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Entry version 200 (02 Jun 2021)
Sequence version 2 (02 Sep 2008)
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Protein

Receptor-interacting serine/threonine-protein kinase 3

Gene

RIPK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Serine/threonine-protein kinase that activates necroptosis and apoptosis, two parallel forms of cell death (PubMed:19524512, PubMed:19524513, PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:29883609).

Necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members, is triggered by RIPK3 following activation by ZBP1 (PubMed:19524512, PubMed:19524513, PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:29883609, PubMed:32298652).

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 (PubMed:19524512, PubMed:19524513, PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:25316792, PubMed:29883609).

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 (By similarity).

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 (PubMed:19524513).

In some cell types, also able to restrict viral replication by promoting cell death-independent responses (By similarity).

In response to Zika virus 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 (By similarity).

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 (PubMed:19498109).

These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production (PubMed:19498109).

By similarity9 Publications

(Microbial infection) In case of herpes simplex virus 1/HHV-1 infection, forms heteromeric amyloid structures with HHV-1 protein RIR1/ICP6 which may inhibit RIPK3-mediated necroptosis, thereby preventing host cell death pathway and allowing viral evasion.

1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activity is stimulated by ZBP1, which senses double-stranded Z-RNA structures (By similarity). 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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei50ATP3 Publications1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei142Proton acceptor1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi27 – 35ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Host-virus interaction, Necrosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.10.2, 2681

Pathway Commons web resource for biological pathway data

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PathwayCommonsi
Q9Y572

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-168927, TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-1810476, RIP-mediated NFkB activation via ZBP1
R-HSA-2562578, TRIF-mediated programmed cell death
R-HSA-3295583, TRP channels
R-HSA-5213460, RIPK1-mediated regulated necrosis
R-HSA-5675482, Regulation of necroptotic cell death
R-HSA-9013957, TLR3-mediated TICAM1-dependent programmed cell death
R-HSA-937041, IKK complex recruitment mediated by RIP1
R-HSA-9686347, Microbial modulation of RIPK1-mediated regulated necrosis

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
Q9Y572

SIGNOR Signaling Network Open Resource

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SIGNORi
Q9Y572

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Receptor-interacting serine/threonine-protein kinase 3Curated (EC:2.7.11.12 Publications)
Alternative name(s):
RIP-like protein kinase 31 Publication
Receptor-interacting protein 31 Publication
Short name:
RIP-31 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:RIPK3Imported
Synonyms:RIP31 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 14

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:10021, RIPK3

Online Mendelian Inheritance in Man (OMIM)

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MIMi
605817, gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_Q9Y572

Eukaryotic Pathogen, Vector and Host Database Resources

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VEuPathDBi
HostDB:ENSG00000129465.15

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi50K → A: Abolishes kinase activity. Loss of PGAM5- and MLKL-binding. No effect on RIPK1-binding. Loss of interaction with PELI1 and PELI1-mediated ubiquitination. No loss of STUB1-mediated ubiquitination. 4 Publications1
Mutagenesisi50K → D: Abolishes kinase activity. 3 Publications1
Mutagenesisi142D → N: Abolishes kinase activity and ability to mediate necroptosis. 1 Publication1
Mutagenesisi182T → A: Abolishes kinase activity. Loss of interaction with PELI1 and PELI1-mediated ubiquitination. No loss of interaction with STUB1 and STUB1-mediated ubiquitination. No loss of interaction with RIPK1. Loss of ability to mediate TNF-induced necroptosis. Loss of autophosphorylation at Ser-227. 1 Publication1
Mutagenesisi182T → S: No loss of interaction with PELI1 and PELI1-mediated ubiquitination. No loss of interaction with RIPK1 and MLKL. 1 Publication1
Mutagenesisi185Y → A or F: Loss of interaction with PELI1 and PELI1-mediated ubiquitination. 1 Publication1
Mutagenesisi227S → A: Abolishes ability to mediate necroptosis. Partial loss of kinase activity. No loss of PELI1-mediated degradation. 2 Publications1
Mutagenesisi227S → D: No loss of PELI1-mediated degradation. 1 Publication1
Mutagenesisi363K → R: Loss of PELI1-mediated ubiquitination. No loss of interaction with PELI1. 1 Publication1

Organism-specific databases

DisGeNET

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DisGeNETi
11035

Open Targets

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OpenTargetsi
ENSG00000129465

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA34396

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
Q9Y572, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL1795199

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2191

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
RIPK3

Domain mapping of disease mutations (DMDM)

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DMDMi
205371831

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000866101 – 518Receptor-interacting serine/threonine-protein kinase 3Add BLAST518

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2PhosphoserineBy similarity1
Modified residuei164PhosphoserineBy similarity1
Modified residuei182Phosphothreonine1 Publication1
Modified residuei199Phosphoserine; by autocatalysis2 Publications1
Modified residuei227Phosphoserine; by autocatalysis2 Publications1
Modified residuei252PhosphothreonineBy similarity1
Modified residuei299PhosphoserineBy similarity1
Modified residuei333PhosphothreonineBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki363Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei389PhosphoserineBy similarity1
Modified residuei401PhosphothreonineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (PubMed:19524513). Autophosphorylated following interaction with ZBP1 (By similarity). Phosphorylation of Ser-199 plays a role in the necroptotic function of RIPK3 (PubMed:11734559, PubMed:19524512). Autophosphorylates at Ser-227 following activation by ZBP1: phosphorylation at these sites is a hallmark of necroptosis and is required for binding MLKL (PubMed:22265413). Phosphorylation at Thr-182 is important for its kinase activity, interaction with PELI1 and PELI1-mediated 'Lys-48'-linked polyubiquitination and for its ability to mediate TNF-induced necroptosis (PubMed:29883609).By similarity5 Publications
Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B (PubMed:21931591). Polyubiquitinated with 'Lys-48'-linked chains by PELI1 leading to its subsequent proteasome-dependent degradation. Ubiquitinated by STUB1 leading to its subsequent proteasome-dependent degradation (PubMed:29883609).2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

The CPTAC Assay portal

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CPTACi
CPTAC-903
CPTAC-904

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q9Y572

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
Q9Y572

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q9Y572

PeptideAtlas

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PeptideAtlasi
Q9Y572

PRoteomics IDEntifications database

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PRIDEi
Q9Y572

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
86299 [Q9Y572-1]
86300 [Q9Y572-2]
86301 [Q9Y572-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q9Y572

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q9Y572

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Highly expressed in the pancreas. Detected at lower levels in heart, placenta, lung and kidney.1 Publication
Expression is significantly increased in colon and lung cancers.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000129465, Expressed in blood and 143 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q9Y572, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q9Y572, HS

Organism-specific databases

Human Protein Atlas

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HPAi
ENSG00000129465, Tissue enhanced (intestine)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts (via RIP homotypic interaction motif) with RIPK1 (via RIP homotypic interaction motif); this interaction induces RIPK1 phosphorylation and formation of a RIPK1-RIPK3 necrosis-inducing complex (PubMed:10339433, PubMed:11734559, PubMed:19524512, PubMed:29681455).

Interacts with MLKL; the interaction is direct and triggers necroptosis (PubMed:22265413, PubMed:22421439).

Interacts with ZBP1 (via RIP homotypic interaction motif); interaction with ZBP1 activates RIPK3, triggering necroptosis (By similarity). Upon TNF-induced necrosis, the RIPK1-RIPK3 dimer further interacts with PGAM5 and MLKL; the formation of this complex leads to PGAM5 phosphorylation and increase in PGAM5 phosphatase activity (PubMed:22265413, PubMed:22265414, PubMed:22421439). Binds TRAF2 and is recruited to the TNFR-1 signaling complex (PubMed:29883609).

Interacts with PYGL, GLUL and GLUD1; these interactions result in activation of these metabolic enzymes (PubMed:19498109).

Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4 (PubMed:21931591).

Interacts with ARHGEF2 (PubMed:21887730).

Interacts with PELI1 (via atypical FHA domain); the phosphorylated form at Thr-182 binds preferentially to PELI1 (PubMed:29883609).

Interacts with BUB1B, TRAF2 and STUB1 (PubMed:29883609).

Interacts with CASP6 (PubMed:32298652).

By similarity12 Publications

(Microbial infection) Interacts (via RIP homotypic interaction motif/RHIM) with herpes simplex virus 1/HHV-1 protein RIR1/ICP6 (via RHIM); this interaction may induce heteromeric amyloid assemblies and prevent necroptosis activation.

1 Publication2 Publications

(Microbial infection) Interacts (via RIP homotypic interaction motif/RHIM) with herpes simplex virus 2/HHV-2 protein RIR1/ICP10 (via RHIM); this interaction prevents necroptosis activation.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

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GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
116224, 40 interactors

Database of interacting proteins

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DIPi
DIP-27519N

Protein interaction database and analysis system

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IntActi
Q9Y572, 16 interactors

Molecular INTeraction database

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MINTi
Q9Y572

STRING: functional protein association networks

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STRINGi
9606.ENSP00000216274

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q9Y572

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
Q9Y572, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1518
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q9Y572

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini21 – 287Protein kinasePROSITE-ProRule annotationAdd BLAST267

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni355 – 443DisorderedSequence analysisAdd BLAST89
Regioni476 – 518DisorderedSequence analysisAdd BLAST43

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi450 – 466RIP homotypic interaction motif (RHIM)1 PublicationAdd BLAST17

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi372 – 440Polar residuesSequence analysisAdd BLAST69

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The RIP homotypic interaction motif/RHIM mediates interaction with the RHIM motif of RIPK1. Both motifs form a hetero-amyloid serpentine fold, stabilized by hydrophobic packing and featuring an unusual Cys-Ser ladder of alternating Ser (from RIPK1) and Cys (from RIPK3).1 Publication
(Microbial infection) The RIP homotypic interaction motif/RHIM mediates interaction with the RHIM motif of the herpes simplex virus 1/HHV-1 protein RIR1/ICP6 to form heteromeric amyloid structures.1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0192, Eukaryota

Ensembl GeneTree

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GeneTreei
ENSGT00940000160206

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
CLU_559689_0_0_1

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q9Y572

Identification of Orthologs from Complete Genome Data

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OMAi
PFRNQMP

Database of Orthologous Groups

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OrthoDBi
769579at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q9Y572

TreeFam database of animal gene trees

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TreeFami
TF106506

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR011009, Kinase-like_dom_sf
IPR000719, Prot_kinase_dom
IPR017441, Protein_kinase_ATP_BS
IPR025735, RHIM_dom
IPR008271, Ser/Thr_kinase_AS

Pfam protein domain database

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Pfami
View protein in Pfam
PF00069, Pkinase, 1 hit
PF12721, RHIM, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00220, S_TKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00107, PROTEIN_KINASE_ATP, 1 hit
PS50011, PROTEIN_KINASE_DOM, 1 hit
PS00108, PROTEIN_KINASE_ST, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9Y572-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSCVKLWPSG APAPLVSIEE LENQELVGKG GFGTVFRAQH RKWGYDVAVK
60 70 80 90 100
IVNSKAISRE VKAMASLDNE FVLRLEGVIE KVNWDQDPKP ALVTKFMENG
110 120 130 140 150
SLSGLLQSQC PRPWPLLCRL LKEVVLGMFY LHDQNPVLLH RDLKPSNVLL
160 170 180 190 200
DPELHVKLAD FGLSTFQGGS QSGTGSGEPG GTLGYLAPEL FVNVNRKAST
210 220 230 240 250
ASDVYSFGIL MWAVLAGREV ELPTEPSLVY EAVCNRQNRP SLAELPQAGP
260 270 280 290 300
ETPGLEGLKE LMQLCWSSEP KDRPSFQECL PKTDEVFQMV ENNMNAAVST
310 320 330 340 350
VKDFLSQLRS SNRRFSIPES GQGGTEMDGF RRTIENQHSR NDVMVSEWLN
360 370 380 390 400
KLNLEEPPSS VPKKCPSLTK RSRAQEEQVP QAWTAGTSSD SMAQPPQTPE
410 420 430 440 450
TSTFRNQMPS PTSTGTPSPG PRGNQGAERQ GMNWSCRTPE PNPVTGRPLV
460 470 480 490 500
NIYNCSGVQV GDNNYLTMQQ TTALPTWGLA PSGKGRGLQH PPPVGSQEGP
510
KDPEAWSRPQ GWYNHSGK
Length:518
Mass (Da):56,887
Last modified:September 2, 2008 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iBF755F8A0B1810A1
GO
Isoform 2 (identifier: Q9Y572-2) [UniParc]FASTAAdd to basket
Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     220-518: VELPTEPSLV...PQGWYNHSGK → CQPNHHSCTKQCATGRTGLHWLSCPKPGLRLPA

Show »
Length:252
Mass (Da):27,574
Checksum:i20D7DFAB11AEECEF
GO
Isoform 3 (identifier: Q9Y572-3) [UniParc]FASTAAdd to basket
Also known as: Gamma

The sequence of this isoform differs from the canonical sequence as follows:
     222-518: LPTEPSLVYE...PQGWYNHSGK → CKTLGGFWDP

Show »
Length:231
Mass (Da):25,326
Checksum:i8E6E045EC3B11DEF
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YJN5H0YJN5_HUMAN
Receptor-interacting serine/threoni...
RIPK3
162Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti30G → D in AAD39005 (PubMed:10339433).Curated1
Sequence conflicti150L → P in AAD39005 (PubMed:10339433).Curated1
Sequence conflicti309R → K in AAD39005 (PubMed:10339433).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_051664260E → V. Corresponds to variant dbSNP:rs7153640Ensembl.1
Natural variantiVAR_041048300T → M1 PublicationCorresponds to variant dbSNP:rs34106261Ensembl.1
Natural variantiVAR_041049492P → Q1 PublicationCorresponds to variant dbSNP:rs3212254Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_035106220 – 518VELPT…NHSGK → CQPNHHSCTKQCATGRTGLH WLSCPKPGLRLPA in isoform 2. 1 PublicationAdd BLAST299
Alternative sequenceiVSP_035107222 – 518LPTEP…NHSGK → CKTLGGFWDP in isoform 3. 2 PublicationsAdd BLAST297

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
AF156884 mRNA Translation: AAD39005.1
AY453693 mRNA Translation: AAS16359.1
AY494982 mRNA Translation: AAS75516.1
AY494983 mRNA Translation: AAS75517.1
AL096870 Genomic DNA No translation available.
AK296140 mRNA Translation: BAG58881.1
CH471078 Genomic DNA Translation: EAW66021.1
BC062584 mRNA Translation: AAH62584.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS9628.1 [Q9Y572-1]

NCBI Reference Sequences

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RefSeqi
NP_006862.2, NM_006871.3 [Q9Y572-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000216274; ENSP00000216274; ENSG00000129465 [Q9Y572-1]
ENST00000554756; ENSP00000452328; ENSG00000129465 [Q9Y572-3]
ENST00000643393; ENSP00000495915; ENSG00000285379 [Q9Y572-3]
ENST00000646516; ENSP00000495490; ENSG00000285379 [Q9Y572-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
11035

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:11035

UCSC genome browser

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UCSCi
uc001wpb.4, human [Q9Y572-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF156884 mRNA Translation: AAD39005.1
AY453693 mRNA Translation: AAS16359.1
AY494982 mRNA Translation: AAS75516.1
AY494983 mRNA Translation: AAS75517.1
AL096870 Genomic DNA No translation available.
AK296140 mRNA Translation: BAG58881.1
CH471078 Genomic DNA Translation: EAW66021.1
BC062584 mRNA Translation: AAH62584.1
CCDSiCCDS9628.1 [Q9Y572-1]
RefSeqiNP_006862.2, NM_006871.3 [Q9Y572-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5V7ZNMR-A/C/E/G448-462[»]
5ZCKX-ray1.27A458-461[»]
SMRiQ9Y572
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi116224, 40 interactors
DIPiDIP-27519N
IntActiQ9Y572, 16 interactors
MINTiQ9Y572
STRINGi9606.ENSP00000216274

Chemistry databases

BindingDBiQ9Y572
ChEMBLiCHEMBL1795199
GuidetoPHARMACOLOGYi2191

PTM databases

iPTMnetiQ9Y572
PhosphoSitePlusiQ9Y572

Genetic variation databases

BioMutaiRIPK3
DMDMi205371831

Proteomic databases

CPTACiCPTAC-903
CPTAC-904
jPOSTiQ9Y572
MassIVEiQ9Y572
PaxDbiQ9Y572
PeptideAtlasiQ9Y572
PRIDEiQ9Y572
ProteomicsDBi86299 [Q9Y572-1]
86300 [Q9Y572-2]
86301 [Q9Y572-3]

Protocols and materials databases

ABCD curated depository of sequenced antibodies

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ABCDi
Q9Y572, 2 sequenced antibodies

Antibodypedia a portal for validated antibodies

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Antibodypediai
9228, 897 antibodies

The DNASU plasmid repository

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DNASUi
11035

Genome annotation databases

EnsembliENST00000216274; ENSP00000216274; ENSG00000129465 [Q9Y572-1]
ENST00000554756; ENSP00000452328; ENSG00000129465 [Q9Y572-3]
ENST00000643393; ENSP00000495915; ENSG00000285379 [Q9Y572-3]
ENST00000646516; ENSP00000495490; ENSG00000285379 [Q9Y572-1]
GeneIDi11035
KEGGihsa:11035
UCSCiuc001wpb.4, human [Q9Y572-1]

Organism-specific databases

Comparative Toxicogenomics Database

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CTDi
11035
DisGeNETi11035

GeneCards: human genes, protein and diseases

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GeneCardsi
RIPK3
HGNCiHGNC:10021, RIPK3
HPAiENSG00000129465, Tissue enhanced (intestine)
MIMi605817, gene
neXtProtiNX_Q9Y572
OpenTargetsiENSG00000129465
PharmGKBiPA34396
VEuPathDBiHostDB:ENSG00000129465.15

GenAtlas: human gene database

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GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG0192, Eukaryota
GeneTreeiENSGT00940000160206
HOGENOMiCLU_559689_0_0_1
InParanoidiQ9Y572
OMAiPFRNQMP
OrthoDBi769579at2759
PhylomeDBiQ9Y572
TreeFamiTF106506

Enzyme and pathway databases

BRENDAi2.7.10.2, 2681
PathwayCommonsiQ9Y572
ReactomeiR-HSA-168927, TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-1810476, RIP-mediated NFkB activation via ZBP1
R-HSA-2562578, TRIF-mediated programmed cell death
R-HSA-3295583, TRP channels
R-HSA-5213460, RIPK1-mediated regulated necrosis
R-HSA-5675482, Regulation of necroptotic cell death
R-HSA-9013957, TLR3-mediated TICAM1-dependent programmed cell death
R-HSA-937041, IKK complex recruitment mediated by RIP1
R-HSA-9686347, Microbial modulation of RIPK1-mediated regulated necrosis
SignaLinkiQ9Y572
SIGNORiQ9Y572

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

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BioGRID-ORCSi
11035, 26 hits in 1019 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

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ChiTaRSi
RIPK3, human

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
RIPK3

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
11035
PharosiQ9Y572, Tchem

Protein Ontology

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PROi
PR:Q9Y572
RNActiQ9Y572, protein

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSG00000129465, Expressed in blood and 143 other tissues
ExpressionAtlasiQ9Y572, baseline and differential
GenevisibleiQ9Y572, HS

Family and domain databases

InterProiView protein in InterPro
IPR011009, Kinase-like_dom_sf
IPR000719, Prot_kinase_dom
IPR017441, Protein_kinase_ATP_BS
IPR025735, RHIM_dom
IPR008271, Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069, Pkinase, 1 hit
PF12721, RHIM, 1 hit
SMARTiView protein in SMART
SM00220, S_TKc, 1 hit
SUPFAMiSSF56112, SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107, PROTEIN_KINASE_ATP, 1 hit
PS50011, PROTEIN_KINASE_DOM, 1 hit
PS00108, PROTEIN_KINASE_ST, 1 hit

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiRIPK3_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9Y572
Secondary accession number(s): B4DJL9
, C4AM87, Q5J795, Q5J796, Q6P5Y1
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: September 2, 2008
Last modified: June 2, 2021
This is version 200 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  3. Human entries with genetic variants
    List of human entries with genetic variants
  4. Human variants curated from literature reports
    Index of human variants curated from literature reports
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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