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P01374 (TNFB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lymphotoxin-alpha

Short name=LT-alpha
Alternative name(s):
TNF-beta
Tumor necrosis factor ligand superfamily member 1
Gene names
Name:LTA
Synonyms:TNFB, TNFSF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length205 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM. In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and cytotoxic for a wide range of tumor cells in vitro and in vivo.

Subunit structure

Homotrimer, and heterotrimer of either two LTB and one LTA subunits or (less prevalent) two LTA and one LTB subunits.

Subcellular location

Secreted. Membrane. Note: The homotrimer is secreted. The heterotrimer is membrane-associated.

Polymorphism

A polymorphism in LTA accounts, in part, for susceptibility to leprosy linked to chromosome 6p21.3 (LPRS4) [MIM:610988].

Involvement in disease

Psoriatic arthritis (PSORAS) [MIM:607507]: An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Sequence similarities

Belongs to the tumor necrosis factor family.

Ontologies

Keywords
   Cellular componentMembrane
Secreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionCytokine
   PTMGlycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Traceable author statement Ref.4. Source: ProtInc

cell-cell signaling

Traceable author statement Ref.4. Source: ProtInc

defense response to Gram-positive bacterium

Inferred from electronic annotation. Source: Ensembl

humoral immune response

Inferred from electronic annotation. Source: Ensembl

lymph node development

Inferred from electronic annotation. Source: Ensembl

negative regulation of fibroblast proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of growth of symbiont in host

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of chronic inflammatory response to antigenic stimulus

Inferred from electronic annotation. Source: Ensembl

positive regulation of humoral immune response mediated by circulating immunoglobulin

Inferred from electronic annotation. Source: Ensembl

positive regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.4. Source: ProtInc

   Cellular_componentextracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionreceptor binding

Traceable author statement PubMed 3001529. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3434
Chain35 – 205171Lymphotoxin-alpha
PRO_0000034463

Amino acid modifications

Glycosylation411O-linked (GalNAc...); partial Ref.13
Glycosylation961N-linked (GlcNAc...) Ref.13
CAR_000048

Natural variations

Natural variant131C → R. Ref.10 Ref.11 Ref.12
Corresponds to variant rs2229094 [ dbSNP | Ensembl ].
VAR_013023
Natural variant511H → P. Ref.10 Ref.11
Corresponds to variant rs2229092 [ dbSNP | Ensembl ].
VAR_013024
Natural variant601T → N in allele TNFB*2. Ref.10 Ref.11 Ref.13 Ref.16
Corresponds to variant rs1041981 [ dbSNP | Ensembl ].
VAR_007511
Natural variant1251T → P in allele 8.1. Ref.17
VAR_007512

Secondary structure

............................... 205
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01374 [UniParc].

Last modified July 1, 1989. Version 2.
Checksum: 1BBD5E7D496A3A82

FASTA20522,297
        10         20         30         40         50         60 
MTPPERLFLP RVCGTTLHLL LLGLLLVLLP GAQGLPGVGL TPSAAQTARQ HPKMHLAHST 

        70         80         90        100        110        120 
LKPAAHLIGD PSKQNSLLWR ANTDRAFLQD GFSLSNNSLL VPTSGIYFVY SQVVFSGKAY 

       130        140        150        160        170        180 
SPKATSSPLY LAHEVQLFSS QYPFHVPLLS SQKMVYPGLQ EPWLHSMYHG AAFQLTQGDQ 

       190        200 
LSTHTDGIPH LVLSPSTVFF GAFAL 

« Hide

References

« Hide 'large scale' references
[1]"Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome."
Nedospasov S.A., Shakhov A.N., Turetskaya R.L., Mett V.A., Azizov M.M., Georgiev G.P., Korobko V.G., Dobrynin V.N., Filippov S.A., Bystrov N.S., Boldyreva E.F., Chuvpilo S.A., Chumakov A.M., Shingarova L.N., Ovchinnikov Y.A.
Cold Spring Harb. Symp. Quant. Biol. 51:611-624(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Structure and chromosomal localization of the human lymphotoxin gene."
Nedwin G.E., Jarrett-Nedwin J., Smith D.H., Naylor S.L., Sakaguchi A.Y., Goeddel D.V., Gray P.W.
J. Cell. Biochem. 29:171-181(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Cloning and expression of human lymphotoxin mRNA derived from a human T cell hybridoma."
Kobayashi Y., Miyamoto D., Asada M., Obinata M., Osawa T.
J. Biochem. 100:727-733(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity."
Gray P.W., Aggarwal B.B., Benton C.V., Bringman T.S., Henzel W.J., Jarrett J.A., Leung D.W., Moffat B., Ng P., Svedersky L.P., Palladino M.A., Nedwin G.E.
Nature 312:721-724(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Nucleotide sequence of a cDNA encoding human tumor necrosis factor beta from B lymphoblastoid cell RPMI 1788."
Matsuyama N., Okawa N., Tsukii Y., Endo T., Kaji A.
FEBS Lett. 302:141-144(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]"Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment."
Iris F.J.M., Bougueleret L., Prieur S., Caterina D., Primas G., Perrot V., Jurka J., Rodriguez-Tome P., Claverie J.-M., Dausset J., Cohen D.
Nat. Genet. 3:137-145(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"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."
Neville M.J., Campbell R.D.
J. Immunol. 162:4745-4754(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse."
Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L.
Genome Res. 13:2621-2636(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region."
Shiina S., Tamiya G., Oka A., Inoko H.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]SeattleSNPs variation discovery resource
Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-13; PRO-51 AND ASN-60.
[11]NIEHS SNPs program
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-13; PRO-51 AND ASN-60.
[12]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-13.
Tissue: Lymph.
[13]"Natural human tumor necrosis factor beta (lymphotoxin). Variable O-glycosylation at Thr7, proteolytic processing, and allelic variation."
Voigt C.G., Maurer-Fogy I., Adolf G.R.
FEBS Lett. 314:85-88(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT THR-41 AND ASN-96, VARIANT ASN-60.
[14]"The structure of human lymphotoxin (tumor necrosis factor-beta) at 1.9-A resolution."
Eck M.J., Ultsch M., Rinderknecht E., de Vos A.M., Sprang S.R.
J. Biol. Chem. 267:2119-2122(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
[15]"Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation."
Banner D.W., D'Arcy A., Janes W., Gentz R., Schoenfeld H.-J., Broger C., Loetscher H., Lesslauer W.
Cell 73:431-445(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 61-205 OF COMPLEX WITH TNFR1.
[16]"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."
Messer G., Spengler U., Jung M.C., Honold G., Bloemer K., Pape G.R., Riethmueller G., Weiss E.H.
J. Exp. Med. 173:209-219(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASN-60.
[17]"Haplotypic polymorphisms of the TNFB gene."
Abraham L.J., Du D.C., Zahedi K., Dawkins R.L., Whitehead A.S.
Immunogenetics 33:50-53(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PRO-125.
[18]"Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity."
Balding J., Kane D., Livingstone W., Mynett-Johnson L., Bresnihan B., Smith O., FitzGerald O.
Arthritis Rheum. 48:1408-1413(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PSORIATIC ARTHRITIS SUSCEPTIBILITY.
[19]"Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy."
Alcaies A., Alter A., Antoni G., Orlova M., Nguyen V.T., Singh M., Vanderborght P.R., Katoch K., Mira M.T., Vu H.T., Ngyuen T.H., Nguyen N.B., Moraes M., Mehra N., Schurr E., Abel L.
Nat. Genet. 39:517-522(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN LPRS4.
+Additional computationally mapped references.

Web resources

Wikipedia

Lymphotoxin entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
SeattleSNPs
SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X01393 mRNA. Translation: CAA25649.1.
X02911 Genomic DNA. Translation: CAA26670.1.
D00102 mRNA. Translation: BAA00064.1.
M16441 Genomic DNA. Translation: AAA61199.1.
D12614 mRNA. Translation: BAA02139.1.
M55913 Genomic DNA. Translation: AAB59455.1.
Z15026 Genomic DNA. Translation: CAA78746.1.
Y14768 Genomic DNA. Translation: CAA75071.1.
AF129756 Genomic DNA. Translation: AAD18092.1.
BA000025 Genomic DNA. Translation: BAB63397.1.
AY070490 Genomic DNA. Translation: AAL49956.1.
AY216498 Genomic DNA. Translation: AAO21135.1.
BC034729 mRNA. Translation: AAH34729.1.
CCDSCCDS4701.1.
PIRQWHUX. A92755.
RefSeqNP_000586.2. NM_000595.3.
NP_001153212.1. NM_001159740.2.
UniGeneHs.36.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TNRX-ray2.85A62-205[»]
4MXVX-ray3.20A/B/D62-205[»]
4MXWX-ray3.60A/X62-205[»]
ProteinModelPortalP01374.
SMRP01374. Positions 62-205.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110227. 7 interactions.
DIPDIP-2910N.
DIP-6228N.
IntActP01374. 3 interactions.
MINTMINT-365276.
STRING9606.ENSP00000372793.

Chemistry

BindingDBP01374.
ChEMBLCHEMBL2059.
DrugBankDB00005. Etanercept.

PTM databases

UniCarbKBP01374.

Polymorphism databases

DMDM135940.

Proteomic databases

PRIDEP01374.

Protocols and materials databases

DNASU4049.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000412851; ENSP00000412555; ENSG00000230279.
ENST00000418386; ENSP00000413450; ENSG00000226979.
ENST00000426845; ENSP00000402413; ENSG00000230279.
ENST00000436519; ENSP00000395976; ENSG00000231408.
ENST00000454550; ENSP00000416509; ENSG00000231408.
ENST00000454783; ENSP00000403495; ENSG00000226979.
GeneID4049.
KEGGhsa:4049.
UCSCuc003nue.2. human.

Organism-specific databases

CTD4049.
GeneCardsGC06P031541.
GC06Pl31579.
GC06Po31529.
HGNCHGNC:6709. LTA.
HPAHPA007729.
MIM153440. gene.
607507. phenotype.
610988. phenotype.
neXtProtNX_P01374.
Orphanet40050. Adult psoriatic arthritis.
PharmGKBPA30474.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG41746.
HOGENOMHOG000048729.
HOVERGENHBG012516.
InParanoidP01374.
KOK05468.
OMAYTLLTHE.
OrthoDBEOG7V4B0Q.
PhylomeDBP01374.
TreeFamTF332169.

Gene expression databases

ArrayExpressP01374.
BgeeP01374.
CleanExHS_LTA.
GenevestigatorP01374.

Family and domain databases

Gene3D2.60.120.40. 1 hit.
InterProIPR006053. TNF.
IPR002960. TNF_beta.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamPF00229. TNF. 1 hit.
[Graphical view]
PRINTSPR01234. TNECROSISFCT.
PR01236. TNFBETA.
SMARTSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMSSF49842. SSF49842. 1 hit.
PROSITEPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01374.
GeneWikiLymphotoxin_alpha.
GenomeRNAi4049.
NextBio15860.
PROP01374.
SOURCESearch...

Entry information

Entry nameTNFB_HUMAN
AccessionPrimary (citable) accession number: P01374
Secondary accession number(s): Q8N4C3, Q9UKS8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 1, 1989
Last modified: July 9, 2014
This is version 164 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM