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 27-MAR-2024, entry version 212. 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=4; 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=4; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 25. DR DIP; DIP-34532N; -. DR IntAct; P25118; 27. DR MINT; P25118; -. DR STRING; 10090.ENSMUSP00000032491; -. DR GlyCosmos; P25118; 4 sites, No reported glycans. DR GlyGen; P25118; 3 sites. DR iPTMnet; P25118; -. DR PhosphoSitePlus; P25118; -. DR SwissPalm; P25118; -. DR PaxDb; 10090-ENSMUSP00000032491; -. DR PeptideAtlas; P25118; -. DR ProteomicsDB; 259146; -. DR Pumba; P25118; -. DR ABCD; P25118; 13 sequenced antibodies. DR Antibodypedia; 1320; 1617 antibodies from 51 providers. DR DNASU; 21937; -. DR Ensembl; ENSMUST00000032491.15; ENSMUSP00000032491.9; ENSMUSG00000030341.18. DR GeneID; 21937; -. DR KEGG; mmu:21937; -. DR UCSC; uc009dul.2; mouse. DR AGR; MGI:1314884; -. 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; IVETPCT; -. DR OrthoDB; 5405615at2759; -. 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 NF-kappa-B 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; 16 hits in 83 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 227 other cell types or tissues. DR ExpressionAtlas; P25118; baseline and differential. DR GO; GO:0030424; C:axon; ISO:MGI. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; ISO:MGI. DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0043235; C:receptor complex; 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:0038023; F:signaling receptor activity; IDA:MGI. DR GO; GO:0043120; F:tumor necrosis factor binding; ISO:MGI. DR GO; GO:0005031; F:tumor necrosis factor receptor activity; IDA: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:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; TAS: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:0034250; P:positive regulation of amide metabolic process; IGI: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:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:MGI. DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IMP:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:MGI. DR GO; GO:0045834; P:positive regulation of lipid metabolic process; IGI: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:1905038; P:regulation of membrane lipid metabolic process; IGI: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; IGI:MGI. DR CDD; cd08313; Death_TNFR1; 1. DR CDD; cd10576; TNFRSF1A; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 1. DR Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 2. 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 PANTHER; PTHR46861; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 1A; 1. DR PANTHER; PTHR46861:SF1; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 1A; 1. 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; DEATH domain; 1. DR SUPFAM; SSF57586; TNF receptor-like; 3. DR PROSITE; PS50017; DEATH_DOMAIN; 1. DR PROSITE; PS00652; TNFR_NGFR_1; 3. DR PROSITE; PS50050; TNFR_NGFR_2; 3. DR Genevisible; P25118; MM. 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 //