Lymphotoxin-alpha

Details

Name
Lymphotoxin-alpha
Kind
protein
Synonyms
  • LT-alpha
  • TNF-beta
  • TNFB
  • TNFSF1
  • Tumor necrosis factor ligand superfamily member 1
Gene Name
LTA
UniProtKB Entry
P01374Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0010761|Lymphotoxin-alpha
MTPPERLFLPRVCGTTLHLLLLGLLLVLLPGAQGLPGVGLTPSAAQTARQHPKMHLAHST
LKPAAHLIGDPSKQNSLLWRANTDRAFLQDGFSLSNNSLLVPTSGIYFVYSQVVFSGKAY
SPKATSSPLYLAHEVQLFSSQYPFHVPLLSSQKMVYPGLQEPWLHSMYHGAAFQLTQGDQ
LSTHTDGIPHLVLSPSTVFFGAFAL
Number of residues
205
Molecular Weight
22296.57
Theoretical pI
9.36
GO Classification
Functions
cytokine activity / signaling receptor binding / tumor necrosis factor receptor binding
Processes
positive regulation of type II interferon production / response to xenobiotic stimulus
General Function
Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM (PubMed:9462508). In its heterotrimeric form with LTB binds to TNFRSF3/LTBR (PubMed:24248355). Lymphotoxin is produced by lymphocytes and is cytotoxic for a wide range of tumor cells in vitro and in vivo
Specific Function
cytokine activity
Pfam Domain Function
Signal Regions
1-34
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0010762|Lymphotoxin-alpha (LTA)
ATGACACCACCTGAACGTCTCTTCCTCCCAAGGGTGTGTGGCACCACCCTACACCTCCTC
CTTCTGGGGCTGCTGCTGGTTCTGCTGCCTGGGGCCCAGGGGCTCCCTGGTGTTGGCCTC
ACACCTTCAGCTGCCCAGACTGCCCGTCAGCACCCCAAGATGCATCTTGCCCACAGCACC
CTCAAACCTGCTGCTCACCTCATTGGAGACCCCAGCAAGCAGAACTCACTGCTCTGGAGA
GCAAACACGGACCGTGCCTTCCTCCAGGATGGTTTCTCCTTGAGCAACAATTCTCTCCTG
GTCCCCACCAGTGGCATCTACTTCGTCTACTCCCAGGTGGTCTTCTCTGGGAAAGCCTAC
TCTCCCAAGGCCACCTCCTCCCCACTCTACCTGGCCCATGAGGTCCAGCTCTTCTCCTCC
CAGTACCCCTTCCATGTGCCTCTCCTCAGCTCCCAGAAGATGGTGTATCCAGGGCTGCAG
GAACCCTGGCTGCACTCGATGTACCACGGGGCTGCGTTCCAGCTCACCCAGGGAGACCAG
CTATCCACCCACACAGATGGCATCCCCCACCTAGTCCTCAGCCCTAGTACTGTCTTCTTT
GGAGCCTTCGCTCTGTAG
Chromosome Location
6
Locus
6p21.33
External Identifiers
ResourceLink
UniProtKB IDP01374
UniProtKB Entry NameTNFB_HUMAN
GenBank Protein ID34445
GenBank Gene IDX01393
GeneCard IDLTA
GenAtlas IDLTA
HGNC IDHGNC:6709
PDB ID(s)1TNR, 4MXV, 4MXW
KEGG IDhsa:4049
NCBI Gene ID4049
General References
  1. Nedospasov SA, Shakhov AN, Turetskaya RL, Mett VA, Azizov MM, Georgiev GP, Korobko VG, Dobrynin VN, Filippov SA, Bystrov NS, et al.: Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:611-24. [Article]
  2. Nedwin GE, Jarrett-Nedwin J, Smith DH, Naylor SL, Sakaguchi AY, Goeddel DV, Gray PW: Structure and chromosomal localization of the human lymphotoxin gene. J Cell Biochem. 1985;29(3):171-81. [Article]
  3. Kobayashi Y, Miyamoto D, Asada M, Obinata M, Osawa T: Cloning and expression of human lymphotoxin mRNA derived from a human T cell hybridoma. J Biochem. 1986 Sep;100(3):727-33. [Article]
  4. Gray PW, Aggarwal BB, Benton CV, Bringman TS, Henzel WJ, Jarrett JA, Leung DW, Moffat B, Ng P, Svedersky LP, et al.: Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature. 1984 Dec 20-1985 Jan 2;312(5996):721-4. [Article]
  5. Matsuyama N, Okawa N, Tsukii Y, Endo T, Kaji A: Nucleotide sequence of a cDNA encoding human tumor necrosis factor beta from B lymphoblastoid cell RPMI 1788. FEBS Lett. 1992 May 11;302(2):141-4. [Article]
  6. Iris FJ, Bougueleret L, Prieur S, Caterina D, Primas G, Perrot V, Jurka J, Rodriguez-Tome P, Claverie JM, Dausset J, et al.: Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment. Nat Genet. 1993 Feb;3(2):137-45. [Article]
  7. Neville MJ, Campbell RD: A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. J Immunol. 1999 Apr 15;162(8):4745-54. [Article]
  8. Xie T, Rowen L, Aguado B, Ahearn ME, Madan A, Qin S, Campbell RD, Hood L: Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse. Genome Res. 2003 Dec;13(12):2621-36. [Article]
  9. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  10. Voigt CG, Maurer-Fogy I, Adolf GR: Natural human tumor necrosis factor beta (lymphotoxin). Variable O-glycosylation at Thr7, proteolytic processing, and allelic variation. FEBS Lett. 1992 Dec 7;314(1):85-8. [Article]
  11. Eck MJ, Ultsch M, Rinderknecht E, de Vos AM, Sprang SR: The structure of human lymphotoxin (tumor necrosis factor-beta) at 1.9-A resolution. J Biol Chem. 1992 Feb 5;267(4):2119-22. [Article]
  12. Banner DW, D'Arcy A, Janes W, Gentz R, Schoenfeld HJ, Broger C, Loetscher H, Lesslauer W: Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell. 1993 May 7;73(3):431-45. [Article]
  13. Messer G, Spengler U, Jung MC, Honold G, Blomer K, Pape GR, Riethmuller G, Weiss EH: Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production. J Exp Med. 1991 Jan 1;173(1):209-19. [Article]
  14. Abraham LJ, Du DC, Zahedi K, Dawkins RL, Whitehead AS: Haplotypic polymorphisms of the TNFB gene. Immunogenetics. 1991;33(1):50-3. [Article]
  15. Balding J, Kane D, Livingstone W, Mynett-Johnson L, Bresnihan B, Smith O, FitzGerald O: Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. Arthritis Rheum. 2003 May;48(5):1408-13. [Article]
  16. Alcais A, Alter A, Antoni G, Orlova M, Nguyen VT, Singh M, Vanderborght PR, Katoch K, Mira MT, Vu HT, Ngyuen TH, Nguyen NB, Moraes M, Mehra N, Schurr E, Abel L: Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy. Nat Genet. 2007 Apr;39(4):517-22. Epub 2007 Mar 11. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Etanerceptapproved, investigationalyestargetantibodyDetails