SP140 Recombinant Rabbit mAb (S-6460)

SP140 (Speckled protein 140, also known as nuclear body protein SP140 or LYSp100) is a nuclear epigenetic "reader" protein encoded by the SP140 gene in the q37.1 region of human chromosome 2, mainly expressed in immune cells (especially mature B cells, macrophages, and dendritic cells); it is a member of the speckled protein (SP) family and contains characteristic domains including an HSR (CARD-like oligomerization) domain, a SAND domain, a PHD zinc finger, and a bromodomain, enabling it to recognize histone modifications and localize to subnuclear structures such as nuclear bodies. Its core function is to act as a transcriptional repressor regulating immune cell transcriptional programs: SP140 maintains macrophage identity and intestinal immune homeostasis by repressing lineage-inappropriate genes (such as HOX genes) and NF-κB-dependent inflammatory genes; in type I interferon regulation, SP140 limits the stabilization of Ifnb1 mRNA by RESIST proteins through repressing expression of the Resist1/2 locus, thereby preventing excessive and sustained IFN-β secretion, and it also directly restricts gammaherpesvirus replication in a RESIST-independent manner. Loss-of-function variants or downregulated expression of SP140 are closely associated with multiple immune-mediated diseases, including Crohn's disease, multiple sclerosis, chronic lymphocytic leukemia (in which SP140 is predicted to be a tumor suppressor), and increased susceptibility to bacterial infection. In addition, recent studies have found that various cancer cells can aberrantly express SP140 under MAPK signaling-driven conditions through alternative promoters derived from intronic endogenous retroviruses, suggesting that it may have roles in tumor immune regulation extending beyond the classical immune cell context.