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Protein

Tumor necrosis factor ligand superfamily member 4

Gene

TNFSF4

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

Functioni

Cytokine that binds to TNFRSF4. Co-stimulates T-cell proliferation and cytokine production.

GO - Molecular functioni

  • receptor binding Source: ProtInc
  • tumor necrosis factor receptor superfamily binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Enzyme and pathway databases

BioCyciZFISH:ENSG00000117586-MONOMER.
ReactomeiR-HSA-5669034. TNFs bind their physiological receptors.
SIGNORiP23510.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor ligand superfamily member 4
Alternative name(s):
Glycoprotein Gp34
OX40 ligand
Short name:
OX40L
TAX transcriptionally-activated glycoprotein 1
CD_antigen: CD252
Gene namesi
Name:TNFSF4
Synonyms:TXGP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:11934. TNFSF4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 23CytoplasmicSequence analysisAdd BLAST23
Transmembranei24 – 50Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST27
Topological domaini51 – 183ExtracellularSequence analysisAdd BLAST133

GO - Cellular componenti

  • cell surface Source: BHF-UCL
  • extracellular space Source: BHF-UCL
  • integral component of plasma membrane Source: BHF-UCL
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Systemic lupus erythematosus (SLE)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry. The upstream region of TNFSF4 contains a single risk haplotype for SLE, which is correlated with increased expression of both cell-surface TNFSF4 and TNFSF4 transcripts. Increased levels of TNFSF4 are thought to augment T-cell-APC interaction and the functional consequences of T-cell activation, thereby destabilizing peripheral tolerance.
Disease descriptionA chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
See also OMIM:152700

Keywords - Diseasei

Systemic lupus erythematosus

Organism-specific databases

DisGeNETi7292.
MalaCardsiTNFSF4.
MIMi152700. phenotype.
OpenTargetsiENSG00000117586.
Orphaneti2073. Narcolepsy-cataplexy.
536. Systemic lupus erythematosus.
PharmGKBiPA36625.

Polymorphism and mutation databases

BioMutaiTNFSF4.
DMDMi121540.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001854931 – 183Tumor necrosis factor ligand superfamily member 4Add BLAST183

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi90N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi97 ↔ 1811 Publication
Glycosylationi114N-linked (GlcNAc...)Sequence analysis1
Glycosylationi152N-linked (GlcNAc...)1 Publication1
Glycosylationi157N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP23510.
PeptideAtlasiP23510.
PRIDEiP23510.

PTM databases

PhosphoSitePlusiP23510.

Expressioni

Inductioni

By HTLV-1 transactivator p40-Tax.

Gene expression databases

BgeeiENSG00000117586.
CleanExiHS_TNFSF4.
ExpressionAtlasiP23510. baseline and differential.
GenevisibleiP23510. HS.

Organism-specific databases

HPAiHPA059579.

Interactioni

Subunit structurei

Homotrimer.1 Publication

GO - Molecular functioni

  • receptor binding Source: ProtInc
  • tumor necrosis factor receptor superfamily binding Source: BHF-UCL

Protein-protein interaction databases

DIPiDIP-3023N.
IntActiP23510. 1 interactor.
STRINGi9606.ENSP00000281834.

Structurei

Secondary structure

1183
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi61 – 70Combined sources10
Turni71 – 73Combined sources3
Beta strandi74 – 78Combined sources5
Beta strandi92 – 94Combined sources3
Beta strandi99 – 120Combined sources22
Beta strandi126 – 143Combined sources18
Beta strandi148 – 155Combined sources8
Beta strandi165 – 174Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HEVX-ray2.41F51-183[»]
ProteinModelPortaliP23510.
SMRiP23510.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23510.

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J0GG. Eukaryota.
ENOG41119SD. LUCA.
GeneTreeiENSGT00390000015127.
HOGENOMiHOG000076309.
HOVERGENiHBG056457.
InParanoidiP23510.
KOiK05469.
OMAiMEGVQPL.
OrthoDBiEOG091G0OEG.
PhylomeDBiP23510.
TreeFamiTF336384.

Family and domain databases

InterProiIPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P23510-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MERVQPLEEN VGNAARPRFE RNKLLLVASV IQGLGLLLCF TYICLHFSAL
60 70 80 90 100
QVSHRYPRIQ SIKVQFTEYK KEKGFILTSQ KEDEIMKVQN NSVIINCDGF
110 120 130 140 150
YLISLKGYFS QEVNISLHYQ KDEEPLFQLK KVRSVNSLMV ASLTYKDKVY
160 170 180
LNVTTDNTSL DDFHVNGGEL ILIHQNPGEF CVL
Length:183
Mass (Da):21,050
Last modified:November 1, 1991 - v1
Checksum:i0D5604AD29D529CF
GO
Isoform 2 (identifier: P23510-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: MERVQPLEENVGNAARPRFERNKLLLVASVIQGLGLLLCFTYICLHFSALQ → M

Show »
Length:133
Mass (Da):15,427
Checksum:i27AF148E6E528C8F
GO

Sequence cautioni

The sequence CAA18438 differs from that shown. Reason: Erroneous gene model prediction.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0562881 – 51MERVQ…FSALQ → M in isoform 2. 2 PublicationsAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D90224 mRNA. Translation: BAA14259.1.
X79929 mRNA. Translation: CAA56284.1.
AK297932 mRNA. Translation: BAG60249.1.
AL022310 Genomic DNA. Translation: CAA18438.2. Sequence problems.
AL022310 Genomic DNA. Translation: CAI20416.1.
CH471067 Genomic DNA. Translation: EAW90938.1.
BC041663 mRNA. Translation: AAH41663.1.
AB042988 Genomic DNA. Translation: BAB18304.1.
CCDSiCCDS1306.1. [P23510-1]
CCDS72985.1. [P23510-2]
PIRiA39680.
RefSeqiNP_001284491.1. NM_001297562.1. [P23510-2]
NP_003317.1. NM_003326.4. [P23510-1]
UniGeneiHs.181097.

Genome annotation databases

EnsembliENST00000281834; ENSP00000281834; ENSG00000117586. [P23510-1]
ENST00000367718; ENSP00000356691; ENSG00000117586. [P23510-2]
GeneIDi7292.
KEGGihsa:7292.
UCSCiuc001giv.4. human. [P23510-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D90224 mRNA. Translation: BAA14259.1.
X79929 mRNA. Translation: CAA56284.1.
AK297932 mRNA. Translation: BAG60249.1.
AL022310 Genomic DNA. Translation: CAA18438.2. Sequence problems.
AL022310 Genomic DNA. Translation: CAI20416.1.
CH471067 Genomic DNA. Translation: EAW90938.1.
BC041663 mRNA. Translation: AAH41663.1.
AB042988 Genomic DNA. Translation: BAB18304.1.
CCDSiCCDS1306.1. [P23510-1]
CCDS72985.1. [P23510-2]
PIRiA39680.
RefSeqiNP_001284491.1. NM_001297562.1. [P23510-2]
NP_003317.1. NM_003326.4. [P23510-1]
UniGeneiHs.181097.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HEVX-ray2.41F51-183[»]
ProteinModelPortaliP23510.
SMRiP23510.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-3023N.
IntActiP23510. 1 interactor.
STRINGi9606.ENSP00000281834.

PTM databases

PhosphoSitePlusiP23510.

Polymorphism and mutation databases

BioMutaiTNFSF4.
DMDMi121540.

Proteomic databases

PaxDbiP23510.
PeptideAtlasiP23510.
PRIDEiP23510.

Protocols and materials databases

DNASUi7292.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000281834; ENSP00000281834; ENSG00000117586. [P23510-1]
ENST00000367718; ENSP00000356691; ENSG00000117586. [P23510-2]
GeneIDi7292.
KEGGihsa:7292.
UCSCiuc001giv.4. human. [P23510-1]

Organism-specific databases

CTDi7292.
DisGeNETi7292.
GeneCardsiTNFSF4.
HGNCiHGNC:11934. TNFSF4.
HPAiHPA059579.
MalaCardsiTNFSF4.
MIMi152700. phenotype.
603594. gene.
neXtProtiNX_P23510.
OpenTargetsiENSG00000117586.
Orphaneti2073. Narcolepsy-cataplexy.
536. Systemic lupus erythematosus.
PharmGKBiPA36625.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0GG. Eukaryota.
ENOG41119SD. LUCA.
GeneTreeiENSGT00390000015127.
HOGENOMiHOG000076309.
HOVERGENiHBG056457.
InParanoidiP23510.
KOiK05469.
OMAiMEGVQPL.
OrthoDBiEOG091G0OEG.
PhylomeDBiP23510.
TreeFamiTF336384.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000117586-MONOMER.
ReactomeiR-HSA-5669034. TNFs bind their physiological receptors.
SIGNORiP23510.

Miscellaneous databases

ChiTaRSiTNFSF4. human.
EvolutionaryTraceiP23510.
GenomeRNAii7292.
PROiP23510.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117586.
CleanExiHS_TNFSF4.
ExpressionAtlasiP23510. baseline and differential.
GenevisibleiP23510. HS.

Family and domain databases

InterProiIPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNFL4_HUMAN
AccessioniPrimary (citable) accession number: P23510
Secondary accession number(s): Q5JZA5, Q8IV74, Q9HCN9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: November 2, 2016
This is version 142 of the entry and version 1 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, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. 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.