Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 175 (02 Jun 2021)
Sequence version 2 (19 Feb 2014)
Previous versions | rss
Add a publicationFeedback
Protein

Receptor-interacting serine/threonine-protein kinase 3

Gene

Ripk3

Organism
Mus musculus (Mouse)
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:27321907, PubMed:27746097, PubMed:27917412, PubMed:28607035, PubMed:32200799, PubMed:32296175).

Necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members, is triggered by RIPK3 following activation by ZBP1 (PubMed:19590578, PubMed:22423968, PubMed:24012422, PubMed:24019532, PubMed:24557836, PubMed:27746097, PubMed:27819681, PubMed:27819682, PubMed:24095729, PubMed:32200799, PubMed:27321907, PubMed:32296175).

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:24813849, PubMed:24813850, PubMed:27321907).

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 (PubMed:32200799, PubMed:32296175).

Also regulates apoptosis: apoptosis depends on RIPK1, FADD and CASP8, and is independent of MLKL and RIPK3 kinase activity (PubMed:27321907).

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 (PubMed:30635240).

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 (PubMed:30635240).

Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes (PubMed:30635240).

RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL (By similarity).

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

By similarity17 Publications

<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 (PubMed:32200799, PubMed:32296175). 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 (PubMed:24813849, PubMed:24813850, PubMed:24557836, PubMed:27321907, PubMed:27819681, PubMed:27819682, PubMed:32296175). Inhibited by type II inhibitor 1-(4-fluorophenyl)-N-[3-fluoro-4-(1H-pyrrolo[2,3- B]pyridin-4-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxamide (PubMed:32184955).9 Publications

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 sitei51ATPCombined sources1 Publication1
Binding sitei51Type II inhibitorCombined sources1 Publication1
Binding sitei98Type II inhibitorCombined sources1 Publication1
<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 sitei143Proton acceptor2 Publications1
Binding sitei161Type II inhibitorCombined sources1 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 bindingi28 – 36ATPPROSITE-ProRule annotationCombined sources1 Publication9

<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

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-MMU-2562578, TRIF-mediated programmed cell death
R-MMU-3295583, TRP channels
R-MMU-5213460, RIPK1-mediated regulated necrosis
R-MMU-5675482, Regulation of necroptotic cell death
R-MMU-937041, IKK complex recruitment mediated by RIP1

<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 31 Publication (EC:2.7.11.14 Publications)
Alternative name(s):
RIP-like protein kinase 31 Publication
Receptor-interacting protein 31 Publication
Short name:
RIP-31 Publication
Short name:
mRIP31 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:Ripk31 PublicationImported
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>OrganismiMus musculus (Mouse)
<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 identifieri10090 [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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<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
  • UP000000589 <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

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:2154952, Ripk3

<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

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

No visible phenotype in normal conditions; mice are viable and indistinguishable from wild-type mice (PubMed:14749364, PubMed:24557836). Mice are resistant to TNF-induced hypothermia (PubMed:24557836). Mice are more susceptible to influenza A virus (IAV) infection than wild-type mice: at a modestly lethal dose of IAV, mice display significantly increased rates of mortality, probably caused by a failure to eliminate infected cells and limit virus spread in pulmonary tissue (PubMed:27321907, PubMed:32200799). Perinatal lethality observed in Ripk1 knockout mice is rescued in knockout mice lacking both Ripk1 and Ripk3; mice however die the first days of postnatal life (PubMed:24813849, PubMed:24813850, PubMed:27819681, PubMed:27819682). Only mice lacking Ripk1, Ripk3 and Casp8 survive past weaning and rescue lethality caused by the absence of Ripk1 (PubMed:24813849, PubMed:24813850).8 Publications

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>Mutagenesisi51K → A: Complete loss of induced necrosis. 1
Mutagenesisi111C → A: No effect. 1 Publication1
Mutagenesisi143D → N: Abolishes kinase activity and ability to mediate necroptosis. No autophosphorylation. 2 Publications1
Mutagenesisi161D → N: Abolished protein kinase activity and ability to activate necroptosis. Knockin mice die during embryogenesis due to constitutive Ripk1- and Casp8-dependent apoptosis. Perinatal lethality observed in Ripk1 knockout mice is rescued in knockin mice carrying this mutation. 2 Publications1
Mutagenesisi230K → A: Slightly affects interaction with MLKL; when associated with A-236. Affects interaction with MLKL; when associated with A-232 and A-236. 1 Publication1
Mutagenesisi231T → A: Abolishes ability to mediate necroptosis. 1 Publication1
Mutagenesisi232S → A: Abolishes ability to mediate necroptosis. Affects interaction with MLKL; when associated with A-230 and A-236. 3 Publications1
Mutagenesisi236E → A: Slightly affects interaction with MLKL; when associated with A-230. Affects interaction with MLKL; when associated with A-230 and A-232. 1 Publication1
Mutagenesisi448 – 451VQIG → AAAA in RIPK3(RHIM); abolished interaction with ZBP1 and subsequent necroptosis. Perinatal lethality observed in Ripk1 knockout mice is rescued in knockin mice carrying this mutation. 2 Publications4

<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_00000866111 – 486Receptor-interacting serine/threonine-protein kinase 3Add BLAST486

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 residuei2Phosphoserine1 Publication1
Modified residuei165Phosphoserine1 Publication1
Modified residuei187PhosphothreonineBy similarity1
Modified residuei204Phosphoserine; by autocatalysisBy similarity1
Modified residuei231Phosphothreonine; by autocatalysis2 Publications1
Modified residuei232Phosphoserine; by autocatalysis2 Publications1
Modified residuei257Phosphothreonine1 Publication1
Modified residuei304Phosphoserine1 Publication1
Modified residuei326Phosphoserine1 Publication1
Modified residuei338Phosphothreonine1 Publication1
Modified residuei353Phosphoserine1 Publication1
Modified residuei369Phosphoserine1 Publication1
Modified residuei380Phosphoserine1 Publication1
Modified residuei392Phosphothreonine1 Publication1
Modified residuei477Omega-N-methylarginineCombined sources1

<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 (By similarity). Autophosphorylated following interaction with ZBP1 (PubMed:27819681). Phosphorylation of Ser-204 plays a role in the necroptotic function of RIPK3 (By similarity). Autophosphorylates at Thr-231 and Ser-232 following activation by ZBP1: phosphorylation at these sites is a hallmark of necroptosis and is required for binding MLKL (PubMed:23612963, PubMed:27819682). Phosphorylation at Thr-187 is important for its kinase activity, interaction with PELI1 and for its ability to mediate TNF-induced necroptosis (By similarity).By similarity3 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. Ubiquitinated by STUB1 leading to its subsequent proteasome-dependent degradation.By similarity

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
Q9QZL0

MaxQB - The MaxQuant DataBase

More...
MaxQBi
Q9QZL0

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

More...
PaxDbi
Q9QZL0

PeptideAtlas

More...
PeptideAtlasi
Q9QZL0

PRoteomics IDEntifications database

More...
PRIDEi
Q9QZL0

ProteomicsDB: a multi-organism proteome resource

More...
ProteomicsDBi
253246

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q9QZL0

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

More...
PhosphoSitePlusi
Q9QZL0

<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

Expressed in embryo and in adult spleen, liver, testis, heart, brain and lung.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSMUSG00000022221, Expressed in fibroblast and 197 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
Q9QZL0, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
Q9QZL0, MM

<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:27321907, PubMed:27819681, PubMed:28842570, PubMed:31519887).

Interacts with MLKL; the interaction is direct and triggers necroptosis (PubMed:24012422, PubMed:27321907).

Interacts with ZBP1 (via RIP homotypic interaction motif); interaction with ZBP1 activates RIPK3, triggering necroptosis (PubMed:19590578, PubMed:22423968, PubMed:27746097, PubMed:27819681, PubMed:27819682, PubMed:28607035, PubMed:32200799). 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 (By similarity). Binds TRAF2 and is recruited to the TNFR-1 signaling complex (By similarity).

Interacts with PYGL, GLUL and GLUD1; these interactions result in activation of these metabolic enzymes (By similarity).

Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4 (By similarity).

Interacts with ARHGEF2 (By similarity).

Interacts with PELI1 (via atypical FHA domain); the phosphorylated form at Thr-187 binds preferentially to PELI1 (PubMed:29883609).

Interacts with BUB1B, TRAF2 and STUB1 (By similarity).

Interacts with CASP6 (By similarity).

By similarity12 Publications

(Microbial infection) Interacts (via RIP homotypic interaction motif) with murid herpesvirus protein RIR1; this interaction disrupts RIP3-RIP1 interactions characteristic of TNF-alpha induced necroptosis, thereby suppressing this death pathway.

2 Publications

<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

Hide details

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...
BioGRIDi
208042, 5 interactors

Database of interacting proteins

More...
DIPi
DIP-54883N

Protein interaction database and analysis system

More...
IntActi
Q9QZL0, 14 interactors

Molecular INTeraction database

More...
MINTi
Q9QZL0

STRING: functional protein association networks

More...
STRINGi
10090.ENSMUSP00000022830

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...
RNActi
Q9QZL0, 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

1486
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

More...
SMRi
Q9QZL0

Database of comparative protein structure models

More...
ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

More...
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>Domaini22 – 292Protein kinasePROSITE-ProRule annotationCombined sources1 PublicationAdd BLAST271

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>Regioni312 – 333DisorderedSequence analysisAdd BLAST22
Regioni349 – 388DisorderedSequence analysisAdd BLAST40
Regioni462 – 486DisorderedSequence analysisAdd BLAST25

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>Motifi440 – 461RIP homotypic interaction motif (RHIM)1 PublicationAdd BLAST22

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 biasi312 – 326Polar residuesSequence analysisAdd BLAST15
Compositional biasi367 – 386Polar residuesSequence analysisAdd BLAST20

<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).By similarity

<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

More...
eggNOGi
KOG0192, Eukaryota

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000160206

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
CLU_559689_0_0_1

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q9QZL0

Identification of Orthologs from Complete Genome Data

More...
OMAi
PFRNQMP

Database of Orthologous Groups

More...
OrthoDBi
769579at2759

TreeFam database of animal gene trees

More...
TreeFami
TF106506

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...
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

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

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00220, S_TKc, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

More...
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>Sequence (1+)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 has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

Q9QZL0-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSSVKLWPTG ASAVPLVSRE ELKKLEFVGK GGFGVVFRAH HRTWNHDVAV
60 70 80 90 100
KIVNSKKISW EVKAMVNLRN ENVLLLLGVT EDLQWDFVSG QALVTRFMEN
110 120 130 140 150
GSLAGLLQPE CPRPWPLLCR LLQEVVLGMC YLHSLNPPLL HRDLKPSNIL
160 170 180 190 200
LDPELHAKLA DFGLSTFQGG SQSGSGSGSG SRDSGGTLAY LDPELLFDVN
210 220 230 240 250
LKASKASDVY SFGILVWAVL AGREAELVDK TSLIRETVCD RQSRPPLTEL
260 270 280 290 300
PPGSPETPGL EKLKELMIHC WGSQSENRPS FQDCEPKTNE VYNLVKDKVD
310 320 330 340 350
AAVSEVKHYL SQHRSSGRNL SAREPSQRGT EMDCPRETMV SKMLDRLHLE
360 370 380 390 400
EPSGPVPGKC PERQAQDTSV GPATPARTSS DPVAGTPQIP HTLPFRGTTP
410 420 430 440 450
GPVFTETPGP HPQRNQGDGR HGTPWYPWTP PNPMTGPPAL VFNNCSEVQI
460 470 480
GNYNSLVAPP RTTASSSAKY DQAQFGRGRG WQPFHK
Length:486
Mass (Da):53,322
Last modified:February 19, 2014 - 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:i31C5EEE77F55778B
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 are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PZP3E9PZP3_MOUSE
Receptor-interacting serine/threoni...
Ripk3
422Annotation 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>
A0A2I3BPT3A0A2I3BPT3_MOUSE
Receptor-interacting serine/threoni...
Ripk3
160Annotation 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>
A0A2I3BQW9A0A2I3BQW9_MOUSE
Receptor-interacting serine/threoni...
Ripk3
158Annotation 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 conflicti136N → D in AAF03133 (PubMed:10490590).Curated1
Sequence conflicti136N → D in BAE32636 (PubMed:16141072).Curated1
Sequence conflicti198D → K in AAF03133 (PubMed:10490590).Curated1
Sequence conflicti198D → K in BAE32636 (PubMed:16141072).Curated1
Sequence conflicti198D → N in AAH29210 (PubMed:15489334).Curated1
Sequence conflicti283D → G in BAE32636 (PubMed:16141072).Curated1
Sequence conflicti471D → G in BAE32636 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AF178953 mRNA Translation: AAF03133.1
AK154505 mRNA Translation: BAE32636.1
AC098877 Genomic DNA No translation available.
CH466535 Genomic DNA Translation: EDL36236.1
BC029210 mRNA Translation: AAH29210.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS27131.1

NCBI Reference Sequences

More...
RefSeqi
NP_064339.2, NM_019955.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000022830; ENSMUSP00000022830; ENSMUSG00000022221

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
56532

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mmu:56532

UCSC genome browser

More...
UCSCi
uc007uav.2, mouse

<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
AF178953 mRNA Translation: AAF03133.1
AK154505 mRNA Translation: BAE32636.1
AC098877 Genomic DNA No translation available.
CH466535 Genomic DNA Translation: EDL36236.1
BC029210 mRNA Translation: AAH29210.1
CCDSiCCDS27131.1
RefSeqiNP_064339.2, NM_019955.2

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4M66X-ray2.40A/B1-313[»]
4M69X-ray2.50A1-313[»]
6JPDNMR-A/B/C/D/E409-486[»]
6OKOX-ray2.10A/B1-313[»]
SMRiQ9QZL0
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi208042, 5 interactors
DIPiDIP-54883N
IntActiQ9QZL0, 14 interactors
MINTiQ9QZL0
STRINGi10090.ENSMUSP00000022830

PTM databases

iPTMnetiQ9QZL0
PhosphoSitePlusiQ9QZL0

Proteomic databases

EPDiQ9QZL0
MaxQBiQ9QZL0
PaxDbiQ9QZL0
PeptideAtlasiQ9QZL0
PRIDEiQ9QZL0
ProteomicsDBi253246

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
9228, 897 antibodies

The DNASU plasmid repository

More...
DNASUi
56532

Genome annotation databases

EnsembliENSMUST00000022830; ENSMUSP00000022830; ENSMUSG00000022221
GeneIDi56532
KEGGimmu:56532
UCSCiuc007uav.2, mouse

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
11035
MGIiMGI:2154952, Ripk3

Phylogenomic databases

eggNOGiKOG0192, Eukaryota
GeneTreeiENSGT00940000160206
HOGENOMiCLU_559689_0_0_1
InParanoidiQ9QZL0
OMAiPFRNQMP
OrthoDBi769579at2759
TreeFamiTF106506

Enzyme and pathway databases

ReactomeiR-MMU-2562578, TRIF-mediated programmed cell death
R-MMU-3295583, TRP channels
R-MMU-5213460, RIPK1-mediated regulated necrosis
R-MMU-5675482, Regulation of necroptotic cell death
R-MMU-937041, IKK complex recruitment mediated by RIP1

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
56532, 1 hit in 52 CRISPR screens

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

More...
ChiTaRSi
Ripk3, mouse

Protein Ontology

More...
PROi
PR:Q9QZL0
RNActiQ9QZL0, protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000022221, Expressed in fibroblast and 197 other tissues
ExpressionAtlasiQ9QZL0, baseline and differential
GenevisibleiQ9QZL0, MM

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

More...
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_MOUSE
<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: Q9QZL0
Secondary accession number(s): G3X8V8, Q3U3Z9, Q8K2Y2
<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: February 19, 2014
Last modified: June 2, 2021
This is version 175 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

<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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again