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General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Gene namei
Official gene symbol, which is typically a short form of the gene name, according to HGNC.
Assigned HPA protein class(es) for the encoded protein(s).
Disease related genes Enzymes Human disease related genes Potential drug targets
Predicted locationi
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Chromosome
6
Cytoband
p25.2
Chromosome location (bp)
3063824 - 3115187
Number of transcriptsi
Number of protein-coding transcripts from the gene as defined by Ensembl.
Useful information about the protein provided by UniProt.
Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways 1,2,3,4,5. Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival 6,7,8,9,10. Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway (By similarity). Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis (By similarity). RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis (By similarity). In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1 11,12,13,14. Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis 15,16,17,18. Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (By similarity). In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) 19,20. Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation 21. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade 22,23. Required for ZBP1-induced NF-kappa-B activation in response to DNA damage (By similarity)....show less
Molecular function (UniProt)i
Keywords assigned by UniProt to proteins due to their particular molecular function.
Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.
ATP-binding, Nucleotide-binding
Gene summary (Entrez)i
Useful information about the gene from Entrez
This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein plays a role in inflammation and cell death in response to tissue damage, pathogen recognition, and as part of developmental regulation. RIPK1/RIPK3 kinase-mediated necrosis is referred to as necroptosis. Genetic disruption of this gene in mice results in death shortly after birth. [provided by RefSeq, Aug 2017]...show less
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The Splice variant identifier links to the Ensembl website protein summary for the selected splice variant. The data in the Swissprot and TrEMBL columns links to corresponding pages in the UniProt database.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide and number of predicted transmembrane region(s) according to in-house majority decision methods based on sets of predictors are also reported.
Enzymes ENZYME proteins Transferases Kinases TKL Ser/Thr protein kinases Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Disease related genes Potential drug targets Human disease related genes Immune system diseases Allergies and autoimmune diseases Primary immunodeficiency Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0000165[MAPK cascade] GO:0000166[nucleotide binding] GO:0001934[positive regulation of protein phosphorylation] GO:0004672[protein kinase activity] GO:0004674[protein serine/threonine kinase activity] GO:0004706[JUN kinase kinase kinase activity] GO:0005123[death receptor binding] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005737[cytoplasm] GO:0005739[mitochondrion] GO:0005829[cytosol] GO:0005886[plasma membrane] GO:0006468[protein phosphorylation] GO:0006915[apoptotic process] GO:0006954[inflammatory response] GO:0007165[signal transduction] GO:0008219[cell death] GO:0010008[endosome membrane] GO:0010468[regulation of gene expression] GO:0010556[regulation of macromolecule biosynthetic process] GO:0010628[positive regulation of gene expression] GO:0010940[positive regulation of necrotic cell death] GO:0010942[positive regulation of cell death] GO:0012501[programmed cell death] GO:0016020[membrane] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0030163[protein catabolic process] GO:0031264[death-inducing signaling complex] GO:0031326[regulation of cellular biosynthetic process] GO:0031349[positive regulation of defense response] GO:0031625[ubiquitin protein ligase binding] GO:0032103[positive regulation of response to external stimulus] GO:0032757[positive regulation of interleukin-8 production] GO:0032760[positive regulation of tumor necrosis factor production] GO:0032991[protein-containing complex] GO:0033209[tumor necrosis factor-mediated signaling pathway] GO:0034612[response to tumor necrosis factor] GO:0036289[peptidyl-serine autophosphorylation] GO:0042327[positive regulation of phosphorylation] GO:0042802[identical protein binding] GO:0042803[protein homodimerization activity] GO:0043065[positive regulation of apoptotic process] GO:0043066[negative regulation of apoptotic process] GO:0043068[positive regulation of programmed cell death] GO:0043123[positive regulation of I-kappaB kinase/NF-kappaB signaling] GO:0043124[negative regulation of I-kappaB kinase/NF-kappaB signaling] GO:0043235[receptor complex] GO:0043410[positive regulation of MAPK cascade] GO:0044093[positive regulation of molecular function] GO:0044877[protein-containing complex binding] GO:0045121[membrane raft] GO:0045651[positive regulation of macrophage differentiation] GO:0045944[positive regulation of transcription by RNA polymerase II] GO:0046330[positive regulation of JNK cascade] GO:0046777[protein autophosphorylation] GO:0050729[positive regulation of inflammatory response] GO:0051092[positive regulation of NF-kappaB transcription factor activity] GO:0060545[positive regulation of necroptotic process] GO:0060546[negative regulation of necroptotic process] GO:0070105[positive regulation of interleukin-6-mediated signaling pathway] GO:0070231[T cell apoptotic process] GO:0070266[necroptotic process] GO:0070301[cellular response to hydrogen peroxide] GO:0070513[death domain binding] GO:0070926[regulation of ATP:ADP antiporter activity] GO:0071345[cellular response to cytokine stimulus] GO:0071356[cellular response to tumor necrosis factor] GO:0071363[cellular response to growth factor stimulus] GO:0097191[extrinsic apoptotic signaling pathway] GO:0097300[programmed necrotic cell death] GO:0097342[ripoptosome] GO:0097343[ripoptosome assembly] GO:0097527[necroptotic signaling pathway] GO:0106310[protein serine kinase activity] GO:1901026[ripoptosome assembly involved in necroptotic process] GO:1903265[positive regulation of tumor necrosis factor-mediated signaling pathway] GO:1905206[positive regulation of hydrogen peroxide-induced cell death] GO:1990000[amyloid fibril formation] GO:2000377[regulation of reactive oxygen species metabolic process] GO:2000379[positive regulation of reactive oxygen species metabolic process] GO:2001237[negative regulation of extrinsic apoptotic signaling pathway] GO:2001238[positive regulation of extrinsic apoptotic signaling pathway] GO:2001240[negative regulation of extrinsic apoptotic signaling pathway in absence of ligand]
Enzymes ENZYME proteins Transferases Kinases TKL Ser/Thr protein kinases Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Disease related genes Potential drug targets Human disease related genes Immune system diseases Allergies and autoimmune diseases Primary immunodeficiency Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Ezkurdia et al 2014)
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GO:0000165[MAPK cascade] GO:0000166[nucleotide binding] GO:0001934[positive regulation of protein phosphorylation] GO:0004672[protein kinase activity] GO:0004674[protein serine/threonine kinase activity] GO:0004706[JUN kinase kinase kinase activity] GO:0005123[death receptor binding] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005737[cytoplasm] GO:0005739[mitochondrion] GO:0005829[cytosol] GO:0005886[plasma membrane] GO:0006468[protein phosphorylation] GO:0006915[apoptotic process] GO:0006954[inflammatory response] GO:0007165[signal transduction] GO:0008219[cell death] GO:0010008[endosome membrane] GO:0010468[regulation of gene expression] GO:0010556[regulation of macromolecule biosynthetic process] GO:0010628[positive regulation of gene expression] GO:0010940[positive regulation of necrotic cell death] GO:0012501[programmed cell death] GO:0016020[membrane] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0030163[protein catabolic process] GO:0031264[death-inducing signaling complex] GO:0031326[regulation of cellular biosynthetic process] GO:0031349[positive regulation of defense response] GO:0031625[ubiquitin protein ligase binding] GO:0032103[positive regulation of response to external stimulus] GO:0032757[positive regulation of interleukin-8 production] GO:0032760[positive regulation of tumor necrosis factor production] GO:0032991[protein-containing complex] GO:0033209[tumor necrosis factor-mediated signaling pathway] GO:0034612[response to tumor necrosis factor] GO:0036289[peptidyl-serine autophosphorylation] GO:0042802[identical protein binding] GO:0042803[protein homodimerization activity] GO:0043065[positive regulation of apoptotic process] GO:0043066[negative regulation of apoptotic process] GO:0043068[positive regulation of programmed cell death] GO:0043123[positive regulation of I-kappaB kinase/NF-kappaB signaling] GO:0043124[negative regulation of I-kappaB kinase/NF-kappaB signaling] GO:0043235[receptor complex] GO:0044093[positive regulation of molecular function] GO:0044877[protein-containing complex binding] GO:0045651[positive regulation of macrophage differentiation] GO:0045944[positive regulation of transcription by RNA polymerase II] GO:0046330[positive regulation of JNK cascade] GO:0046777[protein autophosphorylation] GO:0050729[positive regulation of inflammatory response] GO:0051092[positive regulation of NF-kappaB transcription factor activity] GO:0060545[positive regulation of necroptotic process] GO:0060546[negative regulation of necroptotic process] GO:0070105[positive regulation of interleukin-6-mediated signaling pathway] GO:0070231[T cell apoptotic process] GO:0070266[necroptotic process] GO:0070301[cellular response to hydrogen peroxide] GO:0070513[death domain binding] GO:0070926[regulation of ATP:ADP antiporter activity] GO:0071345[cellular response to cytokine stimulus] GO:0071356[cellular response to tumor necrosis factor] GO:0097191[extrinsic apoptotic signaling pathway] GO:0097300[programmed necrotic cell death] GO:0097342[ripoptosome] GO:0097343[ripoptosome assembly] GO:0097527[necroptotic signaling pathway] GO:0106310[protein serine kinase activity] GO:1905206[positive regulation of hydrogen peroxide-induced cell death] GO:1990000[amyloid fibril formation] GO:2000379[positive regulation of reactive oxygen species metabolic process] GO:2001237[negative regulation of extrinsic apoptotic signaling pathway] GO:2001238[positive regulation of extrinsic apoptotic signaling pathway]
The Human Protein Atlas project is funded
