set-9

T cell immunoreceptor with Ig and ITIM domains (TIGIT), also called VSIG9 and Vstm3, is a member of the CD28 family within the Ig superfamily of proteins. TIGIT contains an immunoglobulin variable domain, a transmembrane domain and an immunoreceptor tyrosine-based inhibitory motif (ITIM), and is expressed on regulatory, memory, activated T cells and NK cells. TIGIT binds to CD155(PVR) that appear on dendritic cells (DC), macrophages and endothelium with high affinity, and CD112(PVRL2) with lower affinity, but not CD113 (PVRL3). TIGIT-Fc fusion protein could interact with PVR on DC and enhance the secretion of IL-10, but inhibit the macrophage activation. Mice lacking TIGIT show increased T cell responses and susceptibility to autoimmune challenges, while knockdown of TIGIT with siRNA in human memory T cells did not affect T cell responses.

Histone-lysine N-methyltransferase SETD7, also known as SET domain containing (lysine methyltransferase) 7, SET7/9, Histone H3-K4 methyltransferase SETD7, H3-K4-HMTase SETD7, and SETD7, is a member of the histone-lysine methyltransferase family and SET7 subfamily. SETD7 is widely expressed and expressed in pancreatic islets. SETD7 contains three MORN repeats and one SET domain. SETD7 plays a central role in the transcriptional activation of genes such as collagenase or insulin. As a protein lysine methyltransferase (PKMT), SETD7 also has methyltransferase activity toward non-histone proteins such as p53/TP53, TAF1, and possibly TAF7 by recognizing and binding in substrate proteins. The mono-methyltransferase activity of SETD7 is achieved by disrupting the formation at near-attack conformations for the dimethylation reaction. SETD7 is also a novel coactivator of NF-kappaB and plays a role in inflammation and diabetes.

KMT5A (known as PR-Set7/9, SETD8 and SET8), a member of the SET domain containing methyltransferase family specifically targeting H4K20 for methylation, has been implicated in multiple biological processes. Inhibition of KMT5A attenuated proliferation and induced apoptosis. Elevated KMT5A expression was significantly correlated with extrathyroidal extension, lymph node metastasis and advanced pathological stage of papillary thyroid cancer. KMT5A may be a novel oncogenic factor, specifically a regulator for lipid metabolism in papillary thyroid carcinoma.

Siglecs are sialic acid specific I‑type lectins that are characterized by an extracellular domain (ECD) with an N‑terminal Ig‑like V‑set domain followed by varying numbers of Ig‑like C2‑set domains. Mouse Siglec‑E, also known as Myeloid Inhibitory Siglec (MIS), is an 80 ‑ 85 kDa member of the CD33‑related subfamily of Siglecs. Rodent and primate Siglec gene families have significantly diverged, and Siglec‑9 is the most likely human ortholog of mouse Siglec‑E. Siglec‑E is expressed as a heavily N‑glycosylated disulfide‑linked homodimer and shows binding preference for disialic acids in the alpha 2‑8 linkage. Siglec‑E is up‑regulated and additionally phosphorylated following cellular stimulation by a variety of TLR agonists. Siglec‑E signaling negatively regulates the LPS‑induced production of TNF‑ alpha and IL‑6 by macrophages. Its up‑regulation in macrophages parallels the development of endotoxin tolerance. Siglec‑E recognition of sialylated determinants on virulent T. cruzi contributes to the suppression of dendritic cell IL‑12 p40 production.