TNFSF9

Protein identityUniProt · HPA

UniProt accession

P41273

Gene

TNFSF9

Ensembl

ENSG00000125657

Chromosome

19

Canonical length

254 aa

Protein class

Plasma proteins, Predicted intracellular proteins

Subcellular location

Golgi apparatus

Quaternary structure

Homotrimer

OverviewNCBI Gene

The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This transmembrane cytokine is a bidirectional signal transducer that acts as a ligand for TNFRSF9/4-1BB, which is a costimulatory receptor molecule in T lymphocytes. This cytokine and its receptor are involved in the antigen presentation process and in the generation of cytotoxic T cells. The receptor TNFRSF9/4-1BB is absent from resting T lymphocytes but rapidly expressed upon antigenic stimulation. The ligand encoded by this gene, TNFSF9/4-1BBL, has been shown to reactivate anergic T lymphocytes in addition to promoting T lymphocyte proliferation. This cytokine has also been shown to be required for the optimal CD8 responses in CD8 T cells. This cytokine is expressed in carcinoma cell lines, and is thought to be involved in T cell-tumor cell interaction.[provided by RefSeq, Oct 2008]

Canonical amino-acid sequenceUniProt

254 residues, UniProt reviewed canonical sequence.

>P41273|TNFSF9
     1  MEYASDASLD PEAPWPPAPR ARACRVLPWA LVAGLLLLLL LAAACAVFLA CPWAVSGARA
    61  SPGSAASPRL REGPELSPDD PAGLLDLRQG MFAQLVAQNV LLIDGPLSWY SDPGLAGVSL
   121  TGGLSYKEDT KELVVAKAGV YYVFFQLELR RVVAGEGSGS VSLALHLQPL RSAAGAAALA
   181  LTVDLPPASS EARNSAFGFQ GRLLHLSAGQ RLGVHLHTEA RARHAWQLTQ GATVLGLFRV
   241  TPEIPAGLPS PRSE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNFSF9 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)

0.44

Highest tissue expression

9.6 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for TNFSF9 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.

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)

1.12

gnomAD pLI

0.32

gnomAD missense Z

-0.48

DepMap mean gene effect

-0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell-cell signaling
• immune response
• positive regulation of activated T cell proliferation
• positive regulation of cytotoxic T cell differentiation
• regulation of apoptotic process
• regulation of T cell proliferation

Molecular functions

• cytokine activity
• signaling receptor binding
• tumor necrosis factor receptor binding
• tumor necrosis factor receptor superfamily binding

Cellular components

• extracellular space
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Tumour necrosis factor domain
• Tumour necrosis factor-like domain superfamily
• Tumour necrosis factor, conserved site
• TNF(Tumour Necrosis Factor) family
• Tumor necrosis factor ligand superfamily member 9

KeywordsUniProt

• Cytokine
• Membrane
• Signal-anchor
• Transmembrane
• Transmembrane helix