DMBT1

Description

The DMBT1 (deleted in malignant brain tumors 1) is a protein-coding gene located on chromosome 10.

Deleted in malignant brain tumors 1 protein is a protein that in humans is encoded by the DMBT1 gene. Loss of sequences from human chromosome 10q has been associated with the progression of human cancers. The gene DMBT1 was originally isolated based on its deletion in a medulloblastoma cell line. DMBT1 is expressed with transcripts of 6.0, 7.5, and 8.0 kb in fetal lung and with one transcript of 8.0 kb in adult lung, although the 7.5 kb transcript has not been characterized. The DMBT1 protein is a glycoprotein containing multiple scavenger receptor cysteine-rich (SRCR) domains separated by SRCR-interspersed domains (SID). Transcript variant 2 (8.0 kb) has been shown to bind surfactant protein D independently of carbohydrate recognition. This indicates that DMBT1 may not be a classical tumor suppressor gene, but rather play a role in the interaction of tumor cells and the immune system. At epithelial barriers molecular pattern recognition mechanisms act as minesweepers against harmful environmental factors and thereby play a crucial role in the defense against invading bacterial and viral pathogens. However, it became evident that some of the proteins participating in these host defense processes may simultaneously function as regulators of tissue regeneration when in the extracellular matrix, thus coupling defense functions with regulation of stem cells. Although molecular pattern recognition has complex physiological roles and we just begin to understand its various functions, the simplicity of the underlying principles for recognition of specific classes of molecules may generate novel starting points for nanomedical approaches in drug delivery across epithelial barriers.

DMBT1 is thought to be a tumor suppressor gene, playing a role in the suppression of various cancers including brain, lung, esophageal, gastric, and colorectal cancers. It is also involved in the mucosal defense system, cellular immune defense, and epithelial differentiation. DMBT1 functions as an opsonin receptor for SFTPD and SPAR in macrophages and epithelial cells of the gastrointestinal tract, contributing to immune responses. DMBT1 plays a role in liver regeneration, impacting the fate and differentiation of hepatic lineage cells. During early embryogenesis, DMBT1 is essential for the terminal differentiation of columnar epithelial cells. In saliva, DMBT1 acts as a binding protein, influencing taste sensation. DMBT1 binds to the HIV-1 envelope protein, potentially affecting viral transmission. Its broad calcium-dependent binding spectrum against Gram-positive and Gram-negative bacteria suggests a role in bacterial defense. This broad binding specificity is likely attributed to DMBT1's interactions with poly-sulfated and poly-phosphorylated ligands. DMBT1 inhibits the cytoinvasion of S.enterica, demonstrating its role in preventing bacterial invasion. By associating with the actin cytoskeleton, DMBT1 participates in its remodeling during regulated exocytosis. DMBT1 interacts with pancreatic zymogens in a pH-dependent manner, potentially acting as a Golgi cargo receptor in the pancreatic acinar cell's regulated secretory pathway. {ECO:0000269|PubMed:10485905, ECO:0000269|PubMed:11007786, ECO:0000269|PubMed:11751412, ECO:0000269|PubMed:16796526, ECO:0000269|PubMed:17548659, ECO:0000269|PubMed:17709527, ECO:0000269|PubMed:19189310, ECO:0000269|PubMed:9288095}

DMBT1 is also known as GP340, SAG, SALSA, muclin.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing