ID   RIK1_HUMAN     STANDARD;      PRT;   671 AA.
AC   Q13546; Q13180;
DT   01-NOV-1997 (Rel. 35, Created)
DT   30-MAY-2000 (Rel. 39, Last sequence update)
DT   15-JUN-2004 (Rel. 44, Last annotation update)
DE   Receptor-interacting serine/threonine-protein kinase 2 (EC 2.7.1.37)
DE   (Serine/threonine-protein kinase RIP) (Cell death protein RIP)
DE   (Receptor interacting protein).
GN   RIPK1 OR RIP.
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   SEQUENCE FROM N.A., AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-45, AND
RP   INTERACTIONS WITH TRADD; TRAF1; TRAF2 AND TRAF3.
RC   TISSUE=Umbilical vein endothelial cells;
RX   MEDLINE=96200892; PubMed=8612133;
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   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   SEQUENCE FROM N.A.
RA   Sycamore N.;
RL   Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   SEQUENCE OF 300-671 FROM N.A.
RC   TISSUE=Leukemic T-cell;
RX   MEDLINE=95277838; PubMed=7538908;
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   [5]
RP   CLEAVAGE BY CASPASE-8, AND MUTAGENESIS OF ASP-324.
RX   MEDLINE=99452794; PubMed=10521396;
RA   Lin Y., Devin A., Rodriguez Y., Liu Z.-G.;
RT   "Cleavage of the death domain kinase RIP by caspase-8 prompts
RT   TNF-induced apoptosis.";
RL   Genes Dev. 13:2514-2526(1999).
RN   [6]
RP   INTERACTION WITH RIPK3.
RX   MEDLINE=99287880; PubMed=10358032;
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   [7]
RP   INTERACTION WITH BNLF1.
RX   MEDLINE=99340272; 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   [8]
RP   INTERACTION WITH IKBKG.
RX   MEDLINE=99128359; PubMed=9927690;
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   [9]
RP   INTERACTION WITH EGFR.
RX   MEDLINE=21153697; PubMed=11116146;
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   [10]
RP   INTERACTION WITH UBCE7IP1.
RX   MEDLINE=21975204; PubMed=11854271;
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
RT   IL1-induced NF-kappa B activation.";
RL   J. Biol. Chem. 277:15985-15991(2002).
CC   -!- FUNCTION: Promotes apoptosis and activation of NF-kappa-B.
CC       Required for TNFRSF1A mediated activation of NF-kappa-B.
CC   -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC   -!- SUBUNIT: Binds to the death domain of TNFRSF6 and TRADD. Is
CC       recruited by TRADD to TNFRSF1A in a TNF-dependent process. Binds
CC       RIPK3, UBCE7IP1, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3. Interacts
CC       with BNLF1.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic.
CC   -!- PTM: Proteolytically cleaved by caspase-8 during TNF-induced
CC       apoptosis. Cleavage abolishes NF-kappa-B activation and enhances
CC       pro-apototic signaling through the TRADD-FADD interaction.
CC   -!- PTM: Autophosphorylated on serine and threonine residues.
CC   -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family.
CC   -!- SIMILARITY: Contains 1 death domain.
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DR   EMBL; U50062; AAC32232.1; -.
DR   EMBL; AL031963; CAD70625.1; -.
DR   EMBL; U25994; AAC50137.1; -.
DR   PIR; T09479; T09479.
DR   HSSP; P41240; 1BYG.
DR   Genew; HGNC:10019; RIPK1.
DR   MIM; 603453; -.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; TAS.
DR   GO; GO:0004871; F:signal transducer activity; IEP.
DR   GO; GO:0006915; P:apoptosis; TAS.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-k...; IEP.
DR   GO; GO:0007165; P:signal transduction; TAS.
DR   InterPro; IPR000488; Death.
DR   InterPro; IPR000719; Prot_kinase.
DR   InterPro; IPR008271; Ser_thr_pkin_AS.
DR   InterPro; IPR001245; Tyr_pkinase.
DR   Pfam; PF00531; death; 1.
DR   Pfam; PF00069; pkinase; 1.
DR   PRINTS; PR00109; TYRKINASE.
DR   ProDom; PD000001; Prot_kinase; 1.
DR   SMART; SM00005; DEATH; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS50017; DEATH_DOMAIN; 1.
KW   Transferase; Serine/threonine-protein kinase; ATP-binding;
KW   Phosphorylation; Apoptosis.
FT   DOMAIN       17    289       Protein kinase.
FT   NP_BIND      23     31       ATP (By similarity).
FT   BINDING      49     49       ATP (By similarity).
FT   ACT_SITE    138    138       Proton acceptor (By similarity).
FT   DOMAIN      583    669       Death.
FT   DOMAIN      411    414       Poly-Arg.
FT   SITE        324    325       Cleavage (by caspase-8).
FT   MUTAGEN      45     45       K->A: Abolishes kinase activity.
FT   MUTAGEN     324    324       D->K: Abolishes cleavage by caspase-8.
FT   CONFLICT    438    438       V -> A (in Ref. 3).
FT   CONFLICT    514    514       T -> S (in Ref. 4).
SQ   SEQUENCE   671 AA;  75958 MW;  BADC4E7E70456ABE 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 NTEGKGTVYS SAASHGNAVH QPSGLTSQPQ VLYQNNGLYS SHGFGTRPLD
     PGTAGPRVWY RPIPSHMPSL HNIPVPETNY LGNTPTMPFS SLPPTDESIK YTIYNSTGIQ
     IGAYNYMEIG GTSSSLLDST NTNFKEEPAA KYQAIFDNTT SLTDKHLDPI RENLGKHWKN
     CARKLGFTQS QIDEIDHDYE RDGLKEKVYQ MLQKWVMREG IKGATVGKLA QALHQCSRID
     LLSSLIYVSQ N
//