DMBT1

Last updated
DMBT1
Identifiers
Aliases DMBT1 , GP340, muclin, SAG, deleted in malignant brain tumors 1, SALSA
External IDs OMIM: 601969 MGI: 106210 HomoloGene: 68990 GeneCards: DMBT1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004406
NM_007329
NM_017579
NM_001320644
NM_001377530

Contents

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 Mb Chr 7: 130.63 – 130.72 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Related Research Articles

Collectins (collagen-containing C-type lectins) are a part of the innate immune system. They form a family of collagenous Ca2+-dependent defense lectins, which are found in animals. Collectins are soluble pattern recognition receptors (PRRs). Their function is to bind to oligosaccharide structure or lipids that are on the surface of microorganisms. Like other PRRs they bind pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) of oligosaccharide origin. Binding of collectins to microorganisms may trigger elimination of microorganisms by aggregation, complement activation, opsonization, activation of phagocytosis, or inhibition of microbial growth. Other functions of collectins are modulation of inflammatory, allergic responses, adaptive immune system and clearance of apoptotic cells.

<span class="mw-page-title-main">CD68</span> Mammalian protein found in Homo sapiens

CD68 is a protein highly expressed by cells in the monocyte lineage, by circulating macrophages, and by tissue macrophages.

<span class="mw-page-title-main">Surfactant protein D</span> Protein-coding gene in the species Homo sapiens

Surfactant protein D, also known as SP-D, is a lung surfactant protein part of the collagenous family of proteins called collectin. In humans, SP-D is encoded by the SFTPD gene and is part of the innate immune system. Each SP-D subunit is composed of an N-terminal domain, a collagenous region, a nucleating neck region, and a C-terminal lectin domain. Three of these subunits assemble to form a homotrimer, which further assemble into a tetrameric complex.

<span class="mw-page-title-main">Heparin-binding EGF-like growth factor</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Integrin alpha 2b</span> Mammalian protein found in Homo sapiens

Integrin alpha-IIb is a protein that in humans is encoded by the ITGA2B gene. ITGA2B, also known as CD41, encodes integrin alpha chain 2b. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. Alpha chain 2b undergoes post-translational cleavage to yield disulfide-linked light and heavy chains that join with beta 3 to form a fibrinogen receptor expressed in platelets that plays a crucial role in coagulation. Mutations that interfere with this role result in thrombasthenia. At least 38 disease-causing mutations in this gene have been discovered. In addition to adhesion, integrins are known to participate in cell-surface mediated signalling.

<span class="mw-page-title-main">AKT2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Mucin 4</span> Protein-coding gene in the species Homo sapiens

Mucin-4 (MUC-4) is a mucin protein that in humans is encoded by the MUC4 gene. Like other mucins, MUC-4 is a high-molecular weight glycoprotein.

<span class="mw-page-title-main">Surfactant protein A1</span> Protein-coding gene in the species Homo sapiens

Surfactant protein A1(SP-A1), also known as Pulmonary surfactant-associated protein A1(PSP-A) is a protein that in humans is encoded by the SFTPA1 gene.

<span class="mw-page-title-main">CEACAM1</span> Mammalian protein found in Homo sapiens

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) also known as CD66a, is a human glycoprotein, and a member of the carcinoembryonic antigen (CEA) gene family.

<span class="mw-page-title-main">Laminin subunit gamma-2</span> Protein-coding gene in the species Homo sapiens

Laminin subunit gamma-2 is a protein that in humans is encoded by the LAMC2 gene.

<span class="mw-page-title-main">Signal-regulatory protein alpha</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">GP1BB</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">LGALS3BP</span> Protein-coding gene in the species Homo sapiens

Galectin-3-binding protein is a protein that in humans is encoded by the LGALS3BP gene.

<span class="mw-page-title-main">Pregnancy-specific beta-1-glycoprotein 1</span> Mammalian protein found in Homo sapiens

Pregnancy-specific beta-1-glycoprotein 1 (PSBG-1) also known as CD66f, is a protein that in humans is encoded by the PSG1 gene and is a member of the carcinoembryonic antigen (CEA) gene family. Pregnancy-specific glycoproteins (PSGs) are a complex consisting of carbohydrate and protein, which is present in the mammalian body specifically during pregnancy. This glycoprotein is the most abundant protein found in the maternal bloodstream during the later stages of pregnancy and it is of vital importance in fetal development. The PSG functions primarily as an immunomodulator to protect the growing fetus.

<span class="mw-page-title-main">ALCAM</span> Protein-coding gene in the species Homo sapiens

CD166 antigen is a 100-105 kD typeI transmembrane glycoprotein that is a member of the immunoglobulin superfamily of proteins. In humans it is encoded by the ALCAM gene. It is also called CD166, MEMD, SC-1/DM-GRASP/BEN in the chicken, and KG-CAM in the rat.

<span class="mw-page-title-main">MARCKSL1</span> Protein-coding gene in the species Homo sapiens

MARCKS-related protein is a protein that in humans is encoded by the MARCKSL1 gene.

<span class="mw-page-title-main">Prolactin-induced protein</span> Mammalian protein found in Homo sapiens

Prolactin-inducible protein also known as gross cystic disease fluid protein 15 (GCDFP-15), extra-parotid glycoprotein (EP-GP), gp17seminal actin-binding protein (SABP) or BRST2 is a protein that in humans is encoded by the PIP gene. It is upregulated by prolactin and androgens and downregulated by estrogen.

<span class="mw-page-title-main">Laminin subunit gamma-3</span> Protein-coding gene in the species Homo sapiens

Laminin subunit gamma-3 also known as LAMC3 is a protein that in humans is encoded by the LAMC3 gene.

Epithelial-myoepithelial carcinoma of the lung is a very rare histologic form of malignant epithelial neoplasm ("carcinoma") arising from lung tissue.

<span class="mw-page-title-main">Fibrinogen c domain containing 1</span> Protein-coding gene in the species Homo sapiens

Fibrinogen C domain containing 1(FIBCD1) is a protein that in humans is encoded by the FIBCD1 gene localized on chromosome 9q34.1 in close proximity to the genes encoding L- and M-ficolin. FIBCD1 is thought to have a role in both host defence and gut homeostasis.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000187908 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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