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Protein

Tumor necrosis factor receptor superfamily member 1A

Gene

Tnfrsf1a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis (By similarity).By similarity

GO - Molecular functioni

  1. tumor necrosis factor-activated receptor activity Source: MGI

GO - Biological processi

  1. cell surface receptor signaling pathway Source: MGI
  2. cellular response to estradiol stimulus Source: Ensembl
  3. cellular response to mechanical stimulus Source: Ensembl
  4. cytokine-mediated signaling pathway Source: MGI
  5. defense response Source: MGI
  6. defense response to bacterium Source: MGI
  7. inflammatory response Source: MGI
  8. intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  9. negative regulation of apoptotic process Source: Ensembl
  10. negative regulation of gene expression Source: Ensembl
  11. negative regulation of inflammatory response Source: MGI
  12. negative regulation of interleukin-6 production Source: Ensembl
  13. positive regulation of angiogenesis Source: Ensembl
  14. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  15. positive regulation of inflammatory response Source: MGI
  16. positive regulation of neuron apoptotic process Source: Ensembl
  17. positive regulation of protein import into nucleus, translocation Source: Ensembl
  18. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  19. positive regulation of tumor necrosis factor production Source: Ensembl
  20. positive regulation of tyrosine phosphorylation of Stat1 protein Source: MGI
  21. prostaglandin metabolic process Source: MGI
  22. protein heterooligomerization Source: Ensembl
  23. response to alkaloid Source: Ensembl
  24. response to amino acid Source: Ensembl
  25. response to ethanol Source: Ensembl
  26. response to hypoxia Source: Ensembl
  27. response to lipopolysaccharide Source: Ensembl
  28. response to wounding Source: Ensembl
  29. tetrapyrrole metabolic process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiREACT_312675. TNF signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 1A
Alternative name(s):
Tumor necrosis factor receptor 1
Short name:
TNF-R1
Tumor necrosis factor receptor type I
Short name:
TNF-RI
Short name:
TNFR-I
p55
p60
CD_antigen: CD120a
Gene namesi
Name:Tnfrsf1a
Synonyms:Tnfr-1, Tnfr1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1314884. Tnfrsf1a.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 212191ExtracellularSequence AnalysisAdd
BLAST
Transmembranei213 – 23523HelicalSequence AnalysisAdd
BLAST
Topological domaini236 – 454219CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. axon Source: Ensembl
  2. cell surface Source: BHF-UCL
  3. cytosol Source: Ensembl
  4. extracellular space Source: MGI
  5. Golgi membrane Source: UniProtKB
  6. integral component of membrane Source: UniProtKB-KW
  7. membrane raft Source: BHF-UCL
  8. mitochondrion Source: Ensembl
  9. nucleus Source: Ensembl
  10. plasma membrane Source: MGI
  11. receptor complex Source: MGI
  12. synapse Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 454433Tumor necrosis factor receptor superfamily member 1APRO_0000034545Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi44 ↔ 58PROSITE-ProRule annotation
Glycosylationi54 – 541N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi59 ↔ 72PROSITE-ProRule annotation
Disulfide bondi62 ↔ 81PROSITE-ProRule annotation
Disulfide bondi84 ↔ 99PROSITE-ProRule annotation
Disulfide bondi102 ↔ 117PROSITE-ProRule annotation
Disulfide bondi105 ↔ 125PROSITE-ProRule annotation
Disulfide bondi127 ↔ 143PROSITE-ProRule annotation
Disulfide bondi146 ↔ 158PROSITE-ProRule annotation
Disulfide bondi149 ↔ 166PROSITE-ProRule annotation
Glycosylationi151 – 1511N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi168 ↔ 179PROSITE-ProRule annotation
Disulfide bondi182 ↔ 195PROSITE-ProRule annotation
Disulfide bondi185 ↔ 191PROSITE-ProRule annotation
Glycosylationi202 – 2021N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP25118.
PRIDEiP25118.

PTM databases

PhosphoSiteiP25118.

Expressioni

Gene expression databases

BgeeiP25118.
ExpressionAtlasiP25118. baseline and differential.
GenevestigatoriP25118.

Interactioni

Subunit structurei

Binding of TNF to the extracellular domain leads to homotrimerization. The aggregated death domains provide a novel molecular interface that interacts specifically with the death domain of TRADD. Various TRADD-interacting proteins such as TRAFS, RIPK1 and possibly FADD, are recruited to the complex by their association with TRADD. This complex activates at least two distinct signaling cascades, apoptosis and NF-kappa-B signaling. Interacts with BAG4, BRE, FEM1B, GRB2, SQSTM1 and TRPC4AP. Interacts with DAB2IP (By similarity). Interacts directly with NOL3 (via CARD domain); inhibits TNF-signaling pathway.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Ern1Q9EQY02EBI-518014,EBI-5480799
Ripk1Q608553EBI-518014,EBI-529119
Slc39a7Q311253EBI-518014,EBI-644519

Protein-protein interaction databases

BioGridi204249. 13 interactions.
DIPiDIP-34532N.
IntActiP25118. 23 interactions.
MINTiMINT-2631249.

Structurei

3D structure databases

ProteinModelPortaliP25118.
SMRiP25118. Positions 41-197, 357-441.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati43 – 8240TNFR-Cys 1Add
BLAST
Repeati83 – 12543TNFR-Cys 2Add
BLAST
Repeati126 – 16641TNFR-Cys 3Add
BLAST
Repeati167 – 19630TNFR-Cys 4Add
BLAST
Domaini356 – 44186DeathPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni339 – 34911N-SMase activation domain (NSD)Add
BLAST

Domaini

Both the cytoplasmic membrane-proximal region and the C-terminal region containing the death domain are involved in the interaction with TRPC4AP.

Sequence similaritiesi

Contains 1 death domain.PROSITE-ProRule annotation
Contains 4 TNFR-Cys repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG39168.
HOGENOMiHOG000133001.
HOVERGENiHBG058842.
InParanoidiP25118.
KOiK03158.
OMAiCLREAHY.
PhylomeDBiP25118.
TreeFamiTF333916.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020419. TNFR_1A.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]
PRINTSiPR01918. TNFACTORR1A.
SMARTiSM00005. DEATH. 1 hit.
SM00208. TNFR. 4 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 3 hits.
PS50050. TNFR_NGFR_2. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P25118-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGLPTVPGLL LSLVLLALLM GIHPSGVTGL VPSLGDREKR DSLCPQGKYV
60 70 80 90 100
HSKNNSICCT KCHKGTYLVS DCPSPGRDTV CRECEKGTFT ASQNYLRQCL
110 120 130 140 150
SCKTCRKEMS QVEISPCQAD KDTVCGCKEN QFQRYLSETH FQCVDCSPCF
160 170 180 190 200
NGTVTIPCKE TQNTVCNCHA GFFLRESECV PCSHCKKNEE CMKLCLPPPL
210 220 230 240 250
ANVTNPQDSG TAVLLPLVIL LGLCLLSFIF ISLMCRYPRW RPEVYSIICR
260 270 280 290 300
DPVPVKEEKA GKPLTPAPSP AFSPTSGFNP TLGFSTPGFS SPVSSTPISP
310 320 330 340 350
IFGPSNWHFM PPVSEVVPTQ GADPLLYESL CSVPAPTSVQ KWEDSAHPQR
360 370 380 390 400
PDNADLAILY AVVDGVPPAR WKEFMRFMGL SEHEIERLEM QNGRCLREAQ
410 420 430 440 450
YSMLEAWRRR TPRHEDTLEV VGLVLSKMNL AGCLENILEA LRNPAPSSTT

RLPR
Length:454
Mass (Da):50,130
Last modified:May 1, 1992 - v1
Checksum:i0710C2E8C3C2B6D9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti394 – 3941R → G in AAA40465 (PubMed:8381516).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60468 mRNA. Translation: AAA39751.1.
M59377 mRNA. Translation: AAA40464.1.
X59238 mRNA. Translation: CAA41922.1.
X57796 mRNA. Translation: CAA40936.1.
L26349 mRNA. Translation: AAA59361.1.
M76656, M88067, M76655 Genomic DNA. Translation: AAA40465.1.
BC004599 mRNA. Translation: AAH04599.1.
BC052675 mRNA. Translation: AAH52675.1.
CCDSiCCDS20550.1.
PIRiA38634. GQMST1.
RefSeqiNP_035739.2. NM_011609.4.
UniGeneiMm.1258.
Mm.474976.

Genome annotation databases

EnsembliENSMUST00000032491; ENSMUSP00000032491; ENSMUSG00000030341.
GeneIDi21937.
KEGGimmu:21937.
UCSCiuc009dul.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60468 mRNA. Translation: AAA39751.1.
M59377 mRNA. Translation: AAA40464.1.
X59238 mRNA. Translation: CAA41922.1.
X57796 mRNA. Translation: CAA40936.1.
L26349 mRNA. Translation: AAA59361.1.
M76656, M88067, M76655 Genomic DNA. Translation: AAA40465.1.
BC004599 mRNA. Translation: AAH04599.1.
BC052675 mRNA. Translation: AAH52675.1.
CCDSiCCDS20550.1.
PIRiA38634. GQMST1.
RefSeqiNP_035739.2. NM_011609.4.
UniGeneiMm.1258.
Mm.474976.

3D structure databases

ProteinModelPortaliP25118.
SMRiP25118. Positions 41-197, 357-441.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204249. 13 interactions.
DIPiDIP-34532N.
IntActiP25118. 23 interactions.
MINTiMINT-2631249.

PTM databases

PhosphoSiteiP25118.

Proteomic databases

PaxDbiP25118.
PRIDEiP25118.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000032491; ENSMUSP00000032491; ENSMUSG00000030341.
GeneIDi21937.
KEGGimmu:21937.
UCSCiuc009dul.2. mouse.

Organism-specific databases

CTDi7132.
MGIiMGI:1314884. Tnfrsf1a.

Phylogenomic databases

eggNOGiNOG39168.
HOGENOMiHOG000133001.
HOVERGENiHBG058842.
InParanoidiP25118.
KOiK03158.
OMAiCLREAHY.
PhylomeDBiP25118.
TreeFamiTF333916.

Enzyme and pathway databases

ReactomeiREACT_312675. TNF signaling.

Miscellaneous databases

NextBioi301546.
PROiP25118.
SOURCEiSearch...

Gene expression databases

BgeeiP25118.
ExpressionAtlasiP25118. baseline and differential.
GenevestigatoriP25118.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020419. TNFR_1A.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]
PRINTSiPR01918. TNFACTORR1A.
SMARTiSM00005. DEATH. 1 hit.
SM00208. TNFR. 4 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 3 hits.
PS50050. TNFR_NGFR_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression of cDNAs for two distinct murine tumor necrosis factor receptors demonstrate one receptor is species specific."
    Lewis M., Tartaglia L.A., Lee A., Bennett G.L., Rice G.C., Wong G.H., Chen E.Y., Goeddel D.V.
    Proc. Natl. Acad. Sci. U.S.A. 88:2830-2834(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Molecular cloning and expression of the type 1 and type 2 murine receptors for tumor necrosis factor."
    Goodwin R.G., Anderson D., Jerzy R., Davis T., Brannan C.I., Copeland N.G., Jenkins N.A., Smith C.A.
    Mol. Cell. Biol. 11:3020-3026(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Cloning, expression and cross-linking analysis of the murine p55 tumor necrosis factor receptor."
    Barrett K., Taylor-Fishwick D.A., Cope A.P., Kissonerghis A.M., Gray P.W., Feldmann M., Foxwell B.M.J.
    Eur. J. Immunol. 21:1649-1656(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "Molecular cloning and expression of the mouse Tnf receptor type b."
    Rothe J.G., Brockhaus M., Gentz R., Lesslauer W.
    Immunogenetics 34:338-340(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Spleen.
  5. "Nucleotide sequence of the TNF type I receptor from a mouse endothelioma cell line."
    Bebo B.F., Linthicum D.S.
    Immunogenetics 39:450-451(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  6. "Genomic organization and promoter function of the murine tumor necrosis factor receptor beta gene."
    Rothe J., Bluethmann H., Gentz R., Lesslauer W., Steinmetz M.
    Mol. Immunol. 30:165-175(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C3H/He.
    Tissue: Mesenchymal cell.
  8. "A novel role for the apoptosis inhibitor ARC in suppressing TNFalpha-induced regulated necrosis."
    Kung G., Dai P., Deng L., Kitsis R.N.
    Cell Death Differ. 21:634-644(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NOL3.

Entry informationi

Entry nameiTNR1A_MOUSE
AccessioniPrimary (citable) accession number: P25118
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: April 1, 2015
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.