CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-014262
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
 Rinp; Rip 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
20ASSDLLEKTDLDSGGacetylation[1]
115IDVPLSLKGRIIVEAubiquitination[2]
307EDVASLKKEYPDQSPubiquitination[2]
612ERDGLKEKVYQMLQKubiquitination[2]
Reference
 [1] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [2] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
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 (By similarity). 
Sequence Annotation
 DOMAIN 17 290 Protein kinase.
 DOMAIN 568 654 Death.
 NP_BIND 23 31 ATP (By similarity).
 REGION 291 567 Interaction with SQSTM1.
 MOTIF 520 536 RIP homotypic interaction motif (RHIM).
 ACT_SITE 138 138 Proton acceptor (By similarity).
 BINDING 46 46 ATP (By similarity).
 MOD_RES 6 6 Phosphoserine (By similarity).
 MOD_RES 25 25 Phosphoserine (By similarity).
 MOD_RES 161 161 Phosphoserine; by RIPK3 and autocatalysis
 MOD_RES 166 166 Phosphoserine; by autocatalysis
 MOD_RES 304 304 Phosphoserine (By similarity).
 MOD_RES 313 313 Phosphoserine.
 MOD_RES 321 321 Phosphoserine (By similarity).
 MOD_RES 334 334 Phosphoserine (By similarity).
 MOD_RES 383 383 Phosphotyrosine (By similarity).  
Keyword
 ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Host-virus interaction; Kinase; Membrane; Necrosis; Nucleotide-binding; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 656 AA 
Protein Sequence
MQPDMSLDNI KMASSDLLEK TDLDSGGFGK VSLCYHRSHG FVILKKVYTG PNRAEYNEVL 60
LEEGKMMHRL RHSRVVKLLG IIIEEGNYSL VMEYMEKGNL MHVLKTQIDV PLSLKGRIIV 120
EAIEGMCYLH DKGVIHKDLK PENILVDRDF HIKIADLGVA SFKTWSKLTK EKDNKQKEVS 180
STTKKNNGGT LYYMAPEHLN DINAKPTEKS DVYSFGIVLW AIFAKKEPYE NVICTEQFVI 240
CIKSGNRPNV EEILEYCPRE IISLMERCWQ AIPEDRPTFL GIEEEFRPFY LSHFEEYVEE 300
DVASLKKEYP DQSPVLQRMF SLQHDCVPLP PSRSNSEQPG SLHSSQGLQM GPVEESWFSS 360
SPEYPQDEND RSVQAKLQEE ASYHAFGIFA EKQTKPQPRQ NEAYNREEER KRRVSHDPFA 420
QQRARENIKS AGARGHSDPS TTSRGIAVQQ LSWPATQTVW NNGLYNQHGF GTTGTGVWYP 480
PNLSQMYSTY KTPVPETNIP GSTPTMPYFS GPVADDLIKY TIFNSSGIQI GNHNYMDVGL 540
NSQPPNNTCK EESTSRHQAI FDNTTSLTDE HLNPIRENLG RQWKNCARKL GFTESQIDEI 600
DHDYERDGLK EKVYQMLQKW LMREGTKGAT VGKLAQALHQ CCRIDLLNHL IRASQS 656 
Gene Ontology
 GO:0031264; C:death-inducing signaling complex; IEA:Compara.
 GO:0045121; C:membrane raft; IEA:Compara.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0043235; C:receptor complex; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
 GO:0060555; P:activation of necroptosis by extracellular signals; IEA:Compara.
 GO:0006915; P:apoptotic process; IEA:Compara.
 GO:0044257; P:cellular protein catabolic process; ISS:UniProtKB.
 GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
 GO:0006917; P:induction of apoptosis; IEA:Compara.
 GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IEA:Compara.
 GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0036289; P:peptidyl-serine autophosphorylation; ISS:UniProtKB.
 GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
 GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IEA:Compara.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; ISS:UniProtKB.
 GO:0032757; P:positive regulation of interleukin-8 production; IEA:Compara.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IEA:Compara.
 GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
 GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Compara.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0051260; P:protein homooligomerization; IEA:Compara.
 GO:0070926; P:regulation of ATP:ADP antiporter activity; IEA:Compara.
 GO:0007165; P:signal transduction; IEA:InterPro.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
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.