Cellular and humoral effects mediated by KIM-1 are involved in a variety of physiological and pathophysiological processes

Cellular and humoral effects mediated by KIM-1 are involved in a variety of physiological and pathophysiological processes. Current understanding of the mechanisms determining the participation LY2365109 hydrochloride of KIM-1 in viral invasion, the immune response regulation, adaptive reactions of the kidney epithelium to acute ischemic or harmful injury, in progression of chronic renal diseases, and kidney cancer development have been presented with this review. whose high manifestation was standard for epithelial cells of the damaged proximal renal tubules. This gene appeared to be a full homolog of [2]. In 2001, McIntire et al. [3] found a gene cluster controlling hyperactivity of the respiratory epithelium (T-cell and airway phenotype regulator, in rats HD3 and in humans and primates [3]. Later, there were identified eight proteins, members of the TIM family (TIM-1, , -8) in mice, six proteins (TIM-1, , -6) in rats, three proteins TIM-1 (KIM-1), TIM-3, and TIM-4 in humans [4]. At present, gene bears its historic name in biological databases while in publications its product preserves the name generally accepted in the appropriate field of investigation, i.e. HAVcr-1, KIM-1, or TIM-1 (CD365). The TIM family glycoproteins are mostly expressed from the cells of the immune system and therefore are involved in numerous physiological and pathological processes associated with the rules of immune reactions [5]. KIM-1, unlike additional members of the TIM family, is definitely presented not only on lymphocytes but in other types of cells determining varied manifestations of its practical activity. The latest data on physiological and pathophysiological properties of HAVcr-1/KIM-1/TIM-1 have been systematized in the present evaluate, some aspects of by using this glycoprotein like a marker in medical investigations have also been analyzed. KIM-1 molecule structure In the human being genome, (Gene ID: 26762) is located within the long arm of chromosome 5 at locus 5q33.3 and contains 11 exons. Variants of KIM-1 generated as a result of an alternative mRNA splicing may consist of from 334 to 401 amino acids with variations of glycoprotein molecular mass from 36 to 44 kDa [6, 7]. The molecular mass of a mature (fully glycosylated) KIM-1 reaches 104 kDa [6]. KIM-1 is definitely localized within the plasma membrane forming extracellular, transmembrane, and cytoplasmic domains (see the Number) [8]. The extracellular portion of KIM-1 includes a globular website similar to the variable fragment of immunoglobulins (IgV), mucin-like sequence, and a short peptide segment. Open in a separate window Schematic structure of the TIM family glycoproteins (based on the materials of Kuchroo et al. [8]) A key feature of the KIM-1 IgV-domain structure is the presence of a hydrophobic pocket (metal-ion-dependent ligand binding site, MILIBS), capable of binding a signaling phospholipid, phosphatidylserine (PS) [9]. Normally, PS is definitely localized within the inner side of the cell plasma membrane and during apoptosis induction techniques to the outer side of the membrane. It serves as a signal for macrophages and epithelial LY2365109 hydrochloride cells to absorb the dying cells [10]. It is believed that due to the ability to interact with PS, KIM-1 in the epithelial cells can perform the function of a scavenger receptor mediating removal of cellular debris in case of tissue damage [11]. Glycoproteins of the TIM family [12, 13], oxidized low-density lipoproteins [14], P-selectin [15], and conjugated blood bilirubin [16] will also be potential ligands binding to which is definitely mediated by IgV website. Highly glycosylated mucin-like website, the most massive portion of KIM-1, contains tandem repeats of amino acids and sites of O-glycosylation. No specific practical properties have been described for this website; however, it is assumed that the LY2365109 hydrochloride organization of this molecular segment is definitely important for the KIM-1 connection.