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Entry version 184 (16 Oct 2019)
Sequence version 1 (01 May 1999)
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Protein

Kelch-like ECH-associated protein 1

Gene

Keap1

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

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination (PubMed:9887101, PubMed:12682069, PubMed:15282312, PubMed:15367669, PubMed:15581590). KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:9887101, PubMed:12193649, PubMed:14764894). In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (PubMed:12193649, PubMed:20498371, PubMed:22014577, PubMed:29590092). In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2 (PubMed:20421418, PubMed:20173742, PubMed:24011591). The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation (PubMed:28380357). The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome (By similarity).By similarity14 Publications

Caution

According to a report, not degraded in reponse to autophagy (PubMed:20495340). However, publications have shown that KEAP1 is degraded via a proteasomal-independent process during selective autophagy (PubMed:22872865, PubMed:24011591).3 Publications
The mechanism of inactivation of the BCR(KEAP1) complex by covalent modifications of reactive cysteines is unclear. Covalent modifications were initially thought to disrupt interaction between KEAP1 and NFE2L2/NRF2 (PubMed:12193649). Recent publications suggest that cysteine modifications disrupt the interaction between KEAP1 and CUL3 without affecting the interaction between KEAP1 and NFE2L2/NRF2 (By similarity).By similarity1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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

Ubiquitin ligase activity of the BCR(KEAP1) complex is inhibited by oxidative stress and electrophile metabolites such as sulforaphane (PubMed:12193649, PubMed:14764894, PubMed:22014577). Electrophile metabolites react with reactive cysteine residues in KEAP1 and trigger non-enzymatic covalent modifications of these cysteine residues, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex (PubMed:20498371, PubMed:22014577). Selective autophagy also inactivates the BCR(KEAP1) complex via interaction between KEAP1 and SQSTM1/p62, which sequesters the complex in inclusion bodies and promotes its degradation (PubMed:20421418, PubMed:20173742, PubMed:24011591).7 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.5 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

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>Sitei151Sensor for electrophilic agents3 Publications1
Sitei257Sensor for electrophilic agentsBy similarity1
Sitei273Sensor for electrophilic agents2 Publications1
Sitei288Sensor for electrophilic agents3 Publications1
Sitei434Sensor for electrophilic agents1 Publication1

<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

Biological processUbl conjugation pathway

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8951664 Neddylation
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...
UniPathwayi
UPA00143

<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_and_taxonomy_section">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:
Kelch-like ECH-associated protein 11 Publication
Alternative name(s):
Cytosolic inhibitor of Nrf21 Publication
Short name:
INrf21 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:Keap11 PublicationImported
Synonyms:Inrf21 Publication, Kiaa01321 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_manual">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 9

Organism-specific databases

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

More...
MGIi
MGI:1858732 Keap1

<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

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

Early postnatal lethality caused by abnormal cornification (PubMed:14517554). Mice survive until weaning and probably die from malnutrition resulting from hyperkeratosis in the esophagus and forestomach that cause gastric obstruction (PubMed:14517554). Defects are caused by constitutive activation Nfe2l2/Nrf2, leading to constitutive expression of phase 2 detoxifying enzymes (PubMed:14517554). Mice lacking both Nfe2l2/Nrf2 and Keap1 reverse the hyperkeratosis phenotype and are healthy and viable in normal conditions (PubMed:14517554).1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'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>Mutagenesisi71R → G: Abolished ability to ubiquitinate NFE2L2/NRF2 without affecting homodimerization. 1 Publication1
Mutagenesisi151C → S: Substitution with a small side chain that prevents covalent modification by an electrophile; promotes constitutive ubiquitination of NFE2L2/NRF2 and subsequent repression of phase 2 detoxifying enzymes. Knockin mice are healthy and viable in normal conditions but do not activate NFE2L2/NRF2 in response to oxidative stress. 2 Publications1
Mutagenesisi273C → A: Abolishes repression of NFE2L2/NRF2-dependent gene expression. Knockin mice die approximately three weeks after birth because of impaired ability of the BCR(KEAP1) complex to ubiquitinate NFE2L2/NRF2; when associated with A-288. 1 Publication1
Mutagenesisi273C → W or M: Retains ability to degrade NFE2L2/NRF2; when associated with E-288. 1 Publication1
Mutagenesisi288C → A: Abolishes repression of NFE2L2/NRF2-dependent gene expression. Slows down degradation of NFE2L2/NRF2. Knockin mice die approximately three weeks after birth because of impaired ability of the BCR(KEAP1) complex to ubiquitinate NFE2L2/NRF2; when associated with A-273. 1 Publication1
Mutagenesisi288C → E, N or R: Retains ability to degrade NFE2L2/NRF2; when associated with W-273. Abolishes ability to be activated by 15-deoxy-delta(12,14)-prostaglandin J2. 1 Publication1
Mutagenesisi334Y → A: Impaired interaction with SQSTM1/p62. 1 Publication1
Mutagenesisi363S → A: Impaired interaction with SQSTM1/p62. 1 Publication1
Mutagenesisi380R → A: Impaired interaction with SQSTM1/p62. Abolished interaction with SQSTM1/p62; when associated with A-415 and A-483. 2 Publications1
Mutagenesisi380R → M: Impaired interaction with NFE2L2/NRF2. 1 Publication1
Mutagenesisi382N → A: Impaired interaction with SQSTM1/p62. 1 Publication1
Mutagenesisi415R → A: Impaired interaction with SQSTM1/p62. Abolished interaction with SQSTM1/p62; when associated with A-380 and A-483. 2 Publications1
Mutagenesisi415R → M: Impaired interaction with NFE2L2/NRF2. 1 Publication1
Mutagenesisi483R → A: Does not affect interaction with SQSTM1/p62. Abolished interaction with SQSTM1/p62; when associated with A-380 and A-415. 2 Publications1
Mutagenesisi483R → M: Impaired interaction with NFE2L2/NRF2. 1 Publication1
Mutagenesisi508S → A: Impaired interaction with SQSTM1/p62. 1 Publication1
Mutagenesisi530Q → A: Impaired interaction with SQSTM1/p62. 1 Publication1
Mutagenesisi555S → A: Impaired interaction with SQSTM1/p62. 1 Publication1
Mutagenesisi599 – 601SGR → AAA: Decreases repression of NFE2L2/NRF2-dependent gene expression. 1 Publication3
Mutagenesisi602 – 604SGV → AAA: Abolishes repression of NFE2L2/NRF2-dependent gene expression. 1 Publication3
Mutagenesisi602S → A: Impaired interaction with SQSTM1/p62. 1 Publication1
Mutagenesisi605 – 608GVAV → AAAA: Decreases repression of NFE2L2/NRF2-dependent gene expression. 1 Publication4

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL3562164

<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.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001190941 – 624Kelch-like ECH-associated protein 1Add BLAST624

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 residuei38S-(2-succinyl)cysteine1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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-linki135N5-[4-(S-L-cysteinyl)-5-methyl-1H-imidazol-2-yl]-L-ornithine (Arg-Cys) (interchain with C-151 in KEAP1)By similarity
Modified residuei151S-(2,3-dicarboxypropyl)cysteine; alternateBy similarity1
Modified residuei151S-(2-succinyl)cysteine; alternate1 Publication1
Modified residuei151S-nitrosocysteine; alternate1 Publication1
Cross-linki151N5-[4-(S-L-cysteinyl)-5-methyl-1H-imidazol-2-yl]-L-ornithine (Cys-Arg) (interchain with R-135 in KEAP1)By similarity
Modified residuei241S-(2-succinyl)cysteine1 Publication1
Modified residuei257S-(2,3-dicarboxypropyl)cysteineBy similarity1
Modified residuei273S-(2,3-dicarboxypropyl)cysteineBy similarity1
Modified residuei288S-(2,3-dicarboxypropyl)cysteine; alternateBy similarity1
Modified residuei288S-(2-succinyl)cysteine; alternate1 Publication1
Modified residuei319S-(2-succinyl)cysteine1 Publication1
Modified residuei434S-cGMP-cysteine1 Publication1
Modified residuei613S-(2-succinyl)cysteine1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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

Non-enzymatic covalent modifications of reactive cysteines by electrophile metabolites inactivate the BCR(KEAP1) complex (PubMed:12193649, PubMed:20498371, PubMed:22014577). Accumulation of fumarate promotes the formation of cysteine S-succination (S-(2-succinyl)cysteine), leading to inactivate the BCR(KEAP1) complex and promote NFE2L2/NRF2 nuclear accumulation and activation (PubMed:22014577). Nitric oxide-dependent 8-Nitro-cGMP formation promotes cysteine guanylation (S-cGMP-cysteine), leading to NFE2L2/NRF2 nuclear accumulation and activation (PubMed:17906641, PubMed:20498371). Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates cysteines, activating NFE2L2/NRF2 (PubMed:29590092). Methylglyoxal, a reactive metabolite that accumulates when the glycolytic enzyme PGK1 is inhibited, promotes formation of a methylimidazole cross-link between proximal Cys-151 and Arg-135 on another KEAP1 molecule, resulting in an inactive dimer that inactivates the BCR(KEAP1) complex (By similarity).By similarity5 Publications
Degraded via a proteasomal-independent process during selective autophagy: interaction with phosphorylated SQSTM1/p62 sequesters KEAP1 in inclusion bodies, leading to its degradation.2 Publications
Auto-ubiquitinated by the BCR(KEAP1) complex. Quinone-induced oxidative stress, but not sulforaphane, increases its ubiquitination. Ubiquitination and subsequent degradation is most pronounced following prolonged exposure of cells to oxidative stress, particularly in glutathione-deficient cells that are highly susceptible to oxidative stress.By similarity

Keywords - PTMi

S-nitrosylation, Thioether bond, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q9Z2X8

MaxQB - The MaxQuant DataBase

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MaxQBi
Q9Z2X8

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

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PaxDbi
Q9Z2X8

PeptideAtlas

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PeptideAtlasi
Q9Z2X8

PRoteomics IDEntifications database

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PRIDEi
Q9Z2X8

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q9Z2X8

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

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PhosphoSitePlusi
Q9Z2X8

SwissPalm database of S-palmitoylation events

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SwissPalmi
Q9Z2X8

<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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSMUSG00000003308 Expressed in 268 organ(s), highest expression level in supraoptic nucleus

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q9Z2X8 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q9Z2X8 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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Component of the BCR(KEAP1) E3 ubiquitin ligase complex, at least composed of 2 molecules of CUL3, 2 molecules of KEAP1, and RBX1 (PubMed:15282312, PubMed:16790436, PubMed:27697860).

Interacts with NFE2L2/NRF2; the interaction is direct (PubMed:15282312, PubMed:15367669, PubMed:15581590, PubMed:16790436, PubMed:16581765, PubMed:27697860, PubMed:16507366).

Forms a ternary complex with NFE2L2/NRF2 and PGAM5 (By similarity).

Interacts with (phosphorylated) SQSTM1/p62; the interaction is direct and inactivates the BCR(KEAP1) complex by sequestering it in inclusion bodies, promoting its degradation (PubMed:20495340, PubMed:20421418, PubMed:20173742, PubMed:24011591).

Interacts with NFE2L1 (By similarity).

Interacts with BPTF and PTMA (By similarity).

Interacts with MAP1LC3B (By similarity).

Interacts indirectly with ENC1 (By similarity).

Interacts with SESN1 and SESN2 (By similarity).

Interacts with HSP90AA1 and HSP90AB1 (By similarity).

By similarity11 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">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="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
206135, 11 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q9Z2X8

Database of interacting proteins

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DIPi
DIP-49698N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
Q9Z2X8

Protein interaction database and analysis system

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IntActi
Q9Z2X8, 9 interactors

Molecular INTeraction database

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MINTi
Q9Z2X8

STRING: functional protein association networks

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STRINGi
10090.ENSMUSP00000131029

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q9Z2X8

<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

1624
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
Q9Z2X8

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...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
Q9Z2X8

<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_and_domains_section">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>Domaini77 – 149BTBPROSITE-ProRule annotationAdd BLAST73
Domaini184 – 286BACKAdd BLAST103
<p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati327 – 372Kelch 1Add BLAST46
Repeati373 – 423Kelch 2Add BLAST51
Repeati424 – 470Kelch 3Add BLAST47
Repeati471 – 517Kelch 4Add BLAST47
Repeati519 – 564Kelch 5Add BLAST46
Repeati565 – 611Kelch 6Add BLAST47

<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 Kelch repeats mediate interaction with NFE2L2/NRF2, BPTF and PGAM5.By similarity
KEAP1 contains reactive cysteine residues that act as sensors for endogenously produced and exogenously encountered small molecules, which react with sulfhydryl groups and modify the cysteine sensors, leading to impair ability of the BCR(KEAP1) complex to ubiquitinate target proteins.5 Publications

<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

Belongs to the KEAP1 family.Curated

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG4441 Eukaryota
ENOG410XNX8 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000159543

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000230814

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q9Z2X8

KEGG Orthology (KO)

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KOi
K10456

Identification of Orthologs from Complete Genome Data

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OMAi
CYHPEND

Database of Orthologous Groups

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OrthoDBi
746011at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q9Z2X8

TreeFam database of animal gene trees

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TreeFami
TF329218

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.120.10.80, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR011705 BACK
IPR017096 BTB-kelch_protein
IPR000210 BTB/POZ_dom
IPR030563 KEAP1
IPR015915 Kelch-typ_b-propeller
IPR006652 Kelch_1
IPR011333 SKP1/BTB/POZ_sf

The PANTHER Classification System

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PANTHERi
PTHR24412:SF162 PTHR24412:SF162, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 6 hits

PIRSF; a whole-protein classification database

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PIRSFi
PIRSF037037 Kelch-like_protein_gigaxonin, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00875 BACK, 1 hit
SM00225 BTB, 1 hit
SM00612 Kelch, 6 hits

Superfamily database of structural and functional annotation

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SUPFAMi
SSF117281 SSF117281, 1 hit
SSF54695 SSF54695, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50097 BTB, 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_length">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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

Q9Z2X8-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MQPEPKLSGA PRSSQFLPLW SKCPEGAGDA VMYASTECKA EVTPSQDGNR
60 70 80 90 100
TFSYTLEDHT KQAFGVMNEL RLSQQLCDVT LQVKYEDIPA AQFMAHKVVL
110 120 130 140 150
ASSSPVFKAM FTNGLREQGM EVVSIEGIHP KVMERLIEFA YTASISVGEK
160 170 180 190 200
CVLHVMNGAV MYQIDSVVRA CSDFLVQQLD PSNAIGIANF AEQIGCTELH
210 220 230 240 250
QRAREYIYMH FGEVAKQEEF FNLSHCQLAT LISRDDLNVR CESEVFHACI
260 270 280 290 300
DWVKYDCPQR RFYVQALLRA VRCHALTPRF LQTQLQKCEI LQADARCKDY
310 320 330 340 350
LVQIFQELTL HKPTQAVPCR APKVGRLIYT AGGYFRQSLS YLEAYNPSNG
360 370 380 390 400
SWLRLADLQV PRSGLAGCVV GGLLYAVGGR NNSPDGNTDS SALDCYNPMT
410 420 430 440 450
NQWSPCASMS VPRNRIGVGV IDGHIYAVGG SHGCIHHSSV ERYEPERDEW
460 470 480 490 500
HLVAPMLTRR IGVGVAVLNR LLYAVGGFDG TNRLNSAECY YPERNEWRMI
510 520 530 540 550
TPMNTIRSGA GVCVLHNCIY AAGGYDGQDQ LNSVERYDVE TETWTFVAPM
560 570 580 590 600
RHHRSALGIT VHQGKIYVLG GYDGHTFLDS VECYDPDSDT WSEVTRMTSG
610 620
RSGVGVAVTM EPCRKQIDQQ NCTC
Length:624
Mass (Da):69,553
Last modified:May 1, 1999 - 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:i4645DB0122FB5F54
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
A0A1L1SS10A0A1L1SS10_MOUSE
Kelch-like ECH-associated protein 1
Keap1
620Annotation 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>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence BAC97871 differs from that shown. Reason: Erroneous initiation.Curated

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 conflicti43T → A in BAE29559 (PubMed:16141072).Curated1
Sequence conflicti43T → A in BAE30980 (PubMed:16141072).Curated1
Sequence conflicti348S → G in BAC32621 (PubMed:16141072).Curated1
Sequence conflicti361P → T in BAE29559 (PubMed:16141072).Curated1
Sequence conflicti361P → T in BAE30980 (PubMed:16141072).Curated1
Sequence conflicti579D → V in BAE32581 (PubMed:16141072).Curated1
Sequence conflicti579D → V in BAE33299 (PubMed:16141072).Curated1

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
AB020063 mRNA Translation: BAA34639.1
AF454353 Genomic DNA Translation: AAL84711.1
AK129061 mRNA Translation: BAC97871.1 Different initiation.
AK046178 mRNA Translation: BAC32621.1
AK076234 mRNA Translation: BAC36267.1
AK150437 mRNA Translation: BAE29559.1
AK150485 mRNA Translation: BAE29601.1
AK152142 mRNA Translation: BAE30980.1
AK154430 mRNA Translation: BAE32581.1
AK155507 mRNA Translation: BAE33299.1
AK159858 mRNA Translation: BAE35433.1
BC055732 mRNA Translation: AAH55732.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS22897.1

NCBI Reference Sequences

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RefSeqi
NP_001103775.1, NM_001110305.1
NP_001103776.1, NM_001110306.1
NP_001103777.1, NM_001110307.1
NP_057888.1, NM_016679.4

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000049567; ENSMUSP00000062467; ENSMUSG00000003308
ENSMUST00000164812; ENSMUSP00000131029; ENSMUSG00000003308
ENSMUST00000193982; ENSMUSP00000141840; ENSMUSG00000003308
ENSMUST00000194542; ENSMUSP00000141807; ENSMUSG00000003308

Database of genes from NCBI RefSeq genomes

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GeneIDi
50868

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
mmu:50868

UCSC genome browser

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UCSCi
uc009oko.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
AB020063 mRNA Translation: BAA34639.1
AF454353 Genomic DNA Translation: AAL84711.1
AK129061 mRNA Translation: BAC97871.1 Different initiation.
AK046178 mRNA Translation: BAC32621.1
AK076234 mRNA Translation: BAC36267.1
AK150437 mRNA Translation: BAE29559.1
AK150485 mRNA Translation: BAE29601.1
AK152142 mRNA Translation: BAE30980.1
AK154430 mRNA Translation: BAE32581.1
AK155507 mRNA Translation: BAE33299.1
AK159858 mRNA Translation: BAE35433.1
BC055732 mRNA Translation: AAH55732.1
CCDSiCCDS22897.1
RefSeqiNP_001103775.1, NM_001110305.1
NP_001103776.1, NM_001110306.1
NP_001103777.1, NM_001110307.1
NP_057888.1, NM_016679.4

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
1X2JX-ray1.60A309-624[»]
1X2RX-ray1.70A309-624[»]
2DYHX-ray1.90A309-624[»]
2Z32X-ray2.00A309-624[»]
3ADEX-ray2.80A309-624[»]
3WDZX-ray2.60A321-609[»]
3WN7X-ray1.57A/L321-609[»]
4ZY3X-ray1.80A/B321-609[»]
5CGJX-ray3.36A309-624[»]
5FNQX-ray1.91A322-624[»]
5FNRX-ray1.89A322-624[»]
5FNSX-ray1.79A322-624[»]
5FNTX-ray1.79A322-624[»]
5FNUX-ray1.78A322-624[»]
5FZJX-ray2.01A322-624[»]
5FZNX-ray1.97A322-624[»]
6QMCX-ray1.77A322-624[»]
6QMDX-ray1.94A322-624[»]
6QMEX-ray1.81A322-624[»]
6QMJX-ray1.86A322-624[»]
6QMKX-ray1.72A322-624[»]
SMRiQ9Z2X8
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi206135, 11 interactors
CORUMiQ9Z2X8
DIPiDIP-49698N
ELMiQ9Z2X8
IntActiQ9Z2X8, 9 interactors
MINTiQ9Z2X8
STRINGi10090.ENSMUSP00000131029

Chemistry databases

BindingDBiQ9Z2X8
ChEMBLiCHEMBL3562164

PTM databases

iPTMnetiQ9Z2X8
PhosphoSitePlusiQ9Z2X8
SwissPalmiQ9Z2X8

Proteomic databases

EPDiQ9Z2X8
MaxQBiQ9Z2X8
PaxDbiQ9Z2X8
PeptideAtlasiQ9Z2X8
PRIDEiQ9Z2X8

Genome annotation databases

EnsembliENSMUST00000049567; ENSMUSP00000062467; ENSMUSG00000003308
ENSMUST00000164812; ENSMUSP00000131029; ENSMUSG00000003308
ENSMUST00000193982; ENSMUSP00000141840; ENSMUSG00000003308
ENSMUST00000194542; ENSMUSP00000141807; ENSMUSG00000003308
GeneIDi50868
KEGGimmu:50868
UCSCiuc009oko.2 mouse

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
9817
MGIiMGI:1858732 Keap1

Rodent Unidentified Gene-Encoded large proteins database

More...
Rougei
Search...

Phylogenomic databases

eggNOGiKOG4441 Eukaryota
ENOG410XNX8 LUCA
GeneTreeiENSGT00940000159543
HOGENOMiHOG000230814
InParanoidiQ9Z2X8
KOiK10456
OMAiCYHPEND
OrthoDBi746011at2759
PhylomeDBiQ9Z2X8
TreeFamiTF329218

Enzyme and pathway databases

UniPathwayiUPA00143
ReactomeiR-MMU-5689880 Ub-specific processing proteases
R-MMU-8951664 Neddylation
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

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

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ChiTaRSi
Keap1 mouse
EvolutionaryTraceiQ9Z2X8

Protein Ontology

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PROi
PR:Q9Z2X8

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000003308 Expressed in 268 organ(s), highest expression level in supraoptic nucleus
ExpressionAtlasiQ9Z2X8 baseline and differential
GenevisibleiQ9Z2X8 MM

Family and domain databases

Gene3Di2.120.10.80, 1 hit
InterProiView protein in InterPro
IPR011705 BACK
IPR017096 BTB-kelch_protein
IPR000210 BTB/POZ_dom
IPR030563 KEAP1
IPR015915 Kelch-typ_b-propeller
IPR006652 Kelch_1
IPR011333 SKP1/BTB/POZ_sf
PANTHERiPTHR24412:SF162 PTHR24412:SF162, 1 hit
PfamiView protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 6 hits
PIRSFiPIRSF037037 Kelch-like_protein_gigaxonin, 1 hit
SMARTiView protein in SMART
SM00875 BACK, 1 hit
SM00225 BTB, 1 hit
SM00612 Kelch, 6 hits
SUPFAMiSSF117281 SSF117281, 1 hit
SSF54695 SSF54695, 1 hit
PROSITEiView protein in PROSITE
PS50097 BTB, 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 nameiKEAP1_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: Q9Z2X8
Secondary accession number(s): Q3U243
, Q3U8N7, Q547S3, Q6ZQI6, Q8BQY3
<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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 1999
Last modified: October 16, 2019
This is version 184 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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