Lymphotoxin beta receptor

Lymphotoxin beta receptor (TNFR superfamily, member 3)
Crystallographic structure of a 24-residue peptide from the lymphotoxin-B receptor bound to TRAF3.[1]
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1RF3​, 4MXW​
Identifiers
Symbols	LTBR ; CD18; D12S370; LT-BETA-R; TNF-R-III; TNFCR; TNFR-RP; TNFR2-RP; TNFR3; TNFRSF3
External IDs	OMIM: 600979 MGI: 104875 HomoloGene: 1753 ChEMBL: 1250360 GeneCards: LTBR Gene
Gene ontology Molecular function • protein binding • ubiquitin protein ligase binding • identical protein binding Cellular component • integral component of membrane Biological process • apoptotic process • signal transduction • viral process • myeloid dendritic cell differentiation • positive regulation of I-kappaB kinase/NF-kappaB signaling • positive regulation of JNK cascade • cellular response to mechanical stimulus • positive regulation of extrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4055	17000
Ensembl	ENSG00000111321	ENSMUSG00000030339
UniProt	P36941	P50284
RefSeq (mRNA)	NM_001270987	NM_010736
RefSeq (protein)	NP_001257916	NP_034866
Location (UCSC)	Chr 12: 6.38 – 6.39 Mb	Chr 6: 125.31 – 125.31 Mb
PubMed search

Lymphotoxin beta receptor (LTBR), also known as tumor necrosis factor receptor superfamily member 3 (TNFRSF3), is a cell surface receptor for lymphotoxin involved in apoptosis and cytokine release.^[2][3][4] It is a member of the tumor necrosis factor receptor superfamily.

Function

The protein encoded by this gene is a member of the tumor necrosis factor (TNF) family of receptors. It is expressed on the surface of most cell types, including cells of epithelial and myeloid lineages, but not on T and B lymphocytes. The protein specifically binds the lymphotoxin membrane form (a complex of lymphotoxin-alpha and lymphtoxin-beta). The encoded protein and its ligand play a role in the development and organization of lymphoid tissue and transformed cells. Activation of the encoded protein can trigger apoptosis.^[2]

Not only does the LTBR help trigger apoptosis, it can lead to the release of the cytokine interleukin 8. Overexpression of LTBR in HEK293 cells increases IL-8 promoter activity and leads to IL-8 release. LTBR is also essential for development and organization of the secondary lymphoid organs and chemokine release.^[5]

Structure

The Ramachandran plots show that 64.6% of all residues were in a favored region. This structure was found using X-ray diffraction. The resolution is 3.50 angstroms. The alpha and beta angles are 90 degrees while the gamma angle is 120 degrees.^[6]

Interactions

Lymphotoxin beta receptor has been shown to interact with Diablo homolog^[7] and TRAF3.^[8][9][10]

References

1. ’PDB: 1RF3​; Li C, Norris PS, Ni CZ, Havert ML, Chiong EM, Tran BR, Cabezas E, Reed JC, Satterthwait AC, Ware CF, Ely KR (December 2003). "Structurally distinct recognition motifs in lymphotoxin-beta receptor and CD40 for tumor necrosis factor receptor-associated factor (TRAF)-mediated signaling". J. Biol. Chem. 278 (50): 50523–9. doi:10.1074/jbc.M309381200. PMID 14517219.
2. "Entrez Gene: LTBR lymphotoxin beta receptor (TNFR superfamily, member 3)".
3. Baens M, Chaffanet M, Cassiman JJ, van den Berghe H, Marynen P (April 1993). "Construction and evaluation of a hncDNA library of human 12p transcribed sequences derived from a somatic cell hybrid". Genomics 16 (1): 214–8. doi:10.1006/geno.1993.1161. PMID 8486360.
4. Crowe PD, VanArsdale TL, Walter BN, Ware CF, Hession C, Ehrenfels B, Browning JL, Din WS, Goodwin RG, Smith CA (April 1994). "A lymphotoxin-beta-specific receptor". Science 264 (5159): 707–10. doi:10.1126/science.8171323. PMID 8171323.
5. Chang YH, Hsieh SL, Chen MC, Lin WW (August 2002). "Lymphotoxin beta receptor induces interleukin 8 gene expression via NF-kappaB and AP-1 activation". Exp. Cell Res. 278 (2): 166–74. doi:10.1006/excr.2002.5573. PMID 12169272.
6. "MolProbity Ramachandran analysis" (PDF).
7. Kuai, Jun; Nickbarg Elliott; Wooters Joe; Qiu Yongchang; Wang Jack; Lin Lih-Ling (Apr 2003). "Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis". J. Biol. Chem. (United States) 278 (16): 14363–9. doi:10.1074/jbc.M208672200. ISSN 0021-9258. PMID 12571250.
8. VanArsdale, T L; VanArsdale S L; Force W R; Walter B N; Mosialos G; Kieff E; Reed J C; Ware C F (Mar 1997). "Lymphotoxin-beta receptor signaling complex: role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor kappaB". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 94 (6): 2460–5. doi:10.1073/pnas.94.6.2460. ISSN 0027-8424. PMC 20110. PMID 9122217.
9. Wu, M Y; Wang P Y; Han S H; Hsieh S L (Apr 1999). "The cytoplasmic domain of the lymphotoxin-beta receptor mediates cell death in HeLa cells". J. Biol. Chem. (UNITED STATES) 274 (17): 11868–73. doi:10.1074/jbc.274.17.11868. ISSN 0021-9258. PMID 10207006.
10. Marsters, S A; Ayres T M; Skubatch M; Gray C L; Rothe M; Ashkenazi A (May 1997). "Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1". J. Biol. Chem. (UNITED STATES) 272 (22): 14029–32. doi:10.1074/jbc.272.22.14029. ISSN 0021-9258. PMID 9162022.

Further reading

• Elewaut D, Ware CF (2007). "The unconventional role of LT alpha beta in T cell differentiation.". Trends Immunol. 28 (4): 169–75. doi:10.1016/j.it.2007.02.005. PMID 17336158.
• Browning JL, Ngam-ek A, Lawton P, et al. (1993). "Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface.". Cell 72 (6): 847–56. doi:10.1016/0092-8674(93)90574-A. PMID 7916655.
• Crowe PD, VanArsdale TL, Walter BN, et al. (1994). "A lymphotoxin-beta-specific receptor.". Science 264 (5159): 707–10. doi:10.1126/science.8171323. PMID 8171323.
• Baens M, Chaffanet M, Cassiman JJ, et al. (1993). "Construction and evaluation of a hncDNA library of human 12p transcribed sequences derived from a somatic cell hybrid.". Genomics 16 (1): 214–8. doi:10.1006/geno.1993.1161. PMID 8486360.
• Baens M, Aerssens J, van Zand K, et al. (1996). "Isolation and regional assignment of human chromosome 12p cDNAs.". Genomics 29 (1): 44–52. doi:10.1006/geno.1995.1213. PMID 8530100.
• Wang X, Bornslaeger EA, Haub O, et al. (1996). "A candidate gene for the amnionless gastrulation stage mouse mutation encodes a TRAF-related protein.". Dev. Biol. 177 (1): 274–90. doi:10.1006/dbio.1996.0162. PMID 8660894.
• Nakano H, Oshima H, Chung W, et al. (1996). "TRAF5, an activator of NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor.". J. Biol. Chem. 271 (25): 14661–4. doi:10.1074/jbc.271.25.14661. PMID 8663299.
• Matsumoto M, Hsieh TY, Zhu N, et al. (1997). "Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor.". J. Virol. 71 (2): 1301–9. PMC 191185. PMID 8995654.
• VanArsdale TL, VanArsdale SL, Force WR, et al. (1997). "Lymphotoxin-beta receptor signaling complex: role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor kappaB.". Proc. Natl. Acad. Sci. U.S.A. 94 (6): 2460–5. doi:10.1073/pnas.94.6.2460. PMC 20110. PMID 9122217.
• Wu MY, Hsu TL, Lin WW, et al. (1997). "Serine/threonine kinase activity associated with the cytoplasmic domain of the lymphotoxin-beta receptor in HepG2 cells.". J. Biol. Chem. 272 (27): 17154–9. doi:10.1074/jbc.272.27.17154. PMID 9202035.
• Chen CM, You LR, Hwang LH, Lee YH (1997). "Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor modulates the signal pathway of the lymphotoxin-beta receptor.". J. Virol. 71 (12): 9417–26. PMC 230246. PMID 9371602.
• Mizushima S, Fujita M, Ishida T, et al. (1998). "Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5).". Gene 207 (2): 135–40. doi:10.1016/S0378-1119(97)00616-1. PMID 9511754.
• Krajewska M, Krajewski S, Zapata JM, et al. (1998). "TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues.". Am. J. Pathol. 152 (6): 1549–61. PMC 1858434. PMID 9626059.
• Boussaud V, Soler P, Moreau J, et al. (1999). "Expression of three members of the TNF-R family of receptors (4-1BB, lymphotoxin-beta receptor, and Fas) in human lung.". Eur. Respir. J. 12 (4): 926–31. doi:10.1183/09031936.98.12040926. PMID 9817170.
• Murphy M, Walter BN, Pike-Nobile L, et al. (1999). "Expression of the lymphotoxin beta receptor on follicular stromal cells in human lymphoid tissues.". Cell Death Differ. 5 (6): 497–505. doi:10.1038/sj.cdd.4400374. PMID 10200501.
• Wu MY, Wang PY, Han SH, Hsieh SL (1999). "The cytoplasmic domain of the lymphotoxin-beta receptor mediates cell death in HeLa cells.". J. Biol. Chem. 274 (17): 11868–73. doi:10.1074/jbc.274.17.11868. PMID 10207006.
• Yu KY, Kwon B, Ni J, et al. (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.
• Rooney IA, Butrovich KD, Glass AA, et al. (2000). "The lymphotoxin-beta receptor is necessary and sufficient for LIGHT-mediated apoptosis of tumor cells.". J. Biol. Chem. 275 (19): 14307–15. doi:10.1074/jbc.275.19.14307. PMID 10799510.
• Langeggen H, Berge KE, Johnson E, Hetland G (2003). "Human umbilical vein endothelial cells express complement receptor 1 (CD35) and complement receptor 4 (CD11c/CD18) in vitro.". Inflammation 26 (3): 103–10. doi:10.1023/A:1015585530204. PMID 12083416.
• Chang YH, Hsieh SL, Chen MC, Lin WW (2002). "Lymphotoxin beta receptor induces interleukin 8 gene expression via NF-kappaB and AP-1 activation.". Exp. Cell Res. 278 (2): 166–74. doi:10.1006/excr.2002.5573. PMID 12169272.

External links

• Lymphotoxin beta Receptor at the US National Library of Medicine Medical Subject Headings (MeSH)