LTA (lymphotoxin alpha)

Gene

• Entrez ID: 4049
• Gene name: Lymphotoxin alpha
• Gene symbol: LTA
• Synonyms: LT, TNFB, TNFSF1, TNLG1E
• Chromosome: 6
• Chromosome location: 6p21.33
• Summary: The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin`s lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT733987	hsa-miR-34a-5p	PCR array	28097098

Transcription factors

Transcription factor	Regulation	Reference
MSC	Repression	15052269

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001666	Process	Response to hypoxia	IEA
GO:0002876	Process	Positive regulation of chronic inflammatory response to antigenic stimulus	IEA
GO:0002925	Process	Positive regulation of humoral immune response mediated by circulating immunoglobulin	IEA
GO:0005102	Function	Signaling receptor binding	TAS	3001529
GO:0005125	Function	Cytokine activity	IEA
GO:0005164	Function	Tumor necrosis factor receptor binding	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005615	Component	Extracellular space	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006915	Process	Apoptotic process	TAS	6334807
GO:0006959	Process	Humoral immune response	IEA
GO:0007165	Process	Signal transduction	TAS	6334807
GO:0007267	Process	Cell-cell signaling	TAS	6334807
GO:0007584	Process	Response to nutrient	IEA
GO:0032496	Process	Response to lipopolysaccharide	IEA
GO:0032729	Process	Positive regulation of interferon-gamma production	IEA
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	TAS
GO:0042493	Process	Response to drug	IEA
GO:0043065	Process	Positive regulation of apoptotic process	IEA
GO:0048147	Process	Negative regulation of fibroblast proliferation	IEA
GO:0048535	Process	Lymph node development	IEA
GO:0050830	Process	Defense response to Gram-positive bacterium	IEA
GO:0060252	Process	Positive regulation of glial cell proliferation	IEA

Other IDs

• MIM: 153440
• HGNC: 6709
• e!Ensembl: ENSG00000226979

Protein

• UniProt ID: P01374
• Protein name: Lymphotoxin-alpha (LT-alpha) (TNF-beta) (Tumor necrosis factor ligand superfamily member 1)
• Protein 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. Lymphotoxin is produced by lymphocytes and is cytotoxic for a wide range of tumor cells in vitro and in vivo.
• PDB: 1TNR, 4MXV, 4MXW
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00229	TNF	77 → 205	TNF(Tumour Necrosis Factor) family	Domain

• Sequence:

  MTPPERLFLPRVCGTTLHLLLLGLLLVLLPGAQGLPGVGLTPSAAQTARQHPKMHLAHST
  LKPAAHLIGDPSKQNSLLWRANTDRAFLQDGFSLSNNSLLVPTSGIYFVYSQVVFSGKAY
  SPKATSSPLYLAHEVQLFSSQYPFHVPLLSSQKMVYPGLQEPWLHSMYHGAAFQLTQGDQ
  LSTHTDGIPHLVLSPSTVFFGAFAL

• Sequence length: 205

Pathways

KEGG:

Cytokine-cytokine receptor interaction
Viral protein interaction with cytokine and cytokine receptor
NF-kappa B signaling pathway
TNF signaling pathway
Type I diabetes mellitus
Human T-cell leukemia virus 1 infection
Herpes simplex virus 1 infection

Reactome:

TNFR2 non-canonical NF-kB pathway
TNFs bind their physiological receptors
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Diabetes mellitus	Diabetes Mellitus, Insulin-Dependent	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs-1, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs371977235, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261	17632545
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs-1, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	12648734
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	15266304
Leprosy	Leprosy	rs121917864, rs2239704	17353895
Myocardial infarction	Myocardial Infarction	rs12316150, rs41303970, rs909253, rs7291467, rs2234693	12426569, 15129282
Esophagus neoplasm	Squamous cell carcinoma of esophagus	rs28934578, rs121918714, rs1567556006, rs1575166666	29379198

Unknown
Disease name	Disease term	dbSNP ID	References
Cervix carcinoma	Cervix carcinoma		28806749
Coronary arteriosclerosis	Coronary Arteriosclerosis		15266304
Fulminant hepatic failure with cerebral edema	Fulminant Hepatic Failure with Cerebral Edema		9696492
Hepatic coma	Hepatic Coma		9696492
Hepatic encephalopathy	Hepatic Encephalopathy		9696492
Hepatic stupor	Hepatic Stupor		9696492
Lupus erythematosus	Lupus Erythematosus, Systemic		24871463
Malignant mesothelioma	Malignant mesothelioma		25162674
Psoriatic arthritis	Arthritis, Psoriatic		12746914
Septicemia	Septicemia		22977509