8j8d

Structural highlights

Disease

DMBT1_HUMAN The gene represented in this entry is involved in disease pathogenesis. Homozygous deletions may be the predominant mechanism of DMBT1 inactivation playing a role in carcinogenesis. DMBT1 is deleted in medulloblastoma and glioblastoma cell lines; point mutations have also been reported in patients with glioma. A loss or reduction of DMBT1 expression has been seen in esophageal, gastric, lung and colorectal carcinomas as well.

Function

DMBT1_HUMAN May be considered as a candidate tumor suppressor gene for brain, lung, esophageal, gastric, and colorectal cancers. May play roles in mucosal defense system, cellular immune defense and epithelial differentiation. May play a role as an opsonin receptor for SFTPD and SPAR in macrophage tissues throughout the body, including epithelial cells lining the gastrointestinal tract. May play a role in liver regeneration. May be an important factor in fate decision and differentiation of transit-amplifying ductular (oval) cells within the hepatic lineage. Required for terminal differentiation of columnar epithelial cells during early embryogenesis. May function as a binding protein in saliva for the regulation of taste sensation. Binds to HIV-1 envelope protein and has been shown to both inhibit and facilitate viral transmission. Displays a broad calcium-dependent binding spectrum against both Gram-positive and Gram-negative bacteria, suggesting a role in defense against bacterial pathogens. Binds to a range of poly-sulfated and poly-phosphorylated ligands which may explain its broad bacterial-binding specificity. Inhibits cytoinvasion of S.enterica. Associates with the actin cytoskeleton and is involved in its remodeling during regulated exocytosis. Interacts with pancreatic zymogens in a pH-dependent manner and may act as a Golgi cargo receptor in the regulated secretory pathway of the pancreatic acinar cell.^{[1] [2] [3] [4] [5] [6] [7] [8]}

References

1. ↑ Holmskov U, Mollenhauer J, Madsen J, Vitved L, Gronlund J, Tornoe I, Kliem A, Reid KB, Poustka A, Skjodt K. Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D. Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10794-9. PMID:10485905
2. ↑ Prakobphol A, Xu F, Hoang VM, Larsson T, Bergstrom J, Johansson I, Frangsmyr L, Holmskov U, Leffler H, Nilsson C, Boren T, Wright JR, Stromberg N, Fisher SJ. Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is the lung scavenger receptor cysteine-rich protein gp-340. J Biol Chem. 2000 Dec 22;275(51):39860-6. doi: 10.1074/jbc.M006928200. PMID:11007786 doi:http://dx.doi.org/10.1074/jbc.M006928200
3. ↑ Mollenhauer J, Herbertz S, Helmke B, Kollender G, Krebs I, Madsen J, Holmskov U, Sorger K, Schmitt L, Wiemann S, Otto HF, Grone HJ, Poustka A. Deleted in Malignant Brain Tumors 1 is a versatile mucin-like molecule likely to play a differential role in digestive tract cancer. Cancer Res. 2001 Dec 15;61(24):8880-6. PMID:11751412
4. ↑ Wu Z, Lee S, Abrams W, Weissman D, Malamud D. The N-terminal SRCR-SID domain of gp-340 interacts with HIV type 1 gp120 sequences and inhibits viral infection. AIDS Res Hum Retroviruses. 2006 Jun;22(6):508-15. doi: 10.1089/aid.2006.22.508. PMID:16796526 doi:http://dx.doi.org/10.1089/aid.2006.22.508
5. ↑ Rosenstiel P, Sina C, End C, Renner M, Lyer S, Till A, Hellmig S, Nikolaus S, Folsch UR, Helmke B, Autschbach F, Schirmacher P, Kioschis P, Hafner M, Poustka A, Mollenhauer J, Schreiber S. Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates bacterial recognition and invasion. J Immunol. 2007 Jun 15;178(12):8203-11. doi: 10.4049/jimmunol.178.12.8203. PMID:17548659 doi:http://dx.doi.org/10.4049/jimmunol.178.12.8203
6. ↑ Stoddard E, Cannon G, Ni H, Kariko K, Capodici J, Malamud D, Weissman D. gp340 expressed on human genital epithelia binds HIV-1 envelope protein and facilitates viral transmission. J Immunol. 2007 Sep 1;179(5):3126-32. doi: 10.4049/jimmunol.179.5.3126. PMID:17709527 doi:http://dx.doi.org/10.4049/jimmunol.179.5.3126
7. ↑ End C, Bikker F, Renner M, Bergmann G, Lyer S, Blaich S, Hudler M, Helmke B, Gassler N, Autschbach F, Ligtenberg AJ, Benner A, Holmskov U, Schirmacher P, Nieuw Amerongen AV, Rosenstiel P, Sina C, Franke A, Hafner M, Kioschis P, Schreiber S, Poustka A, Mollenhauer J. DMBT1 functions as pattern-recognition molecule for poly-sulfated and poly-phosphorylated ligands. Eur J Immunol. 2009 Mar;39(3):833-42. doi: 10.1002/eji.200838689. PMID:19189310 doi:http://dx.doi.org/10.1002/eji.200838689
8. ↑ Mollenhauer J, Wiemann S, Scheurlen W, Korn B, Hayashi Y, Wilgenbus KK, von Deimling A, Poustka A. DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours. Nat Genet. 1997 Sep;17(1):32-9. PMID:9288095 doi:http://dx.doi.org/10.1038/ng0997-32