RIP Recombinant Rabbit Monoclonal Antibody [JJ092-04]

Function

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis, necroptosis, and PANoptosis. Some of the cell survival pathways RIPK1 participates in include NF-κB, Akt, and JNK. RIPK1 is an enzyme that in humans is encoded by the RIPK1 gene, which is located on chromosome 6. This protein belongs to the Receptor Interacting Protein (RIP) kinases family, which consists of seven members, RIPK1 being the first member of the family.

Background References

1. Mannion J et al. A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death. Immunity. 2024 Jul

2. Hou S et al. PARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis. Mol Cell. 2024 Mar

Sequence Similarity

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Post-translational Modification

Proteolytically cleaved by CASP8 at Asp-324. Cleavage is crucial for limiting TNF-induced apoptosis, necroptosis and inflammatory response. Cleavage abolishes NF-kappa-B activation and enhances the interaction of TRADD with FADD.; RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylation of Ser-161 by RIPK3 is necessary for the formation of the necroptosis-inducing complex. Phosphorylation at Ser-25 represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. Phosphorylated at Ser-320 by MAP3K7 which requires prior ubiquitination with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 (By similarity). This phosphorylation positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity).; Ubiquitinated with 'Lys-11'-, 'Lys-48'-, 'Lys-63'- and linear-linked type ubiquitin. Polyubiquitination with 'Lys-63'-linked chains by TRAF2 induces association with the IKK complex. Deubiquitination of 'Lys-63'-linked chains and polyubiquitination with 'Lys-48'-linked chains by TNFAIP3 leads to RIPK1 proteasomal degradation and consequently down-regulates TNF-alpha-induced NFkappa-B signaling. 'Lys-48'-linked polyubiquitination by RFFL or RNF34 also promotes proteasomal degradation and negatively regulates TNF-alpha-induced NF-kappa-B signaling. Linear polyubiquitinated; the head-to-tail linear polyubiquitination ('Met-1'-linked) is mediated by the LUBAC complex and decreases protein kinase activity. Deubiquitination of linear polyubiquitin by CYLD promotes the kinase activity (By similarity). Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B. Ubiquitinated with 'Lys-63'-linked chains by PELI1. Ubiquitination at Lys-377 with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 is essential for its phosphorylation at Ser-320 mediated by MAP3K7 (By similarity). This ubiquitination is required for NF-kB activation, suppresses RIPK1 kinase activity and plays a critical role in preventing cell death during embryonic development (By similarity).

Subcellular Location

Cytoplasm, Cell membrane.

UNIPROT

SwissProt: Q13546 Human

Synonyms