DMBT1

DMBT1
Identifiers
AliasesDMBT1, GP340, muclin, SAG, deleted in malignant brain tumors 1, SALSA
External IDsOMIM: 601969; MGI: 106210; HomoloGene: 68990; GeneCards: DMBT1; OMA:DMBT1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1755

12945

Ensembl

ENSG00000187908

ENSMUSG00000047517

UniProt

Q9UGM3

Q60997

RefSeq (mRNA)

NM_004406
NM_007329
NM_017579
NM_001320644
NM_001377530

NM_007769
NM_001347632

RefSeq (protein)

NP_001307573
NP_004397
NP_015568
NP_060049

NP_001334561
NP_031795

Location (UCSC)Chr 10: 122.56 – 122.64 MbChr 7: 130.63 – 130.72 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Deleted in malignant brain tumors 1 protein is a protein that in humans is encoded by the DMBT1 gene.[5][6]

Function

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.[7]

Pattern recognition and potential use of DMBT1 in nanomedicine

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. The protein DMBT1, showed pattern recognition activity for poly-sulfated and poly-phosphorylated ligands, including nucleic acids, and the ability to aggregate ligands. This raises the interesting question in how far these properties can be utilized to assemble nucleic acidpeptide nano-complexes and whether this can be exploited to modulate the pharmacological properties of nucleic acids and/or for nucleic acid delivery to target cells [8] Recently, DMBT1-derived peptides have been successfully harnessed for siRNA intracellular delivery.[9]

Interactions

DMBT1 has been shown to interact with Surfactant protein D.[10][11] DMBT1-derived peptides also interacts with nucleic acids.[9]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000187908 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000047517 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Mollenhauer J, Wiemann S, Scheurlen W, Korn B, Hayashi Y, Wilgenbus KK, von Deimling A, Poustka A (Oct 1997). "DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours". Nat. Genet. 17 (1): 32–9. doi:10.1038/ng0997-32. PMID 9288095. S2CID 5274568.
  6. ^ Rosenstiel P, Sina C, End C, Renner M, Lyer S, Till A, Hellmig S, Nikolaus S, Fölsch UR, Helmke B, Autschbach F, Schirmacher P, Kioschis P, Hafner M, Poustka A, Mollenhauer J, Schreiber S (Jun 2007). "Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates bacterial recognition and invasion". J. Immunol. 178 (12): 8203–11. doi:10.4049/jimmunol.178.12.8203. PMID 17548659.
  7. ^ "Entrez Gene: DMBT1 deleted in malignant brain tumors 1".
  8. ^ Casella C, Tuttolomondo M, Høilund-Carlsen PF, Mollenhauer J (2014-01-01). "Natural pattern recognition mechanisms at epithelial barriers and potential use in nanomedicine". European Journal of Nanomedicine. 6 (3). doi:10.1515/ejnm-2014-0020. ISSN 1662-596X. S2CID 84103470.
  9. ^ a b Tuttolomondo M, Casella C, Hansen PL, Polo E, Herda LM, Dawson KA, Ditzel HJ, Mollenhauer J (2017). "Human DMBT1-Derived Cell-Penetrating Peptides for Intracellular siRNA Delivery". Molecular Therapy: Nucleic Acids. 8: 264–276. doi:10.1016/j.omtn.2017.06.020. ISSN 2162-2531. PMC 5514624. PMID 28918028.
  10. ^ Tino MJ, Wright JR (1999). "Glycoprotein-340 binds surfactant protein-A (SP-A) and stimulates alveolar macrophage migration in an SP-A-independent manner". Am. J. Respir. Cell Mol. Biol. 20 (4): 759–68. doi:10.1165/ajrcmb.20.4.3439. PMID 10101009.
  11. ^ Holmskov U, Lawson P, Teisner B, Tornoe I, Willis AC, Morgan C, Koch C, Reid KB (1997). "Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule". J. Biol. Chem. 272 (21): 13743–9. doi:10.1074/jbc.272.21.13743. PMID 9153228.

Further reading


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