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receptor-interacting serine/threonine protein kinase 1; serine/threonine protein kinase RIP; cell death protein RIP; receptor-interacting protein (RIPK1, RIP)

Function: - role in the transduction of TNF signaling - TNF stimulation induces binding of RIPK1-TRADD-TRAF2-TRAF5 complex to TNFR1 - TRAF proteins then catalyze the Lys-63-linked polyubiquitination of RIPK1, inducing RIPK1 association with the IKK complex, which is subsequently activated, leading ultimately to activation of NF-kappa-B - the inflammatory response is kept transient by the action of the NF-kappa-B target gene product TNFAIP3 - TNFAIP3 is recruited to RIPK1 within a complex comprising also RNF11, ITCH & TAX1BP1 - TNFAIP3 deubiquitinates Lys-63-polyubiquitin chains on RIPK1 & catalyzes the formation of Lys-48-polyubiquitin chains; this leads to RIPK1 proteosomal degradation & consequently to the termination of the TNF- or LPS-mediated activation of NF-kappa-B - proteolytically cleaved by caspase-8 during TNF-induced apoptosis; cleavage abolishes NF-kappa-B activation & enhances pro-apototic signaling through the TRADD-FADD interaction - autophosphorylated on Ser & Thr - undergoes Lys-63-polyubiquitination catalyzed by TRAF2 after TNF stimulation - down-regulated by Lys-63-deubiquitination & Lys-48- ubiquitination, both reactions being catalyzed by TNFAIP3 - Lys-48-ubiquitination leads to proteasomal degradation - binds to the death domain of TNFRSF6 & TRADD - recruited by TRADD to TNFRSF1A (TNF-dependent) - binds RIPK3, UBCE7IP1 isoform 3 (ZIN), EGFR, IKBKG, TRAF1, TRAF2 & TRAF3 - interacts with BNLF1 - interacts with SQSTM1 upon TNF-alpha stimulation - may interact with MAVS/IPS1 - interacts with ZFAND5 Structure: - belongs to the protein kinase superfamily, TKL Ser/Thr protein kinase family - contains 1 death domain - contains 1 protein kinase domain at its N-terminus Compartment: cytoplasm Alternative splicing: named isoforms=2

Interactions

molecular events

Related

Arf-GAP domain & FG repeat-containing protein 1; HIV-1 Rev-binding protein; nucleoporin-like protein RIP; Rev-interacting protein; Rev/Rex activation domain-binding protein (AGFG1, HRB, RAB, RIP)

General

pro apoptotic protein serine/threonine kinase

Properties

SIZE: entity length = 671 aa MW = 76 kD COMPARTMENT: cytoplasm MOTIF: kinase domain SITE: 17-289 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 23-31 ATP-binding site NAME: ATP-binding site SITE: 49-49 aspartate residue {D138} SQSTM1 interaction {290-582} MOTIF: Ser phosphorylation site {S320} peptide motif {324-325} Tyr phosphorylation site {Y384} Tyr phosphorylation site {Y387} Ser phosphorylation site {S389} arginine-rich region {411-414} MOTIF: arginine residue (SEVERAL) death domain NAME: death domain SITE: 583-669 STATE: active state

Database Correlations

OMIM 603453 UniProt Q13546 PFAM correlations Entrez Gene 8737 KEGG correlations ENZYME 2.7.11.1

References

  1. Prosite :accession PS50017
  2. Stanger BZ et al RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 81:513 1995 PMID: 7538908
  3. UniProt :accession Q13546
  4. SeattleSNPs http://pga.gs.washington.edu/data/ripk1/

Component-of

molecular complex