ID RIPK1_HUMAN Reviewed; 671 AA. AC Q13546; A0AV89; B2RAG1; B4E3F9; Q13180; Q59H33; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-2005, sequence version 3. DT 22-JUL-2015, entry version 168. DE RecName: Full=Receptor-interacting serine/threonine-protein kinase 1; DE EC=2.7.11.1; DE AltName: Full=Cell death protein RIP; DE AltName: Full=Receptor-interacting protein 1; DE Short=RIP-1; DE AltName: Full=Serine/threonine-protein kinase RIP; GN Name=RIPK1; Synonyms=RIP, RIP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AUTOPHOSPHORYLATION, RP MUTAGENESIS OF LYS-45, INTERACTION WITH TRADD; TRAF1; TRAF2 AND TRAF3, RP AND VARIANT VAL-438. RC TISSUE=Umbilical vein endothelial cell; RX PubMed=8612133; DOI=10.1016/S1074-7613(00)80252-6; RA Hsu H., Huang J., Shu H.-B., Baichwal V.R., Goeddel D.V.; RT "TNF-dependent recruitment of the protein kinase RIP to the TNF RT receptor-1 signaling complex."; RL Immunity 4:387-396(1996). RN [2] RP SEQUENCE REVISION TO 120. RA Huang J., Hsu H., Baichwal V.R., Goeddel D.V.; RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 15-671 (ISOFORM 2). RC TISSUE=Adrenal gland, and Uterus; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-234. RG SeattleSNPs variation discovery resource; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP VAL-438. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 153-671. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 300-671, AND VARIANT VAL-438. RC TISSUE=Leukemic T-cell; 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 [9] RP CLEAVAGE BY CASPASE-8, AND MUTAGENESIS OF ASP-324. RX PubMed=10521396; DOI=10.1101/gad.13.19.2514; RA Lin Y., Devin A., Rodriguez Y., Liu Z.-G.; RT "Cleavage of the death domain kinase RIP by caspase-8 prompts TNF- RT induced apoptosis."; RL Genes Dev. 13:2514-2526(1999). RN [10] RP INTERACTION WITH SQSTM1 AND TRAF2, AND DOMAIN. RX PubMed=10356400; DOI=10.1093/emboj/18.11.3044; RA Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J.; RT "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB RT activation."; RL EMBO J. 18:3044-3053(1999). RN [11] RP INTERACTION WITH RIPK3. RX PubMed=10358032; DOI=10.1074/jbc.274.24.16871; RA Sun X., Lee J., Navas T., Baldwin D.T., Stewart T.A., Dixit V.M.; RT "RIP3, a novel apoptosis-inducing kinase."; RL J. Biol. Chem. 274:16871-16875(1999). RN [12] RP INTERACTION WITH BNLF1. RX PubMed=10409763; RA Izumi K.M., Cahir McFarland E., Ting A.T., Riley E.A., Seed B., RA Kieff E.D.; RT "The Epstein-Barr virus oncoprotein latent membrane protein 1 engages RT the tumor necrosis factor receptor-associated proteins TRADD and RT receptor-interacting protein (RIP) but does not induce apoptosis or RT require RIP for NF-kappaB activation."; RL Mol. Cell. Biol. 19:5759-5767(1999). RN [13] RP INTERACTION WITH IKBKG. RX PubMed=9927690; DOI=10.1073/pnas.96.3.1042; RA Li Y., Kang J., Friedman J., Tarassishin L., Ye J., Kovalenko A., RA Wallach D., Horwitz M.S.; RT "Identification of a cell protein (FIP-3) as a modulator of NF-kappaB RT activity and as a target of an adenovirus inhibitor of tumor necrosis RT factor alpha-induced apoptosis."; RL Proc. Natl. Acad. Sci. U.S.A. 96:1042-1047(1999). RN [14] RP FUNCTION. RX PubMed=11101870; DOI=10.1038/82732; RA Holler N., Zaru R., Micheau O., Thome M., Attinger A., Valitutti S., RA Bodmer J.L., Schneider P., Seed B., Tschopp J.; RT "Fas triggers an alternative, caspase-8-independent cell death pathway RT using the kinase RIP as effector molecule."; RL Nat. Immunol. 1:489-495(2000). RN [15] RP INTERACTION WITH EGFR. RX PubMed=11116146; DOI=10.1074/jbc.M008458200; RA Habib A.A., Chatterjee S., Park S.-K., Ratan R.R., Lefebvre S., RA Vartanian T.; RT "The epidermal growth factor receptor engages receptor interacting RT protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to RT activate NF-kappa B. Identification of a novel receptor-tyrosine RT kinase signalosome."; RL J. Biol. Chem. 276:8865-8874(2001). RN [16] RP INTERACTION WITH RNF216. RX PubMed=11854271; DOI=10.1074/jbc.M108675200; RA Chen D., Li X., Zhai Z., Shu H.-B.; RT "A novel zinc finger protein interacts with receptor-interacting RT protein (RIP) and inhibits tumor necrosis factor (TNF)- and IL1- RT induced NF-kappa B activation."; RL J. Biol. Chem. 277:15985-15991(2002). RN [17] RP RIP HOMOTYPIC INTERACTION MOTIF, AND INTERACTION WITH RIPK3. RX PubMed=11734559; DOI=10.1074/jbc.M109488200; RA Sun X., Yin J., Starovasnik M.A., Fairbrother W.J., Dixit V.M.; RT "Identification of a novel homotypic interaction motif required for RT the phosphorylation of receptor-interacting protein (RIP) by RIP3."; RL J. Biol. Chem. 277:9505-9511(2002). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-384, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites RT from human T cells using immobilized metal affinity chromatography and RT tandem mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [19] RP INTERACTION WITH ZFAND5. RX PubMed=14754897; DOI=10.1074/jbc.M309491200; RA Huang J., Teng L., Li L., Liu T., Li L., Chen D., Xu L.-G., Zhai Z., RA Shu H.-B.; RT "ZNF216 is an A20-like and IkappaB kinase gamma-interacting inhibitor RT of NFkappaB activation."; RL J. Biol. Chem. 279:16847-16853(2004). RN [20] RP UBIQUITINATION BY TRAF2, AND DEUBIQUITINATION BY TNFAIP3. RX PubMed=15258597; DOI=10.1038/nature02794; RA Wertz I.E., O'Rourke K.M., Zhou H., Eby M., Aravind L., Seshagiri S., RA Wu P., Wiesmann C., Baker R., Boone D.L., Ma A., Koonin E.V., RA Dixit V.M.; RT "De-ubiquitination and ubiquitin ligase domains of A20 downregulate RT NF-kappaB signalling."; RL Nature 430:694-699(2004). RN [21] RP INTERACTION WITH MAVS. RX PubMed=16127453; DOI=10.1038/ni1243; RA Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., RA Ishii K.J., Takeuchi O., Akira S.; RT "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I RT interferon induction."; RL Nat. Immunol. 6:981-988(2005). RN [22] RP UBIQUITINATION AT LYS-377, AND MUTAGENESIS OF LYS-377. RX PubMed=16603398; DOI=10.1016/j.molcel.2006.03.026; RA Ea C.K., Deng L., Xia Z.P., Pineda G., Chen Z.J.; RT "Activation of IKK by TNFalpha requires site-specific ubiquitination RT of RIP1 and polyubiquitin binding by NEMO."; RL Mol. Cell 22:245-257(2006). RN [23] RP REVIEW. RX PubMed=17301840; DOI=10.1038/sj.cdd.4402085; RA Festjens N., Vanden Berghe T., Cornelis S., Vandenabeele P.; RT "RIP1, a kinase on the crossroads of a cell's decision to live or RT die."; RL Cell Death Differ. 14:400-410(2007). RN [24] RP FUNCTION IN PHOSPHORYLATION OF DAB2IP, AND INTERACTION WITH DAB2IP. RX PubMed=17389591; DOI=10.1074/jbc.M701148200; RA Zhang H., Zhang H., Lin Y., Li J., Pober J.S., Min W.; RT "RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is RT critical for tumor necrosis factor-induced ASK1-JNK/p38 activation."; RL J. Biol. Chem. 282:14788-14796(2007). RN [25] RP INTERACTION WITH RBCK1. RX PubMed=17449468; DOI=10.1074/jbc.M701913200; RA Tian Y., Zhang Y., Zhong B., Wang Y.Y., Diao F.C., Wang R.P., RA Zhang M., Chen D.Y., Zhai Z.H., Shu H.B.; RT "RBCK1 negatively regulates tumor necrosis factor- and interleukin-1- RT triggered NF-kappaB activation by targeting TAB2/3 for degradation."; RL J. Biol. Chem. 282:16776-16782(2007). RN [26] RP INTERACTION WITH RFFL, AND UBIQUITINATION BY RFFL. RX PubMed=18450452; DOI=10.1016/j.cub.2008.04.017; RA Liao W., Xiao Q., Tchikov V., Fujita K., Yang W., Wincovitch S., RA Garfield S., Conze D., El-Deiry W.S., Schuetze S., Srinivasula S.M.; RT "CARP-2 is an endosome-associated ubiquitin ligase for RIP and RT regulates TNF-induced NF-kappaB activation."; RL Curr. Biol. 18:641-649(2008). RN [27] RP MUTAGENESIS OF SER-161, INHIBITION BY NECROSTATIN-1, AND RP PHOSPHORYLATION AT SER-6; SER-20; SER-25; SER-161; SER-166; SER-303; RP SER-320 AND SER-333. RX PubMed=18408713; DOI=10.1038/nchembio.83; RA Degterev A., Hitomi J., Germscheid M., Ch'en I.L., Korkina O., RA Teng X., Abbott D., Cuny G.D., Yuan C., Wagner G., Hedrick S.M., RA Gerber S.A., Lugovskoy A., Yuan J.; RT "Identification of RIP1 kinase as a specific cellular target of RT necrostatins."; RL Nat. Chem. Biol. 4:313-321(2008). RN [28] RP INTERACTION WITH MURID HERPESVIRUS 1 VIRAL INHIBITOR OF RIP RP ACTIVATION. RX PubMed=18442983; DOI=10.1074/jbc.C800051200; RA Upton J.W., Kaiser W.J., Mocarski E.S.; RT "Cytomegalovirus M45 cell death suppression requires receptor- RT interacting protein (RIP) homotypic interaction motif (RHIM)-dependent RT interaction with RIP1."; RL J. Biol. Chem. 283:16966-16970(2008). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND IDENTIFICATION RP BY 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 [30] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=19524513; DOI=10.1016/j.cell.2009.05.037; RA Cho Y.S., Challa S., Moquin D., Genga R., Ray T.D., Guildford M., RA Chan F.K.; RT "Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates RT programmed necrosis and virus-induced inflammation."; RL Cell 137:1112-1123(2009). RN [31] RP FUNCTION, AND INTERACTION WITH RIPK3. RX PubMed=19524512; DOI=10.1016/j.cell.2009.05.021; RA He S., Wang L., Miao L., Wang T., Du F., Zhao L., Wang X.; RT "Receptor interacting protein kinase-3 determines cellular necrotic RT response to TNF-alpha."; RL Cell 137:1100-1111(2009). RN [32] RP INTERACTION WITH RNF34, AND UBIQUITINATION BY RNF34. RX DOI=10.1016/j.cub.2008.11.041; RA Liao W., Fujita K., Xiao Q., Tchikov V., Yang W., Gunsor M., RA Garfield S., Goldsmith P., El-Deiry W.S., Schuetze S., RA Srinivasula S.M.; RT "Response: CARP1 regulates induction of NF-kappaB by TNFalpha."; RL Curr. Biol. 19:R17-R19(2009). RN [33] RP REVIEW. RX PubMed=20354226; DOI=10.1126/scisignal.3115re4; RA Vandenabeele P., Declercq W., Van Herreweghe F., Vanden Berghe T.; RT "The role of the kinases RIP1 and RIP3 in TNF-induced necrosis."; RL Sci. Signal. 3:RE4-RE4(2010). RN [34] 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., RA Buerckstuemmer T., 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 [35] RP UBIQUITINATION BY THE LUBAC COMPLEX. RX PubMed=21455173; DOI=10.1038/nature09816; RA Gerlach B., Cordier S.M., Schmukle A.C., Emmerich C.H., Rieser E., RA Haas T.L., Webb A.I., Rickard J.A., Anderton H., Wong W.W., RA Nachbur U., Gangoda L., Warnken U., Purcell A.W., Silke J., RA Walczak H.; RT "Linear ubiquitination prevents inflammation and regulates immune RT signalling."; RL Nature 471:591-596(2011). RN [36] RP UBIQUITINATION BY BIRC2/C-IAP1 AND BIRC3/C-IAP2, AND INTERACTION WITH RP BIRC2/C-IAP1; BIRC3/C-IAP2 AND XIAP/BIRC4. RX PubMed=21931591; DOI=10.1371/journal.pone.0022356; RA Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R., RA De Medts J., Gevaert K., Declercq W., Vandenabeele P.; RT "cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin RT chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)."; RL PLoS ONE 6:E22356-E22356(2011). RN [37] RP IDENTIFICATION IN COMPLEX WITH PGAM5; RIPK3 AND MLKL. RX PubMed=22265414; DOI=10.1016/j.cell.2011.11.030; RA Wang Z., Jiang H., Chen S., Du F., Wang X.; RT "The mitochondrial phosphatase PGAM5 functions at the convergence RT point of multiple necrotic death pathways."; RL Cell 148:228-243(2012). RN [38] RP INTERACTION WITH ARHGEF2. RX PubMed=21887730; DOI=10.1002/ibd.21851; RA Zhao Y., Alonso C., Ballester I., Song J.H., Chang S.Y., Guleng B., RA Arihiro S., Murray P.J., Xavier R., Kobayashi K.S., Reinecker H.C.; RT "Control of NOD2 and Rip2-dependent innate immune activation by GEF- RT H1."; RL Inflamm. Bowel Dis. 18:603-612(2012). RN [39] RP IDENTIFICATION BY 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [40] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-294 IN COMPLEXES WITH RP NECROSTATIN-TYPE INHIBITORS, CATALYTIC ACTIVITY, ENZYME REGULATION, RP AND AUTOPHOSPHORYLATION. RX PubMed=23473668; DOI=10.1016/j.str.2013.01.016; RA Xie T., Peng W., Liu Y., Yan C., Maki J., Degterev A., Yuan J., RA Shi Y.; RT "Structural basis of RIP1 inhibition by necrostatins."; RL Structure 21:493-499(2013). RN [41] RP VARIANTS [LARGE SCALE ANALYSIS] VAL-64; ILE-81; VAL-220; SER-404; RP VAL-443 AND VAL-569. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Serine-threonine kinase which transduces inflammatory CC and cell-death signals (programmed necrosis) following death CC receptors ligation, activation of pathogen recognition receptors CC (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha CC family cytokines, TRADD and TRAF2 are recruited to the receptor. CC Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent CC manner, and thereby activates the MAP3K5-JNK apoptotic cascade. CC Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a CC critical enhancer of communication with downstream signal CC transducers in the mitogen-activated protein kinase pathway and CC the NF-kappa-B pathway, which in turn mediate downstream events CC including the activation of genes encoding inflammatory molecules. CC Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory CC subunit of the IKK complex, a critical event for NF-kappa-B CC activation. Interaction with other cellular RHIM-containing CC adapters initiates gene activation and cell death. RIPK1 and RIPK3 CC association, in particular, forms a necrosis-inducing complex. CC {ECO:0000269|PubMed:11101870, ECO:0000269|PubMed:17389591, CC ECO:0000269|PubMed:19524512, ECO:0000269|PubMed:19524513}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC {ECO:0000269|PubMed:23473668}. CC -!- ENZYME REGULATION: Inhibited by necrostatins, including CC necrostatin-1, necrostatin-3 and necrostatin-4. CC {ECO:0000269|PubMed:23473668}. CC -!- SUBUNIT: Interacts (via RIP homotypic interaction motif) with CC RIPK3 (via RIP homotypic interaction motif). Upon TNF-induced CC necrosis, the RIPK1-RIPK3 dimer further interacts with PGAM5 and CC MLKL; the formation of this complex leads to PGAM5 phosphorylation CC and increase in PGAM5 phosphatase activity. Interacts (via the CC death domain) with TNFRSF6 (via the death domain) and TRADD (via CC the death domain). Is recruited by TRADD to TNFRSF1A in a TNF- CC dependent process. Binds RNF216, EGFR, IKBKG, TRAF1, TRAF2 and CC TRAF3. Interacts with BNLF1. Interacts with SQSTM1 upon TNF-alpha CC stimulation. May interact with MAVS/IPS1. Interacts with ZFAND5. CC Interacts with RBCK1 (By similarity). Interacts with ZBP1 (By CC similarity). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and CC XIAP/BIRC4. Upon TNF-induced necrosis, forms in complex with CC PGAM5, RIPK3 and MLKL. Interacts (via kinase domain) with DAB2IP CC (via Ras-GAP domain); the interaction occurs in a TNF-alpha- CC dependent manner. Interacts with ARHGEF2. Interacts (via protein CC kinase domain) with RFFL; involved in RIPK1 ubiquitination. CC Interacts with RNF34; involved in RIPK1 ubiquitination. CC {ECO:0000250, ECO:0000269|PubMed:10356400, CC ECO:0000269|PubMed:10358032, ECO:0000269|PubMed:10409763, CC ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11734559, CC ECO:0000269|PubMed:11854271, ECO:0000269|PubMed:14754897, CC ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:17389591, CC ECO:0000269|PubMed:17449468, ECO:0000269|PubMed:18442983, CC ECO:0000269|PubMed:18450452, ECO:0000269|PubMed:19524512, CC ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:21931591, CC ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:8612133, CC ECO:0000269|PubMed:9927690, ECO:0000269|Ref.32}. CC -!- INTERACTION: CC Self; NbExp=6; IntAct=EBI-358507, EBI-358507; CC P04083:ANXA1; NbExp=5; IntAct=EBI-358507, EBI-354007; CC Q13490:BIRC2; NbExp=3; IntAct=EBI-358507, EBI-514538; CC Q13489:BIRC3; NbExp=3; IntAct=EBI-358507, EBI-517709; CC Q92851:CASP10; NbExp=2; IntAct=EBI-358507, EBI-495095; CC Q14790:CASP8; NbExp=23; IntAct=EBI-358507, EBI-78060; CC Q8IVM0:CCDC50; NbExp=2; IntAct=EBI-358507, EBI-723996; CC P48729:CSNK1A1; NbExp=5; IntAct=EBI-358507, EBI-1383726; CC Q13158:FADD; NbExp=5; IntAct=EBI-358507, EBI-494804; CC Q9Y6K9:IKBKG; NbExp=7; IntAct=EBI-358507, EBI-81279; CC Q9Y572:RIPK3; NbExp=24; IntAct=EBI-358507, EBI-298250; CC Q9QZL0:Ripk3 (xeno); NbExp=2; IntAct=EBI-358507, EBI-2367423; CC P19438:TNFRSF1A; NbExp=6; IntAct=EBI-358507, EBI-299451; CC Q13077:TRAF1; NbExp=3; IntAct=EBI-358507, EBI-359224; CC Q12933:TRAF2; NbExp=4; IntAct=EBI-358507, EBI-355744; CC Q13107:USP4; NbExp=4; IntAct=EBI-358507, EBI-723290; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q13546-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13546-2; Sequence=VSP_037690; CC Note=No experimental confirmation available.; CC -!- DOMAIN: Contains a C-terminal death domain (DD) that engages other CC DD-containing proteins as well as a central (intermediate) region CC important for NF-kB activation and RHIM-dependent signaling. CC {ECO:0000269|PubMed:10356400}. CC -!- PTM: Proteolytically cleaved by caspase-8 during TNF-induced CC apoptosis. Cleavage abolishes NF-kappa-B activation and enhances CC pro-apoptotic signaling through the TRADD-FADD interaction. CC {ECO:0000269|PubMed:10521396}. CC -!- PTM: RIPK1 and RIPK3 undergo reciprocal auto- and trans- CC phosphorylation. Phosphorylation of Ser-161 by RIPK3 is necessary CC for the formation of the necroptosis-inducing complex. CC {ECO:0000269|PubMed:18408713, ECO:0000269|PubMed:19524513}. CC -!- PTM: Ubiquitinated by 'Lys-11'-, 'Lys-48'-, 'Lys-63'- and linear- CC linked type ubiquitin. Polyubiquitination with 'Lys-63'-linked CC chains by TRAF2 induces association with the IKK complex. CC Deubiquitination of 'Lys-63'-linked chains and polyubiquitination CC with 'Lys-48'-linked chains by TNFAIP3 leads to RIPK1 proteasomal CC degradation and consequently down-regulates TNF-alpha-induced CC NFkappa-B signaling. 'Lys-48'-linked polyubiquitination by RFFL or CC RNF34 also promotes proteasomal degradation and negatively CC regulates TNF-alpha-induced NFkappa-B signaling. Linear CC polyubiquitinated; the head-to-tail polyubiquitination is mediated CC by the LUBAC complex. LPS-mediated activation of NF-kappa-B. Also CC ubiquitinated with 'Lys-11'-linked chains. Polyubiquitinated with CC 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c- CC IAP2, leading to activation of NF-kappa-B. CC {ECO:0000269|PubMed:15258597, ECO:0000269|PubMed:16603398, CC ECO:0000269|PubMed:18450452, ECO:0000269|PubMed:21455173, CC ECO:0000269|PubMed:21931591, ECO:0000269|Ref.32}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 death domain. {ECO:0000255|PROSITE- CC ProRule:PRU00064}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG65471.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/ripk1/"; 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; U50062; AAC32232.1; -; mRNA. DR EMBL; AK314176; BAG36858.1; -; mRNA. DR EMBL; AK304701; BAG65471.1; ALT_INIT; mRNA. DR EMBL; AY682848; AAT74626.1; -; Genomic_DNA. DR EMBL; AL031963; CAD70625.1; -; Genomic_DNA. DR EMBL; BC126254; AAI26255.1; -; mRNA. DR EMBL; BC126256; AAI26257.1; -; mRNA. DR EMBL; AB208926; BAD92163.1; -; mRNA. DR EMBL; U25994; AAC50137.1; -; mRNA. DR CCDS; CCDS4482.1; -. [Q13546-1] DR PIR; T09479; T09479. DR RefSeq; NP_003795.2; NM_003804.3. [Q13546-1] DR RefSeq; XP_005249514.2; XM_005249457.3. [Q13546-1] DR RefSeq; XP_005249515.1; XM_005249458.1. [Q13546-1] DR UniGene; Hs.519842; -. DR PDB; 4ITH; X-ray; 2.25 A; A/B=1-294. DR PDB; 4ITI; X-ray; 2.86 A; A/B=1-294. DR PDB; 4ITJ; X-ray; 1.80 A; A/B=1-294. DR PDB; 4NEU; X-ray; 2.57 A; A/B=1-324. DR PDBsum; 4ITH; -. DR PDBsum; 4ITI; -. DR PDBsum; 4ITJ; -. DR PDBsum; 4NEU; -. DR ProteinModelPortal; Q13546; -. DR SMR; Q13546; 7-327, 579-661. DR BioGrid; 114274; 71. DR DIP; DIP-433N; -. DR IntAct; Q13546; 33. DR MINT; MINT-128219; -. DR STRING; 9606.ENSP00000259808; -. DR BindingDB; Q13546; -. DR ChEMBL; CHEMBL5464; -. DR GuidetoPHARMACOLOGY; 2189; -. DR PhosphoSite; Q13546; -. DR BioMuta; RIPK1; -. DR DMDM; 60393639; -. DR MaxQB; Q13546; -. DR PaxDb; Q13546; -. DR PRIDE; Q13546; -. DR DNASU; 8737; -. DR Ensembl; ENST00000259808; ENSP00000259808; ENSG00000137275. DR Ensembl; ENST00000380409; ENSP00000369773; ENSG00000137275. DR GeneID; 8737; -. DR KEGG; hsa:8737; -. DR UCSC; uc003muv.4; human. [Q13546-1] DR UCSC; uc011dhs.2; human. [Q13546-2] DR CTD; 8737; -. DR GeneCards; GC06P003064; -. DR HGNC; HGNC:10019; RIPK1. DR HPA; CAB010302; -. DR HPA; HPA015257; -. DR MIM; 603453; gene. DR neXtProt; NX_Q13546; -. DR PharmGKB; PA34394; -. DR eggNOG; COG0515; -. DR GeneTree; ENSGT00550000074536; -. DR HOGENOM; HOG000010270; -. DR HOVERGEN; HBG055612; -. DR InParanoid; Q13546; -. DR KO; K02861; -. DR OMA; VVKRMQS; -. DR OrthoDB; EOG7MPRDN; -. DR PhylomeDB; Q13546; -. DR TreeFam; TF106506; -. DR BRENDA; 2.7.10.2; 2681. DR Reactome; REACT_118563; RIP-mediated NFkB activation via ZBP1. DR Reactome; REACT_1432; TNF signaling. DR Reactome; REACT_1503; Ligand-dependent caspase activation. DR Reactome; REACT_150361; TRIF-mediated programmed cell death. DR Reactome; REACT_164011; Regulation by c-FLIP. DR Reactome; REACT_169333; TRP channels. DR Reactome; REACT_25039; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10. DR Reactome; REACT_25374; IKK complex recruitment mediated by RIP1. DR Reactome; REACT_355072; TNFR1-mediated proapoptotic signaling. DR Reactome; REACT_355311; CASP8 activity is inhibited. DR Reactome; REACT_355409; RIPK1-mediated regulated necrosis. DR Reactome; REACT_832; Dimerization of procaspase-8. DR SignaLink; Q13546; -. DR ChiTaRS; RIPK1; human. DR GeneWiki; RIPK1; -. DR GenomeRNAi; 8737; -. DR NextBio; 32775; -. DR PMAP-CutDB; Q13546; -. DR PRO; PR:Q13546; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; Q13546; -. DR CleanEx; HS_RIPK1; -. DR ExpressionAtlas; Q13546; baseline and differential. DR Genevisible; Q13546; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0031264; C:death-inducing signaling complex; IDA:BHF-UCL. DR GO; GO:0045121; C:membrane raft; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL. DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL. DR GO; GO:0097342; C:ripoptosome; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0070513; F:death domain binding; IPI:BHF-UCL. DR GO; GO:0005123; F:death receptor binding; IPI:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0032403; F:protein complex binding; IDA:UniProtKB. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; TAS:Reactome. DR GO; GO:0097296; P:activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; TAS:Reactome. DR GO; GO:0007257; P:activation of JUN kinase activity; TAS:BHF-UCL. DR GO; GO:1990000; P:amyloid fibril formation; IMP:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:Reactome. DR GO; GO:0044257; P:cellular protein catabolic process; IDA:UniProtKB. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB. DR GO; GO:0071550; P:death-inducing signaling complex assembly; TAS:Reactome. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:BHF-UCL. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0002756; P:MyD88-independent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0070266; P:necroptotic process; IMP:UniProtKB. DR GO; GO:0097527; P:necroptotic signaling pathway; ISS:UniProtKB. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; TAS:Reactome. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl. DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB. DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; IDA:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL. DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB. DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IMP:UniProtKB. DR GO; GO:0060545; P:positive regulation of necroptotic process; IMP:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0043068; P:positive regulation of programmed cell death; IMP:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; TAS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:BHF-UCL. DR GO; GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome. DR GO; GO:0012501; P:programmed cell death; TAS:Reactome. DR GO; GO:0097300; P:programmed necrotic cell death; TAS:Reactome. DR GO; GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL. DR GO; GO:0051291; P:protein heterooligomerization; IMP:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0070926; P:regulation of ATP:ADP antiporter activity; IMP:BHF-UCL. DR GO; GO:1902041; P:regulation of extrinsic apoptotic signaling pathway via death domain receptors; TAS:Reactome. DR GO; GO:0010939; P:regulation of necrotic cell death; TAS:Reactome. DR GO; GO:0034612; P:response to tumor necrosis factor; IMP:BHF-UCL. DR GO; GO:0097343; P:ripoptosome assembly; IMP:UniProtKB. DR GO; GO:1901026; P:ripoptosome assembly involved in necroptotic process; IEA:Ensembl. DR GO; GO:0070231; P:T cell apoptotic process; ISS:UniProtKB. DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome. DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome. DR GO; GO:0002224; P:toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IC:BHF-UCL. DR Gene3D; 1.10.533.10; -; 1. DR InterPro; IPR011029; DEATH-like_dom. DR InterPro; IPR000488; Death_domain. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR025735; RHIM_dom. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR Pfam; PF00531; Death; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF12721; RHIM; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00005; DEATH; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS50017; DEATH_DOMAIN; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Complete proteome; Cytoplasm; Isopeptide bond; Kinase; Membrane; KW Necrosis; Nucleotide-binding; Phosphoprotein; Polymorphism; KW Reference proteome; Serine/threonine-protein kinase; Transferase; KW Ubl conjugation. FT CHAIN 1 671 Receptor-interacting serine/threonine- FT protein kinase 1. FT /FTId=PRO_0000086606. FT DOMAIN 17 289 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT DOMAIN 583 669 Death. {ECO:0000255|PROSITE- FT ProRule:PRU00064}. FT NP_BIND 23 31 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 290 582 Interaction with SQSTM1. FT MOTIF 531 547 RIP homotypic interaction motif (RHIM). FT COMPBIAS 411 414 Poly-Arg. FT ACT_SITE 138 138 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027}. FT BINDING 49 49 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT SITE 324 325 Cleavage; by caspase-8. FT MOD_RES 6 6 Phosphoserine. FT {ECO:0000269|PubMed:18408713}. FT MOD_RES 20 20 Phosphoserine; by autocatalysis. FT {ECO:0000255}. FT MOD_RES 25 25 Phosphoserine. FT {ECO:0000269|PubMed:18408713}. FT MOD_RES 161 161 Phosphoserine; by RIPK3 and FT autocatalysis. {ECO:0000255}. FT MOD_RES 166 166 Phosphoserine; by autocatalysis. FT {ECO:0000255}. FT MOD_RES 303 303 Phosphoserine. FT {ECO:0000269|PubMed:18408713}. FT MOD_RES 320 320 Phosphoserine. FT {ECO:0000269|PubMed:18408713, FT ECO:0000269|PubMed:18669648}. FT MOD_RES 333 333 Phosphoserine. FT {ECO:0000269|PubMed:18408713}. FT MOD_RES 384 384 Phosphotyrosine. FT {ECO:0000269|PubMed:15144186}. FT CROSSLNK 377 377 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000250}. FT VAR_SEQ 108 153 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_037690. FT VARIANT 64 64 A -> V (in a colorectal adenocarcinoma FT sample; somatic mutation). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041039. FT VARIANT 81 81 V -> I (in a colorectal adenocarcinoma FT sample; somatic mutation). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041040. FT VARIANT 220 220 A -> V (in a colorectal adenocarcinoma FT sample; somatic mutation). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041041. FT VARIANT 234 234 E -> K (in dbSNP:rs17548383). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_021109. FT VARIANT 404 404 A -> S (in dbSNP:rs34872409). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041042. FT VARIANT 438 438 A -> V (in dbSNP:rs3173519). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7538908, FT ECO:0000269|PubMed:8612133}. FT /FTId=VAR_058285. FT VARIANT 443 443 A -> V (in dbSNP:rs35722193). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041043. FT VARIANT 569 569 A -> V (in dbSNP:rs55861377). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_041044. FT MUTAGEN 45 45 K->A: Abolishes kinase activity. FT {ECO:0000269|PubMed:8612133}. FT MUTAGEN 161 161 S->A: Decreases RIPK1 kinase activity. FT {ECO:0000269|PubMed:18408713}. FT MUTAGEN 161 161 S->E: No effect on RIPK1 FT autophosphorylation. FT {ECO:0000269|PubMed:18408713}. FT MUTAGEN 324 324 D->K: Abolishes cleavage by caspase-8. FT {ECO:0000269|PubMed:10521396}. FT MUTAGEN 377 377 K->R: Abolishes RIP-mediated NF-Kappa-B FT activation. FT {ECO:0000269|PubMed:16603398}. FT CONFLICT 258 258 R -> I (in Ref. 3; BAG36858). FT {ECO:0000305}. FT CONFLICT 286 286 R -> S (in Ref. 3; BAG36858). FT {ECO:0000305}. FT CONFLICT 514 514 T -> S (in Ref. 8; AAC50137). FT {ECO:0000305}. FT HELIX 14 16 {ECO:0000244|PDB:4ITJ}. FT STRAND 20 22 {ECO:0000244|PDB:4ITJ}. FT TURN 26 28 {ECO:0000244|PDB:4ITI}. FT STRAND 30 36 {ECO:0000244|PDB:4ITJ}. FT TURN 37 39 {ECO:0000244|PDB:4ITJ}. FT STRAND 40 51 {ECO:0000244|PDB:4ITJ}. FT HELIX 54 56 {ECO:0000244|PDB:4ITJ}. FT HELIX 57 68 {ECO:0000244|PDB:4ITJ}. FT STRAND 78 84 {ECO:0000244|PDB:4ITJ}. FT STRAND 87 93 {ECO:0000244|PDB:4ITJ}. FT HELIX 100 104 {ECO:0000244|PDB:4ITJ}. FT STRAND 106 108 {ECO:0000244|PDB:4ITJ}. FT HELIX 112 131 {ECO:0000244|PDB:4ITJ}. FT HELIX 141 143 {ECO:0000244|PDB:4ITJ}. FT STRAND 144 146 {ECO:0000244|PDB:4ITJ}. FT STRAND 152 154 {ECO:0000244|PDB:4ITJ}. FT HELIX 163 168 {ECO:0000244|PDB:4ITJ}. FT STRAND 171 173 {ECO:0000244|PDB:4ITH}. FT HELIX 190 192 {ECO:0000244|PDB:4NEU}. FT HELIX 195 197 {ECO:0000244|PDB:4ITJ}. FT STRAND 201 203 {ECO:0000244|PDB:4ITJ}. FT HELIX 207 223 {ECO:0000244|PDB:4ITJ}. FT HELIX 234 242 {ECO:0000244|PDB:4ITJ}. FT HELIX 249 251 {ECO:0000244|PDB:4ITJ}. FT HELIX 258 267 {ECO:0000244|PDB:4ITJ}. FT HELIX 272 274 {ECO:0000244|PDB:4ITJ}. FT HELIX 278 292 {ECO:0000244|PDB:4ITJ}. FT HELIX 294 296 {ECO:0000244|PDB:4NEU}. FT HELIX 297 309 {ECO:0000244|PDB:4NEU}. FT TURN 310 312 {ECO:0000244|PDB:4NEU}. SQ SEQUENCE 671 AA; 75931 MW; 976E2428D525A9B2 CRC64; MQPDMSLNVI KMKSSDFLES AELDSGGFGK VSLCFHRTQG LMIMKTVYKG PNCIEHNEAL LEEAKMMNRL RHSRVVKLLG VIIEEGKYSL VMEYMEKGNL MHVLKAEMST PLSVKGRIIL EIIEGMCYLH GKGVIHKDLK PENILVDNDF HIKIADLGLA SFKMWSKLNN EEHNELREVD GTAKKNGGTL YYMAPEHLND VNAKPTEKSD VYSFAVVLWA IFANKEPYEN AICEQQLIMC IKSGNRPDVD DITEYCPREI ISLMKLCWEA NPEARPTFPG IEEKFRPFYL SQLEESVEED VKSLKKEYSN ENAVVKRMQS LQLDCVAVPS SRSNSATEQP GSLHSSQGLG MGPVEESWFA PSLEHPQEEN EPSLQSKLQD EANYHLYGSR MDRQTKQQPR QNVAYNREEE RRRRVSHDPF AQQRPYENFQ NTEGKGTAYS SAASHGNAVH QPSGLTSQPQ VLYQNNGLYS SHGFGTRPLD PGTAGPRVWY RPIPSHMPSL HNIPVPETNY LGNTPTMPFS SLPPTDESIK YTIYNSTGIQ IGAYNYMEIG GTSSSLLDST NTNFKEEPAA KYQAIFDNTT SLTDKHLDPI RENLGKHWKN CARKLGFTQS QIDEIDHDYE RDGLKEKVYQ MLQKWVMREG IKGATVGKLA QALHQCSRID LLSSLIYVSQ N //