CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012138
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Receptor-interacting serine/threonine-protein kinase 1 
Protein Synonyms/Alias
 Cell death protein RIP; Receptor-interacting protein 1; RIP-1; Serine/threonine-protein kinase RIP 
Gene Name
 RIPK1 
Gene Synonyms/Alias
 RIP; RIP1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
11DMSLNVIKMKSSDFLubiquitination[1]
13SLNVIKMKSSDFLESubiquitination[1]
140GVIHKDLKPENILVDubiquitination[1]
167ASFKMWSKLNNEEHNubiquitination[1]
185EVDGTAKKNGGTLYYubiquitination[1]
316SNENAVVKRMQSLQLubiquitination[1, 2, 3]
530PPTDESIKYTIYNSTacetylation[4]
585NTTSLTDKHLDPIREubiquitination[1]
625DYERDGLKEKVYQMLubiquitination[1]
642WVMREGIKGATVGKLubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] The NAD-dependent deacetylase SIRT2 is required for programmed necrosis.
 Narayan N, Lee IH, Borenstein R, Sun J, Wong R, Tong G, Fergusson MM, Liu J, Rovira II, Cheng HL, Wang G, Gucek M, Lombard D, Alt FW, Sack MN, Murphy E, Cao L, Finkel T.
 Nature. 2012 Dec 13;492(7428):199-204. [PMID: 23201684] 
Functional Description
 Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex. 
Sequence Annotation
 DOMAIN 17 289 Protein kinase.
 DOMAIN 583 669 Death.
 NP_BIND 23 31 ATP (By similarity).
 REGION 290 582 Interaction with SQSTM1.
 MOTIF 531 547 RIP homotypic interaction motif (RHIM).
 ACT_SITE 138 138 Proton acceptor (By similarity).
 BINDING 49 49 ATP (By similarity).
 MOD_RES 6 6 Phosphoserine.
 MOD_RES 20 20 Phosphoserine; by autocatalysis
 MOD_RES 25 25 Phosphoserine.
 MOD_RES 161 161 Phosphoserine; by RIPK3 and autocatalysis
 MOD_RES 166 166 Phosphoserine; by autocatalysis
 MOD_RES 303 303 Phosphoserine.
 MOD_RES 320 320 Phosphoserine.
 MOD_RES 333 333 Phosphoserine.
 MOD_RES 384 384 Phosphotyrosine.
 CROSSLNK 377 377 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Isopeptide bond; Kinase; Membrane; Necrosis; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 671 AA 
Protein Sequence
MQPDMSLNVI KMKSSDFLES AELDSGGFGK VSLCFHRTQG LMIMKTVYKG PNCIEHNEAL 60
LEEAKMMNRL RHSRVVKLLG VIIEEGKYSL VMEYMEKGNL MHVLKAEMST PLSVKGRIIL 120
EIIEGMCYLH GKGVIHKDLK PENILVDNDF HIKIADLGLA SFKMWSKLNN EEHNELREVD 180
GTAKKNGGTL YYMAPEHLND VNAKPTEKSD VYSFAVVLWA IFANKEPYEN AICEQQLIMC 240
IKSGNRPDVD DITEYCPREI ISLMKLCWEA NPEARPTFPG IEEKFRPFYL SQLEESVEED 300
VKSLKKEYSN ENAVVKRMQS LQLDCVAVPS SRSNSATEQP GSLHSSQGLG MGPVEESWFA 360
PSLEHPQEEN EPSLQSKLQD EANYHLYGSR MDRQTKQQPR QNVAYNREEE RRRRVSHDPF 420
AQQRPYENFQ NTEGKGTAYS SAASHGNAVH QPSGLTSQPQ VLYQNNGLYS SHGFGTRPLD 480
PGTAGPRVWY RPIPSHMPSL HNIPVPETNY LGNTPTMPFS SLPPTDESIK YTIYNSTGIQ 540
IGAYNYMEIG GTSSSLLDST NTNFKEEPAA KYQAIFDNTT SLTDKHLDPI RENLGKHWKN 600
CARKLGFTQS QIDEIDHDYE RDGLKEKVYQ MLQKWVMREG IKGATVGKLA QALHQCSRID 660
LLSSLIYVSQ N 671 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0031264; C:death-inducing signaling complex; IDA:BHF-UCL.
 GO:0045121; C:membrane raft; IEA:Compara.
 GO:0005739; C:mitochondrion; IDA:BHF-UCL.
 GO:0043235; C:receptor complex; IDA:BHF-UCL.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; TAS:Reactome.
 GO:0007257; P:activation of JUN kinase activity; TAS:BHF-UCL.
 GO:0060555; P:activation of necroptosis by extracellular signals; IMP:BHF-UCL.
 GO:0044257; P:cellular protein catabolic process; IDA:UniProtKB.
 GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:BHF-UCL.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
 GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IEA:Compara.
 GO:0036289; P:peptidyl-serine autophosphorylation; IDA:UniProtKB.
 GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
 GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
 GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL.
 GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB.
 GO:0045651; P:positive regulation of macrophage differentiation; IMP:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
 GO:2000379; P:positive regulation of reactive oxygen species metabolic process; TAS:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:BHF-UCL.
 GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
 GO:0070926; P:regulation of ATP:ADP antiporter activity; IMP:BHF-UCL.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IC:BHF-UCL. 
Interpro
 IPR011029; DEATH-like_dom.
 IPR000488; Death_domain.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR025735; RHIM_dom.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00531; Death
 PF07714; Pkinase_Tyr
 PF12721; RHIM 
SMART
 SM00005; DEATH 
PROSITE
 PS50017; DEATH_DOMAIN
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS
 PR00109; TYRKINASE.