TNFSF10L2 (Danio rerio)
Description [+]
- Synonyms: TNFSF10L2, TUMOR NECROSIS FACTOR (LIGAND) SUPERFAMILY MEMBER 10 LIKE 2, DL2, ZGC:92320, DR_TRAIL-LIKE V3
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
- Short gene description: tumor necrosis factor (ligand) superfamily, member 10 like 2 [Source:RefSeq_peptide;Acc:NP_001002593]
- Family: Death ligand
- Process: apoptosis,
- Pathways: extrinsic pathway,
- Criteria: manually curated
- Curator comment: Ectopic expression of Tnfsf10l2 in zebrafish embryos induces apoptosis in the notochord [16888647] . Tnfsf10l2 directly associates with the zebrafish death receptor Tnfrsfa and Tnfsf10l2-induced apoptosis can be blocked by knockdown of endogenous Tnfrsfa [16888647] . Zebrafish Tnfsf10l2 exhibits greater structural similarity to mammalian Apo2L/TRAIL than other zebrafish Apo2L/TRAIL homologs 16888647 .
- Human ortholog(s): TNFSF10
- WIKI: TNFSF10L2-D_rerio
References [+]
- Delineation of the cell-extrinsic apoptosis pathway in the zebrafish.
- Eimon PM, Kratz E, Varfolomeev E, Hymowitz SG, Stern H, Zha J, Ashkenazi A
- The mammalian extrinsic apoptosis pathway is triggered by Fas ligand (FasL) and Apo2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL). Ligand binding to cognate receptors activates initiator caspases directly in a death-inducing signaling complex. In Drosophila, TNF ligand binding activates initiator caspases indirectly, through JNK. We characterized the extrinsic pathway in zebrafish to determine how it operates in a nonmammalian vertebrate. We identified homologs of FasL and Apo2L/TRAIL, their receptors, and other components of the cell death machinery. Studies with three Apo2L/TRAIL homologs demonstrated that they bind the receptors zHDR (previously linked to hematopoiesis) and ovarian TNFR (zOTR). Ectopic expression of these ligands during embryogenesis induced apoptosis in erythroblasts and notochord cells. Inhibition of zHDR, zOTR, the adaptor zFADD, or caspase-8-like proteases blocked ligand-induced apoptosis, as did antiapoptotic Bcl-2 family members. Thus, the extrinsic apoptosis pathway in zebrafish closely resembles its mammalian counterpart and cooperates with the intrinsic pathway to trigger tissue-specific apoptosis during embryogenesis in response to ectopic Apo2L/TRAIL expression. Cell Death Differ. 2006 Oct;13(10):1619-30. Epub 2006 Aug 4.
- Early diversification of the TNF superfamily in teleosts: genomic characterization and expression analysis.
- Glenney GW,Wiens GD
- The TNF superfamily (TNFSF) of proteins are cytokines involved in diverse immunological and developmental pathways. Little is known about their evolution or expression in lower vertebrate species. Bioinformatic searches of Zebrafish, Tetraodon, and Fugu genome and other teleost expressed sequence tag databases identified 44 novel gene sequences containing a TNF homology domain. This work reveals the following: 1) teleosts possess orthologs of BAFF, APRIL, EDA, TWEAK, 4-1BBL, Fas ligand, LIGHT, CD40L, RANKL, and possibly TL1A; 2) the BAFF-APRIL subfamily is enriched by a third member, BALM, unique to fish; 3) orthologs of lymphotoxins alpha and beta were not clearly identified in teleosts and are substituted by a related ligand, TNF-New; 4) as many as four TRAIL-like genes are present in teleosts, as compared with only one in mammals; and 5) T cell activation ligands OX40L, CD27L, CD30L, and GITRL were not identified in any fish species. Finally, we characterize mRNA expression of TNFSF members CD40L, LIGHT, BALM, APRIL, Fas ligand, RANKL, TRAIL-like, and TNF-New in rainbow trout, Oncorhynchus mykiss, immune and nonimmune tissues. In conclusion, we identified a total of 14 distinct TNFSF members in fishes, indicating expansion of this superfamily before the divergence of bony fish and tetrapods, approximately 360-450 million years ago. Based on these findings, we extend a model of TNFSF evolution and the co-emergence of the vertebrate adaptive immune system. J Immunol. 2007 Jun 15;178(12):7955-73.
- References from Human ortholog(s):
- 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.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | TNF | 158 | 298 |
Protein sequence [+]
tnfsf10l2 | Danio rerio | 7955 | length:299
MVSMTSSHTMQYIGLLLLAAILLQTIAVAVTFIYFSNVLSTMKETFSKSSVSCLMRANLR
TIKGQELNGAEGKDDPCWQVTQQLHFLIEKSMSSRYQKEITSAVKDEVSRVLPSLVIQDQ
EDSSRPKIAAHVTGSYTPESEKDGAGLPNRKVYGQKIQSWESEKGLAFLQNVELSDGELV
VPQAGLYYIYSQTYFRHTLIEEDESAREDEYGSMGESVRGKPMLQYVYKKVSSYQVPILL
MKNARTTCWSRDSEYGLYSIYQAGLFQLGSGDRVFVTVSNVSTIDMDEKSSFFGAFLVS
TIKGQELNGAEGKDDPCWQVTQQLHFLIEKSMSSRYQKEITSAVKDEVSRVLPSLVIQDQ
EDSSRPKIAAHVTGSYTPESEKDGAGLPNRKVYGQKIQSWESEKGLAFLQNVELSDGELV
VPQAGLYYIYSQTYFRHTLIEEDESAREDEYGSMGESVRGKPMLQYVYKKVSSYQVPILL
MKNARTTCWSRDSEYGLYSIYQAGLFQLGSGDRVFVTVSNVSTIDMDEKSSFFGAFLVS
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 (1 of 2) | orthology | Fugu |
| TNFSF10 | orthology | Gorilla |
| TNFSF10 | orthology | Horse |
| TNFSF10 | orthology | Human |
| TNFSF10 | orthology | Lyzard |
| TNFSF10 | orthology | Macaca |
| TNFSF10 (1 of 2) | orthology | Medaka |
| TNFSF10 | orthology | Monodelphis |
| TRAIL | orthology | Mouse |
| TNFSF10 | orthology | Orangutan |
| TNFSF10 | orthology | Ornithorhynchus |
| O_cuniculus_ENSOCUP00000004879 | orthology | Rabbit |
| O_cuniculus_ENSOCUP00000012761 | orthology | Rabbit |
| Tnfsf10 | orthology | Rat |
| TNFSF10 (1 of 2) | orthology | Tetraodon |
| TNFSF10 | orthology | Zebra finch |
| 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 |
| TNFB_PANTR | paralogy | Chimpanzee |
| TNFA_PANTR | paralogy | Chimpanzee |
| TNFSF15 | paralogy | Chimpanzee |
| TNFC_PANTR | paralogy | Chimpanzee |
| TNFB_BOVIN | paralogy | Cow |
| IPI00690656.3 | paralogy | Cow |
| A6QQA4_BOVIN | paralogy | Cow |
| Q9TTJ2_BOVIN | paralogy | Cow |
| TNFA_BOVIN | paralogy | Cow |
| IPI00694513.2 | paralogy | Cow |
| NP_001095325.1 | paralogy | Cow |
| NP_001092329.1 | paralogy | Cow |
| NP_001092329.1 | paralogy | Cow |
| TNFB_CANFA | paralogy | Dog |
| TNFA_CANFA | paralogy | Dog |
| LTB | paralogy | Dog |
| TNFSF15 | paralogy | Dog |
| TNFSF11 | paralogy | Dog |
| FASLG | paralogy | Dog |
| TNFSF14 | paralogy | Dog |
| T_rubripes_ENSTRUP00000014307 | paralogy | Fugu |
| NP_001033074.1 | paralogy | Fugu |
| TNFSF11 | paralogy | Fugu |
| TNFSF10 (2 of 2) | paralogy | Fugu |
| FASLG | paralogy | Fugu |
| TNFSF10 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000017676 | paralogy | Gasterosteus |
| LTA | paralogy | Gorilla |
| Q8HZD8_9PRIM | paralogy | Gorilla |
| LTB | paralogy | Gorilla |
| TNFSF15 | paralogy | Gorilla |
| TNFSF11 | paralogy | Gorilla |
| TNFSF14 | paralogy | Gorilla |
| LTA | paralogy | Horse |
| LTB | paralogy | Horse |
| TNFSF15 | paralogy | Horse |
| FASLG | paralogy | Horse |
| TNFSF11 | paralogy | Horse |
| TNFSF14 | paralogy | Horse |
| LTB | paralogy | Human |
| H_sapiens_ENSP00000372790 | paralogy | Human |
| LTA | paralogy | Human |
| LTB | paralogy | Human |
| H_sapiens_ENSP00000372988 | paralogy | Human |
| LTA | paralogy | Human |
| LTA | paralogy | Human |
| TNFSF11 | paralogy | Human |
| TNFSF14 | paralogy | Human |
| FASL | paralogy | Human |
| TNFSF15 | paralogy | Human |
| LTB | paralogy | Human |
| TNF | paralogy | Human |
| A_carolinensis_ENSACAP00000001868 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000006055 | paralogy | Lyzard |
| TNFSF14 | paralogy | Lyzard |
| TNFL6_MACMU | paralogy | Macaca |
| TNFB_MACMU | paralogy | Macaca |
| TNFA_MACMU | paralogy | Macaca |
| TNFC_MACMU | paralogy | Macaca |
| TNFSF15 | paralogy | Macaca |
| TNFSF11 | paralogy | Macaca |
| O_latipes_ENSORLP00000010677 | paralogy | Medaka |
| TNFSF10 (2 of 2) | paralogy | Medaka |
| O_latipes_ENSORLP00000020071 | paralogy | Medaka |
| LTB | paralogy | Monodelphis |
| LTA | paralogy | Monodelphis |
| TNFSF15 | paralogy | Monodelphis |
| TNF | paralogy | Monodelphis |
| TNFSF14 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000036348 | paralogy | Monodelphis |
| Fasl | paralogy | Mouse |
| Tnfsf14 | paralogy | Mouse |
| Tnfsf11 | paralogy | Mouse |
| Ltb | paralogy | Mouse |
| Tnf | paralogy | Mouse |
| Lta | paralogy | Mouse |
| Tnfsf15 | paralogy | Mouse |
| FASLG | paralogy | Orangutan |
| TNFSF11 | paralogy | Orangutan |
| LTA | paralogy | Orangutan |
| Q8HZD7_PONPY | paralogy | Orangutan |
| LTB | paralogy | Orangutan |
| TNFSF15 | paralogy | Orangutan |
| TNFSF15 | paralogy | Ornithorhynchus |
| CD40LG | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000022049 | paralogy | Ornithorhynchus |
| FASLG | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000007357 | paralogy | Ornithorhynchus |
| TNFSF14 | paralogy | Ornithorhynchus |
| TNFB_RABIT | paralogy | Rabbit |
| LTB | paralogy | Rabbit |
| TNFSF14 | paralogy | Rabbit |
| TNFSF11 | paralogy | Rabbit |
| TNFSF15 | paralogy | Rabbit |
| Faslg | paralogy | Rat |
| Tnfsf15 | paralogy | Rat |
| Tnfsf11 | paralogy | Rat |
| Ltb | paralogy | Rat |
| Tnf | paralogy | Rat |
| TNF | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000008505 | paralogy | Tetraodon |
| TNFSF10 (2 of 2) | paralogy | Tetraodon |
| TNFSF11 | 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 |
| tnfsf10l3 | paralogy | Zebrafish |
| tnfsf10l4 | paralogy | Zebrafish |
| LOC564826 | paralogy | Zebrafish |
| tnfb | paralogy | Zebrafish |
| tnfsf10l | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006955 | immune response | biological_proccess | IEA |
| GO:0005164 | tumor necrosis factor receptor binding | mollecular_function | IEA |
| GO:0016020 | membrane | cell_component | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Information from other databases [+]
- Gene info from ZFIN [?] ZDB-GENE-040718-335
- Ensembl genome browser [?] : ENSDARG00000057241
- Expression info from Arrayexpress [?] : ENSDARG00000057241
- Protein expression from Protein Atlas: [?] ENSDARG00000057241
- Community gene edition from Wikigenes: [?] 436866
- entrezgene: 436866
- refseq_dna: NM_001002593
- refseq_peptide: NP_001002593
Click on [?] for more information.
