SP100

SP100 Full Name

SP100 nuclear antigen

SP100 Introduction

SP100 (Nuclear autoantigen Sp-100) encodes a major protein component of nuclear structures known as PML nuclear bodies (PML-NBs), also referred to as ND10 or nuclear dots. The gene is located on chromosome 2q37.1 and produces a protein that is constitutively localized within these punctate nuclear organelles. Within PML-NBs, SP100 interacts with members of the HP1 family of heterochromatin proteins, establishing a structural and functional link between these nuclear bodies and the broader chromatin compartment. The protein undergoes covalent modification by SUMO-1, a process considered crucial for mediating interactions within the nuclear body environment and for its proper subnuclear targeting.

Figure 1. Functional Domains and Disease-Associated Mutations in Human Speckled Proteins (SPs) and Autoimmune Regulator (Aire).(Fraschilla I, 2020)

Isoform Diversity and Functional Specialization
The SP100 gene generates multiple alternatively spliced isoforms—primarily Sp100A, Sp100B, Sp100C, and Sp100HMG—which exhibit distinct and sometimes opposing functions in transcriptional regulation. Sp100A, the most abundant isoform, promotes chromatin decondensation and increases lysine acetylation at target gene loci, thereby facilitating transcriptional activation. In contrast, isoforms containing a SAND domain (Sp100B, Sp100C, and Sp100HMG) function as transcriptional repressors, with Sp100C additionally possessing bromodomains and plant homeodomains that enable interactions with acetylated and methylated histones. Sp100-HMG contains a high-mobility group box domain, granting it DNA-binding potential. Interferon stimulation modulates the alternative splicing of SP100 transcripts, shifting the balance toward the repressive Sp100C isoform to enhance antiviral defenses.

Role in Intrinsic Antiviral Immunity
SP100 functions as a critical component of the cell's intrinsic antiviral defense mechanism, acting before the innate immune response is mobilized. The SAND domain-containing isoforms specifically suppress viral immediate-early gene expression at the promoter level, targeting herpes simplex virus type 1 proteins ICP0 and ICP4. Unlike PML, SP100 isoforms are resistant to degradation by the viral ICP0 E3 ubiquitin ligase, and all four isoforms stabilize ND10 structures by protecting PML from ICP0-mediated hydrolysis. This interdependency between PML and SP100 enhances the cellular capacity to restrict viral replication and suggests that both proteins cooperate through multiple mechanisms to establish an antiviral state at the immediate-early stage of infection.

Alternate Names for SP100

SP100; SP100 nuclear antigen; lysp100b; nuclear autoantigen Sp-100; speckled 100 kDa; SP100-HMG nuclear autoantigen; nuclear dot-associated Sp100 protein;

• Autoimmunity Catalogue
• Autoimmunity Catalogue