TNR6_HUMAN
ID TNR6_HUMAN Reviewed; 335 AA.
AC P25445; A9UJX4; B6VNV4; Q14292; Q14293; Q14294; Q14295; Q16652; Q5T9P1;
AC Q5T9P2; Q5T9P3; Q6SSE9;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 258.
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, FAS1, TNFRSF6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX PubMed=1713127; DOI=10.1016/0092-8674(91)90614-5;
RA Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M.,
RA Hase A., Seto Y., Nagata S.;
RT "The polypeptide encoded by the cDNA for human cell surface antigen Fas can
RT mediate apoptosis.";
RL Cell 66:233-243(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 226-240;
RP 269-291 AND 321-335.
RX PubMed=1375228; DOI=10.1016/s0021-9258(19)50076-x;
RA Oehm A., Behrmann I., Falk W., Pawlita M., Maier G., Klas C., Li-Weber M.,
RA Richards S., Dhein J., Trauth B.C., Ponstingl H., Krammer P.H.;
RT "Purification and molecular cloning of the APO-1 cell surface antigen, a
RT member of the tumor necrosis factor/nerve growth factor receptor
RT superfamily. Sequence identity with the Fas antigen.";
RL J. Biol. Chem. 267:10709-10715(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 6), AND TISSUE
RP SPECIFICITY.
RX PubMed=7575433; DOI=10.1042/bj3100957;
RA Liu C., Cheng J., Mountz J.D.;
RT "Differential expression of human Fas mRNA species upon peripheral blood
RT mononuclear cell activation.";
RL Biochem. J. 310:957-963(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 6), AND FUNCTION.
RX PubMed=7533181;
RA Cascino I., Fiucci G., Papoff G., Ruberti G.;
RT "Three functional soluble forms of the human apoptosis-inducing Fas
RT molecule are produced by alternative splicing.";
RL J. Immunol. 154:2706-2713(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7).
RX PubMed=8598453;
RA Cascino I., Papoff G., De Maria R., Testi R., Ruberti G.;
RT "Fas/Apo-1 (CD95) receptor lacking the intracytoplasmic signaling domain
RT protects tumor cells from Fas-mediated apoptosis.";
RL J. Immunol. 156:13-17(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5).
RX PubMed=8648105;
RA Papoff G., Cascino I., Eramo A., Starace G., Lynch D.H., Ruberti G.;
RT "An N-terminal domain shared by Fas/Apo-1 (CD95) soluble variants prevents
RT cell death in vitro.";
RL J. Immunol. 156:4622-4630(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALPS1A SER-262.
RX PubMed=17336828; DOI=10.1016/j.imbio.2006.12.003;
RA Del-Rey M.J., Manzanares J., Bosque A., Aguilo J.I., Gomez-Rial J.,
RA Roldan E., Serrano A., Anel A., Paz-Artal E., Allende L.M.;
RT "Autoimmune lymphoproliferative syndrome (ALPS) in a patient with a new
RT germline Fas gene mutation.";
RL Immunobiology 212:73-83(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Peripheral blood lymphocyte;
RA Schaetzlein C.E., Poehlmann R., Philippsen P., Eibel H.;
RL Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA De La Calle-Martin O.;
RL Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-16; ILE-122 AND
RP ILE-305.
RG NIEHS SNPs program;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Urinary bladder;
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 [15]
RP INTERACTION WITH RIPK1.
RX PubMed=7538908; DOI=10.1016/0092-8674(95)90072-1;
RA Stanger B.Z., Leder P., Lee T.-H., Kim E., Seed B.;
RT "RIP: a novel protein containing a death domain that interacts with
RT Fas/APO-1 (CD95) in yeast and causes cell death.";
RL Cell 81:513-523(1995).
RN [16]
RP INTERACTION WITH FEM1B.
RX PubMed=10542291; DOI=10.1074/jbc.274.45.32461;
RA Chan S.-L., Tan K.-O., Zhang L., Yee K.S.Y., Ronca F., Chan M.-Y., Yu V.C.;
RT "F1Aalpha, a death receptor-binding protein homologous to the
RT Caenorhabditis elegans sex-determining protein, FEM-1, is a caspase
RT substrate that mediates apoptosis.";
RL J. Biol. Chem. 274:32461-32468(1999).
RN [17]
RP INTERACTION WITH FAIM2.
RX PubMed=10535980; DOI=10.1073/pnas.96.22.12667;
RA Somia N.V., Schmitt M.J., Vetter D.E., Van Antwerp D., Heinemann S.F.,
RA Verma I.M.;
RT "LFG: an anti-apoptotic gene that provides protection from fas-mediated
RT cell death.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:12667-12672(1999).
RN [18]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [19]
RP INTERACTION WITH BABAM2.
RX PubMed=15465831; DOI=10.1074/jbc.m408678200;
RA Li Q., Ching A.K.-K., Chan B.C.-L., Chow S.K.-Y., Lim P.-L., Ho T.C.-Y.,
RA Ip W.-K., Wong C.-K., Lam C.W.-K., Lee K.K.-H., Chan J.Y.-H., Chui Y.-L.;
RT "A death receptor-associated anti-apoptotic protein, BRE, inhibits
RT mitochondrial apoptotic pathway.";
RL J. Biol. Chem. 279:52106-52116(2004).
RN [20]
RP INTERACTION WITH DDX3X; GSK3B AND BIRC2.
RX PubMed=18846110; DOI=10.1038/cdd.2008.124;
RA Sun M., Song L., Li Y., Zhou T., Jope R.S.;
RT "Identification of an antiapoptotic protein complex at death receptors.";
RL Cell Death Differ. 15:1887-1900(2008).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-209, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [23]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-118.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [24]
RP INTERACTION WITH FADD.
RX PubMed=21109225; DOI=10.1016/j.ajhg.2010.10.028;
RA Bolze A., Byun M., McDonald D., Morgan N.V., Abhyankar A., Premkumar L.,
RA Puel A., Bacon C.M., Rieux-Laucat F., Pang K., Britland A., Abel L.,
RA Cant A., Maher E.R., Riedl S.J., Hambleton S., Casanova J.L.;
RT "Whole-exome-sequencing-based discovery of human FADD deficiency.";
RL Am. J. Hum. Genet. 87:873-881(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [27]
RP GLYCOSYLATION AT THR-28, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [28]
RP GLYCOSYLATION AT ARG-250 (MICROBIAL INFECTION).
RX PubMed=23955153; DOI=10.1038/nature12436;
RA Li S., Zhang L., Yao Q., Li L., Dong N., Rong J., Gao W., Ding X., Sun L.,
RA Chen X., Chen S., Shao F.;
RT "Pathogen blocks host death receptor signalling by arginine GlcNAcylation
RT of death domains.";
RL Nature 501:242-246(2013).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [30]
RP SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-199, AND MUTAGENESIS OF
RP CYS-199.
RX PubMed=25301068; DOI=10.1038/cdd.2014.153;
RA Rossin A., Durivault J., Chakhtoura-Feghali T., Lounnas N.,
RA Gagnoux-Palacios L., Hueber A.O.;
RT "Fas palmitoylation by the palmitoyl acyltransferase DHHC7 regulates Fas
RT stability.";
RL Cell Death Differ. 22:643-653(2015).
RN [31]
RP GLYCOSYLATION AT ARG-250 (MICROBIAL INFECTION), AND MUTAGENESIS OF ARG-250.
RX PubMed=30979585; DOI=10.1016/j.molcel.2019.03.028;
RA Ding J., Pan X., Du L., Yao Q., Xue J., Yao H., Wang D.C., Li S., Shao F.;
RT "Structural and functional insights into host death domains inactivation by
RT the bacterial arginine GlcNAcyltransferase effector.";
RL Mol. Cell 74:922-935(2019).
RN [32]
RP STRUCTURE BY NMR OF 218-335.
RX PubMed=8967952; DOI=10.1038/384638a0;
RA Huang B., Eberstadt M., Olejniczak E.T., Meadows R.P., Fesik S.W.;
RT "NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain.";
RL Nature 384:638-641(1996).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS) OF 223-335 IN COMPLEX WITH FADD,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-291 AND
RP ILE-313.
RX PubMed=19118384; DOI=10.1038/nature07606;
RA Scott F.L., Stec B., Pop C., Dobaczewska M.K., Lee J.J., Monosov E.,
RA Robinson H., Salvesen G.S., Schwarzenbacher R., Riedl S.J.;
RT "The Fas-FADD death domain complex structure unravels signalling by
RT receptor clustering.";
RL Nature 457:1019-1022(2009).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 230-254 IN COMPLEX WITH CALM, AND
RP CALMODULIN-BINDING.
RX PubMed=24914971; DOI=10.1107/s1399004714006919;
RA Jiang T., Cao P., Gong Y., Yu H.J., Gui W.J., Zhang W.T.;
RT "Structural insights into the mechanism of calmodulin binding to death
RT receptors.";
RL Acta Crystallogr. D 70:1604-1613(2014).
RN [35]
RP VARIANT ALPS1A PRO-241.
RX PubMed=7540117; DOI=10.1016/0092-8674(95)90013-6;
RA Fisher G.H., Rosenberg F.J., Straus S.E., Dale J.K., Middleton L.A.,
RA Lin A.Y., Strober W., Lenardo M.J., Puck J.M.;
RT "Dominant interfering Fas gene mutations impair apoptosis in a human
RT autoimmune lymphoproliferative syndrome.";
RL Cell 81:935-946(1995).
RN [36]
RP VARIANT ALPS1A TYR-260.
RX PubMed=8929361; DOI=10.1056/nejm199611283352204;
RA Drappa J., Vaishnaw A.K., Sullivan K.E., Chu J.-L., Elkon K.B.;
RT "Fas gene mutations in the Canale-Smith syndrome, an inherited
RT lymphoproliferative disorder associated with autoimmunity.";
RL N. Engl. J. Med. 335:1643-1649(1996).
RN [37]
RP VARIANTS ALPS1A TRP-121 AND CYS-232.
RX PubMed=9028321;
RA Bettinardi A., Brugnoni D., Quiros-Roldan E., Malagoli A., La Grutta S.,
RA Correra A., Notarangelo L.D.;
RT "Missense mutations in the Fas gene resulting in autoimmune
RT lymphoproliferative syndrome: a molecular and immunological analysis.";
RL Blood 89:902-909(1997).
RN [38]
RP VARIANTS ALPS1A ASP-257 AND SER-310.
RX PubMed=9028957;
RA Sneller M.C., Wang J., Dale J.K., Strober W., Middelton L.A., Choi Y.,
RA Fleisher T.A., Lim M.S., Jaffe E.S., Puck J.M., Lenardo M.J., Straus S.E.;
RT "Clinical, immunologic, and genetic features of an autoimmune
RT lymphoproliferative syndrome associated with abnormal lymphocyte
RT apoptosis.";
RL Blood 89:1341-1348(1997).
RN [39]
RP VARIANT ALPS1A ALA-28.
RX PubMed=9322534; DOI=10.1053/gast.1997.v113.pm9322534;
RA Pensati L., Costanzo A., Ianni A., Accapezzato D., Iorio R., Natoli G.,
RA Nisini R., Almerighi C., Balsano C., Vajro P., Vegnente A., Levrero M.;
RT "Fas/Apo1 mutations and autoimmune lymphoproliferative syndrome in a
RT patient with type 2 autoimmune hepatitis.";
RL Gastroenterology 113:1384-1389(1997).
RN [40]
RP VARIANTS NON-HODGKIN LYMPHOMA THR-25; PHE-180; LEU-183; ILE-198; VAL-260;
RP LYS-264; LYS-272; PHE-278 AND ASN-299.
RX PubMed=9787134;
RA Groenbaek K., Straten P.T., Ralfkiaer E., Ahrenkiel V., Andersen M.K.,
RA Hansen N.E., Zeuthen J., Hou-Jensen K., Guldberg P.;
RT "Somatic Fas mutations in non-Hodgkin's lymphoma: association with
RT extranodal disease and autoimmunity.";
RL Blood 92:3018-3024(1998).
RN [41]
RP VARIANT ALPS1A VAL-260.
RX PubMed=9821419; DOI=10.1016/s0022-3476(98)70102-7;
RA Infante A.J., Britton H.A., DeNapoli T., Middelton L.A., Lenardo M.J.,
RA Jackson C.E., Wang J., Fleisher T., Straus S.E., Puck J.M.;
RT "The clinical spectrum in a large kindred with autoimmune
RT lymphoproliferative syndrome caused by a Fas mutation that impairs
RT lymphocyte apoptosis.";
RL J. Pediatr. 133:629-633(1998).
RN [42]
RP VARIANTS ALPS1A LYS-241 AND GLN-250.
RX PubMed=10090885; DOI=10.1086/302333;
RA Jackson C.E., Fischer R.E., Hsu A.P., Anderson S.M., Choi Y., Wang J.,
RA Dale J.K., Fleisher T.A., Middelton L.A., Sneller M.C., Lenardo M.J.,
RA Straus S.E., Puck J.M.;
RT "Autoimmune lymphoproliferative syndrome with defective Fas: genotype
RT influences penetrance.";
RL Am. J. Hum. Genet. 64:1002-1014(1999).
RN [43]
RP VARIANTS ALPS1A LEU-249; PRO-250; ASP-253; SER-253; ARG-259; LYS-270 AND
RP LYS-272.
RX PubMed=10515860;
RA Rieux-Laucat F., Blachere S., Danielan S., De Villartay J.P., Oleastro M.,
RA Solary E., Bader-Meunier B., Arkwright P., Pondare C., Bernaudin F.,
RA Chapel H., Nielsen S., Berrah M., Fischer A., Le Deist F.;
RT "Lymphoproliferative syndrome with autoimmunity: A possible genetic basis
RT for dominant expression of the clinical manifestations.";
RL Blood 94:2575-2582(1999).
RN [44]
RP VARIANT ALPS1A GLY-272.
RX PubMed=10340403; DOI=10.1016/s0301-472x(99)00033-8;
RA Peters A.M., Kohfink B., Martin H., Griesinger F., Wormann B., Gahr M.,
RA Roesler J.;
RT "Defective apoptosis due to a point mutation in the death domain of CD95
RT associated with autoimmune lymphoproliferative syndrome, T-cell lymphoma,
RT and Hodgkin's disease.";
RL Exp. Hematol. 27:868-874(1999).
RN [45]
RP VARIANTS ALPS1A ARG-82; PRO-250; GLY-260 AND ILE-270.
RX PubMed=9927496; DOI=10.1172/jci5121;
RA Vaishnaw A.K., Orlinick J.R., Chu J.-L., Krammer P.H., Chao M.V.,
RA Elkon K.B.;
RT "The molecular basis for apoptotic defects in patients with CD95 (Fas/Apo-
RT 1) mutations.";
RL J. Clin. Invest. 103:355-363(1999).
RN [46]
RP VARIANTS SQUAMOUS CELL CARCINOMA SER-118; ARG-178 AND ASP-255.
RX PubMed=10620127; DOI=10.1046/j.1523-1747.2000.00819.x;
RA Lee S.H., Shin M.S., Kim H.S., Park W.S., Kim S.Y., Jang J.J., Rhim K.J.,
RA Jang J., Lee H.K., Park J.Y., Oh R.R., Han S.Y., Lee J.H., Lee J.Y.,
RA Yoo N.J.;
RT "Somatic mutations of Fas (Apo-1/CD95) gene in cutaneous squamous cell
RT carcinoma arising from a burn scar.";
RL J. Invest. Dermatol. 114:122-126(2000).
RN [47]
RP VARIANTS ALPS1A PRO-241; VAL-260; ILE-270 AND GLY-272.
RX PubMed=11418480; DOI=10.1182/blood.v98.1.194;
RA Straus S.E., Jaffe E.S., Puck J.M., Dale J.K., Elkon K.B., Roesen-Wolff A.,
RA Peters A.M.J., Sneller M.C., Hallahan C.W., Wang J., Fischer R.E.,
RA Jackson C.M., Lin A.Y., Baeumler C., Siegert E., Marx A., Vaishnaw A.K.,
RA Grodzicky T., Fleisher T.A., Lenardo M.J.;
RT "The development of lymphomas in families with autoimmune
RT lymphoproliferative syndrome with germline Fas mutations and defective
RT lymphocyte apoptosis.";
RL Blood 98:194-200(2001).
RN [48]
RP CHARACTERIZATION OF VARIANTS ALPS1A CYS-232; GLN-250; ASP-257; TYR-260;
RP VAL-260; LYS-270 AND LYS-272, AND MUTAGENESIS OF ARG-250; GLU-261; GLN-283
RP AND LYS-287.
RX PubMed=20935634; DOI=10.1038/nsmb.1920;
RA Wang L., Yang J.K., Kabaleeswaran V., Rice A.J., Cruz A.C., Park A.Y.,
RA Yin Q., Damko E., Jang S.B., Raunser S., Robinson C.V., Siegel R.M.,
RA Walz T., Wu H.;
RT "The Fas-FADD death domain complex structure reveals the basis of DISC
RT assembly and disease mutations.";
RL Nat. Struct. Mol. Biol. 17:1324-1329(2010).
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. The secreted isoforms 2
CC to 6 block apoptosis (in vitro). {ECO:0000269|PubMed:19118384,
CC ECO:0000269|PubMed:7533181}.
CC -!- SUBUNIT: Binds DAXX. Interacts with HIPK3 (By similarity). Part of a
CC complex containing HIPK3 and FADD (By similarity). Binds RIPK1 and
CC FAIM2 (PubMed:7538908, PubMed:10535980). Interacts with BABAM2 and
CC FEM1B (PubMed:10542291, PubMed:15465831). Interacts with FADD
CC (PubMed:21109225, PubMed:19118384). Interacts directly (via DED domain)
CC with NOL3 (via CARD domain); inhibits death-inducing signaling complex
CC (DISC) assembly by inhibiting the increase in FAS-FADD binding induced
CC by FAS activation (By similarity). Interacts with CALM
CC (PubMed:24914971). In the absence of stimulation, interacts with BIRC2,
CC DDX3X and GSK3B. The interaction with BIRC2 and DDX3X is further
CC enhanced upon receptor stimulation and accompanied by DDX3X and BIRC2
CC cleavage (PubMed:18846110). {ECO:0000250|UniProtKB:P25446,
CC ECO:0000250|UniProtKB:Q63199, ECO:0000269|PubMed:10535980,
CC ECO:0000269|PubMed:10542291, ECO:0000269|PubMed:15465831,
CC ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19118384,
CC ECO:0000269|PubMed:21109225, ECO:0000269|PubMed:24914971,
CC ECO:0000269|PubMed:7538908}.
CC -!- INTERACTION:
CC P25445; P62158: CALM3; NbExp=4; IntAct=EBI-494743, EBI-397435;
CC P25445; Q14790: CASP8; NbExp=14; IntAct=EBI-494743, EBI-78060;
CC P25445; Q03135: CAV1; NbExp=3; IntAct=EBI-494743, EBI-603614;
CC P25445; Q9UER7: DAXX; NbExp=3; IntAct=EBI-494743, EBI-77321;
CC P25445; Q13158: FADD; NbExp=21; IntAct=EBI-494743, EBI-494804;
CC P25445; P25445: FAS; NbExp=3; IntAct=EBI-494743, EBI-494743;
CC P25445; P48023: FASLG; NbExp=4; IntAct=EBI-494743, EBI-495538;
CC P25445; P29590: PML; NbExp=4; IntAct=EBI-494743, EBI-295890;
CC P25445; Q15156: PML-RAR; NbExp=6; IntAct=EBI-494743, EBI-867256;
CC P25445; Q12923: PTPN13; NbExp=3; IntAct=EBI-494743, EBI-355227;
CC P25445; P12931: SRC; NbExp=2; IntAct=EBI-494743, EBI-621482;
CC P25445; P12815: Pdcd6; Xeno; NbExp=2; IntAct=EBI-494743, EBI-309164;
CC P25445-1; Q14790: CASP8; NbExp=3; IntAct=EBI-15749113, EBI-78060;
CC P25445-1; Q03135: CAV1; NbExp=3; IntAct=EBI-15749113, EBI-603614;
CC P25445-1; Q13158: FADD; NbExp=17; IntAct=EBI-15749113, EBI-494804;
CC P25445-1; P07947: YES1; NbExp=2; IntAct=EBI-15749113, EBI-515331;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:1713127, ECO:0000269|PubMed:25301068}; Single-pass
CC type I membrane protein {ECO:0000305}. Membrane raft
CC {ECO:0000269|PubMed:25301068}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform 6]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=P25445-1; Sequence=Displayed;
CC Name=2; Synonyms=del2, D;
CC IsoId=P25445-2; Sequence=VSP_006481, VSP_006482;
CC Name=3; Synonyms=del3, E;
CC IsoId=P25445-3; Sequence=VSP_006483, VSP_006484;
CC Name=4; Synonyms=B;
CC IsoId=P25445-4; Sequence=VSP_006485, VSP_006486;
CC Name=5; Synonyms=C;
CC IsoId=P25445-5; Sequence=VSP_006487, VSP_006488;
CC Name=6; Synonyms=TMdel, A;
CC IsoId=P25445-6; Sequence=VSP_006489;
CC Name=7; Synonyms=FasExo8Del;
CC IsoId=P25445-7; Sequence=VSP_045235, VSP_045236;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 6 are expressed at equal
CC levels in resting peripheral blood mononuclear cells. After activation
CC there is an increase in isoform 1 and decrease in the levels of isoform
CC 6. {ECO:0000269|PubMed:7575433}.
CC -!- DOMAIN: Contains a death domain involved in the binding of FADD, and
CC maybe to other cytosolic adapter proteins.
CC -!- PTM: (Microbial infection) Glycosylated at Arg-250 by enteropathogenic
CC E.coli protein NleB1: arginine GlcNAcylation prevents
CC homotypic/heterotypic death domain interactions.
CC {ECO:0000305|PubMed:23955153}.
CC -!- PTM: Palmitoylated (PubMed:25301068). Palmitoylation by ZDHHC7 prevents
CC the lysosomal degradation of FAS regulating its expression at the
CC plasma membrane (PubMed:25301068). {ECO:0000269|PubMed:25301068}.
CC -!- PTM: N- and O-glycosylated. O-glycosylated with core 1 or possibly core
CC 8 glycans. {ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:22171320}.
CC -!- DISEASE: Autoimmune lymphoproliferative syndrome 1A (ALPS1A)
CC [MIM:601859]: A disorder of apoptosis that manifests in early childhood
CC and results in the accumulation of autoreactive lymphocytes. It is
CC characterized by non-malignant lymphadenopathy with hepatosplenomegaly,
CC and autoimmune hemolytic anemia, thrombocytopenia and neutropenia.
CC {ECO:0000269|PubMed:10090885, ECO:0000269|PubMed:10340403,
CC ECO:0000269|PubMed:10515860, ECO:0000269|PubMed:11418480,
CC ECO:0000269|PubMed:17336828, ECO:0000269|PubMed:20935634,
CC ECO:0000269|PubMed:7540117, ECO:0000269|PubMed:8929361,
CC ECO:0000269|PubMed:9028321, ECO:0000269|PubMed:9028957,
CC ECO:0000269|PubMed:9322534, ECO:0000269|PubMed:9821419,
CC ECO:0000269|PubMed:9927496}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 7]: Dominant negative isoform, resistant to
CC Fas-mediated apoptosis. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Autoimmune Lymphoproliferative Syndrome Database
CC (ALPSbase); Note=Mutations in TNFRSF6 causing ALPS type Ia;
CC URL="https://www.niaid.nih.gov/diseases-conditions/autoimmune-lymphoproliferative-syndrome-alps";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tnfrsf6/";
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DR EMBL; M67454; AAA63174.1; -; mRNA.
DR EMBL; X63717; CAA45250.1; -; mRNA.
DR EMBL; X83490; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; X83491; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; X83492; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; X83493; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; Z47993; CAA88031.1; -; mRNA.
DR EMBL; Z47994; CAA88032.1; -; mRNA.
DR EMBL; Z47995; CAA88033.1; -; mRNA.
DR EMBL; Z66556; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; Z70519; CAA94430.1; -; mRNA.
DR EMBL; Z70520; CAA94431.1; -; mRNA.
DR EMBL; AY495076; AAS76663.1; -; mRNA.
DR EMBL; X89101; CAA61473.1; -; mRNA.
DR EMBL; FM246458; CAR92543.1; -; mRNA.
DR EMBL; AK290978; BAF83667.1; -; mRNA.
DR EMBL; AY450925; AAR08906.1; -; Genomic_DNA.
DR EMBL; AL157394; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW50151.1; -; Genomic_DNA.
DR EMBL; BC012479; AAH12479.1; -; mRNA.
DR CCDS; CCDS7393.1; -. [P25445-1]
DR CCDS; CCDS7394.1; -. [P25445-6]
DR CCDS; CCDS7395.1; -. [P25445-7]
DR PIR; A40036; A40036.
DR PIR; I37383; I37383.
DR PIR; I37384; I37384.
DR PIR; S58662; S58662.
DR RefSeq; NP_000034.1; NM_000043.5. [P25445-1]
DR RefSeq; NP_001307548.1; NM_001320619.1.
DR RefSeq; NP_690610.1; NM_152871.3. [P25445-6]
DR RefSeq; NP_690611.1; NM_152872.3. [P25445-7]
DR PDB; 1DDF; NMR; -; A=218-335.
DR PDB; 2NA7; NMR; -; A/B/C=171-198.
DR PDB; 3EWT; X-ray; 2.40 A; E=230-254.
DR PDB; 3EZQ; X-ray; 2.73 A; A/C/E/G/I/K/M/O=223-335.
DR PDB; 3THM; X-ray; 2.10 A; F=17-172.
DR PDB; 3TJE; X-ray; 1.93 A; F=17-172.
DR PDBsum; 1DDF; -.
DR PDBsum; 2NA7; -.
DR PDBsum; 3EWT; -.
DR PDBsum; 3EZQ; -.
DR PDBsum; 3THM; -.
DR PDBsum; 3TJE; -.
DR AlphaFoldDB; P25445; -.
DR SMR; P25445; -.
DR BioGRID; 106851; 153.
DR CORUM; P25445; -.
DR DIP; DIP-924N; -.
DR IntAct; P25445; 84.
DR MINT; P25445; -.
DR STRING; 9606.ENSP00000347979; -.
DR ChEMBL; CHEMBL4523207; -.
DR GlyConnect; 773; 1 O-Linked glycan (1 site).
DR GlyGen; P25445; 7 sites, 4 O-linked glycans (4 sites).
DR iPTMnet; P25445; -.
DR PhosphoSitePlus; P25445; -.
DR SwissPalm; P25445; -.
DR BioMuta; FAS; -.
DR DMDM; 119833; -.
DR EPD; P25445; -.
DR jPOST; P25445; -.
DR MassIVE; P25445; -.
DR MaxQB; P25445; -.
DR PaxDb; P25445; -.
DR PeptideAtlas; P25445; -.
DR PRIDE; P25445; -.
DR ProteomicsDB; 54273; -. [P25445-1]
DR ProteomicsDB; 54276; -. [P25445-4]
DR ProteomicsDB; 54277; -. [P25445-5]
DR ProteomicsDB; 54278; -. [P25445-6]
DR ProteomicsDB; 64806; -.
DR TopDownProteomics; P25445-7; -. [P25445-7]
DR ABCD; P25445; 12 sequenced antibodies.
DR Antibodypedia; 4525; 2990 antibodies from 54 providers.
DR CPTC; P25445; 2 antibodies.
DR DNASU; 355; -.
DR Ensembl; ENST00000355279.2; ENSP00000347426.2; ENSG00000026103.23. [P25445-7]
DR Ensembl; ENST00000357339.6; ENSP00000349896.2; ENSG00000026103.23. [P25445-6]
DR Ensembl; ENST00000479522.5; ENSP00000424113.1; ENSG00000026103.23. [P25445-3]
DR Ensembl; ENST00000484444.5; ENSP00000420975.1; ENSG00000026103.23. [P25445-2]
DR Ensembl; ENST00000488877.5; ENSP00000425159.1; ENSG00000026103.23. [P25445-4]
DR Ensembl; ENST00000492756.5; ENSP00000422453.1; ENSG00000026103.23. [P25445-5]
DR Ensembl; ENST00000494410.5; ENSP00000423755.1; ENSG00000026103.23. [P25445-4]
DR Ensembl; ENST00000652046.1; ENSP00000498466.1; ENSG00000026103.23. [P25445-1]
DR GeneID; 355; -.
DR KEGG; hsa:355; -.
DR MANE-Select; ENST00000652046.1; ENSP00000498466.1; NM_000043.6; NP_000034.1.
DR UCSC; uc001kfr.4; human. [P25445-1]
DR CTD; 355; -.
DR DisGeNET; 355; -.
DR GeneCards; FAS; -.
DR GeneReviews; FAS; -.
DR HGNC; HGNC:11920; FAS.
DR HPA; ENSG00000026103; Low tissue specificity.
DR MalaCards; FAS; -.
DR MIM; 134637; gene.
DR MIM; 601859; phenotype.
DR neXtProt; NX_P25445; -.
DR OpenTargets; ENSG00000026103; -.
DR Orphanet; 3261; Autoimmune lymphoproliferative syndrome.
DR Orphanet; 117; Behcet disease.
DR Orphanet; 3437; Vogt-Koyanagi-Harada disease.
DR PharmGKB; PA36613; -.
DR VEuPathDB; HostDB:ENSG00000026103; -.
DR eggNOG; ENOG502S0SV; Eukaryota.
DR GeneTree; ENSGT00950000183126; -.
DR HOGENOM; CLU_067123_1_0_1; -.
DR InParanoid; P25445; -.
DR OMA; QDTKCRC; -.
DR OrthoDB; 993446at2759; -.
DR PhylomeDB; P25445; -.
DR TreeFam; TF333916; -.
DR PathwayCommons; P25445; -.
DR Reactome; R-HSA-140534; Caspase activation via Death Receptors in the presence of ligand.
DR Reactome; R-HSA-3371378; Regulation by c-FLIP.
DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis.
DR Reactome; R-HSA-5218900; CASP8 activity is inhibited.
DR Reactome; R-HSA-6803211; TP53 Regulates Transcription of Death Receptors and Ligands.
DR Reactome; R-HSA-69416; Dimerization of procaspase-8.
DR Reactome; R-HSA-75157; FasL/ CD95L signaling.
DR SignaLink; P25445; -.
DR SIGNOR; P25445; -.
DR BioGRID-ORCS; 355; 8 hits in 1067 CRISPR screens.
DR ChiTaRS; FAS; human.
DR EvolutionaryTrace; P25445; -.
DR GeneWiki; Fas_receptor; -.
DR GenomeRNAi; 355; -.
DR Pharos; P25445; Tbio.
DR PRO; PR:P25445; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P25445; protein.
DR Bgee; ENSG00000026103; Expressed in rectum and 189 other tissues.
DR ExpressionAtlas; P25445; baseline and differential.
DR Genevisible; P25445; HS.
DR GO; GO:0031265; C:CD95 death-inducing signaling complex; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031264; C:death-inducing signaling complex; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019900; F:kinase binding; IPI:BHF-UCL.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0005031; F:tumor necrosis factor receptor activity; IBA:GO_Central.
DR GO; GO:0006924; P:activation-induced cell death of T cells; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:CAFA.
DR GO; GO:0071455; P:cellular response to hyperoxia; IMP:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IBA:GO_Central.
DR GO; GO:0036337; P:Fas signaling pathway; IMP:CAFA.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0097049; P:motor neuron apoptotic process; IBA:GO_Central.
DR GO; GO:0097527; P:necroptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IMP:CAFA.
DR GO; GO:2001269; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IMP:CAFA.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:CAFA.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB.
DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; IMP:CAFA.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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; 2.
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 3D-structure; Alternative splicing; Apoptosis; Calmodulin-binding;
KW Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond;
KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..335
FT /note="Tumor necrosis factor receptor superfamily member 6"
FT /id="PRO_0000034563"
FT TOPO_DOM 26..173
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..335
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 47..83
FT /note="TNFR-Cys 1"
FT REPEAT 84..127
FT /note="TNFR-Cys 2"
FT REPEAT 128..166
FT /note="TNFR-Cys 3"
FT DOMAIN 230..314
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 212..317
FT /note="Interaction with HIPK3"
FT /evidence="ECO:0000250"
FT REGION 230..254
FT /note="Interaction with CALM"
FT /evidence="ECO:0000269|PubMed:24914971"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 214
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P25446"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT LIPID 199
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:25301068"
FT CARBOHYD 28
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 250
FT /note="(Microbial infection) N-beta-linked (GlcNAc)
FT arginine"
FT /evidence="ECO:0000269|PubMed:30979585,
FT ECO:0000305|PubMed:23955153"
FT DISULFID 59..73
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 63..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 85..101
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 104..119
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 107..127
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 129..143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 146..157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 149..165
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT VAR_SEQ 66..103
FT /note="GERKARDCTVNGDEPDCVPCQEGKEYTDKAHFSSKCRR -> DVNMESSRNA
FT HSPATPSAKRKDPDLTWGGFVFFFCQFH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7533181,
FT ECO:0000303|PubMed:7575433"
FT /id="VSP_006481"
FT VAR_SEQ 66..86
FT /note="GERKARDCTVNGDEPDCVPCQ -> DVNMESSRNAHSPATPSAKRK (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:7533181,
FT ECO:0000303|PubMed:7575433"
FT /id="VSP_006483"
FT VAR_SEQ 87..335
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:7533181,
FT ECO:0000303|PubMed:7575433"
FT /id="VSP_006484"
FT VAR_SEQ 104..335
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7533181,
FT ECO:0000303|PubMed:7575433"
FT /id="VSP_006482"
FT VAR_SEQ 112..149
FT /note="GLEVEINCTRTQNTKCRCKPNFFCNSTVCEHCDPCTKC -> DVNMESSRNA
FT HSPATPSAKRKDPDLTWGGFVFFFCQFH (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:7575433,
FT ECO:0000303|PubMed:8648105"
FT /id="VSP_006485"
FT VAR_SEQ 112..132
FT /note="GLEVEINCTRTQNTKCRCKPN -> DVNMESSRNAHSPATPSAKRK (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:8648105, ECO:0000303|Ref.8"
FT /id="VSP_006487"
FT VAR_SEQ 133..335
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:8648105, ECO:0000303|Ref.8"
FT /id="VSP_006488"
FT VAR_SEQ 150..335
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:7575433,
FT ECO:0000303|PubMed:8648105"
FT /id="VSP_006486"
FT VAR_SEQ 169..189
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:7533181,
FT ECO:0000303|PubMed:7575433"
FT /id="VSP_006489"
FT VAR_SEQ 218..220
FT /note="ETV -> MLT (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:8598453"
FT /id="VSP_045235"
FT VAR_SEQ 221..335
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:8598453"
FT /id="VSP_045236"
FT VARIANT 16
FT /note="A -> T (in dbSNP:rs3218619)"
FT /evidence="ECO:0000269|Ref.11"
FT /id="VAR_020008"
FT VARIANT 25
FT /note="A -> T (in non-Hodgkin lymphoma; somatic mutation;
FT dbSNP:rs606231364)"
FT /evidence="ECO:0000269|PubMed:9787134"
FT /id="VAR_013416"
FT VARIANT 28
FT /note="T -> A (in ALPS1A; associated with autoimmune
FT hepatitis type 2)"
FT /evidence="ECO:0000269|PubMed:9322534"
FT /id="VAR_013417"
FT VARIANT 82
FT /note="C -> R (in ALPS1A)"
FT /evidence="ECO:0000269|PubMed:9927496"
FT /id="VAR_013418"
FT VARIANT 118
FT /note="N -> S (in squamous cell carcinoma; burn-scar
FT related; somatic mutation; dbSNP:rs121913083)"
FT /evidence="ECO:0000269|PubMed:10620127"
FT /id="VAR_018321"
FT VARIANT 121
FT /note="R -> W (in ALPS1A; dbSNP:rs121913078)"
FT /evidence="ECO:0000269|PubMed:9028321"
FT /id="VAR_013419"
FT VARIANT 122
FT /note="T -> I (in dbSNP:rs3218614)"
FT /evidence="ECO:0000269|Ref.11"
FT /id="VAR_020009"
FT VARIANT 178
FT /note="C -> R (in squamous cell carcinoma; burn-scar
FT related; somatic mutation; dbSNP:rs121913084)"
FT /evidence="ECO:0000269|PubMed:10620127"
FT /id="VAR_018322"
FT VARIANT 180
FT /note="L -> F (in non-Hodgkin lymphoma; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:9787134"
FT /id="VAR_013420"
FT VARIANT 183
FT /note="P -> L (in non-Hodgkin lymphoma; somatic mutation;
FT dbSNP:rs758835365)"
FT /evidence="ECO:0000269|PubMed:9787134"
FT /id="VAR_013421"
FT VARIANT 184
FT /note="I -> V (in dbSNP:rs28362322)"
FT /id="VAR_052347"
FT VARIANT 198
FT /note="T -> I (in non-Hodgkin lymphoma; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:9787134"
FT /id="VAR_013422"
FT VARIANT 232
FT /note="Y -> C (in ALPS1A; no effect on interaction with
FT FADD; dbSNP:rs121913079)"
FT /evidence="ECO:0000269|PubMed:20935634,
FT ECO:0000269|PubMed:9028321"
FT /id="VAR_013423"
FT VARIANT 241
FT /note="T -> K (in ALPS1A; dbSNP:rs201072885)"
FT /evidence="ECO:0000269|PubMed:10090885"
FT /id="VAR_013424"
FT VARIANT 241
FT /note="T -> P (in ALPS1A; dbSNP:rs121913076)"
FT /evidence="ECO:0000269|PubMed:11418480,
FT ECO:0000269|PubMed:7540117"
FT /id="VAR_013425"
FT VARIANT 249
FT /note="V -> L (in ALPS1A)"
FT /evidence="ECO:0000269|PubMed:10515860"
FT /id="VAR_065128"
FT VARIANT 250
FT /note="R -> P (in ALPS1A; dbSNP:rs121913080)"
FT /evidence="ECO:0000269|PubMed:10515860,
FT ECO:0000269|PubMed:9927496"
FT /id="VAR_013426"
FT VARIANT 250
FT /note="R -> Q (in ALPS1A; no effect on interaction with
FT FADD)"
FT /evidence="ECO:0000269|PubMed:10090885,
FT ECO:0000269|PubMed:20935634"
FT /id="VAR_013427"
FT VARIANT 253
FT /note="G -> D (in ALPS1A)"
FT /evidence="ECO:0000269|PubMed:10515860"
FT /id="VAR_065129"
FT VARIANT 253
FT /note="G -> S (in ALPS1A)"
FT /evidence="ECO:0000269|PubMed:10515860"
FT /id="VAR_065130"
FT VARIANT 255
FT /note="N -> D (in squamous cell carcinoma; burn-scar
FT related; somatic mutation; dbSNP:rs121913082)"
FT /evidence="ECO:0000269|PubMed:10620127"
FT /id="VAR_018323"
FT VARIANT 257
FT /note="A -> D (in ALPS1A; loss of interaction with FADD)"
FT /evidence="ECO:0000269|PubMed:20935634,
FT ECO:0000269|PubMed:9028957"
FT /id="VAR_013428"
FT VARIANT 259
FT /note="I -> R (in ALPS1A)"
FT /evidence="ECO:0000269|PubMed:10515860"
FT /id="VAR_065131"
FT VARIANT 260
FT /note="D -> G (in ALPS1A)"
FT /evidence="ECO:0000269|PubMed:9927496"
FT /id="VAR_013429"
FT VARIANT 260
FT /note="D -> V (in ALPS1A; also found in non-Hodgkin
FT lymphoma; somatic mutation; loss of interaction with FADD;
FT dbSNP:rs28929498)"
FT /evidence="ECO:0000269|PubMed:11418480,
FT ECO:0000269|PubMed:20935634, ECO:0000269|PubMed:9787134,
FT ECO:0000269|PubMed:9821419"
FT /id="VAR_013431"
FT VARIANT 260
FT /note="D -> Y (in ALPS1A; loss of interaction with FADD;
FT dbSNP:rs121913086)"
FT /evidence="ECO:0000269|PubMed:20935634,
FT ECO:0000269|PubMed:8929361"
FT /id="VAR_013430"
FT VARIANT 262
FT /note="I -> S (in ALPS1A)"
FT /evidence="ECO:0000269|PubMed:17336828"
FT /id="VAR_058910"
FT VARIANT 264
FT /note="N -> K (in non-Hodgkin lymphoma; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:9787134"
FT /id="VAR_013432"
FT VARIANT 270
FT /note="T -> I (in ALPS1A; dbSNP:rs121913081)"
FT /evidence="ECO:0000269|PubMed:11418480,
FT ECO:0000269|PubMed:9927496"
FT /id="VAR_013433"
FT VARIANT 270
FT /note="T -> K (in ALPS1A; loss of interaction with FADD)"
FT /evidence="ECO:0000269|PubMed:10515860,
FT ECO:0000269|PubMed:20935634"
FT /id="VAR_065132"
FT VARIANT 272
FT /note="E -> G (in ALPS1A)"
FT /evidence="ECO:0000269|PubMed:10340403,
FT ECO:0000269|PubMed:11418480"
FT /id="VAR_013434"
FT VARIANT 272
FT /note="E -> K (in ALPS1A; also found in non-Hodgkin
FT lymphoma; somatic mutation; loss of interaction with FADD)"
FT /evidence="ECO:0000269|PubMed:10515860,
FT ECO:0000269|PubMed:20935634, ECO:0000269|PubMed:9787134"
FT /id="VAR_013435"
FT VARIANT 278
FT /note="L -> F (in non-Hodgkin lymphoma; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:9787134"
FT /id="VAR_013436"
FT VARIANT 299
FT /note="K -> N (in non-Hodgkin lymphoma; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:9787134"
FT /id="VAR_013437"
FT VARIANT 305
FT /note="T -> I (in dbSNP:rs3218611)"
FT /evidence="ECO:0000269|Ref.11"
FT /id="VAR_020942"
FT VARIANT 310
FT /note="I -> S (in ALPS1A)"
FT /evidence="ECO:0000269|PubMed:9028957"
FT /id="VAR_013438"
FT MUTAGEN 199
FT /note="C->V: Loss of palmitoylation."
FT /evidence="ECO:0000269|PubMed:25301068"
FT MUTAGEN 250
FT /note="R->A: Abolished GlcNAcylation by E.coli NleB1."
FT /evidence="ECO:0000269|PubMed:30979585"
FT MUTAGEN 250
FT /note="R->E: Strongly decreased interaction with FADD."
FT /evidence="ECO:0000269|PubMed:20935634"
FT MUTAGEN 261
FT /note="E->K: Loss of interaction with FADD."
FT /evidence="ECO:0000269|PubMed:20935634"
FT MUTAGEN 283
FT /note="Q->K: Loss of interaction with FADD."
FT /evidence="ECO:0000269|PubMed:20935634"
FT MUTAGEN 287
FT /note="K->D: Strongly decreased interaction with FADD."
FT /evidence="ECO:0000269|PubMed:20935634"
FT MUTAGEN 291
FT /note="Y->D: Decreased interaction with FADD."
FT /evidence="ECO:0000269|PubMed:19118384"
FT MUTAGEN 313
FT /note="I->D: Constitutive activation. Promotes apoptosis,
FT both in the presence and in the absence of stimulation by a
FT ligand."
FT /evidence="ECO:0000269|PubMed:19118384"
FT CONFLICT 224
FT /note="L -> F (in Ref. 11; AAR08906)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="L -> P (in Ref. 9; CAR92543)"
FT /evidence="ECO:0000305"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:3TJE"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:3TJE"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:3TJE"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:3TJE"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:3TJE"
FT STRAND 113..117
FT /evidence="ECO:0007829|PDB:3TJE"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:3TJE"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:3TJE"
FT HELIX 174..181
FT /evidence="ECO:0007829|PDB:2NA7"
FT HELIX 184..193
FT /evidence="ECO:0007829|PDB:2NA7"
FT HELIX 232..242
FT /evidence="ECO:0007829|PDB:3EWT"
FT TURN 251..253
FT /evidence="ECO:0007829|PDB:1DDF"
FT HELIX 256..265
FT /evidence="ECO:0007829|PDB:3EZQ"
FT HELIX 270..282
FT /evidence="ECO:0007829|PDB:3EZQ"
FT HELIX 287..319
FT /evidence="ECO:0007829|PDB:3EZQ"
FT HELIX 327..334
FT /evidence="ECO:0007829|PDB:3EZQ"
SQ SEQUENCE 335 AA; 37732 MW; 0139942535111410 CRC64;
MLGIWTLLPL VLTSVARLSS KSVNAQVTDI NSKGLELRKT VTTVETQNLE GLHHDGQFCH
KPCPPGERKA RDCTVNGDEP DCVPCQEGKE YTDKAHFSSK CRRCRLCDEG HGLEVEINCT
RTQNTKCRCK PNFFCNSTVC EHCDPCTKCE HGIIKECTLT SNTKCKEEGS RSNLGWLCLL
LLPIPLIVWV KRKEVQKTCR KHRKENQGSH ESPTLNPETV AINLSDVDLS KYITTIAGVM
TLSQVKGFVR KNGVNEAKID EIKNDNVQDT AEQKVQLLRN WHQLHGKKEA YDTLIKDLKK
ANLCTLAEKI QTIILKDITS DSENSNFRNE IQSLV
