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Entry version 198 (12 Aug 2020)
Sequence version 1 (01 Nov 1997)
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Protein

Receptor-interacting serine/threonine-protein kinase 1

Gene

Ripk1

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 kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways (PubMed:24813849, PubMed:24813850, PubMed:24557836, PubMed:27819681, PubMed:28842570, PubMed:31511692, PubMed:31827280, PubMed:31827281). Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:24813849, PubMed:24813850, PubMed:24557836, PubMed:28842570, PubMed:31519886, PubMed:31519887). 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 (PubMed:31519886, PubMed:31519887). 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 (PubMed:28842570, PubMed:27819681, PubMed:27819682, PubMed:29440439, PubMed:30988283, PubMed:31519886, PubMed:31519887). RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis (PubMed:24813849, PubMed:24813850, PubMed:24557836). 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 (PubMed:24557836, PubMed:27819681, PubMed:27819682, PubMed:31358656). Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:31358656). Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (PubMed:30867408, PubMed:30185824). In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) (PubMed:31827280, PubMed:31827281). Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (By similarity). Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (By similarity). Required for ZBP1-induced NF-kappa-B activation in response to DNA damage (PubMed:12654725, PubMed:19590578).By similarity18 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

Serine-threonine kinase activity is inhibited by linear polyubiquitination ('Met-1'-linked) by the LUBAC complex.1 Publication

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 sitei45ATPPROSITE-ProRule annotation1
<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 sitei138Proton acceptorPROSITE-ProRule annotation2 Publications1

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 bindingi23 – 31ATPPROSITE-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, Inflammatory response, Necrosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.10.2, 3474

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-MMU-140534, Caspase activation via Death Receptors in the presence of ligand
R-MMU-2562578, TRIF-mediated programmed cell death
R-MMU-3295583, TRP channels
R-MMU-3371378, Regulation by c-FLIP
R-MMU-5213460, RIPK1-mediated regulated necrosis
R-MMU-5218900, CASP8 activity is inhibited
R-MMU-5357786, TNFR1-induced proapoptotic signaling
R-MMU-5357905, Regulation of TNFR1 signaling
R-MMU-5357956, TNFR1-induced NFkappaB signaling pathway
R-MMU-5689880, Ub-specific processing proteases
R-MMU-5689896, Ovarian tumor domain proteases
R-MMU-69416, Dimerization of procaspase-8
R-MMU-75893, TNF signaling
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 1Curated (EC:2.7.11.17 Publications)
Alternative name(s):
Cell death protein RIP1 Publication
Receptor-interacting protein 11 Publication
Short name:
RIP-11 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:Ripk1Imported
Synonyms:Rinp, Rip1 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 13

Organism-specific databases

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

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MGIi
MGI:108212, Ripk1

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

<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

Mice exhibit severe multi-organ inflammation and systemic cell death, which causes lethality of animals late in gestation or shortly after birth (PubMed:24813849, PubMed:30185824). 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). Perinatal lethality observed in Ripk1 knockout mice is rescued in knockout mice lacking both Ripk1 and Casp8; mice however die the first days of postnatal life (PubMed:24813849). Only mice lacking Ripk1, Ripk3 and Casp8 survive past weaning and rescue lethality caused by the absence of Ripk1 (PubMed:24813849, PubMed:24813850).5 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>Mutagenesisi6S → A: Loss of phosphorylation. Does not protect cells from TNF-induced cell death. 1 Publication1
Mutagenesisi6S → D: Phophomimetic mutant. Does not protect cells from TNF-induced cell death. 1 Publication1
Mutagenesisi25S → A: Loss of phosphorylation. Does not protect cells from TNF-induced cell death. 1 Publication1
Mutagenesisi25S → D: Phophomimetic mutant. Significant loss of kinase activity. Protects cells from TNF-induced cell death. 1 Publication1
Mutagenesisi45K → A: Loss of kinase activity. Protects cells from TNF-induced cell death. 1 Publication1
Mutagenesisi45K → M: Loss of kinase activity. 1 Publication1
Mutagenesisi138D → N: Abolished protein kinase activity and ability to regulate apoptosis and necroptosis. Knockin mice are viable. 1 Publication1
Mutagenesisi138D → N: Loss of kinase activity. 4 Publications1
Mutagenesisi321S → A: Loss of phosphorylation. Promotes activation of its kinase activity, proteolytic cleavage, ubiquitination and interaction with FADD to mediate apoptosis. Loss of phosphorylation at Ser-332 and Ser-334; when associated with A-332; A-334 and A-336. 1 Publication1
Mutagenesisi321S → E: Inhibits its proteolytic cleavage and interaction with FADD. Promotes its interaction with RIPK3 to mediate necroptosis; when associated with E-332; E-334 and E-336. 1 Publication1
Mutagenesisi325D → A: Loss of CASP8-mediated cleavage. Promotes both FADD-dependent apoptosis and RIPK3-dependent necroptosis, thus leading to embryonic lethality at midgestation stages in knockin mice. Heterozygous knockin mice are viable and grossly normal, but are hyperresponsive to inflammatory stimuli. 3 Publications1
Mutagenesisi325D → V or H: Loss of CASP8-mediated cleavage. Embryonic lethality in knockin mice. Promotes activation of the protein kinase activity, leading to increased cell death. 1 Publication1
Mutagenesisi332S → A: Loss of phosphorylation at Ser-332 and Ser-334; when associated with A-321; A-334 and A-336. 1 Publication1
Mutagenesisi332S → E: Promotes its interaction with RIPK3 to mediate necroptosis; when associated with E-321; E-334 and E-336. 1 Publication1
Mutagenesisi334S → A: Loss of phosphorylation at Ser-332 and Ser-334; when associated with A-321; A-332 and A-336. 1 Publication1
Mutagenesisi334S → E: Promotes its interaction with RIPK3 to mediate necroptosis; when associated with E-321; E-332 and E-336. 1 Publication1
Mutagenesisi336S → A: Loss of phosphorylation at Ser-332 and Ser-334; when associated with A-321; A-332 and A-334. 1 Publication1
Mutagenesisi336S → E: Promotes its interaction with RIPK3 to mediate necroptosis; when associated with E-321; E-332 and E-334. 1 Publication1
Mutagenesisi376K → R: Loss of ubiquitination. Decreases TNF-alpha-mediated NF-kappaB activation. Increases interaction with CFLAR, CASP8, FADD AND RIPK3. Decreases interaction with MAP3K7. Enhances kinase activity and promotes apoptosis and necroptosis. Knockin mice display early embryonic lethality resulting from excessive cell death and severe inflammation. 2 Publications1
Mutagenesisi529 – 531QIG → AAA in RIPK1(mRHIM); perinatal lethality in knockin mice caused by Ripk3- and Zbp1-dependent necroptosis. Lethality is prevented by Ripk3, Mlkl or Zbp1 deficiency. Knockin mice do not show defects caused by Casp8-dependent apoptosis observed in knockout mice. 2 Publications3
Mutagenesisi584K → R: Blocks homodimerization, activation of its kinase activity, formation of complex IIa, necroptosis and apoptosis. 1 Publication1

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL3784911

<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_00000866071 – 656Receptor-interacting serine/threonine-protein kinase 1Add BLAST656

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 residuei6Phosphoserine; by IKKA and IKKB1 Publication1
Modified residuei25Phosphoserine; by IKKA and IKKB1 Publication1
Modified residuei161Phosphoserine; by RIPK3 and autocatalysisSequence analysis1
Modified residuei166Phosphoserine; by autocatalysis6 Publications1
Modified residuei169Phosphothreonine1 Publication1
Modified residuei304PhosphoserineBy similarity1
Modified residuei313PhosphoserineCombined sources1
Modified residuei321Phosphoserine; by MAP3K7Combined sources1 Publication1
Modified residuei332Phosphoserine; by MAP3K71 Publication1
Modified residuei334Phosphoserine; by MAP3K71 Publication1
<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-linki376Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
Modified residuei383PhosphotyrosineBy 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

Proteolytically cleaved by CASP8 at Asp-325 (PubMed:30867408, PubMed:31511692, PubMed:31827280). Cleavage is crucial for limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:30867408, PubMed:31511692, PubMed:31827281, PubMed:31827280). Cleavage abolishes NF-kappa-B activation and enhances the interaction of TRADD with FADD (By similarity).By similarity4 Publications
RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (By similarity). Phosphorylation of Ser-161 by RIPK3 is necessary for the formation of the necroptosis-inducing complex (By similarity). Phosphorylation at Ser-25 represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (PubMed:30988283). Phosphorylated at Ser-321 by MAP3K7 which requires prior ubiquitination with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 (PubMed:28842570). This phosphorylation positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (PubMed:28842570).By similarity2 Publications
Ubiquitinated with 'Lys-11'-, 'Lys-48'-, 'Lys-63'- and linear-linked type ubiquitin (By similarity). Polyubiquitination with 'Lys-63'-linked chains by TRAF2 induces association with the IKK complex (By similarity). Deubiquitination of 'Lys-63'-linked chains and polyubiquitination with 'Lys-48'-linked chains by TNFAIP3 leads to RIPK1 proteasomal degradation and consequently down-regulates TNF-alpha-induced NF-kappa-B signaling (By similarity). 'Lys-48'-linked polyubiquitination by RFFL or RNF34 also promotes proteasomal degradation and negatively regulates TNF-alpha-induced NF-kappa-B signaling (By similarity). Linear polyubiquitinated; the head-to-tail linear polyubiquitination ('Met-1'-linked) is mediated by the LUBAC complex and decreases protein kinase activity (PubMed:28701375). Deubiquitination of linear polyubiquitin by CYLD promotes the kinase activity (PubMed:28701375). Polyubiquitinated with 'Lys-48' by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B (By similarity). Ubiquitinated with 'Lys-63'-linked chains by PELI1 (By similarity). Ubiquitination at Lys-376 with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 is essential for its phosphorylation at Ser-321 mediated by MAP3K7 (PubMed:28842570, PubMed:31519887, PubMed:31519886). This ubiquitination is required for NF-kB activation, suppresses RIPK1 kinase activity and plays a critical role in preventing cell death during embryonic development (PubMed:31519887, PubMed:31519886).By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei325 – 326Cleavage; by CASP83 Publications2

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q60855

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q60855

MaxQB - The MaxQuant DataBase

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MaxQBi
Q60855

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

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PaxDbi
Q60855

PeptideAtlas

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PeptideAtlasi
Q60855

PRoteomics IDEntifications database

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PRIDEi
Q60855

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q60855

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

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PhosphoSitePlusi
Q60855

<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

Found at low levels in all tissues.1 Publication

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

In concanavalin A-treated splenocytes.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSMUSG00000021408, Expressed in granulocyte and 169 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q60855, 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

Homodimer (PubMed:29440439).

Interacts (via RIP homotypic interaction motif) with RIPK3 (via RIP homotypic interaction motif); this interaction induces RIPK1 phosphorylation and formation of a RIPK1-RIPK3 necroptosis-inducing complex (PubMed:31519887, PubMed:28842570). 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).

Interacts (via the death domain) with TNFRSF6 (via the death domain) and TRADD (via the death domain) (By similarity). Is recruited by TRADD to TNFRSF1A in a TNF-dependent process (By similarity). Binds RNF216, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3 (By similarity).

Interacts with BNLF1 (By similarity).

Interacts with SQSTM1 upon TNF-alpha stimulation (By similarity). May interact with MAVS/IPS1 (By similarity).

Interacts with ZFAND5 (By similarity).

Interacts with RBCK1 (By similarity).

Interacts with ZBP1 (PubMed:19590578, PubMed:23283962).

Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4.

Interacts (via kinase domain) with DAB2IP (via Ras-GAP domain); the interaction occurs in a TNF-alpha-dependent manner (By similarity).

Interacts with ARHGEF2 (By similarity).

Interacts (via protein kinase domain) with RFFL; involved in RIPK1 ubiquitination (By similarity).

Interacts with RNF34; involved in RIPK1 ubiquitination (By similarity).

Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (By similarity).

Interacts with PELI1 (PubMed:29883609).

Interacts (via death domain) with CRADD (via death domain); the interaction is direct (By similarity).

Component of complex IIa composed of at least RIPK1, FADD and CASP8 (PubMed:29440439).

Interacts with MAP3K7, CFLAR and CASP8 (PubMed:31519887).

Interacts with FADD (PubMed:29440439, PubMed:31519887, PubMed:28842570).

Interacts with NEMO (PubMed:31519886).

By similarity6 Publications

(Microbial infection) Interacts with Murid herpesvirus 1 protein RIR1.

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

Hide details

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
202896, 25 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-1914, Ripoptosome

Database of interacting proteins

More...
DIPi
DIP-34962N

Protein interaction database and analysis system

More...
IntActi
Q60855, 25 interactors

Molecular INTeraction database

More...
MINTi
Q60855

STRING: functional protein association networks

More...
STRINGi
10090.ENSMUSP00000129831

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
Q60855

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...
RNActi
Q60855, 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

3D structure databases

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

More...
SMRi
Q60855

Database of comparative protein structure models

More...
ModBasei
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>Domaini17 – 290Protein kinasePROSITE-ProRule annotationAdd BLAST274
Domaini568 – 654DeathPROSITE-ProRule annotationAdd BLAST87

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>Regioni291 – 567Interaction with SQSTM1By similarityAdd BLAST277

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>Motifi520 – 536RIP homotypic interaction motif (RHIM)3 PublicationsAdd BLAST17

<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 death domain mediates dimerization and activation of its kinase activity during necroptosis and apoptosis (PubMed:29440439). It engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling (By similarity).By similarity1 Publication
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
ENSGT00940000159347

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
CLU_017229_0_0_1

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q60855

KEGG Orthology (KO)

More...
KOi
K02861

Identification of Orthologs from Complete Genome Data

More...
OMAi
NDFHIKI

Database of Orthologous Groups

More...
OrthoDBi
346354at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q60855

TreeFam database of animal gene trees

More...
TreeFami
TF106506

Family and domain databases

Conserved Domains Database

More...
CDDi
cd08777, Death_RIP1, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR011029, DEATH-like_dom_sf
IPR000488, Death_domain
IPR011009, Kinase-like_dom_sf
IPR000719, Prot_kinase_dom
IPR025735, RHIM_dom
IPR037934, RIP1_Death
IPR001245, Ser-Thr/Tyr_kinase_cat_dom
IPR008271, Ser/Thr_kinase_AS

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00531, Death, 1 hit
PF07714, Pkinase_Tyr, 1 hit
PF12721, RHIM, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR00109, TYRKINASE

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00005, DEATH, 1 hit
SM00220, S_TKc, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF47986, SSF47986, 1 hit
SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50017, DEATH_DOMAIN, 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 1 potential isoform that is computationally mapped.Show allAlign All

Q60855-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MQPDMSLDNI KMASSDLLEK TDLDSGGFGK VSLCYHRSHG FVILKKVYTG
60 70 80 90 100
PNRAEYNEVL LEEGKMMHRL RHSRVVKLLG IIIEEGNYSL VMEYMEKGNL
110 120 130 140 150
MHVLKTQIDV PLSLKGRIIV EAIEGMCYLH DKGVIHKDLK PENILVDRDF
160 170 180 190 200
HIKIADLGVA SFKTWSKLTK EKDNKQKEVS STTKKNNGGT LYYMAPEHLN
210 220 230 240 250
DINAKPTEKS DVYSFGIVLW AIFAKKEPYE NVICTEQFVI CIKSGNRPNV
260 270 280 290 300
EEILEYCPRE IISLMERCWQ AIPEDRPTFL GIEEEFRPFY LSHFEEYVEE
310 320 330 340 350
DVASLKKEYP DQSPVLQRMF SLQHDCVPLP PSRSNSEQPG SLHSSQGLQM
360 370 380 390 400
GPVEESWFSS SPEYPQDEND RSVQAKLQEE ASYHAFGIFA EKQTKPQPRQ
410 420 430 440 450
NEAYNREEER KRRVSHDPFA QQRARENIKS AGARGHSDPS TTSRGIAVQQ
460 470 480 490 500
LSWPATQTVW NNGLYNQHGF GTTGTGVWYP PNLSQMYSTY KTPVPETNIP
510 520 530 540 550
GSTPTMPYFS GPVADDLIKY TIFNSSGIQI GNHNYMDVGL NSQPPNNTCK
560 570 580 590 600
EESTSRHQAI FDNTTSLTDE HLNPIRENLG RQWKNCARKL GFTESQIDEI
610 620 630 640 650
DHDYERDGLK EKVYQMLQKW LMREGTKGAT VGKLAQALHQ CCRIDLLNHL

IRASQS
Length:656
Mass (Da):74,854
Last modified:November 1, 1997 - v1
<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:iABB350B523879933
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
F7D1J2F7D1J2_MOUSE
Receptor-interacting serine/threoni...
Ripk1
597Annotation 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 conflicti66M → K in BAC27194 (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
U25995 mRNA Translation: AAB60487.1
AK030959 mRNA Translation: BAC27194.1
AK156803 mRNA Translation: BAE33860.1
BC050905 mRNA Translation: AAH50905.2
BC054542 mRNA Translation: AAH54542.1
BC058162 mRNA Translation: AAH58162.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS26443.1

Protein sequence database of the Protein Information Resource

More...
PIRi
I49299

NCBI Reference Sequences

More...
RefSeqi
NP_033094.3, NM_009068.3
XP_006516670.1, XM_006516607.3
XP_006516672.1, XM_006516609.3

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000021844; ENSMUSP00000021844; ENSMUSG00000021408
ENSMUST00000167374; ENSMUSP00000129831; ENSMUSG00000021408

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
19766

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mmu:19766

UCSC genome browser

More...
UCSCi
uc007qax.1, 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
U25995 mRNA Translation: AAB60487.1
AK030959 mRNA Translation: BAC27194.1
AK156803 mRNA Translation: BAE33860.1
BC050905 mRNA Translation: AAH50905.2
BC054542 mRNA Translation: AAH54542.1
BC058162 mRNA Translation: AAH58162.1
CCDSiCCDS26443.1
PIRiI49299
RefSeqiNP_033094.3, NM_009068.3
XP_006516670.1, XM_006516607.3
XP_006516672.1, XM_006516609.3

3D structure databases

SMRiQ60855
ModBaseiSearch...

Protein-protein interaction databases

BioGRIDi202896, 25 interactors
ComplexPortaliCPX-1914, Ripoptosome
DIPiDIP-34962N
IntActiQ60855, 25 interactors
MINTiQ60855
STRINGi10090.ENSMUSP00000129831

Chemistry databases

BindingDBiQ60855
ChEMBLiCHEMBL3784911

PTM databases

iPTMnetiQ60855
PhosphoSitePlusiQ60855

Proteomic databases

EPDiQ60855
jPOSTiQ60855
MaxQBiQ60855
PaxDbiQ60855
PeptideAtlasiQ60855
PRIDEiQ60855

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
4145, 599 antibodies

Genome annotation databases

EnsembliENSMUST00000021844; ENSMUSP00000021844; ENSMUSG00000021408
ENSMUST00000167374; ENSMUSP00000129831; ENSMUSG00000021408
GeneIDi19766
KEGGimmu:19766
UCSCiuc007qax.1, mouse

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
8737
MGIiMGI:108212, Ripk1

Phylogenomic databases

eggNOGiKOG0192, Eukaryota
GeneTreeiENSGT00940000159347
HOGENOMiCLU_017229_0_0_1
InParanoidiQ60855
KOiK02861
OMAiNDFHIKI
OrthoDBi346354at2759
PhylomeDBiQ60855
TreeFamiTF106506

Enzyme and pathway databases

BRENDAi2.7.10.2, 3474
ReactomeiR-MMU-140534, Caspase activation via Death Receptors in the presence of ligand
R-MMU-2562578, TRIF-mediated programmed cell death
R-MMU-3295583, TRP channels
R-MMU-3371378, Regulation by c-FLIP
R-MMU-5213460, RIPK1-mediated regulated necrosis
R-MMU-5218900, CASP8 activity is inhibited
R-MMU-5357786, TNFR1-induced proapoptotic signaling
R-MMU-5357905, Regulation of TNFR1 signaling
R-MMU-5357956, TNFR1-induced NFkappaB signaling pathway
R-MMU-5689880, Ub-specific processing proteases
R-MMU-5689896, Ovarian tumor domain proteases
R-MMU-69416, Dimerization of procaspase-8
R-MMU-75893, TNF signaling
R-MMU-937041, IKK complex recruitment mediated by RIP1

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
19766, 7 hits in 21 CRISPR screens

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

More...
ChiTaRSi
Ripk1, mouse

Protein Ontology

More...
PROi
PR:Q60855
RNActiQ60855, protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000021408, Expressed in granulocyte and 169 other tissues
GenevisibleiQ60855, MM

Family and domain databases

CDDicd08777, Death_RIP1, 1 hit
InterProiView protein in InterPro
IPR011029, DEATH-like_dom_sf
IPR000488, Death_domain
IPR011009, Kinase-like_dom_sf
IPR000719, Prot_kinase_dom
IPR025735, RHIM_dom
IPR037934, RIP1_Death
IPR001245, Ser-Thr/Tyr_kinase_cat_dom
IPR008271, Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00531, Death, 1 hit
PF07714, Pkinase_Tyr, 1 hit
PF12721, RHIM, 1 hit
PRINTSiPR00109, TYRKINASE
SMARTiView protein in SMART
SM00005, DEATH, 1 hit
SM00220, S_TKc, 1 hit
SUPFAMiSSF47986, SSF47986, 1 hit
SSF56112, SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50017, DEATH_DOMAIN, 1 hit
PS50011, PROTEIN_KINASE_DOM, 1 hit
PS00108, PROTEIN_KINASE_ST, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

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 nameiRIPK1_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: Q60855
Secondary accession number(s): Q3U0J3, Q8CD90
<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: November 1, 1997
Last sequence update: November 1, 1997
Last modified: August 12, 2020
This is version 198 of the entry and version 1 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

Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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