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Protein

Lymphotoxin-alpha

Gene

LTA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • receptor binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Names & Taxonomyi

Protein namesi
Recommended name:
Lymphotoxin-alpha
Short name:
LT-alpha
Alternative name(s):
TNF-beta
Tumor necrosis factor ligand superfamily member 1
Gene namesi
Name:LTA
Synonyms:TNFB, TNFSF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componentsi: Chromosome 6, Unplaced

Organism-specific databases

HGNCiHGNC:6709. LTA.

Subcellular locationi

  • Secreted
  • Membrane

  • Note: The homotrimer is secreted. The heterotrimer is membrane-associated.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Psoriatic arthritis (PSORAS)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionAn 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).

See also OMIM:607507

Organism-specific databases

MIMi607507. phenotype.
610988. phenotype.
Orphaneti40050. Adult psoriatic arthritis.
PharmGKBiPA30474.

Chemistry

DrugBankiDB00005. Etanercept.

Polymorphism and mutation databases

BioMutaiLTA.
DMDMi135940.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3434Add
BLAST
Chaini35 – 205171Lymphotoxin-alphaPRO_0000034463Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi41 – 411O-linked (GalNAc...); partial1 Publication
Glycosylationi96 – 961N-linked (GlcNAc...)1 PublicationCAR_000048

Keywords - PTMi

Glycoprotein

Proteomic databases

PRIDEiP01374.

PTM databases

UniCarbKBiP01374.

Expressioni

Gene expression databases

BgeeiP01374.
CleanExiHS_LTA.
ExpressionAtlasiP01374. baseline and differential.
GenevisibleiP01374. HS.

Organism-specific databases

HPAiHPA007729.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi110227. 7 interactions.
DIPiDIP-2910N.
IntActiP01374. 3 interactions.
MINTiMINT-365276.
STRINGi9606.ENSP00000403495.

Structurei

Secondary structure

1
205
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi64 – 696Combined sources
Turni71 – 733Combined sources
Beta strandi74 – 763Combined sources
Beta strandi87 – 893Combined sources
Beta strandi93 – 953Combined sources
Beta strandi98 – 1003Combined sources
Beta strandi103 – 11715Combined sources
Helixi122 – 1254Combined sources
Beta strandi129 – 13810Combined sources
Beta strandi142 – 1443Combined sources
Beta strandi146 – 15510Combined sources
Beta strandi163 – 17513Combined sources
Beta strandi180 – 1867Combined sources
Helixi188 – 1903Combined sources
Turni195 – 1973Combined sources
Beta strandi198 – 2047Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TNRX-ray2.85A62-205[»]
4MXVX-ray3.20A/B/D62-205[»]
4MXWX-ray3.60A/X62-205[»]
ProteinModelPortaliP01374.
SMRiP01374. Positions 62-205.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01374.

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG41746.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP01374.
KOiK05468.
OMAiYTLLTHE.
OrthoDBiEOG7V4B0Q.
PhylomeDBiP01374.
TreeFamiTF332169.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006053. TNF.
IPR002960. TNF_beta.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01234. TNECROSISFCT.
PR01236. TNFBETA.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01374-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTPPERLFLP RVCGTTLHLL LLGLLLVLLP GAQGLPGVGL TPSAAQTARQ
60 70 80 90 100
HPKMHLAHST LKPAAHLIGD PSKQNSLLWR ANTDRAFLQD GFSLSNNSLL
110 120 130 140 150
VPTSGIYFVY SQVVFSGKAY SPKATSSPLY LAHEVQLFSS QYPFHVPLLS
160 170 180 190 200
SQKMVYPGLQ EPWLHSMYHG AAFQLTQGDQ LSTHTDGIPH LVLSPSTVFF

GAFAL
Length:205
Mass (Da):22,297
Last modified:July 1, 1989 - v2
Checksum:i1BBD5E7D496A3A82
GO

Polymorphismi

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti13 – 131C → R.3 Publications
Corresponds to variant rs2229094 [ dbSNP | Ensembl ].
VAR_013023
Natural varianti51 – 511H → P.2 Publications
Corresponds to variant rs2229092 [ dbSNP | Ensembl ].
VAR_013024
Natural varianti60 – 601T → N in allele TNFB*2. 4 Publications
Corresponds to variant rs1041981 [ dbSNP | Ensembl ].
VAR_007511
Natural varianti125 – 1251T → P in allele 8.1. 1 Publication
VAR_007512

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4701.1.
PIRiA92755. QWHUX.
RefSeqiNP_000586.2. NM_000595.3.
NP_001153212.1. NM_001159740.2.
UniGeneiHs.36.

Genome annotation databases

EnsembliENST00000412851; ENSP00000412555; ENSG00000230279.
ENST00000418386; ENSP00000413450; ENSG00000226979.
ENST00000426845; ENSP00000402413; ENSG00000230279.
ENST00000436519; ENSP00000395976; ENSG00000231408.
ENST00000454550; ENSP00000416509; ENSG00000231408.
ENST00000454783; ENSP00000403495; ENSG00000226979.
GeneIDi4049.
KEGGihsa:4049.
UCSCiuc003nue.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Lymphotoxin entry

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

The Singapore human mutation and polymorphism database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4701.1.
PIRiA92755. QWHUX.
RefSeqiNP_000586.2. NM_000595.3.
NP_001153212.1. NM_001159740.2.
UniGeneiHs.36.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TNRX-ray2.85A62-205[»]
4MXVX-ray3.20A/B/D62-205[»]
4MXWX-ray3.60A/X62-205[»]
ProteinModelPortaliP01374.
SMRiP01374. Positions 62-205.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110227. 7 interactions.
DIPiDIP-2910N.
IntActiP01374. 3 interactions.
MINTiMINT-365276.
STRINGi9606.ENSP00000403495.

Chemistry

BindingDBiP01374.
ChEMBLiCHEMBL2059.
DrugBankiDB00005. Etanercept.

PTM databases

UniCarbKBiP01374.

Polymorphism and mutation databases

BioMutaiLTA.
DMDMi135940.

Proteomic databases

PRIDEiP01374.

Protocols and materials databases

DNASUi4049.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000412851; ENSP00000412555; ENSG00000230279.
ENST00000418386; ENSP00000413450; ENSG00000226979.
ENST00000426845; ENSP00000402413; ENSG00000230279.
ENST00000436519; ENSP00000395976; ENSG00000231408.
ENST00000454550; ENSP00000416509; ENSG00000231408.
ENST00000454783; ENSP00000403495; ENSG00000226979.
GeneIDi4049.
KEGGihsa:4049.
UCSCiuc003nue.2. human.

Organism-specific databases

CTDi4049.
GeneCardsiGC06P031541.
GC06Pl31579.
GC06Po31529.
HGNCiHGNC:6709. LTA.
HPAiHPA007729.
MIMi153440. gene.
607507. phenotype.
610988. phenotype.
neXtProtiNX_P01374.
Orphaneti40050. Adult psoriatic arthritis.
PharmGKBiPA30474.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG41746.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP01374.
KOiK05468.
OMAiYTLLTHE.
OrthoDBiEOG7V4B0Q.
PhylomeDBiP01374.
TreeFamiTF332169.

Miscellaneous databases

EvolutionaryTraceiP01374.
GeneWikiiLymphotoxin_alpha.
GenomeRNAii4049.
NextBioi15860.
PROiP01374.
SOURCEiSearch...

Gene expression databases

BgeeiP01374.
CleanExiHS_LTA.
ExpressionAtlasiP01374. baseline and differential.
GenevisibleiP01374. HS.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006053. TNF.
IPR002960. TNF_beta.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01234. TNECROSISFCT.
PR01236. TNFBETA.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiTNFB_HUMAN
AccessioniPrimary (citable) accession number: P01374
Secondary accession number(s): Q8N4C3, Q9UKS8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 1, 1989
Last modified: June 24, 2015
This is version 171 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.