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Protein

Lymphotoxin-alpha

Gene

LTA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • cytokine activity Source: UniProtKB-KW
  • signaling receptor binding Source: ProtInc
  • tumor necrosis factor receptor binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000226979.8
HGNCiHGNC:6709 LTA
MIMi153440 gene
neXtProtiNX_P01374

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
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...) threonine; partial1 Publication1
GlycosylationiCAR_00004896N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiP01374
PaxDbiP01374
PeptideAtlasiP01374
PRIDEiP01374
ProteomicsDBi51378

PTM databases

GlyConnecti354
iPTMnetiP01374
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.

Binary interactionsi

WithEntry#Exp.IntActNotes
LGALS2P051623EBI-524105,EBI-7181544

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • signaling receptor binding Source: ProtInc
  • tumor necrosis factor receptor binding Source: InterPro

Protein-protein interaction databases

BioGridi110227, 8 interactors
CORUMiP01374
DIPiDIP-2910N
IntActiP01374, 10 interactors
MINTiP01374
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

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
OMAiQYPFHVP
OrthoDBiEOG091G0HIG
PhylomeDBiP01374
TreeFamiTF332169

Family and domain databases

Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR006053 TNF
IPR002960 TNF_beta
IPR021184 TNF_CS
IPR006052 TNF_dom
IPR008983 Tumour_necrosis_fac-like_dom
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PRINTSiPR01234 TNECROSISFCT
PR01236 TNFBETA
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS00251 TNF_1, 1 hit
PS50049 TNF_2, 1 hit

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 → R3 PublicationsCorresponds to variant dbSNP:rs2229094Ensembl.1
Natural variantiVAR_01302451H → P2 PublicationsCorresponds to variant dbSNP:rs2229092Ensembl.1
Natural variantiVAR_00751160T → N in allele TNFB*2. 4 PublicationsCorresponds to variant dbSNP:rs1041981EnsemblClinVar.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

Similar proteinsi

Entry informationi

Entry nameiTNFB_HUMAN
AccessioniPrimary (citable) accession number: P01374
Secondary accession number(s): Q8N4C3, Q9UKS8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 1, 1989
Last modified: July 18, 2018
This is version 195 of the entry and version 2 of the sequence. See 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

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