Lymphotoxin beta receptor

LTBR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1RF3, 4MXW
Identifiers
Aliases	LTBR, CD18, D12S370, LT-BETA-R, TNF-R-III, TNFCR, TNFR-RP, TNFR2-RP, TNFR3, TNFRSF3, lymphotoxin beta receptor
External IDs	OMIM: 600979; MGI: 104875; HomoloGene: 1753; GeneCards: LTBR; OMA:LTBR - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12p13.31 Start 6,375,045 bp[1] End 6,391,571 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 F3|6 59.32 cM Start 125,283,534 bp[2] End 125,290,848 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of thyroid gland left lobe of thyroid gland minor salivary glands body of pancreas body of stomach upper lobe of left lung muscle layer of sigmoid colon right lobe of liver left uterine tube skin of abdomen Top expressed in granulocyte duodenum gastric mucosa epithelium of stomach yolk sac mucous cell of stomach right kidney saccule membranous bone left lobe of liver More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding tumor necrosis factor-activated receptor activity identical protein binding ubiquitin protein ligase binding Cellular component integral component of membrane membrane plasma membrane integral component of plasma membrane Golgi apparatus Biological process myeloid dendritic cell differentiation tumor necrosis factor-mediated signaling pathway positive regulation of JNK cascade multicellular organism development cellular response to mechanical stimulus response to lipopolysaccharide regulation of cell population proliferation positive regulation of extrinsic apoptotic signaling pathway inflammatory response viral process signal transduction apoptotic process immune response positive regulation of I-kappaB kinase/NF-kappaB signaling hematopoietic or lymphoid organ development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4055 17000 Ensembl ENSG00000111321 ENSMUSG00000030339 UniProt P36941 P50284 RefSeq (mRNA) NM_001270987 NM_002342 NM_010736 RefSeq (protein) NP_001257916 NP_002333 NP_034866 Location (UCSC) Chr 12: 6.38 – 6.39 Mb Chr 6: 125.28 – 125.29 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[5][6][7] 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 lymphotoxin-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.^[5]

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.^[8]

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.^[9]

Interactions

Lymphotoxin beta receptor has been shown to interact with Diablo homolog^[10] and TRAF3.^[11][12][13]

References

1. GRCh38: Ensembl release 89: ENSG00000111321 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030339 – 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. "Entrez Gene: LTBR lymphotoxin beta receptor (TNFR superfamily, member 3)".
6. 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.
7. 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. Bibcode:1994Sci...264..707C. doi:10.1126/science.8171323. PMID 8171323.
8. 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.
9. "MolProbity Ramachandran analysis" (PDF). Archived from the original (PDF) on 2012-10-12.
10. 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. 278 (16). United States: 14363–9. doi:10.1074/jbc.M208672200. ISSN 0021-9258. PMID 12571250.
11. 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. 94 (6). UNITED STATES: 2460–5. Bibcode:1997PNAS...94.2460V. doi:10.1073/pnas.94.6.2460. ISSN 0027-8424. PMC 20110. PMID 9122217.
12. 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. 274 (17). UNITED STATES: 11868–73. doi:10.1074/jbc.274.17.11868. ISSN 0021-9258. PMID 10207006.
13. 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. 272 (22). UNITED STATES: 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. S2CID 28961163.
• Crowe PD, VanArsdale TL, Walter BN, et al. (1994). "A lymphotoxin-beta-specific receptor". Science. 264 (5159): 707–10. Bibcode:1994Sci...264..707C. 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. doi:10.1128/JVI.71.2.1301-1309.1997. 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. Bibcode:1997PNAS...94.2460V. 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. doi:10.1128/JVI.71.12.9417-9426.1997. 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. S2CID 54700.
• 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 U.S. National Library of Medicine Medical Subject Headings (MeSH)