Decoy receptor 3

Decoy receptor 3 (Dcr3), also known as tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), TR6 and M68, is a soluble protein of the tumor necrosis factor receptor superfamily which inhibits Fas ligand-induced apoptosis.^[3][4][5]

TNFRSF6B
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 3K51, 3MHD, 3MI8, 4J6G, 4KGG, 4KGQ, 4MSV
Identifiers
Aliases	TNFRSF6B, DCR3, DJ583P15.1.1, M68, M68E, TR6, tumor necrosis factor receptor superfamily member 6b, TNF receptor superfamily member 6b
External IDs	OMIM: 603361; HomoloGene: 48242; GeneCards: TNFRSF6B; OMA:TNFRSF6B - orthologs
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.33 Start 63,696,652 bp[1] End 63,698,684 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in olfactory zone of nasal mucosa spleen subcutaneous adipose tissue right lung upper lobe of left lung C1 segment right hemisphere of cerebellum appendix anterior pituitary Amygdala n/a More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding tumor necrosis factor-activated receptor activity signaling receptor activity Cellular component extracellular region integral component of plasma membrane extracellular space Biological process multicellular organism development apoptotic signaling pathway response to lipopolysaccharide inflammatory response tumor necrosis factor-mediated signaling pathway negative regulation of apoptotic process regulation of cell population proliferation immune response apoptotic process negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8771 n/a Ensembl ENSG00000243509 n/a UniProt O95407 n/a RefSeq (mRNA) NM_032945 NM_003823 n/a RefSeq (protein) NP_003814 n/a Location (UCSC) Chr 20: 63.7 – 63.7 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

Discovery

Dcr3 was identified in 1998 by the search of genes with homology to the TNFR gene superfamily in expressed sequence tag (EST) database.

Structure

The open reading frame of TNFRSF6B encodes 300 amino acids with a 29-residue signal sequence and four tandem cystein-rich repeats. Two transcript variants encoding the same isoform, but differing in the 5' UTR, have been observed for this gene.^[5] Unlike most of the other members of TNFR superfamily, TNFRSF6 is a soluble protein which contains no transmembrane domain.

Function

This gene belongs to the tumor necrosis factor receptor superfamily. It acts as a decoy receptor that competes with death receptors for ligand binding. The encoded protein is postulated to play a regulatory role in suppressing FasL- and LIGHT-mediated cell death and T cell activation as well as to induce angiogenesis via neutralization of TL1A. Overexpression of this gene has been noted in various tumors e.g. gastrointestinal tract tumors, and it is located in a gene-rich cluster on chromosome 20, with other potentially tumor-related genes.^[5]

Interactions

TNFRSF6B has been shown to interact with:

• TNFSF14^[4][6][7]
• Fas ligand.^[3][4][7]

References

1. GRCh38: Ensembl release 89: ENSG00000243509 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Pitti RM, Marsters SA, Lawrence DA, Roy M, Kischkel FC, Dowd P, Huang A, Donahue CJ, Sherwood SW, Baldwin DT, Godowski PJ, Wood WI, Gurney AL, Hillan KJ, Cohen RL, Goddard AD, Botstein D, Ashkenazi A (Jan 1999). "Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer". Nature. 396 (6712): 699–703. doi:10.1038/25387. PMID 9872321. S2CID 4427455.
4. Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS (Jun 1999). "A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis". J Biol Chem. 274 (20): 13733–6. doi:10.1074/jbc.274.20.13733. PMID 10318773.
5. "Entrez Gene: TNFRSF6B tumor necrosis factor receptor superfamily, member 6b, decoy".
6. Zhang J, Salcedo TW, Wan X, Ullrich S, Hu B, Gregorio T, Feng P, Qi S, Chen H, Cho YH, Li Y, Moore PA, Wu J (June 2001). "Modulation of T-cell responses to alloantigens by TR6/DcR3". J. Clin. Invest. 107 (11): 1459–68. doi:10.1172/JCI12159. PMC 209323. PMID 11390428.
7. Hsu TL, Chang YC, Chen SJ, Liu YJ, Chiu AW, Chio CC, Chen L, Hsieh SL (May 2002). "Modulation of dendritic cell differentiation and maturation by decoy receptor 3". J. Immunol. 168 (10): 4846–53. doi:10.4049/jimmunol.168.10.4846. PMID 11994433.

Further reading

• Kikuno R, Nagase T, Ishikawa K, et al. (1999). "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (3): 197–205. doi:10.1093/dnares/6.3.197. PMID 10470851.
• Bai C, Connolly B, Metzker ML, et al. (2000). "Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster". Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1230–5. Bibcode:2000PNAS...97.1230B. doi:10.1073/pnas.97.3.1230. PMC 15578. PMID 10655513.
• Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. Bibcode:2001Natur.414..865D. doi:10.1038/414865a. PMID 11780052.
• Migone TS, Zhang J, Luo X, et al. (2002). "TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator". Immunity. 16 (3): 479–92. doi:10.1016/S1074-7613(02)00283-2. PMID 11911831.
• Hsu TL, Chang YC, Chen SJ, et al. (2002). "Modulation of dendritic cell differentiation and maturation by decoy receptor 3". J. Immunol. 168 (10): 4846–53. doi:10.4049/jimmunol.168.10.4846. PMID 11994433.
• Mild G, Bachmann F, Boulay JL, et al. (2002). "DCR3 locus is a predictive marker for 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer". Int. J. Cancer. 102 (3): 254–7. doi:10.1002/ijc.10711. PMID 12397645. S2CID 23680078.
• Gill RM; Ni J; Hunt JS (2003). "Differential Expression of LIGHT and Its Receptors in Human Placental Villi and Amniochorion Membranes". Am. J. Pathol. 161 (6): 2011–7. doi:10.1016/S0002-9440(10)64479-3. PMC 1850908. PMID 12466117.
• Wan X, Zhang J, Luo H, et al. (2003). "A TNF family member LIGHT transduces costimulatory signals into human T cells". J. Immunol. 169 (12): 6813–21. doi:10.4049/jimmunol.169.12.6813. PMID 12471113.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Wan X, Shi G, Semenuk M, et al. (2003). "DcR3/TR6 modulates immune cell interactions". J. Cell. Biochem. 89 (3): 603–12. doi:10.1002/jcb.10523. PMID 12761893. S2CID 39322989.
• Tsuji S, Hosotani R, Yonehara S, et al. (2003). "Endogenous decoy receptor 3 blocks the growth inhibition signals mediated by Fas ligand in human pancreatic adenocarcinoma" (PDF). Int. J. Cancer. 106 (1): 17–25. doi:10.1002/ijc.11170. hdl:2433/148465. PMID 12794752. S2CID 34900944.
• Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Shi G; Wu Y; Zhang J; Wu J (2004). "Death decoy receptor TR6/DcR3 inhibits T cell chemotaxis in vitro and in vivo". J. Immunol. 171 (7): 3407–14. doi:10.4049/jimmunol.171.7.3407. PMID 14500635.
• Wu SF, Liu TM, Lin YC, et al. (2004). "Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in nonobese diabetic mice: from regulatory mechanism to clinical implication". J. Leukoc. Biol. 75 (2): 293–306. doi:10.1189/jlb.0303119. PMID 14634066. S2CID 14226200.
• Chang YC, Hsu TL, Lin HH, et al. (2004). "Modulation of macrophage differentiation and activation by decoy receptor 3". J. Leukoc. Biol. 75 (3): 486–94. doi:10.1189/jlb.0903448. PMID 14657214. S2CID 31939119.
• Kim S, McAuliffe WJ, Zaritskaya LS, et al. (2004). "Selective Induction of Tumor Necrosis Receptor Factor 6/Decoy Receptor 3 Release by Bacterial Antigens in Human Monocytes and Myeloid Dendritic Cells". Infect. Immun. 72 (1): 89–93. doi:10.1128/IAI.72.1.89-93.2004. PMC 343977. PMID 14688085.
• Hsu MJ, Lin WW, Tsao WC, et al. (2004). "Enhanced adhesion of monocytes via reverse signaling triggered by decoy receptor 3". Exp. Cell Res. 292 (2): 241–51. doi:10.1016/j.yexcr.2003.09.019. PMID 14697332.
• Gill RM; Hunt JS (2004). "Soluble Receptor (DcR3) and Cellular Inhibitor of Apoptosis-2 (cIAP-2) Protect Human Cytotrophoblast Cells Against LIGHT-Mediated Apoptosis". Am. J. Pathol. 165 (1): 309–17. doi:10.1016/S0002-9440(10)63298-1. PMC 1618528. PMID 15215185.

External links

• GeneReviews/NCBI/NIH/UW entry on Autoimmune Lymphoproliferative Syndrome

This article incorporates text from the United States National Library of Medicine, which is in the public domain.