A and LYSP100B. LYSP100A encodes a deduced 412-amino acid protein with a calculated molecular mass of 46 kD, and LYSP100B encodes a deduced 882-amino acid protein with a calculated molecular mass of 100 kD. The N-terminal 353 amino acids of LYSP100A and LYSP100B are identical, and the N-terminal 158 amino acids of both proteins share 61% amino acid homology with the N-terminal region of SP100 (604585). LYSP100B has a C-terminal PHD domain and a bromodomain. Northern blot analysis detected transcripts of 0.9, 1.6, and 3.0 kb in spleen, thymus, and tonsil, but not in brain, liver, and muscle. LYSP100 expression was detected in all mature B-lymphocyte and plasma cell lines tested, as well as in some T-lymphocyte cell lines, but not in nonlymphoid cell lines. Western blot analysis detected LYSP100 isoforms ranging in size from 65 to 150 kD. Using confocal microscopy and electron microscopy, Dent et al. (1996) localized LYSP100 to subnuclear structures morphologically and spatially distinct from nuclear bodies containing PML (102578).
By screening a hepatocarcinoma cDNA expression library using autoantibodies in serum from a patient with primary biliary cirrhosis (PBC; 109720), followed by screening hepatocarcinoma and umbilical vein endothelial cell cDNA libraries, Bloch et al. (1996) cloned SP140. The deduced protein contains 753 amino acids. The N terminus of SP140, between amino acids 29 and 157, is 49% identical to a corresponding N-terminal region of SP100. The C terminus of SP140 contains a cysteine-rich zinc finger motif and a bromodomain. SP140 also has a central nuclear localization signal. RNA dot blot analysis detected high SP140 expression in spleen and peripheral blood leukocytes, with much lower levels in thymus, prostate, ovary, small intestine, and colon; other tissues showed little to no expression. Low expression of a smaller transcript was also observed. Western blot analysis with PBC autoantibodies detected SP140 at an apparent molecular mass of 140 kD following in vitro transcription and translation. Immunohistochemistry demonstrated that SP140 colocalized with PML in dense nuclear bodies in activated myeloid precursor cells.
Bloch et al. (1996) found that expression of SP140 increased in myeloid precursor cell lines following activation with phorbol ester, dimethyl sulfoxide, or all-trans retinoic acid. Expression was also enhanced by treatment of cells with gamma-interferon (147570).
The International Radiation Hybrid Mapping Consortium mapped the SP140 gene to chromosome 2 (SHGC-34902).
Bloch, D. B., de la Monte, S. M., Guigaouri, P., Filippov, A., Bloch, K. D. Identification and characterization of a leukocyte-specific component of the nuclear body. J. Biol. Chem. 271: 29198-29204, 1996. [PubMed: 8910577] [Full Text: https://doi.org/10.1074/jbc.271.46.29198]
Dent, A. L., Yewdell, J., Puvion-Dutilleul, F., Koken, M. H. M., de The, H., Staudt, L. M. LYSP100-associated nuclear domains (LANDs): description of a new class of subnuclear structures and their relationship to PML nuclear bodies. Blood 88: 1423-1436, 1996. [PubMed: 8695863]