TNFSF10 (Homo sapiens)
Description [+]
- Synonyms: TNFSF10, TRAIL, APO-2L, APO2L TL2, CD253
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Tumor necrosis factor ligand superfamily member 10 (TNF-related apoptosis-inducing ligand)(Protein TRAIL)(Apoptosis ligand 2, Apo-2 ligand)(Apo-2L)(Apo2L)(CD253 antigen)
- Family: Death ligand
- Process: apoptosis,
- Pathways: extrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): TRAIL
- WIKI: TNFSF10-H_sapiens
References [+]
- Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family.
- Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A
- Cytokines in the tumor necrosis factor (TNF) family regulate development and function of the immune system. We have isolated a new member of this family, designated Apo-2 ligand (Apo-2L), via an expressed sequence tag. Apo-2L is a 281-amino acid protein, related most closely to Fas/Apo-1 ligand. Transfected Apo-2L is expressed at the cell surface with its C terminus exposed, indicating a type II transmembrane protein topology. Like Fas/Apo-1 ligand and TNF, the C-terminal extracellular region of Apo-2L (amino acids 114-281) exhibits a homotrimeric subunit structure. Soluble Apo-2L induces extensive apoptosis in lymphoid as well as non-lymphoid tumor cell lines. The effect of Apo-2L is not inhibited by soluble Fas/Apo-1 and TNF receptors; moreover, expression of human Fas/Apo-1 in mouse fibroblasts, which confers sensitivity to induction of apoptosis by agonistic anti-Fas/Apo-1 antibody, does not confer sensitivity to Apo-2L. Hence, Apo-2L acts via a receptor which is distinct from Fas/Apo-1 and TNF receptors. These results suggest that, along with other family members such as Fas/Apo-1 ligand and TNF, Apo-2L may serve as an extracellular signal that triggers programmed cell death. J Biol Chem. 1996 May 31;271(22):12687-90.
- References from Mouse ortholog(s):
- Characterization of the in vivo function of TNF-alpha-related apoptosis-inducing ligand, TRAIL/Apo2L, using TRAIL/Apo2L gene-deficient mice.
- Sedger LM, Glaccum MB, Schuh JC, Kanaly ST, Williamson E, Kayagaki N, Yun T, Smolak P, Le T, Goodwin R, Gliniak B
- To define the normal physiological role for the TRAIL/Apo2L in vivo, we generated TRAIL/Apo2L gene-targeted mice. These mice develop normally and show no defects in lymphoid or myeloid cell homeostasis or function. Although TRAIL/Apo2L kills transformed cells in vitro, TRAIL/Apo2L(-/-) mice do not spontaneously develop overt tumors at an early age. However, in the A20 B cell lymphoma-transferred tumor model, TRAIL/Apo2L(-/-) mice are clearly more susceptible to death from overwhelming tumor burden, due to increased lymphoma load in the liver. A20 tumors are susceptible to TRAIL/Apo2L killing in vitro, indicating that TRAIL/Apo2L may act directly to control A20 cells in vivo. Despite the fact that TRAIL binds osteoprotegerin and osteoprotegerin-transgenic mice are osteopetrotic, TRAIL/Apo2L(-/-) mice show no evidence of altered gross bone density, and no alterations in frequency or in vitro differentiation of bone marrow precursor osteoclasts. Moreover, leucine zipper TRAIL has no toxicity when repeatedly administered to osteoprotegerin(-/-) mice. Thus, TRAIL/Apo2L is important in controlling tumors in vivo, but is not an essential regulator of osteoprotegerin-mediated biology, under normal physiological conditions. Eur J Immunol. 2002 Aug;32(8):2246-54.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | TNF | 152 | 280 |
Protein sequence [+]
TNFSF10 | Homo sapiens | 9606 | length:299
MAMMEVQGGPSLGQTCVLIVIFTVLLQSLCVAVTYVYFTNELKQMQDKYSKSGIACFLKE
DDSYWDPNDEESMNSPCWQVKWQLRQLVRKMILRTSEETISTVQEKQQNISPLVRERGPQ
RVAAHITGTRGRSNTLSSPNSKNEKALGRKINSWESSRSGHSFLSNLHLRNGELVIHEKG
FYYIYSQTYFRFQEEIKENTKNDKQMVQYIYKYTSYPDPILLMKSARNSCWSKDAEYGLY
SIYQGGIFELKENDRIFVSVTNEHLIDMDHEASFFGLFSWLTDLERKSNNLKVTIQFSG
DDSYWDPNDEESMNSPCWQVKWQLRQLVRKMILRTSEETISTVQEKQQNISPLVRERGPQ
RVAAHITGTRGRSNTLSSPNSKNEKALGRKINSWESSRSGHSFLSNLHLRNGELVIHEKG
FYYIYSQTYFRFQEEIKENTKNDKQMVQYIYKYTSYPDPILLMKSARNSCWSKDAEYGLY
SIYQGGIFELKENDRIFVSVTNEHLIDMDHEASFFGLFSWLTDLERKSNNLKVTIQFSG
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| NP_989710.1 | orthology | Chicken |
| TNFSF10 | orthology | Chimpanzee |
| IPI00701832.3 | orthology | Cow |
| TNFSF10 | orthology | Dog |
| TNFSF10 (2 of 2) | orthology | Fugu |
| TNFSF10 (1 of 2) | orthology | Fugu |
| TNFSF10 | orthology | Gasterosteus |
| TNFSF10 | orthology | Gorilla |
| TNFSF10 | orthology | Horse |
| TNFSF10 | orthology | Lyzard |
| TNFSF10 | orthology | Macaca |
| TNFSF10 (2 of 2) | orthology | Medaka |
| TNFSF10 (1 of 2) | orthology | Medaka |
| TNFSF10 | orthology | Monodelphis |
| TRAIL | orthology | Mouse |
| TNFSF10 | orthology | Orangutan |
| TNFSF10 | orthology | Ornithorhynchus |
| O_cuniculus_ENSOCUP00000012761 | orthology | Rabbit |
| O_cuniculus_ENSOCUP00000004879 | orthology | Rabbit |
| Tnfsf10 | orthology | Rat |
| TNFSF10 (2 of 2) | orthology | Tetraodon |
| TNFSF10 (1 of 2) | orthology | Tetraodon |
| TNFSF10 | orthology | Zebra finch |
| tnfsf10l2 | orthology | Zebrafish |
| NP_001026730.1 | paralogy | Chicken |
| NP_989922.1 | paralogy | Chicken |
| A3RF19_CHICK | paralogy | Chicken |
| G_gallus_ENSGALP00000034816 | paralogy | Chicken |
| NP_001019749.1 | paralogy | Chicken |
| FASLG | paralogy | Chimpanzee |
| TNFSF11 | paralogy | Chimpanzee |
| TNFSF14 | paralogy | Chimpanzee |
| TNFSF15 | paralogy | Chimpanzee |
| IPI00694513.2 | paralogy | Cow |
| NP_001095325.1 | paralogy | Cow |
| NP_001092329.1 | paralogy | Cow |
| NP_001092329.1 | paralogy | Cow |
| IPI00690656.3 | paralogy | Cow |
| Q9TTJ2_BOVIN | paralogy | Cow |
| TNFSF15 | paralogy | Dog |
| TNFSF11 | paralogy | Dog |
| FASLG | paralogy | Dog |
| TNFSF14 | paralogy | Dog |
| FASLG | paralogy | Fugu |
| T_rubripes_ENSTRUP00000014307 | paralogy | Fugu |
| TNFSF11 | paralogy | Fugu |
| G_aculeatus_ENSGACP00000013603 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000017676 | paralogy | Gasterosteus |
| TNFSF15 | paralogy | Gorilla |
| TNFSF11 | paralogy | Gorilla |
| TNFSF14 | paralogy | Gorilla |
| CD40LG | paralogy | Horse |
| TNFSF15 | paralogy | Horse |
| FASLG | paralogy | Horse |
| TNFSF11 | paralogy | Horse |
| TNFSF14 | paralogy | Horse |
| TNFSF11 | paralogy | Human |
| TNFSF14 | paralogy | Human |
| FASL | paralogy | Human |
| TNFSF15 | paralogy | Human |
| A_carolinensis_ENSACAP00000001868 | paralogy | Lyzard |
| TNFSF15 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000006055 | paralogy | Lyzard |
| TNFSF14 | paralogy | Lyzard |
| TNFL6_MACMU | paralogy | Macaca |
| TNFSF15 | paralogy | Macaca |
| TNFSF11 | paralogy | Macaca |
| O_latipes_ENSORLP00000008487 | paralogy | Medaka |
| O_latipes_ENSORLP00000010677 | paralogy | Medaka |
| O_latipes_ENSORLP00000020071 | paralogy | Medaka |
| CD40LG | paralogy | Monodelphis |
| TNFSF15 | paralogy | Monodelphis |
| TNFSF14 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000036348 | paralogy | Monodelphis |
| Fasl | paralogy | Mouse |
| Tnfsf14 | paralogy | Mouse |
| Tnfsf11 | paralogy | Mouse |
| Tnfsf15 | paralogy | Mouse |
| FASLG | paralogy | Orangutan |
| TNFSF11 | paralogy | Orangutan |
| TNFSF15 | paralogy | Orangutan |
| FASLG | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000007357 | paralogy | Ornithorhynchus |
| TNFSF14 | paralogy | Ornithorhynchus |
| TNFSF15 | paralogy | Ornithorhynchus |
| CD40LG | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000022049 | paralogy | Ornithorhynchus |
| TNFSF11 | paralogy | Rabbit |
| TNFSF15 | paralogy | Rabbit |
| Faslg | paralogy | Rat |
| Tnfsf15 | paralogy | Rat |
| Tnfsf11 | paralogy | Rat |
| T_nigroviridis_ENSTNIP00000008505 | paralogy | Tetraodon |
| TNFSF11 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000017112 | paralogy | Tetraodon |
| FASLG | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000005341 | paralogy | Xenopus |
| TNFSF10 | paralogy | Xenopus |
| CD40LG | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000054163 | paralogy | Xenopus |
| TNFSF15 | paralogy | Xenopus |
| CD40LG | paralogy | Zebra finch |
| TNFSF15 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000005543 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000012735 | paralogy | Zebra finch |
| FASLG | paralogy | Zebra finch |
| tnfb | paralogy | Zebrafish |
| tnfsf10l | paralogy | Zebrafish |
| tnfa | paralogy | Zebrafish |
| tnfsf10l3 | paralogy | Zebrafish |
| faslg | paralogy | Zebrafish |
| tnfsf10l4 | paralogy | Zebrafish |
| LOC564826 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006955 | immune response | biological_proccess | IEA |
| GO:0006917 | induction of apoptosis | biological_proccess | TAS |
| GO:0007165 | signal transduction | biological_proccess | TAS |
| GO:0007267 | cell-cell signaling | biological_proccess | TAS |
| GO:0008633 | activation of pro-apoptotic gene products | biological_proccess | EXP |
| GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB cascade | biological_proccess | IEP |
| GO:0005164 | tumor necrosis factor receptor binding | mollecular_function | IEA |
| GO:0005125 | cytokine activity | mollecular_function | IEA |
| GO:0008270 | zinc ion binding | mollecular_function | IEA |
| GO:0046872 | metal ion binding | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0016020 | membrane | cell_component | IEA |
| GO:0005625 | soluble fraction | cell_component | TAS |
| GO:0005887 | integral to plasma membrane | cell_component | TAS |
| GO:0005576 | extracellular region | cell_component | EXP |
| GO:0005615 | extracellular space | cell_component | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Curated Isoforms [+]
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :11925
- Gene related info from GeneCards [?] : TNFSF10
- Ensembl genome browser [?] : ENSG00000121858
- Expression info from Arrayexpress [?] : ENSG00000121858
- Protein expression from Protein Atlas: [?] ENSG00000121858
- Community gene edition from Wikigenes: [?] 8743
- OMIM gene information: 603598
- OMIM disease information:
Click on [?] for more information.
