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Protein

Tumor necrosis factor ligand superfamily member 4

Gene

TNFSF4

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

Functioni

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000117586.10
HGNCiHGNC:11934 TNFSF4
MIMi603594 gene
neXtProtiNX_P23510

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

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

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

Chemistry databases

ChEMBLiCHEMBL3712900

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...) asparagineSequence analysis1
Disulfide bondi97 ↔ 1811 Publication
Glycosylationi114N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi152N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi157N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP23510
PeptideAtlasiP23510
PRIDEiP23510
ProteomicsDBi54122

PTM databases

iPTMnetiP23510
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

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-3023N
IntActiP23510, 3 interactors
MINTiP23510
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

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

Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR021184 TNF_CS
IPR006052 TNF_dom
IPR008983 Tumour_necrosis_fac-like_dom
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS00251 TNF_1, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiTNFL4_HUMAN
AccessioniPrimary (citable) accession number: P23510
Secondary accession number(s): Q5JZA5, Q8IV74, Q9HCN9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: June 20, 2018
This is version 152 of the entry and version 1 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, 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

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