TNR1A_MOUSE
ID TNR1A_MOUSE Reviewed; 454 AA.
AC P25118;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 1A;
DE AltName: Full=Tumor necrosis factor receptor 1;
DE Short=TNF-R1;
DE AltName: Full=Tumor necrosis factor receptor type I;
DE Short=TNF-RI;
DE Short=TNFR-I;
DE AltName: Full=p55;
DE AltName: Full=p60;
DE AltName: CD_antigen=CD120a;
DE Flags: Precursor;
GN Name=Tnfrsf1a; Synonyms=Tnfr-1, Tnfr1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1849278; DOI=10.1073/pnas.88.7.2830;
RA Lewis M., Tartaglia L.A., Lee A., Bennett G.L., Rice G.C., Wong G.H.,
RA Chen E.Y., Goeddel D.V.;
RT "Cloning and expression of cDNAs for two distinct murine tumor necrosis
RT factor receptors demonstrate one receptor is species specific.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:2830-2834(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1645445; DOI=10.1128/mcb.11.6.3020-3026.1991;
RA Goodwin R.G., Anderson D., Jerzy R., Davis T., Brannan C.I., Copeland N.G.,
RA Jenkins N.A., Smith C.A.;
RT "Molecular cloning and expression of the type 1 and type 2 murine receptors
RT for tumor necrosis factor.";
RL Mol. Cell. Biol. 11:3020-3026(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1647956; DOI=10.1002/eji.1830210710;
RA Barrett K., Taylor-Fishwick D.A., Cope A.P., Kissonerghis A.M., Gray P.W.,
RA Feldmann M., Foxwell B.M.J.;
RT "Cloning, expression and cross-linking analysis of the murine p55 tumor
RT necrosis factor receptor.";
RL Eur. J. Immunol. 21:1649-1656(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RX PubMed=1657766; DOI=10.1007/bf00211997;
RA Rothe J.G., Brockhaus M., Gentz R., Lesslauer W.;
RT "Molecular cloning and expression of the mouse Tnf receptor type b.";
RL Immunogenetics 34:338-340(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8188324; DOI=10.1007/bf00176168;
RA Bebo B.F., Linthicum D.S.;
RT "Nucleotide sequence of the TNF type I receptor from a mouse endothelioma
RT cell line.";
RL Immunogenetics 39:450-451(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8381516; DOI=10.1016/0161-5890(93)90088-s;
RA Rothe J., Bluethmann H., Gentz R., Lesslauer W., Steinmetz M.;
RT "Genomic organization and promoter function of the murine tumor necrosis
RT factor receptor beta gene.";
RL Mol. Immunol. 30:165-175(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C3H/He; TISSUE=Mesenchymal cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH NOL3.
RX PubMed=24440909; DOI=10.1038/cdd.2013.195;
RA Kung G., Dai P., Deng L., Kitsis R.N.;
RT "A novel role for the apoptosis inhibitor ARC in suppressing TNFalpha-
RT induced regulated necrosis.";
RL Cell Death Differ. 21:634-644(2014).
RN [9]
RP GLYCOSYLATION AT ARG-376 (MICROBIAL INFECTION).
RX PubMed=30902834; DOI=10.1074/mcp.ra118.001093;
RA Newson J.P.M., Scott N.E., Yeuk Wah Chung I., Wong Fok Lung T., Giogha C.,
RA Gan J., Wang N., Strugnell R.A., Brown N.F., Cygler M., Pearson J.S.,
RA Hartland E.L.;
RT "Salmonella effectors SseK1 and SseK3 target death domain proteins in the
RT TNF and TRAIL signaling pathways.";
RL Mol. Cell. Proteomics 18:1138-1156(2019).
CC -!- FUNCTION: Receptor for TNFSF2/TNF-alpha and homotrimeric
CC TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8
CC to the activated receptor. The resulting death-inducing signaling
CC complex (DISC) performs caspase-8 proteolytic activation which
CC initiates the subsequent cascade of caspases (aspartate-specific
CC cysteine proteases) mediating apoptosis (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binding of TNF to the extracellular domain leads to
CC homotrimerization. The aggregated death domains provide a novel
CC molecular interface that interacts specifically with the death domain
CC of TRADD. Various TRADD-interacting proteins such as TRAFS, RIPK1 and
CC possibly FADD, are recruited to the complex by their association with
CC TRADD. This complex activates at least two distinct signaling cascades,
CC apoptosis and NF-kappa-B signaling. Interacts with BAG4, BABAM2, FEM1B,
CC GRB2, SQSTM1 and TRPC4AP. Interacts with DAB2IP (By similarity).
CC Interacts directly with NOL3 (via CARD domain); inhibits TNF-signaling
CC pathway (PubMed:24440909). Interacts with SH3RF2, TRADD and RIPK1.
CC SH3RF2 facilitates the recruitment of RIPK1 and TRADD to TNFRSF1A in a
CC TNF-alpha-dependent process (By similarity). Interacts with PGLYRP1;
CC this interaction is important for cell death induction (By similarity).
CC Interacts (via death domain) with MADD (via death domain) (By
CC similarity). {ECO:0000250|UniProtKB:P19438,
CC ECO:0000269|PubMed:24440909}.
CC -!- INTERACTION:
CC P25118; Q9EQY0: Ern1; NbExp=2; IntAct=EBI-518014, EBI-5480799;
CC P25118; Q60855: Ripk1; NbExp=3; IntAct=EBI-518014, EBI-529119;
CC P25118; Q31125: Slc39a7; NbExp=3; IntAct=EBI-518014, EBI-644519;
CC P25118; P62991: Ubc; NbExp=2; IntAct=EBI-518014, EBI-413074;
CC P25118; P01375: TNF; Xeno; NbExp=3; IntAct=EBI-518014, EBI-359977;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Golgi apparatus membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- DOMAIN: Both the cytoplasmic membrane-proximal region and the C-
CC terminal region containing the death domain are involved in the
CC interaction with TRPC4AP.
CC -!- PTM: (Microbial infection) Glycosylated at Arg-376 by S.typhimurium
CC protein Ssek3: arginine GlcNAcylation prevents homotypic/heterotypic
CC death domain interactions. {ECO:0000269|PubMed:30902834}.
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DR EMBL; M60468; AAA39751.1; -; mRNA.
DR EMBL; M59377; AAA40464.1; -; mRNA.
DR EMBL; X59238; CAA41922.1; -; mRNA.
DR EMBL; X57796; CAA40936.1; -; mRNA.
DR EMBL; L26349; AAA59361.1; -; mRNA.
DR EMBL; M76656; AAA40465.1; -; Genomic_DNA.
DR EMBL; M88067; AAA40465.1; JOINED; Genomic_DNA.
DR EMBL; M76655; AAA40465.1; JOINED; Genomic_DNA.
DR EMBL; BC004599; AAH04599.1; -; mRNA.
DR EMBL; BC052675; AAH52675.1; -; mRNA.
DR CCDS; CCDS20550.1; -.
DR PIR; A38634; GQMST1.
DR RefSeq; NP_035739.2; NM_011609.4.
DR AlphaFoldDB; P25118; -.
DR SMR; P25118; -.
DR BioGRID; 204249; 22.
DR DIP; DIP-34532N; -.
DR IntAct; P25118; 27.
DR MINT; P25118; -.
DR STRING; 10090.ENSMUSP00000032491; -.
DR GlyGen; P25118; 3 sites.
DR iPTMnet; P25118; -.
DR PhosphoSitePlus; P25118; -.
DR PaxDb; P25118; -.
DR PeptideAtlas; P25118; -.
DR PRIDE; P25118; -.
DR ProteomicsDB; 259146; -.
DR Antibodypedia; 1320; 1478 antibodies from 51 providers.
DR DNASU; 21937; -.
DR Ensembl; ENSMUST00000032491; ENSMUSP00000032491; ENSMUSG00000030341.
DR GeneID; 21937; -.
DR KEGG; mmu:21937; -.
DR UCSC; uc009dul.2; mouse.
DR CTD; 7132; -.
DR MGI; MGI:1314884; Tnfrsf1a.
DR VEuPathDB; HostDB:ENSMUSG00000030341; -.
DR eggNOG; ENOG502S050; Eukaryota.
DR GeneTree; ENSGT00940000159540; -.
DR HOGENOM; CLU_050864_0_0_1; -.
DR InParanoid; P25118; -.
DR OMA; ICRCKPQ; -.
DR OrthoDB; 726174at2759; -.
DR PhylomeDB; P25118; -.
DR TreeFam; TF333916; -.
DR Reactome; R-MMU-5357786; TNFR1-induced proapoptotic signaling.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-5626978; TNFR1-mediated ceramide production.
DR Reactome; R-MMU-5669034; TNFs bind their physiological receptors.
DR Reactome; R-MMU-75893; TNF signaling.
DR BioGRID-ORCS; 21937; 15 hits in 78 CRISPR screens.
DR ChiTaRS; Tnfrsf1a; mouse.
DR PRO; PR:P25118; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P25118; protein.
DR Bgee; ENSMUSG00000030341; Expressed in granulocyte and 224 other tissues.
DR ExpressionAtlas; P25118; baseline and differential.
DR Genevisible; P25118; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; TAS:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0043120; F:tumor necrosis factor binding; ISO:MGI.
DR GO; GO:0005031; F:tumor necrosis factor receptor activity; IMP:MGI.
DR GO; GO:0003176; P:aortic valve development; IGI:BHF-UCL.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IMP:MGI.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:MGI.
DR GO; GO:0006952; P:defense response; IMP:MGI.
DR GO; GO:0042742; P:defense response to bacterium; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; IGI:BHF-UCL.
DR GO; GO:0003332; P:negative regulation of extracellular matrix constituent secretion; IGI:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR GO; GO:1902339; P:positive regulation of apoptotic process involved in morphogenesis; IGI:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0006693; P:prostaglandin metabolic process; TAS:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0003177; P:pulmonary valve development; IGI:BHF-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; ISO:MGI.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IGI:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR CDD; cd08313; Death_TNFR1; 1.
DR CDD; cd10576; TNFRSF1A; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR InterPro; IPR020419; TNFR_1A.
DR InterPro; IPR033994; TNFRSF1A_death.
DR InterPro; IPR033993; TNFRSF1A_N.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF00020; TNFR_c6; 3.
DR PRINTS; PR01918; TNFACTORR1A.
DR SMART; SM00005; DEATH; 1.
DR SMART; SM00208; TNFR; 4.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
DR PROSITE; PS00652; TNFR_NGFR_1; 3.
DR PROSITE; PS50050; TNFR_NGFR_2; 3.
PE 1: Evidence at protein level;
KW Apoptosis; Cell membrane; Disulfide bond; Glycoprotein; Golgi apparatus;
KW Membrane; Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000250|UniProtKB:P19438"
FT CHAIN 30..454
FT /note="Tumor necrosis factor receptor superfamily member
FT 1A"
FT /id="PRO_0000034545"
FT TOPO_DOM 30..212
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..454
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 43..82
FT /note="TNFR-Cys 1"
FT REPEAT 83..125
FT /note="TNFR-Cys 2"
FT REPEAT 126..166
FT /note="TNFR-Cys 3"
FT REPEAT 167..196
FT /note="TNFR-Cys 4"
FT DOMAIN 356..441
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 339..349
FT /note="N-SMase activation domain (NSD)"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 376
FT /note="(Microbial infection) N-beta-linked (GlcNAc)
FT arginine"
FT /evidence="ECO:0000269|PubMed:30902834"
FT DISULFID 44..58
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 59..72
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 62..81
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 84..99
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 102..117
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 105..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 127..143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 146..158
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 149..166
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 168..179
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 182..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 185..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT CONFLICT 394
FT /note="R -> G (in Ref. 6; AAA40465)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 454 AA; 50130 MW; 0710C2E8C3C2B6D9 CRC64;
MGLPTVPGLL LSLVLLALLM GIHPSGVTGL VPSLGDREKR DSLCPQGKYV HSKNNSICCT
KCHKGTYLVS DCPSPGRDTV CRECEKGTFT ASQNYLRQCL SCKTCRKEMS QVEISPCQAD
KDTVCGCKEN QFQRYLSETH FQCVDCSPCF NGTVTIPCKE TQNTVCNCHA GFFLRESECV
PCSHCKKNEE CMKLCLPPPL ANVTNPQDSG TAVLLPLVIL LGLCLLSFIF ISLMCRYPRW
RPEVYSIICR DPVPVKEEKA GKPLTPAPSP AFSPTSGFNP TLGFSTPGFS SPVSSTPISP
IFGPSNWHFM PPVSEVVPTQ GADPLLYESL CSVPAPTSVQ KWEDSAHPQR PDNADLAILY
AVVDGVPPAR WKEFMRFMGL SEHEIERLEM QNGRCLREAQ YSMLEAWRRR TPRHEDTLEV
VGLVLSKMNL AGCLENILEA LRNPAPSSTT RLPR
