TNFSF4
Tumor necrosis factor ligand superfamily member 4
Also known as: CD252, gp34, OX-40L, TNFL4_HUMAN, TXGP1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P23510
- Gene
- TNFSF4
- Ensembl
- ENSG00000117586
- Chromosome
- 1
- Canonical length
- 183 aa
- Protein class
- Cancer-related genes, CD markers, Disease related genes, Human disease related genes, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Vesicles
- Quaternary structure
- Homotrimer
OverviewNCBI Gene
This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Canonical amino-acid sequenceUniProt
183 residues, UniProt reviewed canonical sequence.
>P23510|TNFSF4
1 MERVQPLEEN VGNAARPRFE RNKLLLVASV IQGLGLLLCF TYICLHFSAL QVSHRYPRIQ
61 SIKVQFTEYK KEKGFILTSQ KEDEIMKVQN NSVIINCDGF YLISLKGYFS QEVNISLHYQ
121 KDEEPLFQLK KVRSVNSLMV ASLTYKDKVY LNVTTDNTSL DDFHVNGGEL ILIHQNPGEF
181 CVLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against TNFSF4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.4
- Highest tissue expression
- 3.7 nTPM
Expression across tissuesHPA
Tissue
- testis: 3.7 nTPM
- thymus: 3.5 nTPM
- appendix: 2.1 nTPM
- lymph node: 2.1 nTPM
- adrenal gland: 1.9 nTPM
- cerebellum: 1.9 nTPM
Single-cell type
- platelets: 442 nCPM
- thymocytes: 43 nCPM
- innate lymphoid cells: 37 nCPM
- hematopoietic stem cells: 28 nCPM
- megakaryocyte progenitors: 9.6 nCPM
- astrocytes: 8.9 nCPM
Immune cell
- total PBMC: 2.8 nTPM
- NK-cell: 1.7 nTPM
- plasmacytoid DC: 1.2 nTPM
- neutrophil: 0.7 nTPM
- gdT-cell: 0.5 nTPM
- memory B-cell: 0.5 nTPM
Brain region
- cerebellum: 4.6 nTPM
- basal ganglia: 4 nTPM
- cerebral cortex: 4 nTPM
- medulla oblongata: 3.9 nTPM
- pons: 3.9 nTPM
- midbrain: 3.7 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about TNFSF4.
Disease | AllUniProt
Conditions TNFSF4 is implicated in, by any mechanism.
- Systemic lupus erythematosus (SLE) MIM:152700
ReferencesPubMed · IEDB
Publications for TNFSF4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
1 publication
- Blockade of OX40/OX40L signaling using anti-OX40L alleviates murine lupus nephritis.
2024 · Eur J Immunol · RCR 1 · 6 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.68
- gnomAD pLI
- 0.05
- gnomAD missense Z
- 0.92
- DepMap mean gene effect
- 0.09
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- acute inflammatory response
- cellular response to lipopolysaccharide
- cellular response to prostaglandin E stimulus
- defense response to nematode
- immune response
- inflammatory response
- memory T cell activation
- negative regulation of interleukin-17 production
- negative regulation of regulatory T cell differentiation
- negative regulation of T-helper 1 cell differentiation
- negative regulation of transcription by RNA polymerase II
- negative regulation of type II interferon production
- positive regulation of alpha-beta T cell proliferation
- positive regulation of B cell activation
- positive regulation of CD4-positive, alpha-beta T cell differentiation
- positive regulation of cell population proliferation
- positive regulation of chemokine production
- positive regulation of cytokine production
- positive regulation of immunoglobulin mediated immune response
- positive regulation of immunoglobulin production
- positive regulation of inflammatory response
- positive regulation of interleukin-10 production
- positive regulation of interleukin-12 production
- positive regulation of interleukin-13 production
- positive regulation of interleukin-4 production
- positive regulation of interleukin-6 production
- positive regulation of memory T cell differentiation
- positive regulation of T cell cytokine production
- positive regulation of T cell proliferation
- positive regulation of T-helper 2 cell differentiation
- positive regulation of type 2 immune response
- positive regulation of type II interferon production
- regulation of adaptive immune response
- regulation of inflammatory response
- response to virus
- signal transduction
- positive regulation of CD4-positive, alpha-beta T cell costimulation
- positive regulation of interleukin-4-dependent isotype switching to IgE isotypes
- response to nitrogen dioxide
- T-helper 2 cell activation
Molecular functions
- cytokine activity
- signaling receptor binding
- tumor necrosis factor receptor binding
- tumor necrosis factor receptor superfamily binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Tumour necrosis factor domain
- Tumour necrosis factor-like domain superfamily
- Tumour necrosis factor, conserved site
- Tumor necrosis factor ligand superfamily member 4
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads TNFSF4 as an antibody target. Whether an autoantibody or antibody against TNFSF4 could matter depends on whether native TNFSF4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
TNFSF4 is annotated at the cell surface, where native TNFSF4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label TNFSF4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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