TNR6_RAT
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 03-AUG-2022, entry version 158.
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-8 to the activated receptor. The resulting death-inducing
CC signaling complex (DISC) performs caspase-8 proteolytic activation
CC which 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}.
CC -!- SUBUNIT: Binds DAXX. Interacts with HIPK3. Part of a complex containing
CC HIPK3 and FADD (By similarity). Binds RIPK1 and FAIM2. Interacts with
CC BABAM2 and FEM1B. Interacts with FADD (By similarity). Interacts
CC directly (via DED domain) with NOL3 (via CARD domain); inhibits death-
CC inducing signaling complex (DISC) assembly by inhibiting the increase
CC in FAS-FADD binding induced by FAS activation (PubMed:15383280).
CC Interacts with CALM (By similarity). In the absence of stimulation,
CC interacts with BIRC2, DDX3X and GSK3B. The interaction with BIRC2 and
CC DDX3X is further enhanced upon receptor stimulation and accompanied by
CC DDX3X and BIRC2 cleavage (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P25445, ECO:0000250|UniProtKB:P25446,
CC 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}.
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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 GlyGen; Q63199; 3 sites.
DR PaxDb; Q63199; -.
DR PRIDE; Q63199; -.
DR GeneID; 246097; -.
DR KEGG; rno:246097; -.
DR UCSC; RGD:619831; rat.
DR CTD; 355; -.
DR RGD; 619831; Fas.
DR eggNOG; ENOG502S0SV; Eukaryota.
DR InParanoid; Q63199; -.
DR OrthoDB; 993446at2759; -.
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:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031264; C:death-inducing signaling complex; IDA:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA: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: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:0038023; F:signaling receptor activity; TAS: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:0071346; P:cellular response to interferon-gamma; 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: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:0010876; P:lipid localization; IEP: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:0010942; P:positive regulation of cell death; IMP:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:RGD.
DR GO; GO:2001269; P:positive regulation of cysteine-type endopeptidase activity involved in 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:0042127; P:regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0010468; P:regulation of gene expression; IMP:RGD.
DR GO; GO:0010883; P:regulation of lipid storage; IEP:RGD.
DR GO; GO:0045619; P:regulation of lymphocyte differentiation; ISO: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: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: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; -; 1.
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; PTHR46874; 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; SSF47986; 1.
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
