to remain unmolested, undisturbed, or uninterrupted -- used only in infinitive form; "let her be"
work in a specific place, with a specific subject, or in a specific function; "He is a herpetologist"; "She is our resident philosopher" (同)follow
have life, be alive; "Our great leader is no more"; "My grandfather lived until the end of war" (同)live
be identical to; be someone or something; "The president of the company is John Smith"; "This is my house"
happen, occur, take place; "I lost my wallet; this was during the visit to my parents house"; "There were two hundred people at his funeral"; "There was a lot of noise in the kitchen"
have the quality of being; (copula, used with an adjective or a predicate noun); "John is rich"; "This is not a good answer"
occupy a certain position or area; be somewhere; "Where is my umbrella?" "The toolshed is in the back"; "What is behind this behavior?"
spend or use time; "I may be an hour"
stake on the outcome of an issue; "I bet $100 on that new horse"; "She played all her money on the dark horse" (同)wager, play
the act of gambling; "he did it on a bet" (同)wager
maintain with or as if with a bet; "I bet she will be there!" (同)wager
second in order of importance; "the candidate, considered a beta male, was perceived to be unable to lead his party to victory"
the 2nd letter of the Greek alphabet
preliminary or testing stage of a software or hardware product; "a beta version"; "beta software"
receptors postulated to exist on nerve cell membranes of the sympathetic nervous system in order to explain the specificity of certain agents that affect only some sympathetic activities (such as vasodilation and increased heart beat) (同)beta-adrenergic_receptor, beta-adrenoceptor
a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
• 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 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: 125.31 – 125.31 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.
Contents
1Function
2Structure
3Interactions
4References
5Further reading
6External links
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.[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
^ abcGRCh38: Ensembl release 89: ENSG00000111321 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000030339 - Ensembl, May 2017
^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.
^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.
^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.
^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. Bibcode:1997PNAS...94.2460V. doi:10.1073/pnas.94.6.2460. ISSN 0027-8424. PMC 20110. PMID 9122217.
^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.
^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. 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. 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. 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.
…BPH with any of 17 single-nucleotide polymorphisms in genes involved in obesity . The lymphotoxin-beta-receptor (LT-beta-R) gene has been reported to be involved in autoimmune disease and inflammatory disorders …
…Tumor necrosis factor receptor gene family – The presence of an additional group of genes, including those for the lymphotoxin beta receptor (LTBR) and tumor necrosis factor receptor 1 (TNFRSF1A), provides …
…changes on chromosomes 3p, 9p, 11q, 12p, and 14q), gene alterations (eg, p16 deletion and lymphotoxin-beta receptor [LTBR] amplification), and epigenetic changes (eg, RASSF1A and TSLC1 methylation) have been…
… The development of these ectopic lymphoid structures is dependent on the expression of lymphotoxin-beta and lymphoid chemokines (eg,… including antibodies to the muscarinic receptor that may impair neural innervation of the gland and…
… presence of ligand-receptor pairs on the surface of each cell type. Lining macrophage-like cells express CD97, a member of the secretin superfamily of transmembrane receptors; and lining fibroblast-like… IL-1-beta, IL-6, GM-CSF, and transforming growth factor (TGF)-beta 1 have been identified by immunohistochemistry…
English Journal
Cerebrospinal fluid-targeted delivery of neutralizing anti-IFNγ antibody delays motor decline in an ALS mouse model.
Otsmane B, Aebischer J, Moumen A, Raoul C.SourceaMediterranean Institute of Neurobiology, INMED, INSERM U901, Marseille bNeuroscience Institute Montpellier (INM), INSERM UMR1051, Saint Eloi Hospital, Montpellier, France cNeurodegenerative Studies Laboratory, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Neuroreport.Neuroreport.2014 Jan 8;25(1):49-54. doi: 10.1097/WNR.0000000000000043.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the selective and gradual loss of motoneurons in the brain and spinal cord. A persistent inflammation, typified by the activation of astrocytes and microglia, accompanies the progressive degeneration of
Evidence that TNF-beta (Lymphotoxin alpha) can activate the inflammatory environment in human chondrocytes.
Buhrmann C, Shayan P, Aggarwal BB, Shakibaei M.AbstractINTRODUCTION: Inflammatory cytokines play a key role in the pathogenesis of joint diseases such as rheumatoid arthritis (RA). Current therapies target mainly tumor necrosis factor alpha (TNF-alpha) as this has proven benefits. However, a large number of patients do not respond to or become resistant to anti-TNF-alpha therapy. While the role of TNF-alpha in RA is quite evident, the role of TNF-beta, also called Lymphotoxin-alpha (LT-alpha), is unclear. In this study we investigated whether TNF-beta and its receptor play a role in chondrocytes in the inflammatory environment.
Arthritis research & therapy.Arthritis Res Ther.2013 Nov 28;15(6):R202. [Epub ahead of print]
INTRODUCTION: Inflammatory cytokines play a key role in the pathogenesis of joint diseases such as rheumatoid arthritis (RA). Current therapies target mainly tumor necrosis factor alpha (TNF-alpha) as this has proven benefits. However, a large number of patients do not respond to or become resistant
Genetic variation in the lymphotoxin-α (LTA)/tumour necrosis factor-α (TNFα) locus as a risk factor for idiopathic achalasia.
Wouters MM, Lambrechts D, Becker J, Cleynen I, Tack J, Vigo AG, Ruiz de León A, Urcelay E, Pérez de la Serna J, Rohof W, Annese V, Latiano A, Palmieri O, Mattheisen M, Mueller M, Lang H, Fumagalli U, Laghi L, Zaninotto G, Cuomo R, Sarnelli G, Nöthen MM, Vermeire S, Knapp M, Gockel I, Schumacher J, Boeckxstaens GE.SourceTranslational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, , Leuven, Belgium.
Gut.Gut.2013 Nov 20. doi: 10.1136/gutjnl-2013-304848. [Epub ahead of print]
BACKGROUND: Idiopathic achalasia is a rare motor disorder of the oesophagus characterised by neuronal loss at the lower oesophageal sphincter. Achalasia is generally accepted as a multifactorial disorder with various genetic and environmental factors being risk-associated. Since genetic factors pred
Treg engage lymphotoxinbetareceptor for afferent lymphatic transendothelial migration
Brinkman C. Colin,Iwami Daiki,Hritzo Molly K.,Xiong Yanbao,Ahmad Sarwat,Simon Thomas,Hippen Keli L.,Blazar Bruce R.,Bromberg Jonathan S.
Nature communications (7), 12021, 2016-06-21
… Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. …
CXCL13 production by an established lymph node stromal cell line via lymphotoxin-betareceptor engagement involves the cooperation of multiple signaling pathways
This gene encodes a member of the tumor necrosis factor receptor superfamily. The major ligands of this receptor include lymphotoxin alpha/beta and tumor necrosis factor ligand superfamily member 14. The encoded ...
LTBR A gene on chromosome 12p13 that encodes lymphotoxin beta receptor, which belongs to the tumour-necrosis-factor-receptor superfamily and is expressed on the surface of most cell types (e.g., epithelial and myeloid ...