SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P01374

- TNFB_HUMAN

UniProt

P01374 - TNFB_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Lymphotoxin-alpha

Gene
LTA, TNFB, TNFSF1
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. receptor binding Source: ProtInc

GO - Biological processi

  1. apoptotic process Source: ProtInc
  2. cell-cell signaling Source: ProtInc
  3. defense response to Gram-positive bacterium Source: Ensembl
  4. humoral immune response Source: Ensembl
  5. lymph node development Source: Ensembl
  6. negative regulation of fibroblast proliferation Source: Ensembl
  7. negative regulation of growth of symbiont in host Source: Ensembl
  8. positive regulation of apoptotic process Source: Ensembl
  9. positive regulation of chronic inflammatory response to antigenic stimulus Source: Ensembl
  10. positive regulation of humoral immune response mediated by circulating immunoglobulin Source: Ensembl
  11. positive regulation of interferon-gamma production Source: Ensembl
  12. response to drug Source: Ensembl
  13. response to hypoxia Source: Ensembl
  14. response to lipopolysaccharide Source: Ensembl
  15. response to nutrient Source: Ensembl
  16. signal transduction Source: ProtInc
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: Chromosome 6

Organism-specific databases

HGNCiHGNC:6709. LTA.

Subcellular locationi

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

GO - Cellular componenti

  1. extracellular space Source: UniProtKB-KW
  2. membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

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.

Organism-specific databases

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

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

ArrayExpressiP01374.
BgeeiP01374.
CleanExiHS_LTA.
GenevestigatoriP01374.

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.
DIP-6228N.
IntActiP01374. 3 interactions.
MINTiMINT-365276.
STRINGi9606.ENSP00000372793.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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.

Miscellaneous databases

EvolutionaryTraceiP01374.

Family & Domainsi

Sequence similaritiesi

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

MTPPERLFLP RVCGTTLHLL LLGLLLVLLP GAQGLPGVGL TPSAAQTARQ    50
HPKMHLAHST LKPAAHLIGD PSKQNSLLWR ANTDRAFLQD GFSLSNNSLL 100
VPTSGIYFVY SQVVFSGKAY SPKATSSPLY LAHEVQLFSS QYPFHVPLLS 150
SQKMVYPGLQ EPWLHSMYHG AAFQLTQGDQ LSTHTDGIPH LVLSPSTVFF 200
GAFAL 205
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:
EMBL
GenBank
DDBJ
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.

Polymorphism databases

DMDMi135940.

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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS4701.1.
PIRi A92755. QWHUX.
RefSeqi NP_000586.2. NM_000595.3.
NP_001153212.1. NM_001159740.2.
UniGenei Hs.36.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1TNR X-ray 2.85 A 62-205 [» ]
4MXV X-ray 3.20 A/B/D 62-205 [» ]
4MXW X-ray 3.60 A/X 62-205 [» ]
ProteinModelPortali P01374.
SMRi P01374. Positions 62-205.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110227. 7 interactions.
DIPi DIP-2910N.
DIP-6228N.
IntActi P01374. 3 interactions.
MINTi MINT-365276.
STRINGi 9606.ENSP00000372793.

Chemistry

BindingDBi P01374.
ChEMBLi CHEMBL2059.
DrugBanki DB00005. Etanercept.

PTM databases

UniCarbKBi P01374.

Polymorphism databases

DMDMi 135940.

Proteomic databases

PRIDEi P01374.

Protocols and materials databases

DNASUi 4049.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000412851 ; ENSP00000412555 ; ENSG00000230279 .
ENST00000418386 ; ENSP00000413450 ; ENSG00000226979 .
ENST00000426845 ; ENSP00000402413 ; ENSG00000230279 .
ENST00000436519 ; ENSP00000395976 ; ENSG00000231408 .
ENST00000454550 ; ENSP00000416509 ; ENSG00000231408 .
ENST00000454783 ; ENSP00000403495 ; ENSG00000226979 .
GeneIDi 4049.
KEGGi hsa:4049.
UCSCi uc003nue.2. human.

Organism-specific databases

CTDi 4049.
GeneCardsi GC06P031541.
GC06Pl31579.
GC06Po31529.
HGNCi HGNC:6709. LTA.
HPAi HPA007729.
MIMi 153440. gene.
607507. phenotype.
610988. phenotype.
neXtProti NX_P01374.
Orphaneti 40050. Adult psoriatic arthritis.
PharmGKBi PA30474.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG41746.
HOGENOMi HOG000048729.
HOVERGENi HBG012516.
InParanoidi P01374.
KOi K05468.
OMAi YTLLTHE.
OrthoDBi EOG7V4B0Q.
PhylomeDBi P01374.
TreeFami TF332169.

Miscellaneous databases

EvolutionaryTracei P01374.
GeneWikii Lymphotoxin_alpha.
GenomeRNAii 4049.
NextBioi 15860.
PROi P01374.
SOURCEi Search...

Gene expression databases

ArrayExpressi P01374.
Bgeei P01374.
CleanExi HS_LTA.
Genevestigatori P01374.

Family and domain databases

Gene3Di 2.60.120.40. 1 hit.
InterProi IPR006053. TNF.
IPR002960. TNF_beta.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view ]
Pfami PF00229. TNF. 1 hit.
[Graphical view ]
PRINTSi PR01234. TNECROSISFCT.
PR01236. TNFBETA.
SMARTi SM00207. TNF. 1 hit.
[Graphical view ]
SUPFAMi SSF49842. SSF49842. 1 hit.
PROSITEi PS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: July 9, 2014
This is version 164 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