TNFRSF1A (Homo sapiens)
Description [+]
- Synonyms: TNFRSF1A, TNF-R, TNFAR, TNFR60, TNF-R-I, CD120A, TNF-R55
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Tumor necrosis factor receptor superfamily member 1A Precursor (p60)(TNF-R1)(TNF-RI)(TNFR-I)(p55)(CD120a antigen) [Contains Tumor necrosis factor receptor superfamily member 1A, membrane form;Tumor necrosis factor-binding protein 1(TBPI)] [Source:UniProtKB/Swiss-Prot;Acc:P19438]
- Family: death receptor
- Process: apoptosis, necroptosis,
- Pathways: extrinsic pathway, TNF/NF-kappaB signaling,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Tnfrsf1a
- WIKI: TNFRSF1A-H_sapiens
References [+]
- A novel domain within the 55 kd TNF receptor signals cell death.
- Tartaglia LA, Ayres TM, Wong GH, Goeddel DV
- Deletion mutagenesis of the intracellular region of the 55 kd TNF receptor (TNF-R1) identified an approximately 80 amino acid domain near the C-terminus responsible for signaling cytotoxicity. This domain shows weak homology with the intracellular domain of Fas antigen, a transmembrane polypeptide that can also initiate a signal for cytotoxicity. Alanine-scanning mutagenesis of TNF-R1 confirmed that many of the amino acids conserved with Fas antigen are critical for the cytotoxic signal. This region of TNF-R1-Fas homology is therefore likely to define a novel domain (death domain) that signals programmed cell death. Mutations within the death domain of TNF-R1 also disrupted its ability to signal anti-viral activity and nitric oxide (NO) synthase induction. In addition, large deletions in the membrane-proximal half of the intracellular domain did not block signaling of cytotoxicity or anti-viral activity but did block induction of NO synthase. Cell. 1993 Sep 10;74(5):845-53.
- The TNF and TNF receptor superfamilies: integrating mammalian biology.
- Locksley RM, Killeen N, Lenardo MJ
- Cell. 2001 Feb 23;104(4):487-501.
- 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.
- The two different receptors for tumor necrosis factor mediate distinct cellular responses.
- Tartaglia LA, Weber RF, Figari IS, Reynolds C, Palladino MA Jr, Goeddel DV
- The individual roles of the murine type 1 and type 2 tumor necrosis factor (TNF) receptors (TNF-R1 and TNF-R2) were investigated utilizing (i) the strong species specificity of TNF-R2 for murine TNF compared to human TNF and (ii) agonistic rabbit polyclonal antibodies directed against the individual TNF receptors. Proliferation of mouse thymocytes and the murine cytotoxic T-cell line CT-6 is stimulated by murine TNF but not by human TNF. Consistent with this observation, polyclonal antibodies directed against TNF-R2 induced proliferation in both of these cell types, whereas polyclonal antibodies directed against TNF-R1 had no effect. In contrast, cytotoxicity in murine LM cells (which are sensitive to murine and human TNF) was induced by antibodies against TNF-R1 but not by antibodies against TNF-R2. Also, the steady-state level of manganous superoxide dismutase mRNA in the murine NIH 3T3 cell line was induced by murine TNF, human TNF, and anti-TNF-R1 but not by anti-TNF-R2. These results suggest that TNF-R2 initiates signals for the proliferation of thymocytes and cytotoxic T cells, whereas TNF-R1 initiates signals for cytotoxicity and the induction of the protective activity, manganous superoxide dismutase. The nonredundant signaling observed for the two TNF receptors cannot be explained simply by the differential expression of the two TNF receptors in the various cell types, because LM cells express on their surface higher levels of TNF-R2 than TNF-R1, and LM cells, NIH 3T3 cells, and thymus cells all express mRNA corresponding to both receptor types. It is therefore likely that the two receptors initiate distinct signaling pathways that result in the induction of different cellular responses. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9292-6.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
Source | Domain Name | Start | End |
---|---|---|---|
PFAM A | TNFR_c6 | 44 | 81 |
PFAM A | TNFR_c6 | 84 | 125 |
PFAM A | TNFR_c6 | 127 | 166 |
PFAM A | Death | 357 | 441 |
Protein sequence [+]
TNFRSF1A | Homo sapiens | 9606 | length:455
MGLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCT
KCHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVD
RDTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECV
SCSNCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVIFFGLCLLSLLFIGLMYRYQRWK
SKLYSIVCGKSTPEKEGELEGTTTKPLAPNPSFSPTPGFTPTLGFSPVPSSTFTSSSTYT
PGDCPNFAAPRREVAPPYQGADPILATALASDPIPNPLQKWEDSAHKPQSLDTDDPATLY
AVVENVPPLRWKEFVRRLGLSDHEIDRLELQNGRCLREAQYSMLATWRRRTPRREATLEL
LGRVLRDMDLLGCLEDIEEALCGPAALPPAPSLLR
KCHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVD
RDTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECV
SCSNCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVIFFGLCLLSLLFIGLMYRYQRWK
SKLYSIVCGKSTPEKEGELEGTTTKPLAPNPSFSPTPGFTPTLGFSPVPSSTFTSSSTYT
PGDCPNFAAPRREVAPPYQGADPILATALASDPIPNPLQKWEDSAHKPQSLDTDDPATLY
AVVENVPPLRWKEFVRRLGLSDHEIDRLELQNGRCLREAQYSMLATWRRRTPRREATLEL
LGRVLRDMDLLGCLEDIEEALCGPAALPPAPSLLR
Structure links:
- Smartdomain prediction information: SM00208
- Smartdomain prediction information: SM00005
- Prosite motif and domain information: PS00652
- Prosite motif and domain information: PS01186
- Profile motif and domain profile information: PS50311
- Profile motif and domain profile information: PS50017
- Profile motif and domain profile information: PS50050
- Interpro domain information: P19438
- PFAM domain and domain family information: P19438
- Protein 3D structures from PDB: 1EXT 1TNR
Evolution [+]
View protein alignment and tree with Jalview:  
Explore tree at phylomeDB:   Click here.
Homologs list [+]
Name | Relationship | Species |
---|---|---|
NP_001025950.1 | orthology | Chicken |
TNFRSF1A | orthology | Chimpanzee |
TNR1A_BOVIN | orthology | Cow |
O97530_CANFA | orthology | Dog |
TNFRSF25 | orthology | Fugu |
TNFRSF25 | orthology | Gasterosteus |
TNFRSF1A | orthology | Gorilla |
TNFRSF1A | orthology | Horse |
A_carolinensis_ENSACAP00000011266 | orthology | Lyzard |
TNFRSF1A | orthology | Macaca |
TNFRSF25 | orthology | Medaka |
TNFRSF1A | orthology | Monodelphis |
Tnfrsf1a | orthology | Mouse |
TNFRSF1A | orthology | Orangutan |
TNFRSF1A | orthology | Ornithorhynchus |
TNFRSF1A | orthology | Rabbit |
Tnfrsf1a | orthology | Rat |
TNFRSF25 | orthology | Tetraodon |
TNFRSF1A | orthology | Zebra finch |
tnfrsf1a | orthology | Zebrafish |
TNFRSF11A | paralogy | Chicken |
LTBR | paralogy | Chimpanzee |
NGFR | paralogy | Chimpanzee |
TNFRSF25 | paralogy | Chimpanzee |
TNFRSF11B | paralogy | Chimpanzee |
NP_001096698.1 | paralogy | Cow |
IPI00704229.2 | paralogy | Cow |
A5PJV7_BOVIN | paralogy | Cow |
NP_001091525.1 | paralogy | Cow |
TNFRSF25 | paralogy | Dog |
NGFR | paralogy | Dog |
LTBR | paralogy | Dog |
T_rubripes_ENSTRUP00000035238 | paralogy | Fugu |
LTBR | paralogy | Fugu |
LTBR | paralogy | Gasterosteus |
LTBR | paralogy | Gorilla |
NGFR | paralogy | Gorilla |
TNFRSF11B | paralogy | Horse |
LTBR | paralogy | Horse |
TNFRSF11B | paralogy | Human |
LTBR | paralogy | Human |
NGFR | paralogy | Human |
TNFRSF25 | paralogy | Human |
TNFRSF11B | paralogy | Macaca |
TNFRSF14 | paralogy | Macaca |
TNFRSF25 | paralogy | Macaca |
Q5XTR8_MACMU | paralogy | Macaca |
LTBR | paralogy | Macaca |
TNFRSF25 | paralogy | Monodelphis |
TNFRSF11B | paralogy | Monodelphis |
Tnfrsf25 | paralogy | Mouse |
Tnfrsf14 | paralogy | Mouse |
Fas | paralogy | Mouse |
Tnfrsf10b | paralogy | Mouse |
Ngfr | paralogy | Mouse |
M_musculus_ENSMUSP00000078705 | paralogy | Mouse |
Cd40 | paralogy | Mouse |
NGFR | paralogy | Orangutan |
TNFRSF11B | paralogy | Orangutan |
TNFRSF25 | paralogy | Ornithorhynchus |
TNFRSF11B | paralogy | Rabbit |
LTBR | paralogy | Rabbit |
Ltbr | paralogy | Rat |
Ngfr | paralogy | Rat |
Tnfrsf11b | paralogy | Rat |
LOC500592 | paralogy | Rat |
LTBR | paralogy | Tetraodon |
nrh1a | paralogy | Xenopus |
TNFRSF11A | paralogy | Zebra finch |
ngfrl | paralogy | Zebrafish |
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Gene Ontology [+]
GO id | Name | Ontology type | Evidence |
---|---|---|---|
GO:0007165 | signal transduction | biological_proccess | IEA |
GO:0006915 | apoptosis | biological_proccess | IEA |
GO:0044419 | interspecies interaction between organisms | biological_proccess | IEA |
GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB cascade | biological_proccess | IEP |
GO:0006693 | prostaglandin metabolic process | biological_proccess | ISS |
GO:0019221 | cytokine-mediated signaling pathway | biological_proccess | ISS |
GO:0045944 | positive regulation of transcription from RNA polymerase II promoter | biological_proccess | ISS |
GO:0050729 | positive regulation of inflammatory response | biological_proccess | ISS |
GO:0051291 | protein heterooligomerization | biological_proccess | IEA |
GO:0045471 | response to ethanol | biological_proccess | IEA |
GO:0032496 | response to lipopolysaccharide | biological_proccess | IEA |
GO:0045766 | positive regulation of angiogenesis | biological_proccess | IEA |
GO:0045944 | positive regulation of transcription from RNA polymerase II promoter | biological_proccess | IEA |
GO:0006954 | inflammatory response | biological_proccess | IEA |
GO:0006952 | defense response | biological_proccess | IEA |
GO:0019221 | cytokine-mediated signaling pathway | biological_proccess | IEA |
GO:0007166 | cell surface receptor linked signal transduction | biological_proccess | IEA |
GO:0050729 | positive regulation of inflammatory response | biological_proccess | IEA |
GO:0009816 | defense response to bacterium, incompatible interaction | biological_proccess | IEA |
GO:0004872 | receptor activity | mollecular_function | IEA |
GO:0005031 | tumor necrosis factor receptor activity | mollecular_function | TAS |
GO:0005515 | protein binding | mollecular_function | IPI |
GO:0032403 | protein complex binding | mollecular_function | IEA |
GO:0005515 | protein binding | mollecular_function | IEA |
GO:0005031 | tumor necrosis factor receptor activity | mollecular_function | IEA |
GO:0045121 | membrane raft | cell_component | IDA |
GO:0005887 | integral to plasma membrane | cell_component | TAS |
GO:0005886 | plasma membrane | cell_component | EXP |
GO:0005576 | extracellular region | cell_component | NAS |
GO:0043234 | protein complex | cell_component | IEA |
GO:0045121 | membrane raft | cell_component | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Information from other databases [+]
- Gene info from HGNC [?] :11916
- Gene related info from GeneCards [?] : TNFRSF1A
- Ensembl genome browser [?] : ENSG00000067182
- Expression info from Arrayexpress [?] : ENSG00000067182
- Protein expression from Protein Atlas: [?] ENSG00000067182
- Community gene edition from Wikigenes: [?] 7132
Click on [?] for more information.