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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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000173503-MONOMER.
ReactomeiR-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5669034. TNFs bind their physiological receptors.
R-HSA-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
SIGNORiP01374.

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
Proteomesi
  • UP000005640 Componenti: 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

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

DisGeNETi4049.
MalaCardsiLTA.
MIMi607507. phenotype.
610988. phenotype.
OpenTargetsiENSG00000226979.
ENSG00000230279.
ENSG00000231408.
Orphaneti40050. Adult psoriatic arthritis.
PharmGKBiPA30474.

Chemistry databases

ChEMBLiCHEMBL2059.
DrugBankiDB00005. Etanercept.

Polymorphism and mutation databases

BioMutaiLTA.
DMDMi135940.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34Add BLAST34
ChainiPRO_000003446335 – 205Lymphotoxin-alphaAdd BLAST171

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi41O-linked (GalNAc...); partial1 Publication1
GlycosylationiCAR_00004896N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiP01374.
PaxDbiP01374.
PRIDEiP01374.

PTM databases

UniCarbKBiP01374.

Expressioni

Gene expression databases

BgeeiENSG00000226979.
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.

GO - Molecular functioni

  • receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi110227. 8 interactors.
DIPiDIP-2910N.
IntActiP01374. 3 interactors.
MINTiMINT-365276.
STRINGi9606.ENSP00000403495.

Chemistry databases

BindingDBiP01374.

Structurei

Secondary structure

1205
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi64 – 69Combined sources6
Turni71 – 73Combined sources3
Beta strandi74 – 76Combined sources3
Beta strandi87 – 89Combined sources3
Beta strandi93 – 95Combined sources3
Beta strandi98 – 100Combined sources3
Beta strandi103 – 117Combined sources15
Helixi122 – 125Combined sources4
Beta strandi129 – 138Combined sources10
Beta strandi142 – 144Combined sources3
Beta strandi146 – 155Combined sources10
Beta strandi163 – 175Combined sources13
Beta strandi180 – 186Combined sources7
Helixi188 – 190Combined sources3
Turni195 – 197Combined sources3
Beta strandi198 – 204Combined sources7

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP01374.

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IWT9. Eukaryota.
ENOG410YQC4. LUCA.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP01374.
KOiK05468.
OMAiYTLLTHE.
OrthoDBiEOG091G0HIG.
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_01302313C → R.3 PublicationsCorresponds to variant rs2229094dbSNPEnsembl.1
Natural variantiVAR_01302451H → P.2 PublicationsCorresponds to variant rs2229092dbSNPEnsembl.1
Natural variantiVAR_00751160T → N in allele TNFB*2. 4 PublicationsCorresponds to variant rs1041981dbSNPEnsembl.1
Natural variantiVAR_007512125T → P in allele 8.1. 1 Publication1

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.
XP_011512917.1. XM_011514615.2.
XP_011512918.1. XM_011514616.2.
XP_011512919.1. XM_011514617.2.
XP_011512920.1. XM_011514618.1.
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.

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.
XP_011512917.1. XM_011514615.2.
XP_011512918.1. XM_011514616.2.
XP_011512919.1. XM_011514617.2.
XP_011512920.1. XM_011514618.1.
UniGeneiHs.36.

3D structure databases

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

Protein-protein interaction databases

BioGridi110227. 8 interactors.
DIPiDIP-2910N.
IntActiP01374. 3 interactors.
MINTiMINT-365276.
STRINGi9606.ENSP00000403495.

Chemistry databases

BindingDBiP01374.
ChEMBLiCHEMBL2059.
DrugBankiDB00005. Etanercept.

PTM databases

UniCarbKBiP01374.

Polymorphism and mutation databases

BioMutaiLTA.
DMDMi135940.

Proteomic databases

EPDiP01374.
PaxDbiP01374.
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.

Organism-specific databases

CTDi4049.
DisGeNETi4049.
GeneCardsiLTA.
HGNCiHGNC:6709. LTA.
HPAiHPA007729.
MalaCardsiLTA.
MIMi153440. gene.
607507. phenotype.
610988. phenotype.
neXtProtiNX_P01374.
OpenTargetsiENSG00000226979.
ENSG00000230279.
ENSG00000231408.
Orphaneti40050. Adult psoriatic arthritis.
PharmGKBiPA30474.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IWT9. Eukaryota.
ENOG410YQC4. LUCA.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP01374.
KOiK05468.
OMAiYTLLTHE.
OrthoDBiEOG091G0HIG.
PhylomeDBiP01374.
TreeFamiTF332169.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000173503-MONOMER.
ReactomeiR-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5669034. TNFs bind their physiological receptors.
R-HSA-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
SIGNORiP01374.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000226979.
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...

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: November 2, 2016
This is version 182 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

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 one 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.