LTA lymphotoxin alpha (TNF superfamily, member 1) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: LTAprovided by HGNC
Official Full Name: lymphotoxin alpha (TNF superfamily, member 1)provided by HGNC
Primary source: HGNC:6709
Locus tag: DAMA-25N12.13-004
See related: Ensembl:ENSG00000226979; HPRD:01084; MIM:153440; Vega:OTTHUMG00000031135
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LT; TNFB; TNFSF1
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]

Genomic context

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Location :: 6p21.3

Sequence :: Chromosome: 6; NC_000006.11 (31539876..31542101)

See LTA in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

This meta-analysis suggested that the 252A/G polymorphism in the lymphotoxin-alpha gene is a risk factor for asthma in adults and atopic populations. [meta-analysis]
Title: The +252A/G polymorphism in the lymphotoxin-α gene increases the risk of asthma: a meta-analysis.
The high affinity associated with LT-(TNFR1)1 is due to the interaction between the CRD4 domain with LT.
Title: Are different stoichiometries feasible for complexes between lymphotoxin-alpha and tumor necrosis factor receptor 1?
OR revealed statistically significant risk for CHD with respect to IFN-gamma +874 T allele, whereas OR for TNF-beta +252 A/G showed three fold risk in homozygous condition though not significant. No such trend could be observed for TNF-alpha -308 G/A polymorphism.
Title: Pro-inflammatory cytokine gene polymorphisms and threat for coronary heart disease in a North Indian Agrawal population.
the present study did not support a role for the tested LTA variants in migraine, investigation of other variants within the LTA gene is still warranted.
Title: Investigation of lymphotoxin α genetic variants in migraine.
Lymphotoxin-alpha 252A>G polymorphism is not associated with breast cancer.
Title: The lymphotoxin-α 252A>G polymorphism and breast cancer: a meta-analysis.
No lymphotoxin-alpha SNP association was found with respect to sepsis susceptibility.
Title: Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) single nucleotide polymorphisms: importance in ARDS in septic pediatric critically ill patients.
Data indicate that the biologic activity of pateclizumab on the lymphotoxin alpha (LTalpha) pathway.
Title: Safety, pharmacokinetics, and biologic activity of pateclizumab, a novel monoclonal antibody targeting lymphotoxin α: results of a phase I randomized, placebo-controlled trial.
Results do not support a major role of LTA gene polymorphism at position 252 in the susceptibility to systemic lupus erythematosus in Portuguese Caucasian patients.
Title: TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus.
single nucleotide polymorphisms within the PTGS2 and LTA inflammatory markers were associated with pain and quality of life in a large sample of long term lung cancer survivors
Title: SNPs in PTGS2 and LTA predict pain and quality of life in long term lung cancer survivors.
In vivo depletion of lymphotoxin-alpha expressing lymphocytes inhibits xenogeneic graft-versus-host-disease.
Title: In vivo depletion of lymphotoxin-alpha expressing lymphocytes inhibits xenogeneic graft-versus-host-disease.

Submit: New GeneRIF Correction See all (149)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Psoriatic arthritis, susceptibility to

MIM: 607507

Genetic Testing Registry

NHGRI GWAS Catalog

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.

Identification of candidate loci at 6p21 and 21q22 in a genome-wide association study of cardiac manifestations of neonatal lupus.

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	In endometrial epithelium-derived cells, gp120 from CCR5-tropic HIV-1 increases the release of monocytes/chemokines-attracting chemokines (IL-8 and GRO) and proinflammatory cytokines (TNF-beta and IL-1alpha)	PubMed
Tat, p14	tat	HIV-1 Tat downregulates TNF-beta expression in central nervous system-derived glial cells, suggesting a novel mechanism whereby HIV-1 is able to establish latent infection of glial cells	PubMed
	tat	HIV-1 Tat upregulates TNF-beta expression through binding to a TAR-like RNA structure in the TNF-beta promoter	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_000586.2	NP_006489.1	LGALS2	BIND	PubMed	LTA interacts with galectin-2.
P01374	P05162	LGALS2	HPRD	PubMed
P01374	P01374	LTA	HPRD	PubMed
P01374	Q06643	LTB	HPRD	PubMed
P01374	P36941	LTBR	HPRD	PubMed
P01374	Q92956	TNFRSF14	HPRD	PubMed
P01374	P19438	TNFRSF1A	HPRD	PubMed
P01374	P20333	TNFRSF1B	HPRD	PubMed
P01374	P68366	TUBA4A	HPRD	PubMed
P01374	P07911	UMOD	HPRD	PubMed
BioGRID:110227	BioGRID:122015	CLSPN	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110227	BioGRID:110148	LGALS2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110227	BioGRID:110228	LTB	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110227	BioGRID:112986	TNFRSF1A	BioGRID	PubMed	Co-crystal Structure
BioGRID:110227	BioGRID:115651	TUBA1B	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110227	BioGRID:113216	UMOD	BioGRID	PubMed	Reconstituted Complex

Pathways from BioSystems

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Apoptosis, organism-specific biosystem (from WikiPathways)
Apoptosis, organism-specific biosystemApoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and ...
Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
HTLV-I infection, organism-specific biosystem (from KEGG)
HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
HTLV-I infection, conserved biosystem (from KEGG)
HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
Herpes simplex infection, organism-specific biosystem (from KEGG)
Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
Herpes simplex infection, conserved biosystem (from KEGG)
Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
IL2 signaling events mediated by STAT5, organism-specific biosystem (from Pathway Interaction Database)
IL2 signaling events mediated by STAT5, organism-specific biosystem
IL2 signaling events mediated by STAT5
IL4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
IL4-mediated signaling events, organism-specific biosystem
IL4-mediated signaling events
NF-kappa B signaling pathway, organism-specific biosystem (from KEGG)
NF-kappa B signaling pathway, organism-specific biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
Type I diabetes mellitus, organism-specific biosystem (from KEGG)
Type I diabetes mellitus, organism-specific biosystemType I diabetes mellitus is a disease that results from autoimmune destruction of the insulin-producing beta-cells. Certain beta-cell proteins act as autoantigens after being processed by antigen-pre...
Type I diabetes mellitus, conserved biosystem (from KEGG)
Type I diabetes mellitus, conserved biosystemType I diabetes mellitus is a disease that results from autoimmune destruction of the insulin-producing beta-cells. Certain beta-cell proteins act as autoantigens after being processed by antigen-pre...

General gene information

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Markers

RH17367 (e-PCR)
- UniSTS:56874

GDB:192948 (e-PCR)
- UniSTS:155729

RH71008 (e-PCR)
- UniSTS:53844

LTA_189 (e-PCR)
- UniSTS:277457

PMC32163P1 (e-PCR)
- UniSTS:273125

GDB:182383 (e-PCR)
- UniSTS:155378

Genotypes

See LTA SNP Geneview Report
See LTA SNP Genotype Report
See LTA SNP Variation Viewer Report

Homology

Homologs of the LTA gene: The LTA gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cytokine activity	IEA Inferred from Electronic Annotation more info
receptor binding	TAS Traceable Author Statement more info	PubMed
tumor necrosis factor receptor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cell-cell signaling	TAS Traceable Author Statement more info	PubMed
defense response to Gram-positive bacterium	IEA Inferred from Electronic Annotation more info
humoral immune response	IEA Inferred from Electronic Annotation more info
induction of apoptosis	TAS Traceable Author Statement more info	PubMed
lymph node development	IEA Inferred from Electronic Annotation more info
negative regulation of fibroblast proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of growth of symbiont in host	IEA Inferred from Electronic Annotation more info
positive regulation of chronic inflammatory response to antigenic stimulus	IEA Inferred from Electronic Annotation more info
positive regulation of humoral immune response mediated by circulating immunoglobulin	IEA Inferred from Electronic Annotation more info
positive regulation of interferon-gamma production	IEA Inferred from Electronic Annotation more info
response to drug	IEA Inferred from Electronic Annotation more info
response to hypoxia	IEA Inferred from Electronic Annotation more info
response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
response to nutrient	IEA Inferred from Electronic Annotation more info
signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
extracellular space	IEA Inferred from Electronic Annotation more info
membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: lymphotoxin-alpha

Names: lymphotoxin-alpha; LT-alpha; TNF-beta; tumor necrosis factor beta; tumor necrosis factor ligand superfamily member 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012010.1 RefSeqGene

Range

5001..7226

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000595.3 → NP_000586.2 lymphotoxin-alpha precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

BG685356, BX108399, D12614

Consensus CDS

CCDS4701.1

UniProtKB/Swiss-Prot

P01374

UniProtKB/TrEMBL

Q5STV3

Related

ENSP00000413450, OTTHUMP00000029184, ENST00000418386, OTTHUMT00000076237

Conserved Domains (1) summary

cd00184
Location:63 – 203
Blast Score: 316

TNF; Tumor Necrosis Factor; TNF superfamily members include the cytokines: TNF (TNF-alpha), LT (lymphotoxin-alpha, TNF-beta), CD40 ligand, Apo2L (TRAIL), Fas ligand, and osteoprotegerin (OPG) ligand. These proteins generally have an intracellular N-terminal ...
NM_001159740.2 → NP_001153212.1 lymphotoxin-alpha precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

BP338937, BX108399, D12614

Consensus CDS

CCDS4701.1

UniProtKB/Swiss-Prot

P01374

UniProtKB/TrEMBL

Q5STV3

Related

ENSP00000403495, OTTHUMP00000165897, ENST00000454783, OTTHUMT00000259097

Conserved Domains (1) summary

cd00184
Location:63 – 203
Blast Score: 316

TNF; Tumor Necrosis Factor; TNF superfamily members include the cytokines: TNF (TNF-alpha), LT (lymphotoxin-alpha, TNF-beta), CD40 ligand, Apo2L (TRAIL), Fas ligand, and osteoprotegerin (OPG) ligand. These proteins generally have an intracellular N-terminal ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 ALT_REF_LOCI_2

Genomic

NT_113891.2 Reference GRCh37.p10 ALT_REF_LOCI_2

Range

3049492..3051717

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 ALT_REF_LOCI_3

Genomic

NT_167245.1 Reference GRCh37.p10 ALT_REF_LOCI_3

Range

2825415..2827642

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 ALT_REF_LOCI_4

Genomic

NT_167246.1 Reference GRCh37.p10 ALT_REF_LOCI_4

Range

2882760..2884985

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 ALT_REF_LOCI_5

Genomic

NT_167247.1 Reference GRCh37.p10 ALT_REF_LOCI_5

Range

2919580..2921807

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 ALT_REF_LOCI_6

Genomic

NT_167248.1 Reference GRCh37.p10 ALT_REF_LOCI_6

Range

2833512..2835739

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 ALT_REF_LOCI_7

Genomic

NT_167249.1 Reference GRCh37.p10 ALT_REF_LOCI_7

Range

2870677..2872902

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p10 Primary Assembly

Range

31539876..31542101

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

31326608..31328835

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018917.1 Alternate CHM1_1.0

Range

31456828..31459053

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB088112.1	BAC54943.1
genomic	AB103618.1	BAF31278.1
genomic	AB202113.1	BAE78638.1
genomic	ABBA01038081.1 (33787..36014)	None
genomic	AF129756.1	AAD18092.1
genomic	AL662801.7 (44769..46991)	None
genomic	AL662847.6 (58535..60757)	None
genomic	AL929587.5 (19927..22154)	None
genomic	AMYH01016217.1 (73619..75844)	None
genomic	AY070490.1	AAL49956.1
genomic	AY216498.1	AAO21135.1
genomic	AY274903.1	AAP51421.1
genomic	AY274904.1	AAP51422.1
genomic	AY274905.1	AAP51423.1
genomic	AY274906.1	AAP51424.1
genomic	AY274907.1	AAP51425.1
genomic	AY274908.1	AAP51426.1
genomic	AY274909.1	AAP51427.1
genomic	AY274910.1	AAP51428.1
genomic	AY274911.1	AAP51429.1
genomic	AY274912.1	AAP51430.1
genomic	AY274913.1	AAP51431.1
genomic	AY274914.1	AAP51432.1
genomic	AY274915.1	AAP51433.1
genomic	AY274916.1	AAP51434.1
genomic	AY274917.1	AAP51435.1
genomic	AY274918.1	AAP51436.1
genomic	AY274919.1	AAP51437.1
genomic	AY274920.1	AAP51438.1
genomic	AY274921.1	AAP51439.1
genomic	AY274922.1	AAP51440.1
genomic	AY274923.1	AAP51441.1
genomic	AY274924.1	AAP51442.1
genomic	AY274925.1	AAP51443.1
genomic	AY274926.1	AAP51444.1
genomic	BA000025.2	BAB63397.1
genomic	BX248519.7 (4492..6717)	None
genomic	BX927320.5 (71806..74031)	None
genomic	CH471081.1	EAX03422.1
		EAX03423.1
genomic	CR753892.5 (29166..31173)	None
genomic	CR942185.8 (27702..29709)	None
genomic	CS081477.1	CAI95949.1
genomic	M16441.1	AAA61199.1
genomic	M55913.1	AAB59455.1
genomic	X02911.1	CAA26670.1
genomic	Y14768.1	CAA75071.1
genomic	Z15026.1	CAA78746.1
mRNA	BC034729.1	AAH34729.1
mRNA	BG685356.1	None
mRNA	BP338937.1	None
mRNA	BX108399.1	None
mRNA	CR542253.1	CAG47049.1
mRNA	CR542273.1	CAG47069.1
mRNA	D00102.1	BAA00064.1
mRNA	D12614.1	BAA02139.1
mRNA	DQ123821.1	AAZ32914.1
mRNA	DQ123822.1	AAZ32915.1
mRNA	DQ123823.1	AAZ32916.1
mRNA	DQ123824.1	AAZ32917.1
mRNA	DQ123825.2	AAZ32918.2
mRNA	DQ123826.1	AAZ32919.1
mRNA	DQ123827.1	AAZ32920.1
mRNA	X01393.1	CAA25649.1
mRNA	A06316.1	CAA00536.1
other-genetic	DQ891119.2	ABM82045.1
other-genetic	DQ894298.2	ABM85224.1