ID TNR6_RAT Reviewed; 324 AA. AC Q63199; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 166. DE RecName: Full=Tumor necrosis factor receptor superfamily member 6; DE AltName: Full=Apo-1 antigen; DE AltName: Full=Apoptosis-mediating surface antigen FAS; DE AltName: Full=FASLG receptor; DE AltName: CD_antigen=CD95; DE Flags: Precursor; GN Name=Fas; Synonyms=Apt1, Tnfrsf6; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley; TISSUE=Liver; RX PubMed=7507668; DOI=10.1006/bbrc.1994.1097; RA Kimura K., Yamamoto M., Wakatsuki T.; RT "A variant mRNA species encoding a truncated form of Fas antigen in the rat RT liver."; RL Biochem. Biophys. Res. Commun. 198:666-674(1994). RN [2] RP INTERACTION WITH NOL3. RX PubMed=15383280; DOI=10.1016/j.molcel.2004.08.020; RA Nam Y.J., Mani K., Ashton A.W., Peng C.F., Krishnamurthy B., Hayakawa Y., RA Lee P., Korsmeyer S.J., Kitsis R.N.; RT "Inhibition of both the extrinsic and intrinsic death pathways through RT nonhomotypic death-fold interactions."; RL Mol. Cell 15:901-912(2004). CC -!- FUNCTION: Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits CC caspase CASP8 to the activated receptor. The resulting death-inducing CC signaling complex (DISC) performs CASP8 proteolytic activation which CC initiates the subsequent cascade of caspases (aspartate-specific CC cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may CC have a role in the induction of peripheral tolerance, in the antigen- CC stimulated suicide of mature T-cells, or both (By similarity). CC {ECO:0000250|UniProtKB:P25445}. CC -!- SUBUNIT: Component of the death-induced signaling complex (DISC) CC composed of cell surface receptor FAS/CD95, adapter protein FADD and CC the CASP8 protease; recruitment of CASP8 to the complex is required for CC processing of CASP8 into the p18 and p10 subunits (By similarity). CC Interacts directly (via DED domain) with NOL3 (via CARD domain); CC inhibits death-inducing signaling complex (DISC) assembly by inhibiting CC the increase in FAS-FADD binding induced by FAS activation CC (PubMed:15383280). Binds DAXX. Interacts with HIPK3. Part of a complex CC containing HIPK3 and FADD (By similarity). Binds RIPK1 and FAIM2. CC Interacts with BABAM2 and FEM1B. Interacts with CALM (By similarity). CC In the absence of stimulation, interacts with BIRC2, DDX3X and GSK3B. CC The interaction with BIRC2 and DDX3X is further enhanced upon receptor CC stimulation and accompanied by DDX3X and BIRC2 cleavage (By CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P25445, CC ECO:0000250|UniProtKB:P25446, ECO:0000269|PubMed:15383280}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P51867}; CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P51867}. CC Membrane raft {ECO:0000250|UniProtKB:P25445}. CC -!- DOMAIN: Contains a death domain involved in the binding of FADD, and CC maybe to other cytosolic adapter proteins. CC -!- PTM: Palmitoylated. Palmitoylation by ZDHHC7 prevents the lysosomal CC degradation of FAS regulating its expression at the plasma membrane. CC {ECO:0000250|UniProtKB:P25445}. 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; D26112; BAA05108.1; -; mRNA. DR PIR; JC2395; JC2395. DR RefSeq; NP_631933.2; NM_139194.2. DR AlphaFoldDB; Q63199; -. DR SMR; Q63199; -. DR IntAct; Q63199; 1. DR STRING; 10116.ENSRNOP00000025928; -. DR BindingDB; Q63199; -. DR ChEMBL; CHEMBL2417350; -. DR GlyCosmos; Q63199; 3 sites, No reported glycans. DR GlyGen; Q63199; 3 sites. DR PhosphoSitePlus; Q63199; -. DR PaxDb; 10116-ENSRNOP00000025928; -. DR GeneID; 246097; -. DR KEGG; rno:246097; -. DR UCSC; RGD:619831; rat. DR AGR; RGD:619831; -. DR CTD; 355; -. DR RGD; 619831; Fas. DR eggNOG; ENOG502S0SV; Eukaryota. DR InParanoid; Q63199; -. DR OrthoDB; 24515at2759; -. DR PhylomeDB; Q63199; -. DR Reactome; R-RNO-3371378; Regulation by c-FLIP. DR Reactome; R-RNO-5218900; CASP8 activity is inhibited. DR Reactome; R-RNO-69416; Dimerization of procaspase-8. DR Reactome; R-RNO-75157; FasL/ CD95L signaling. DR PRO; PR:Q63199; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0097440; C:apical dendrite; IDA:RGD. DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD. DR GO; GO:0031265; C:CD95 death-inducing signaling complex; IDA:RGD. DR GO; GO:0009986; C:cell surface; IDA:RGD. DR GO; GO:0031264; C:death-inducing signaling complex; IDA:RGD. DR GO; GO:0009897; C:external side of plasma membrane; IDA:RGD. DR GO; GO:0005576; C:extracellular region; ISO:RGD. DR GO; GO:0005615; C:extracellular space; IDA:RGD. DR GO; GO:0045121; C:membrane raft; ISO:RGD. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0042383; C:sarcolemma; IDA:RGD. DR GO; GO:0030141; C:secretory granule; IDA:RGD. DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:RGD. DR GO; GO:0019900; F:kinase binding; ISO:RGD. DR GO; GO:0002020; F:protease binding; IPI:RGD. DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD. DR GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:RGD. DR GO; GO:0005031; F:tumor necrosis factor receptor activity; IMP:RGD. DR GO; GO:0006924; P:activation-induced cell death of T cells; ISO:RGD. DR GO; GO:0006915; P:apoptotic process; ISO:RGD. DR GO; GO:0097190; P:apoptotic signaling pathway; IMP:RGD. DR GO; GO:0019724; P:B cell mediated immunity; ISO:RGD. DR GO; GO:0034198; P:cellular response to amino acid starvation; ISO:RGD. DR GO; GO:0071279; P:cellular response to cobalt ion; IEP:RGD. DR GO; GO:0071345; P:cellular response to cytokine stimulus; IEP:RGD. DR GO; GO:0071391; P:cellular response to estrogen stimulus; IEP:RGD. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD. DR GO; GO:0071464; P:cellular response to hydrostatic pressure; IEP:RGD. DR GO; GO:0071455; P:cellular response to hyperoxia; ISO:RGD. DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD. DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD. DR GO; GO:0071285; P:cellular response to lithium ion; ISO:RGD. DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD. DR GO; GO:0071234; P:cellular response to phenylalanine; IEP:RGD. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD. DR GO; GO:0071346; P:cellular response to type II interferon; IEP:RGD. DR GO; GO:0043009; P:chordate embryonic development; IEP:RGD. DR GO; GO:0007623; P:circadian rhythm; ISO:RGD. DR GO; GO:0031104; P:dendrite regeneration; IMP:RGD. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD. DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD. DR GO; GO:0036337; P:Fas signaling pathway; ISO:RGD. DR GO; GO:0010467; P:gene expression; ISO:RGD. DR GO; GO:0097284; P:hepatocyte apoptotic process; ISO:RGD. DR GO; GO:0006925; P:inflammatory cell apoptotic process; ISO:RGD. DR GO; GO:0097421; P:liver regeneration; IEP:RGD. DR GO; GO:0070227; P:lymphocyte apoptotic process; ISO:RGD. DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD. DR GO; GO:0097049; P:motor neuron apoptotic process; ISO:RGD. DR GO; GO:0097527; P:necroptotic signaling pathway; ISO:RGD. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD. DR GO; GO:0050869; P:negative regulation of B cell activation; ISO:RGD. DR GO; GO:1900148; P:negative regulation of Schwann cell migration; IMP:RGD. DR GO; GO:0010626; P:negative regulation of Schwann cell proliferation; IMP:RGD. DR GO; GO:0045060; P:negative thymic T cell selection; ISO:RGD. DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD. DR GO; GO:0001552; P:ovarian follicle atresia; IEP:RGD. DR GO; GO:0042698; P:ovulation cycle; IEP:RGD. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:RGD. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD. DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:RGD. DR GO; GO:0042981; P:regulation of apoptotic process; IMP:RGD. DR GO; GO:0045577; P:regulation of B cell differentiation; ISO:RGD. DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:RGD. DR GO; GO:1901532; P:regulation of hematopoietic progenitor cell differentiation; ISO:RGD. DR GO; GO:0010883; P:regulation of lipid storage; IEP:RGD. DR GO; GO:0045637; P:regulation of myeloid cell differentiation; ISO:RGD. DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; ISO:RGD. DR GO; GO:0045580; P:regulation of T cell differentiation; ISO:RGD. DR GO; GO:0046898; P:response to cycloheximide; IEP:RGD. DR GO; GO:0034097; P:response to cytokine; IEP:RGD. DR GO; GO:0043627; P:response to estrogen; IEP:RGD. DR GO; GO:0045471; P:response to ethanol; IEP:RGD. DR GO; GO:1902617; P:response to fluoride; IEP:RGD. DR GO; GO:0051384; P:response to glucocorticoid; ISO:RGD. DR GO; GO:0070848; P:response to growth factor; IEP:RGD. DR GO; GO:0001666; P:response to hypoxia; IEP:RGD. DR GO; GO:0010035; P:response to inorganic substance; IEP:RGD. DR GO; GO:0002931; P:response to ischemia; IEP:RGD. DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD. DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD. DR GO; GO:0009636; P:response to toxic substance; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0007283; P:spermatogenesis; IEP:RGD. DR GO; GO:0048536; P:spleen development; ISO:RGD. DR GO; GO:0043029; P:T cell homeostasis; ISO:RGD. DR GO; GO:0021537; P:telencephalon development; IEP:RGD. DR CDD; cd08316; Death_FAS_TNFRSF6; 1. DR CDD; cd10579; TNFRSF6; 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; IPR008063; Fas_rcpt. DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg. DR InterPro; IPR033998; TNFRSF6_death. DR InterPro; IPR033999; TNFRSF6_N. DR PANTHER; PTHR46874; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 6; 1. DR PANTHER; PTHR46874:SF1; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 6; 1. DR Pfam; PF00531; Death; 1. DR Pfam; PF00020; TNFR_c6; 1. DR PRINTS; PR01680; TNFACTORR6. DR SMART; SM00005; DEATH; 1. DR SMART; SM00208; TNFR; 3. DR SUPFAM; SSF47986; DEATH domain; 1. DR SUPFAM; SSF57586; TNF receptor-like; 2. DR PROSITE; PS50017; DEATH_DOMAIN; 1. DR PROSITE; PS00652; TNFR_NGFR_1; 2. DR PROSITE; PS50050; TNFR_NGFR_2; 2. PE 1: Evidence at protein level; KW Apoptosis; Calmodulin-binding; Cell membrane; Disulfide bond; Glycoprotein; KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..324 FT /note="Tumor necrosis factor receptor superfamily member 6" FT /id="PRO_0000034569" FT TOPO_DOM 22..171 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 172..188 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 189..324 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 43..79 FT /note="TNFR-Cys 1" FT REPEAT 80..123 FT /note="TNFR-Cys 2" FT REPEAT 124..163 FT /note="TNFR-Cys 3" FT DOMAIN 219..303 FT /note="Death" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064" FT REGION 201..306 FT /note="Interaction with HIPK3" FT /evidence="ECO:0000250" FT REGION 219..243 FT /note="Interaction with CALM" FT /evidence="ECO:0000250|UniProtKB:P25445" FT MOD_RES 214 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P25445" FT CARBOHYD 43 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 114 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 132 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 44..55 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206" FT DISULFID 56..69 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206" FT DISULFID 59..78 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206" FT DISULFID 81..97 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206" FT DISULFID 100..115 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206" FT DISULFID 103..123 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206" FT DISULFID 125..139 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206" FT DISULFID 142..154 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206" FT DISULFID 145..162 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206" SQ SEQUENCE 324 AA; 36835 MW; D25D583C909D9D09 CRC64; MLWIMAVLPL VLAGPELNVR MQGTDSIFEG LELKRSVRET DNNCSEGLYQ VGPFCCQPCQ PGERKVKDCT TSGGAPTCHP CTEGEEYTDR KHYSDKCRRC AFCDEGHGLE VETNCTRTQN TKCRCKENFY CNASLCDHCY HCTSCGLEDI LEPCTRTSNT KCKKQSSNYK LLWLLILPGL AILFVFIYKR YRKRQPGDPE SGIPSPESVP MNVSDVNLNK YIWRTAEKMK ICDAKKFARQ HKIPESKIDE IEHNSPQDAA EQKIQLLQCW YQSHGKTGAC QALIQGLRKA NRCDIAEEIQ AMVWEDHENS ISNSRNENEG QSLE //