Chemicals & Small Molecules

PVRIG (poliovirus receptor related immunoglobulin domain-containing protein), also known as CD112 receptor (CD112R), is an approximately 34 kDa single transmembrane protein in the poliovirus receptor-like protein (PVR) family. The extracellular domain sequence of human and mouse PVRIG have approximately 65% similarity. PVRIG functions as a cell surface receptor for Nectin-2/CD112, a cell surface protein that is widely expressed on antigen-presenting cells and tumor cells. Disrupting the PVRIG/Nectin-2 interaction enhances human T cell response, suggesting PVRIG is a novel checkpoint for human T cells. PVRIG may act as a coinhibitory receptor that suppresses T-cell receptor-mediated signals.

SECTM1A (secreted and transmembrane 1A), is 192 amino acid (aa) protein, appears to share structural and functional characteristics with other SECTM1 proteins. Human SECTM1 can be found either found as an approximately 27 kDa intracellular type I transmembrane protein that shows a perinuclear, Golgi like staining pattern, or as a 20 kDa soluble, secreted form, and is produced by some myeloid cells and by thymic epithelia and fibroblasts. Stimulation with IFN gamma is often necessary to detect human SECTM1 expression, and it is thought to be an interferon early response gene. Mouse SECTM1A cDNA encodes a signal sequence, an extracellular domain with four potential N linked glycosylation sites, a transmembrane sequence, and a very short (approximately 6 aa) cytoplasmic sequence. SECTM1 proteins from human and mouse show species specific binding of CD7 and co stimulation of T cells, including enhancement of CD3 induced proliferation.

Butyrophilin-like 6 (BTNL6) is a member of the BTN/MOG Ig-superfamily and functions with BTNL1 as a regulator of immune cell proliferation. The Btnl6 gene is found only in mice. BTNL6 expression is coordinated as a heteromeric protein with BTNL1, and the presence of this complex is correlated with expansion of gamma δ T cells, especially those containing V gamma 7Vδ4 TCR. Btnl6 shows striking sequence similarity to Skint1; is also largely restricted to an epithelial tissue (the small intestine) replete with T cells. Our in-house studies showed BTNL6 co-inhibited anti-CD3 induced IL-2 secretion on CD3+ cells.

Cdh1 is one of the substrate adaptor protein of the anaphase-promoting complex (APC) in the budding yeast Saccharomyces cerevisiae. Functioning as an activator of the APC/C, Cdh1 regulates the activity and substrate specificity of this ubiquitin E3-ligase.

Otolin (OTOL1), also known as C1qTNF15, is an approximately 65 kDa protein found in the otoconial membrane lining the cochlea and vestibular labyrinth of the inner ear. Collagen-like protein specifically expressed in the inner ear, which provides an organic scaffold for otoconia, a calcium carbonate structure in the saccule and utricle of the ear. It associates into multimers and disulfide-linked oligomers and also associates with other otoconial proteins including and Otoconin-90 (also known as PLA2G2A, PLA2L, and phospholipase A2 homolog) and Cerebellin-1. It is extensively glycosylated and has multiple hydroxylated proline residues in the collagenous regions.

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a secretory subtilase belonging to the proteinase K subfamily. PCSK9 is synthesized as a soluble zymogen that undergoes autocatalytic intramolecular processing in the ER , the pro domain and mature chain secrete together through noncovalent interactions. PCSK9 binds with low-density lipoprotein receptor (LDLR) and plays a major regulatory role in cholesterol homeostasis. PCSK9 also plays a role in the neural development.

Siglecs (sialic acid binding Ig-like lectins) are I-type (Ig-type) lectins belonging to the Ig superfamily. They are characterized by an N-terminal Ig-like V-type domain which mediates sialic acid binding, followed by varying numbers of Ig-like C2-type domains. Human Siglec-2, also known as B-cell antigen CD22 or B-lymphocyte cell adhesion molecule (BL-CAM), is a B-cell restricted glycoprotein that is expressed in the cytoplasm of progenitor B and pre-B cells and on the surface of mature B cells. Two distinct human Siglec-2/CD22 cDNAs that arise from differential RNA processing of the same gene have been isolated. Siglec-2/CD22 is an adhesion molecule that preferentially binds alpha 2,6- linked sialic acid on the same (cis) or adjacent (trans) cells. Interaction of CD22 with trans ligands on opposing cells was found to be favored over the binding of ligands in cis.

Bone sialoprotein 2(IBSP) is a monomeric non‑collagenous member of the SIBLING family of extracellular matrix proteins. It is principally associated with the early stages of bone mineralization. Mouse IBSP is synthesized as a 324 amino acid (aa) precursor that contains a 16 aa signal sequence and a 308 aa mature region. The mature segment is divided into a basic N‑terminus (aa 17 ‑ 62), a central region (aa 63 ‑ 233), and an acidic C‑terminus (aa 234 ‑ 317). IBSP is highly glycosylated, sulfated and phosphorylated. Phosphorylation promotes HAp nucleation, while carbohydrate may regulate cell adhesion. IBSP binds tightly to hydroxyapatite, appears to form an integral part of the mineralized matrix. It is probably important to cell-matrix interaction and promotes Arg-Gly-Asp-dependent cell attachment.

MMP3 is a member of the matrix metalloproteinase (MMP) family whose members are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, tissue remodeling, and disease processes including arthritis and metastasis. The MMP-3 enzyme degrades collagen types II, III, IV, IX, and X, proteoglycans, fibronectin, laminin, and elastin. In addition, MMP-3 can also activate other MMPs such as MMP-1, MMP-7, and MMP-9, rendering MMP-3 crucial in connective tissue remodeling.[3] The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation.