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

More general terms

• serine/threonine kinase
• pro apoptotic protein

Additional terms

• 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)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8737
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8737
• Kegg: http://www.genome.jp/dbget-bin/www_bget?
• OMIM: https://mirror.omim.org/entry/603453
• UniProt: http://www.uniprot.org/uniprot/Q13546.html