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UniProtKB - P45983 (MK08_HUMAN)

Entry version 211 (08 May 2019)
Sequence version 2 (01 Nov 1997)
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Protein

Mitogen-activated protein kinase 8

Gene

MAPK8

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

Annotation score:5 out of 5

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

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

Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity).By similarity2 Publications
JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+1 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

Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by SERPINB3.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 sitei55ATPPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 sitei151Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 bindingi32 – 40ATPPROSITE-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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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 processBiological rhythms
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		2.7.11.24 2681

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-111446 Activation of BIM and translocation to mitochondria
R-HSA-139910 Activation of BMF and translocation to mitochondria
R-HSA-193648 NRAGE signals death through JNK
R-HSA-205043 NRIF signals cell death from the nucleus
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-376172 DSCAM interactions
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-450341 Activation of the AP-1 family of transcription factors
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-9007892 Interleukin-38 signaling

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

More...SignaLinki		P45983

SIGNOR Signaling Network Open Resource

More...SIGNORi		P45983

<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:
Mitogen-activated protein kinase 8 (EC:2.7.11.247 Publications)
Short name:
MAP kinase 8
Short name:
MAPK 8
Alternative name(s):
JNK-46
Stress-activated protein kinase 1c
Short name:
SAPK1c
Stress-activated protein kinase JNK1
c-Jun N-terminal kinase 1
<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:MAPK8
Synonyms:JNK1, PRKM8, SAPK1, SAPK1C
<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>OrganismiHomo sapiens (Human)
<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 identifieri9606 [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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<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
  • UP000005640 <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 10

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:6881 MAPK8

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		601158 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P45983

<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

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>Mutagenesisi183T → A: Phosphorylation blocked. 1 Publication1
Mutagenesisi185Y → F: Phosphorylation blocked. 1 Publication1

Organism-specific databases

DisGeNET

More...DisGeNETi		5599

Open Targets

More...OpenTargetsi		ENSG00000107643

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA283

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL2276

Drug and drug target database

More...DrugBanki		DB07268 2-({2-[(3-HYDROXYPHENYL)AMINO]PYRIMIDIN-4-YL}AMINO)BENZAMIDE

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		1496

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		MAPK8

Domain mapping of disease mutations (DMDM)

More...DMDMi		2507195

<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_00001862621 – 427Mitogen-activated protein kinase 8Add BLAST427

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 residuei116S-nitrosocysteineBy similarity1
Modified residuei183Phosphothreonine; by MAP2K71 Publication1
Modified residuei185Phosphotyrosine; by MAP2K41 Publication1
Modified residuei377PhosphoserineBy similarity1
Isoform 5 (identifier: P45983-5)
Modified residuei301PhosphoserineCombined sources1
Isoform 1 (identifier: P45983-2)
Modified residuei377PhosphoserineCombined sources1
Isoform 3 (identifier: P45983-3)
Modified residuei377PhosphoserineCombined sources1

<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

Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme (PubMed:11062067). Phosphorylated by TAOK2 (PubMed:17158878). May be phosphorylated at Thr-183 and Tyr-185 by MAP3K1/MEKK1 (PubMed:17761173).3 Publications

Keywords - PTMi

Phosphoprotein, S-nitrosylation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P45983

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P45983

MaxQB - The MaxQuant DataBase

More...MaxQBi		P45983

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

More...PaxDbi		P45983

PeptideAtlas

More...PeptideAtlasi		P45983

PRoteomics IDEntifications database

More...PRIDEi		P45983

ProteomicsDB human proteome resource

More...ProteomicsDBi		55694
55695 [P45983-2]
55696 [P45983-3]
55697 [P45983-4]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P45983

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

More...PhosphoSitePlusi		P45983

<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

More...Bgeei		ENSG00000107643 Expressed in 205 organ(s), highest expression level in forebrain

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P45983 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P45983 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		CAB004463
CAB069396

<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

Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 (PubMed:15693750). These proteins also bind other components of the JNK signaling pathway. Interacts with TP53 and WWOX (PubMed:12514174). Interacts with JAMP (By similarity). Forms a complex with MAPK8IP1 and ARHGEF28 (By similarity). Interacts with HSF1 (via D domain and preferentially with hyperphosphorylated form); this interaction occurs under both normal growth conditions and immediately upon heat shock (PubMed:10747973). Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells (By similarity). Interacts with NFATC4 (PubMed:17875713). Interacts with MECOM; regulates JNK signaling (PubMed:10856240). Interacts with PIN1; this interaction mediates MAPK8 conformational changes leading to the binding of MAPK8 to its substrates (PubMed:21660049). Interacts with GRIPAP1 (PubMed:17761173). Interacts with POU5F1; phosphorylates POU5F1 at 'Ser-355'. Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8IP1/JIP1. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK9/JNK2 (By similarity).By similarity9 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

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		111585, 187 interactors

Database of interacting proteins

More...DIPi		DIP-249N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		P45983

Protein interaction database and analysis system

More...IntActi		P45983, 91 interactors

Molecular INTeraction database

More...MINTi		P45983

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000378974

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P45983

<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

1427
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

More...SMRi		P45983

Database of comparative protein structure models

More...ModBasei		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P45983

<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>Domaini26 – 321Protein kinasePROSITE-ProRule annotationAdd BLAST296

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>Motifi183 – 185TXY3

<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 TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

<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 protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG0665 Eukaryota
ENOG410XSHI LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000153692

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		HOG000233024

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P45983

KEGG Orthology (KO)

More...KOi		K04440

Identification of Orthologs from Complete Genome Data

More...OMAi		REFKLMN

Database of Orthologous Groups

More...OrthoDBi		741207at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P45983

TreeFam database of animal gene trees

More...TreeFami		TF105100

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008351 MAPK_JNK
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS

Pfam protein domain database

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

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR01772 JNKMAPKINASE

Simple Modular Architecture Research Tool; a protein domain database

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

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS01351 MAPK, 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_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>Sequences (5+)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 describes 5 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 2 (identifier: P45983-1) [UniParc]FASTAAdd to basket
Also known as: JNK1-alpha-2

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER 
        60         70         80         90        100
NVAIKKLSRP FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE 
       110        120        130        140        150
FQDVYIVMEL MDANLCQVIQ MELDHERMSY LLYQMLCGIK HLHSAGIIHR 
       160        170        180        190        200
DLKPSNIVVK SDCTLKILDF GLARTAGTSF MMTPYVVTRY YRAPEVILGM 
       210        220        230        240        250
GYKENVDLWS VGCIMGEMVC HKILFPGRDY IDQWNKVIEQ LGTPCPEFMK 
       260        270        280        290        300
KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK 
       310        320        330        340        350
MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE 
       360        370        380        390        400
EWKELIYKEV MDLEERTKNG VIRGQPSPLG AAVINGSQHP SSSSSVNDVS 
       410        420 
SMSTDPTLAS DTDSSLEAAA GPLGCCR
Length:427
Mass (Da):48,296
Last modified:November 1, 1997 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i94FB6BE0358B9B60
GO
Isoform 1 (identifier: P45983-2) [UniParc]FASTAAdd to basket
Also known as: JNK1-alpha-1

The sequence of this isoform differs from the canonical sequence as follows:
     380-427: GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR → AQVQQ

Show »
Length:384
Mass (Da):44,229
Checksum:iA7320EF933E9CF85
GO
Isoform 3 (identifier: P45983-3) [UniParc]FASTAAdd to basket
Also known as: JNK1-beta-1

The sequence of this isoform differs from the canonical sequence as follows:
     208-208: L → I
     219-230: VCHKILFPGRDY → IKGGVLFPGTDH
     380-427: GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR → AQVQQ

Show »
Length:384
Mass (Da):44,022
Checksum:i76E49A950E64C1A1
GO
Isoform 4 (identifier: P45983-4) [UniParc]FASTAAdd to basket
Also known as: JNK1-beta-2

The sequence of this isoform differs from the canonical sequence as follows:
     208-208: L → I
     219-230: VCHKILFPGRDY → IKGGVLFPGTDH

Show »
Length:427
Mass (Da):48,088
Checksum:i3F5CC3F6A4F3EF2D
GO
Isoform 5 (identifier: P45983-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     206-281: Missing.
     380-427: GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR → AQVQQ

Show »
Length:308
Mass (Da):35,333
Checksum:i914B803A1223601D
GO

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

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J762C9J762_HUMAN
Mitogen-activated protein kinase 8
MAPK8
142Annotation 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>
A0A3B3IRW7A0A3B3IRW7_HUMAN
Mitogen-activated protein kinase 8
MAPK8
169Annotation 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>
C9JWQ4C9JWQ4_HUMAN
Mitogen-activated protein kinase 8
MAPK8
40Annotation 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>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_042258171G → S in a renal clear cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042259177G → R in a glioblastoma multiforme sample; somatic mutation. 1 Publication1
Natural variantiVAR_050592365E → K. Corresponds to variant dbSNP:rs45483593Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_054554206 – 281Missing in isoform 5. 1 PublicationAdd BLAST76
Alternative sequenceiVSP_004831208L → I in isoform 3 and isoform 4. 1 Publication1
Alternative sequenceiVSP_004832219 – 230VCHKI…PGRDY → IKGGVLFPGTDH in isoform 3 and isoform 4. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_004833380 – 427GAAVI…LGCCR → AQVQQ in isoform 1, isoform 3 and isoform 5. 3 PublicationsAdd BLAST48

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
L26318 mRNA Translation: AAA36131.1
U34822 mRNA Translation: AAC50607.1
U35004 mRNA Translation: AAC50610.1
U35005 mRNA Translation: AAC50611.1
DQ234352 mRNA Translation: ABB29981.1
AC016397 Genomic DNA No translation available.
AC074325 Genomic DNA No translation available.
AB451231 mRNA Translation: BAG70045.1
CH471187 Genomic DNA Translation: EAW93132.1
CH471187 Genomic DNA Translation: EAW93129.1
CH471187 Genomic DNA Translation: EAW93130.1
CH471187 Genomic DNA Translation: EAW93133.1
CH471187 Genomic DNA Translation: EAW93134.1
CH471187 Genomic DNA Translation: EAW93136.1
BC144063 mRNA Translation: AAI44064.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS60527.1 [P45983-5]
CCDS7223.1 [P45983-4]
CCDS7224.1 [P45983-1]
CCDS7225.1 [P45983-2]
CCDS7226.1 [P45983-3]

Protein sequence database of the Protein Information Resource

More...PIRi		S71097
S71099

NCBI Reference Sequences

More...RefSeqi		NP_001265476.1, NM_001278547.1 [P45983-4]
NP_001265477.1, NM_001278548.1 [P45983-5]
NP_001310231.1, NM_001323302.1 [P45983-2]
NP_001310250.1, NM_001323321.1 [P45983-3]
NP_001310251.1, NM_001323322.1 [P45983-4]
NP_001310252.1, NM_001323323.1 [P45983-4]
NP_001310253.1, NM_001323324.1 [P45983-2]
NP_001310254.1, NM_001323325.1 [P45983-3]
NP_001310255.1, NM_001323326.1 [P45983-2]
NP_001310256.1, NM_001323327.1 [P45983-2]
NP_001310257.1, NM_001323328.1 [P45983-1]
NP_001310258.1, NM_001323329.1 [P45983-1]
NP_001310259.1, NM_001323330.1 [P45983-4]
NP_001310260.1, NM_001323331.1 [P45983-1]
NP_620634.1, NM_139046.3 [P45983-3]
NP_620637.1, NM_139049.3 [P45983-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000360332; ENSP00000353483; ENSG00000107643 [P45983-5]
ENST00000374176; ENSP00000363291; ENSG00000107643 [P45983-4]
ENST00000374179; ENSP00000363294; ENSG00000107643 [P45983-3]
ENST00000374182; ENSP00000363297; ENSG00000107643 [P45983-2]
ENST00000374189; ENSP00000363304; ENSG00000107643 [P45983-1]
ENST00000395611; ENSP00000378974; ENSG00000107643 [P45983-4]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		5599

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:5599

UCSC genome browser

More...UCSCi		uc001jgm.5 human [P45983-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Wikipedia

C-Jun N-terminal kinases entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L26318 mRNA Translation: AAA36131.1
U34822 mRNA Translation: AAC50607.1
U35004 mRNA Translation: AAC50610.1
U35005 mRNA Translation: AAC50611.1
DQ234352 mRNA Translation: ABB29981.1
AC016397 Genomic DNA No translation available.
AC074325 Genomic DNA No translation available.
AB451231 mRNA Translation: BAG70045.1
CH471187 Genomic DNA Translation: EAW93132.1
CH471187 Genomic DNA Translation: EAW93129.1
CH471187 Genomic DNA Translation: EAW93130.1
CH471187 Genomic DNA Translation: EAW93133.1
CH471187 Genomic DNA Translation: EAW93134.1
CH471187 Genomic DNA Translation: EAW93136.1
BC144063 mRNA Translation: AAI44064.1
CCDSiCCDS60527.1 [P45983-5]
CCDS7223.1 [P45983-4]
CCDS7224.1 [P45983-1]
CCDS7225.1 [P45983-2]
CCDS7226.1 [P45983-3]
PIRiS71097
S71099
RefSeqiNP_001265476.1, NM_001278547.1 [P45983-4]
NP_001265477.1, NM_001278548.1 [P45983-5]
NP_001310231.1, NM_001323302.1 [P45983-2]
NP_001310250.1, NM_001323321.1 [P45983-3]
NP_001310251.1, NM_001323322.1 [P45983-4]
NP_001310252.1, NM_001323323.1 [P45983-4]
NP_001310253.1, NM_001323324.1 [P45983-2]
NP_001310254.1, NM_001323325.1 [P45983-3]
NP_001310255.1, NM_001323326.1 [P45983-2]
NP_001310256.1, NM_001323327.1 [P45983-2]
NP_001310257.1, NM_001323328.1 [P45983-1]
NP_001310258.1, NM_001323329.1 [P45983-1]
NP_001310259.1, NM_001323330.1 [P45983-4]
NP_001310260.1, NM_001323331.1 [P45983-1]
NP_620634.1, NM_139046.3 [P45983-3]
NP_620637.1, NM_139049.3 [P45983-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UKHX-ray2.35A1-363[»]
1UKIX-ray2.70A1-363[»]
2G01X-ray3.50A/B1-364[»]
2GMXX-ray3.50A/B1-364[»]
2H96X-ray3.00A/B1-364[»]
2NO3X-ray3.20A/B1-364[»]
2XRWX-ray1.33A2-364[»]
2XS0X-ray2.60A1-379[»]
3ELJX-ray1.80A1-364[»]
3O17X-ray3.00A/B1-364[»]
3O2MX-ray2.70A/B1-364[»]
3PZEX-ray2.00A7-364[»]
3V3VX-ray2.70A1-366[»]
3VUDX-ray3.50A1-364[»]
3VUGX-ray3.24A1-364[»]
3VUHX-ray2.70A1-364[»]
3VUIX-ray2.80A1-364[»]
3VUKX-ray2.95A1-364[»]
3VULX-ray2.81A1-364[»]
3VUMX-ray2.69A1-364[»]
4AWIX-ray1.91A1-364[»]
4E73X-ray2.27A1-363[»]
4G1WX-ray2.45A1-363[»]
4HYSX-ray2.42A1-363[»]
4HYUX-ray2.15A1-363[»]
4IZYX-ray2.30A1-363[»]
4L7FX-ray1.95A7-362[»]
4QTDX-ray1.50A1-363[»]
4UX9X-ray2.34A/B/C/D1-364[»]
4YR8X-ray2.40A/C/E/F1-363[»]
5LW1X-ray3.20B/E/H2-363[»]
6F5EX-ray2.70B2-363[»]
SMRiP45983
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111585, 187 interactors
DIPiDIP-249N
ELMiP45983
IntActiP45983, 91 interactors
MINTiP45983
STRINGi9606.ENSP00000378974

Chemistry databases

BindingDBiP45983
ChEMBLiCHEMBL2276
DrugBankiDB07268 2-({2-[(3-HYDROXYPHENYL)AMINO]PYRIMIDIN-4-YL}AMINO)BENZAMIDE
GuidetoPHARMACOLOGYi1496

PTM databases

iPTMnetiP45983
PhosphoSitePlusiP45983

Polymorphism and mutation databases

BioMutaiMAPK8
DMDMi2507195

Proteomic databases

EPDiP45983
jPOSTiP45983
MaxQBiP45983
PaxDbiP45983
PeptideAtlasiP45983
PRIDEiP45983
ProteomicsDBi55694
55695 [P45983-2]
55696 [P45983-3]
55697 [P45983-4]

Protocols and materials databases

The DNASU plasmid repository

More...DNASUi		5599
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360332; ENSP00000353483; ENSG00000107643 [P45983-5]
ENST00000374176; ENSP00000363291; ENSG00000107643 [P45983-4]
ENST00000374179; ENSP00000363294; ENSG00000107643 [P45983-3]
ENST00000374182; ENSP00000363297; ENSG00000107643 [P45983-2]
ENST00000374189; ENSP00000363304; ENSG00000107643 [P45983-1]
ENST00000395611; ENSP00000378974; ENSG00000107643 [P45983-4]
GeneIDi5599
KEGGihsa:5599
UCSCiuc001jgm.5 human [P45983-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		5599
DisGeNETi5599

GeneCards: human genes, protein and diseases

More...GeneCardsi		MAPK8
HGNCiHGNC:6881 MAPK8
HPAiCAB004463
CAB069396
MIMi601158 gene
neXtProtiNX_P45983
OpenTargetsiENSG00000107643
PharmGKBiPA283

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG0665 Eukaryota
ENOG410XSHI LUCA
GeneTreeiENSGT00940000153692
HOGENOMiHOG000233024
InParanoidiP45983
KOiK04440
OMAiREFKLMN
OrthoDBi741207at2759
PhylomeDBiP45983
TreeFamiTF105100

Enzyme and pathway databases

BRENDAi2.7.11.24 2681
ReactomeiR-HSA-111446 Activation of BIM and translocation to mitochondria
R-HSA-139910 Activation of BMF and translocation to mitochondria
R-HSA-193648 NRAGE signals death through JNK
R-HSA-205043 NRIF signals cell death from the nucleus
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-376172 DSCAM interactions
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-450341 Activation of the AP-1 family of transcription factors
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-9007892 Interleukin-38 signaling
SignaLinkiP45983
SIGNORiP45983

Miscellaneous databases

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

More...ChiTaRSi		MAPK8 human
EvolutionaryTraceiP45983

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		MAPK8

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

More...GenomeRNAii		5599

Protein Ontology

More...PROi		PR:P45983

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000107643 Expressed in 205 organ(s), highest expression level in forebrain
ExpressionAtlasiP45983 baseline and differential
GenevisibleiP45983 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008351 MAPK_JNK
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01772 JNKMAPKINASE
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01351 MAPK, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		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 nameiMK08_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P45983
Secondary accession number(s): B5BTZ5
, B7ZLV4, D3DX88, D3DX92, Q15709, Q15712, Q15713, Q308M2
<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: November 1, 1995
Last sequence update: November 1, 1997
Last modified: May 8, 2019
This is version 211 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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

Keywords - Technical termi

3D-structure, 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. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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