Ripk3
entrez
246240
canonical
uniprot
Q9Z2P5
canonical
ensembl
ENSRNOG00000020465
resolver
ensp
ENSRNOP00000027759
resolver
genesymbol
Ripk3
resolver
genesymbol_syn
Rip3
resolver
uniprot
B0BMV6
resolver
uniprot_entry
RIPK3_RAT
resolver
uniprot_sec
B0BMV6
resolver
activity_regulation
ACTIVITY REGULATION: Activity is stimulated by ZBP1, which senses double-stranded Z-RNA structures. RIPK3-dependent necroptosis is inhibited by RIPK1: RIPK1 prevents the ZBP1-induced activation of RIPK3 via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis. {ECO:0000250|UniProtKB:Q9QZL0}.
uniprot
proteins
amino_acid_sequence
MSSVKLWLNGASSISLVGSEELENLGFVGKGGFGAVFRARHTAWNLDVAVKIVNSKKISREVKAMVNLRHENVLLLLGVTENLEWDYVYGPALVTGFMENGSLSGLLQPSCPRPWPLLCRLLEEVVLGMCYLHSLNPSLLHRDLKPSNVLLDPELHAKLADFGLSTFQGGSQSGSGSGSRDSGGTLAYLAPELLDNDGKASKASDVYSFGVLVWTVLAGREAEVVDKTSLIRGAVCNRQRRPPLTELPPDSPETPGLEGLKELMTHCWSSEPKDRPSFQDCESKTNNVYILVQDKVDAAVSKVKHYLSQYRSSDTKLSARESSQKGTEVDCPRETIVYEMLDRLHLEEPSGSVPERLTSLTERRGKEASFGHATPAGTSSDTLAGTPQIPHTLPSRGTTPRPAFTETPGPDPQRNQGDGRNSNPWYTWNAPNPMTGLQSIVLNNCSEVQIGQHNCMSVQPRTAFPKKEPAQFGRGRGW
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Serine/threonine-protein kinase that activates necroptosis and apoptosis, two parallel forms of cell death. Necroptosis, a programmed cell death process in response to death-inducing TNF family members, is triggered by RIPK3 following activation by ZBP1. Activated RIPK3 forms a necrosis-inducing complex and mediates phosphorylation of MLKL, promoting MLKL localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage. In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol. Also regulates apoptosis: apoptosis depends on RIPK1, FADD and CASP8, and is independent of MLKL and RIPK3 kinase activity (By similarity). Phosphorylates RIPK1: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (By similarity). In some cell types, also able to restrict viral replication by promoting cell death-independent responses. In response to flavivirus infection in neurons, promotes a cell death-independent pathway that restricts viral replication: together with ZBP1, promotes a death-independent transcriptional program that modifies the cellular metabolism via up-regulation expression of the enzyme ACOD1/IRG1 and production of the metabolite itaconate. Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes (By similarity). RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production (By similarity). {ECO:0000250|UniProtKB:Q9QZL0, ECO:0000250|UniProtKB:Q9Y572}.
uniprot
proteins
mass_dalton
52218
uniprot
proteins
post_translational_modification
PTM: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Autophosphorylated following interaction with ZBP1. Phosphorylation of Ser-201 plays a role in the necroptotic function of RIPK3. Autophosphorylates at Thr-228 and Ser-229 following activation by ZBP1: phosphorylation at these sites is a hallmark of necroptosis and is required for binding MLKL. Phosphorylation at Thr-185 is important for its kinase activity, interaction with PELI1 and for its ability to mediate TNF-induced necroptosis (By similarity). {ECO:0000250|UniProtKB:Q9Y572}.; PTM: 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 by STUB1 leading to its subsequent proteasome-dependent degradation. {ECO:0000250|UniProtKB:Q9Y572}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
TKL Ser/Thr protein kinase family
uniprot
proteins
pubmed
15057822
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
22673903
uniprot
proteins
sequence_length
478
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9QZL0}. Nucleus {ECO:0000250|UniProtKB:Q9QZL0}. Note=Mainly cytoplasmic. Present in the nucleus in response to influenza A virus (IAV) infection. {ECO:0000250|UniProtKB:Q9QZL0}.
uniprot
proteins