TNFRSF1B (Homo sapiens)
Description [+]
- Synonyms: TNFRSF1B, TNFBR, TNFR80, TNF-R75, TNF-R-II, P75, CD120B
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Tumor necrosis factor receptor superfamily member 1B Precursor (Tumor necrosis factor receptor 2)(TNF-R2)(Tumor necrosis factor receptor type II)(p75)(p80 TNF-alpha receptor)(CD120b antigen)(Etanercept) [Contains Tumor necrosis factor receptor superfamily member 1b, membrane form;Tumor necrosis factor-binding protein 2(TBPII)(TBP-2)] [Source:UniProtKB/Swiss-Prot;Acc:P20333]
- Family: death receptor
- Process: apoptosis,
- Pathways: extrinsic pathway, TNF/NF-kappaB signaling,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Tnfrsf1b
- WIKI: TNFRSF1B-H_sapiens
References [+]
- The TNF and TNF receptor superfamilies: integrating mammalian biology.
- Locksley RM, Killeen N, Lenardo MJ
- Cell. 2001 Feb 23;104(4):487-501.
- Both TNF receptors are required for TNF-mediated induction of apoptosis in PC60 cells.
- Vandenabeele P, Declercq W, Vanhaesebroeck B, Grooten J, Fiers W
- A rat/mouse T cell hybridoma (PC60) was transfected either with human (h) TNF-R p55 (TNF-R55), p75 (TNF-R75) or both cDNAs. hTNF-R55 expression was below 50 molecules/cell, whereas the number of hTNF-R75 reached about 4000 molecules/cell. Only cells co-expressing the two types of receptor showed TNF-dependent apoptosis, in contrast to cells expressing similar levels of only one receptor type, indicating that both TNF-R55 and TNF-R75 are required. Stable co-transfection of the bcl-2 proto-oncogene largely prevented this TNF-mediated induction of apoptosis. We found that a high level of hTNF-R75 expression was essential for obtaining TNF-dependent apoptosis in PC60 cells in addition to a low number of hTNF-R55. Both receptors are signal transducing because simultaneous triggering of hTNF-R55 and hTNF-R75 by agonistic mAbs or by TNF-R-specific TNF muteins induced similar levels of apoptosis as wild-type hTNF. Apoptotic killing of only those lymphocytes expressing a high, induced level of TNF-R75, in addition to TNF-R55, may play a physiologically important role. J Immunol. 1995 Mar 15;154(6):2904-13.
- References from Mouse ortholog(s):
- Molecular cloning and expression of the type 1 and type 2 murine receptors for tumor necrosis factor.
- Goodwin RG, Anderson D, Jerzy R, Davis T, Brannan CI, Copeland NG, Jenkins NA, Smith CA
- Clones encoding the type 1 (p80) and type 2 (p60) forms of the murine receptors for tumor necrosis factor (TNF) were isolated by cross-hybridization using probes derived from the cloned human TNF receptors. Each of the murine receptors shows strong sequence homology to the corresponding human receptor (approximately 65% amino acid identity) throughout the molecule but only modest homology, limited to ligand-binding domains, between themselves. The ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs: both receptor types bind TNF-alpha and -beta with multiple affinity classes, and the ligands cross-compete. Analysis of the murine transcripts encoding these receptors revealed the presence of RNAs for one or both forms of the receptors in all cells examined. It was also demonstrated that for both types of human TNF receptor, variably sized transcripts are observed in different cells. The murine cDNAs were further used to determine the chromosomal locations of the TNF receptor genes. They are not linked, in contrast to the ligands, and map to chromosomes 4 (type 1) and 6 (type 2). Mol Cell Biol. 1991 Jun;11(6):3020-6.
- A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses.
- Chan FK, Shisler J, Bixby JG, Felices M, Zheng L, Appel M, Orenstein J, Moss B, Lenardo MJ
- Members of the tumor necrosis factor (TNF) receptor (TNFR) superfamily are potent regulators of apoptosis, a process that is important for the maintenance of immune homeostasis. Recent evidence suggests that TNFR-1 and Fas and TRAIL receptors can also trigger an alternative form of cell death that is morphologically distinct from apoptosis. Because distinct molecular components including the serine/threonine protein kinase receptor-interacting protein (RIP) are required, we have referred to this alternative form of cell death as programmed necrosis. We show that TNFR-2 signaling can potentiate programmed necrosis via TNFR-1. When cells were pre-stimulated through TNFR-2 prior to subsequent activation of TNFR-1, enhanced cell death and recruitment of RIP to the TNFR-1 complex were observed. However, TNF-induced programmed necrosis was normally inhibited by caspase-8 cleavage of RIP. To ascertain the physiological significance of RIP and programmed necrosis, we infected Jurkat cells with vaccinia virus (VV) and found that VV-infected cells underwent programmed necrosis in response to TNF, but deficiency of RIP rescued the infected cells from TNF-induced cytotoxicity. Moreover, TNFR-2-/- mice exhibited reduced inflammation in the liver and defective viral clearance during VV infection. Interestingly, death effector domain-containing proteins such as MC159, E8, K13, and cellular FLIP, but not the apoptosis inhibitors Bcl-xL, p35, and XIAP, potently suppressed programmed necrosis. Thus, TNF-induced programmed necrosis is facilitated by TNFR-2 signaling and caspase inhibition and may play a role in controlling viral infection. J Biol Chem. 2003 Dec 19;278(51):51613-21. Epub 2003 Oct 7.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | TNFR_c6 | 40 | 75 |
| PFAM A | TNFR_c6 | 78 | 118 |
Protein sequence [+]
TNFRSF1B | Homo sapiens | 9606 | length:461
MAPVAVWAALAVGLELWAAAHALPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPG
QHAKVFCTKTSDTVCDSCEDSTYTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTC
RPGWYCALSKQEGCRLCAPLRKCRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICR
PHQICNVVAIPGNASMDAVCTSTSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTS
FLLPMGPSPPAEGSTGDFALPVGLIVGVTALGLLIIGVVNCVIMTQVKKKPLCLQREAKV
PHLPADKARGTQGPEQQHLLITAPSSSSSSLESSASALDRRAPTRNQPQAPGVEASGAGE
ARASTGSSDSSPGGHGTQVNVTCIVNVCSSSDHSSQCSSQASSTMGDTDSSPSESPKDEQ
VPFSKEECAFRSQLETPETLLGSTEEKPLPLGVPDAGMKPS
QHAKVFCTKTSDTVCDSCEDSTYTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTC
RPGWYCALSKQEGCRLCAPLRKCRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICR
PHQICNVVAIPGNASMDAVCTSTSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTS
FLLPMGPSPPAEGSTGDFALPVGLIVGVTALGLLIIGVVNCVIMTQVKKKPLCLQREAKV
PHLPADKARGTQGPEQQHLLITAPSSSSSSLESSASALDRRAPTRNQPQAPGVEASGAGE
ARASTGSSDSSPGGHGTQVNVTCIVNVCSSSDHSSQCSSQASSTMGDTDSSPSESPKDEQ
VPFSKEECAFRSQLETPETLLGSTEEKPLPLGVPDAGMKPS
Structure links:
- Smartdomain prediction information: SM00208
- Prosite motif and domain information: PS00652
- Profile motif and domain profile information: PS50311
- Profile motif and domain profile information: PS50050
- Profile motif and domain profile information: PS50324
- Profile motif and domain profile information: PS50323
- Interpro domain information: P20333
- PFAM domain and domain family information: P20333
- Protein 3D structures from PDB: 1CA9
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| NP_989770.2 | orthology | Chicken |
| TNFRSF1B | orthology | Chimpanzee |
| NP_001035580.1 | orthology | Cow |
| TNFRSF1B | orthology | Dog |
| TNFRSF1B | orthology | Gorilla |
| TNFRSF1B | orthology | Horse |
| TNFRSF1B | orthology | Macaca |
| Tnfrsf1b | orthology | Mouse |
| TNFRSF1B | orthology | Orangutan |
| TNFRSF1B | orthology | Ornithorhynchus |
| TNFRSF1B | orthology | Rabbit |
| Tnfrsf1b | orthology | Rat |
| TNFRSF1B | orthology | Zebra finch |
| TNFRSF11A | paralogy | Chicken |
| NP_001028813.1 | paralogy | Chicken |
| TNR16_CHICK | paralogy | Chicken |
| TNFRSF21 | paralogy | Chicken |
| NP_989775.1 | paralogy | Chicken |
| NP_989996.1 | paralogy | Chicken |
| Q7ZZY5_CHICK | paralogy | Chicken |
| TNFRSF8 | paralogy | Chimpanzee |
| LTBR | paralogy | Chimpanzee |
| NGFR | paralogy | Chimpanzee |
| TNFRSF11B | paralogy | Chimpanzee |
| TNFRSF11A | paralogy | Chimpanzee |
| TNR5_BOVIN | paralogy | Cow |
| IPI00699053.2 | paralogy | Cow |
| NP_001091525.1 | paralogy | Cow |
| NP_001070379.1 | paralogy | Cow |
| NP_001096698.1 | paralogy | Cow |
| LOC785024 | paralogy | Cow |
| TNFRSF11B | paralogy | Dog |
| TNFRSF11A | paralogy | Dog |
| TNFRSF14 | paralogy | Dog |
| LTBR | paralogy | Dog |
| TNR5_CANFA | paralogy | Dog |
| TNFRSF21 | paralogy | Fugu |
| NGFR (2 of 2) | paralogy | Fugu |
| TNFRSF1B | paralogy | Fugu |
| TNFRSF21 | paralogy | Gasterosteus |
| TNFRSF1B | paralogy | Gasterosteus |
| NGFR (1 of 2) | paralogy | Gasterosteus |
| TNFRSF11B | paralogy | Gasterosteus |
| LTBR | paralogy | Gorilla |
| TNR5_HORSE | paralogy | Horse |
| TNFRSF4 | paralogy | Horse |
| TNFRSF11A | paralogy | Horse |
| TNFRSF8 | paralogy | Horse |
| TNFRSF11B | paralogy | Horse |
| LTBR | paralogy | Horse |
| TNFRSF21 | paralogy | Horse |
| TNFRSF11B | paralogy | Human |
| NGFR | paralogy | Human |
| CD40 | paralogy | Human |
| TNFRSF8 | paralogy | Human |
| TNFRSF4 | paralogy | Human |
| TNFRSF21 | paralogy | Human |
| LTBR | paralogy | Human |
| TNFRSF11A | paralogy | Human |
| TNFRSF11B | paralogy | Lyzard |
| TNFRSF11A | paralogy | Lyzard |
| TNFRSF21 | paralogy | Lyzard |
| CD40 | paralogy | Macaca |
| LTBR | paralogy | Macaca |
| TNFRSF11B | paralogy | Macaca |
| TNFRSF11B | paralogy | Medaka |
| O_latipes_ENSORLP00000010317 | paralogy | Medaka |
| TNFRSF1B | paralogy | Medaka |
| TNFRSF21 | paralogy | Medaka |
| NGFR (2 of 2) | paralogy | Medaka |
| O_latipes_ENSORLP00000000867 | paralogy | Medaka |
| NGFR (1 of 2) | paralogy | Medaka |
| M_domestica_ENSMODP00000027815 | paralogy | Monodelphis |
| TNFRSF11A | paralogy | Monodelphis |
| TNFRSF11B | paralogy | Monodelphis |
| LTBR | paralogy | Monodelphis |
| TNFRSF1A | paralogy | Monodelphis |
| M_musculus_ENSMUSP00000078705 | paralogy | Mouse |
| Cd40 | paralogy | Mouse |
| Tnfrsf21 | paralogy | Mouse |
| Tnfrsf14 | paralogy | Mouse |
| Tnfrsf4 | paralogy | Mouse |
| Ltbr | paralogy | Mouse |
| Tnfrsf11a | paralogy | Mouse |
| TNFRSF11B | paralogy | Orangutan |
| TNFRSF21 | paralogy | Orangutan |
| TNFRSF8 | paralogy | Orangutan |
| TNFRSF21 | paralogy | Ornithorhynchus |
| TNFRSF11A | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000007822 | paralogy | Ornithorhynchus |
| LTBR | paralogy | Rabbit |
| TNFRSF11A | paralogy | Rabbit |
| CD40 | paralogy | Rabbit |
| TNFRSF11B | paralogy | Rabbit |
| TNFRSF21 | paralogy | Rabbit |
| Tnfrsf14 | paralogy | Rat |
| Tnfrsf11b | paralogy | Rat |
| Tnfrsf11a_predicted | paralogy | Rat |
| Tnfrsf5 | paralogy | Rat |
| NP_001101677.1 | paralogy | Rat |
| Tnfrsf4 | paralogy | Rat |
| Ltbr | paralogy | Rat |
| LTBR | paralogy | Tetraodon |
| TNFRSF21 | paralogy | Tetraodon |
| TNFRSF1B | paralogy | Tetraodon |
| TNFRSF21 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000002526 | paralogy | Zebra finch |
| TNFRSF11A | paralogy | Zebra finch |
| TNFRSF11B | paralogy | Zebra finch |
| CD40 | paralogy | Zebra finch |
| LOC795974 | paralogy | Zebrafish |
| zgc:153759 | paralogy | Zebrafish |
| LOC797761 | paralogy | Zebrafish |
| zgc:153631 | paralogy | Zebrafish |
| LOC572204 | paralogy | Zebrafish |
| tnfrsf1a | paralogy | Zebrafish |
| zgc:153631 | paralogy | Zebrafish |
| ngfrl | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0006955 | immune response | biological_proccess | IEA |
| GO:0007165 | signal transduction | biological_proccess | IEA |
| GO:0006954 | inflammatory response | biological_proccess | IEA |
| GO:0008219 | cell death | biological_proccess | IEA |
| GO:0050728 | negative regulation of inflammatory response | biological_proccess | IEA |
| GO:0007166 | cell surface receptor linked signal transduction | biological_proccess | IEA |
| GO:0050779 | RNA destabilization | biological_proccess | IEA |
| GO:0004872 | receptor activity | mollecular_function | IEA |
| GO:0004888 | transmembrane receptor activity | mollecular_function | IEA |
| GO:0005031 | tumor necrosis factor receptor activity | mollecular_function | TAS |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0005031 | tumor necrosis factor receptor activity | mollecular_function | IEA |
| GO:0016020 | membrane | cell_component | IEA |
| GO:0045121 | membrane raft | cell_component | IDA |
| GO:0005886 | plasma membrane | cell_component | IEA |
| GO:0016021 | integral to membrane | cell_component | IEA |
| GO:0005576 | extracellular region | cell_component | IEA |
| GO:0005624 | membrane fraction | cell_component | IEA |
| GO:0045121 | membrane raft | cell_component | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Curated Isoforms [+]
| Transcript | Translation |
|---|---|
| OTTHUMT00000005133 * | OTTHUMP00000001784 * |
| OTTHUMT00000005134 | |
| OTTHUMT00000005135 |
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :11917
- Gene related info from GeneCards [?] : TNFRSF1B
- Ensembl genome browser [?] : ENSG00000028137
- Expression info from Arrayexpress [?] : ENSG00000028137
- Protein expression from Protein Atlas: [?] ENSG00000028137
- Community gene edition from Wikigenes: [?] 7133
- OMIM gene information: 191191
- OMIM disease information:
Click on [?] for more information.
