Apoptosis Database

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 [+]

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
TNFRSF11B	paralogy	Chimpanzee
LTBR	paralogy	Chimpanzee
NGFR	paralogy	Chimpanzee
TNFRSF25	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
LTBR	paralogy	Macaca
TNFRSF11B	paralogy	Macaca
TNFRSF14	paralogy	Macaca
TNFRSF25	paralogy	Macaca
Q5XTR8_MACMU	paralogy	Macaca
TNFRSF25	paralogy	Monodelphis
TNFRSF11B	paralogy	Monodelphis
Cd40	paralogy	Mouse
Tnfrsf25	paralogy	Mouse
Tnfrsf14	paralogy	Mouse
Fas	paralogy	Mouse
Tnfrsf10b	paralogy	Mouse
Ngfr	paralogy	Mouse
M_musculus_ENSMUSP00000078705	paralogy	Mouse
NGFR	paralogy	Orangutan
TNFRSF11B	paralogy	Orangutan
TNFRSF25	paralogy	Ornithorhynchus
TNFRSF11B	paralogy	Rabbit
LTBR	paralogy	Rabbit
LOC500592	paralogy	Rat
Ltbr	paralogy	Rat
Ngfr	paralogy	Rat
Tnfrsf11b	paralogy	Rat
LTBR	paralogy	Tetraodon
nrh1a	paralogy	Xenopus
TNFRSF11A	paralogy	Zebra finch
ngfrl	paralogy	Zebrafish

Download tree (Newick format): Click here.

Display HTML alignment Click here.

Download alignment (Fasta format): Click here.

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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 related links:

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

Protein related links:

Uniprot protein info: P19438
PIR protein info: P19438
Protein interactions from IntAct: P19438

Gene and disease information from OMIM: (For a full disease description table, click here.)

OMIM gene information: 191190
OMIM disease information: 142680

Other links

entrezgene: 7132
refseq_dna: NM_001065
refseq_peptide: NP_001056

Click on [?] for more information.

TNFRSF1A (Homo sapiens)