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HGNC Approved Gene Symbol: SP100
Cytogenetic location: 2q37.1 Genomic coordinates (GRCh38) : 2:230,416,201-230,545,606 (from NCBI)
The PML/SP100 nuclear bodies (NBs), also referred to as Kr-bodies, ND10, or PODs, represent a subnuclear 'organelle' whose integrity is compromised in promyelocytic leukemia (PML). NBs contain the SP100 autoantigen as well as the PML protein (102578) that is part of the leukemogenic PML-RARA (180240) fusion protein associated with acute PML.
To characterize further the 95- to 100-kD SP100 autoantigen, Szostecki et al. (1990) isolated overlapping cDNA fragments from HeLa, placenta, and liver cDNA libraries and obtained a full-length SP100 cDNA. SP100 encodes a 480-amino acid acidic (pI 4.7) protein with multiple phosphorylation sites for casein kinase type II. Szostecki et al. (1990) found that anti-SP100 autoantibodies occur predominantly in patients with primary biliary cirrhosis (109720). The authors noted sequence similarities with alpha-1 and alpha-2 membrane-associated regions of human and nonhuman MHC class I antigens.
Using SP100 as bait in a yeast 2-hybrid system and by GST 'pull down' experiments, Seeler et al. (1998) showed that SP100 complexes with members of the HP1 family of nonhistone chromosomal proteins (e.g., CBX5, 604478). A variant of SP100, termed SP100B by the authors, contains additional 3-prime sequence encoding a 688-amino acid protein. A splice variant of SP100B, termed SP100-HMG, is joined to an 81-amino acid HMG1 (163905)-like peptide by a 14-amino acid bridge. The HMG1-like domain is 87% identical and 93% similar to HMG1. SP100-HMG has the potential to be a DNA-binding protein. All 3 variants, SP100, SP100B, and SP100-HMG, colocalize with HP1 in NBs, suggesting that the N-terminal portion of SP100 is responsible for the interaction. HP1 expression is enhanced when SP100 synthesis is induced by interferon.
By Northern blot analysis, Dent et al. (1996) found that SP100B, which they called LYSP100, is expressed only in lymphoid tissues (spleen, tonsil, and thymus), mature B-cell lines, and some T-cell lines, but not in brain, liver, muscle, or nonlymphoid cell lines. They noted that SP100 expression is widespread. By confocal immunofluorescence microscopy, they determined that a minority of the nuclear dots for SP100B overlapped with SP100 and PML, whereas most localized to another class of subnuclear structures, which they termed LANDs (LYSP100-associated nuclear domains), which are morphologically and spatially distinct from PML NBs.
Dent, A. L., Yewdell, J., Puvion-Dutilleul, F., Koken, M. H., 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: 1423-1426, 1996. [PubMed: 8695863]
Seeler, J. S., Marchio, A., Sitterlin, D., Transy, C., Dejean, A. Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment. Proc. Nat. Acad. Sci. 95: 7316-7321, 1998. [PubMed: 9636146] [Full Text: https://doi.org/10.1073/pnas.95.13.7316]
Szostecki, C., Guldner, H. H., Netter, H. J., Will, H. Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis. J. Immun. 145: 4338-4347, 1990. [PubMed: 2258622]