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Protein

Dual specificity mitogen-activated protein kinase kinase 4

Gene

MAP2K4

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

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.1 Publication

<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 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 in response to a variety of cellular stresses, including UV and gamma-irradiation, heat shock, hyperosmolarity, T-cell receptor stimulation, peroxide and inflammatory cytokines. Also activated by developmental cues. MAP2K4/MKK4 is activated by the majority of MKKKs, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K7/TAK1, MAP3K10/MLK2, MAP3K11/MLK3, MAP3K12/DLK and MAP3K13/LZK.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ 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 sitei131ATPPROSITE-ProRule annotation1
<p>This subsection of the ‘Function’ 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 sitei229Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ 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 bindingi108 – 116ATPPROSITE-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, Tyrosine-protein kinase
Biological processApoptosis, Stress response
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...
BRENDAi
2.7.12.2 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-5210891 Uptake and function of anthrax toxins
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation

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

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SignaLinki
P45985

SIGNOR Signaling Network Open Resource

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SIGNORi
P45985

<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:
Dual specificity mitogen-activated protein kinase kinase 4 (EC:2.7.12.2)
Short name:
MAP kinase kinase 4
Short name:
MAPKK 4
Alternative name(s):
JNK-activating kinase 1
MAPK/ERK kinase 4
Short name:
MEK 4
SAPK/ERK kinase 1
Short name:
SEK1
Stress-activated protein kinase kinase 1
Short name:
SAPK kinase 1
Short name:
SAPKK-1
Short name:
SAPKK1
c-Jun N-terminal kinase kinase 1
Short name:
JNKK
<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:MAP2K4
Synonyms:JNKK1, MEK4, MKK4, PRKMK4, SEK1, SERK1, SKK1
<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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<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 17

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000065559.14

Human Gene Nomenclature Database

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HGNCi
HGNC:6844 MAP2K4

Online Mendelian Inheritance in Man (OMIM)

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MIMi
601335 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P45985

<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; 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

Organism-specific databases

DisGeNET

More...
DisGeNETi
6416

Open Targets

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OpenTargetsi
ENSG00000065559

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA30589

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL2897

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2065

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
MAP2K4

Domain mapping of disease mutations (DMDM)

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DMDMi
1170596

<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 <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedCombined sources
<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_00000863812 – 399Dual specificity mitogen-activated protein kinase kinase 4Add BLAST398

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 residuei2N-acetylalanineCombined sources1
Modified residuei58Asymmetric dimethylarginine; alternateCombined sources1
Modified residuei58Omega-N-methylarginine; alternateCombined sources1
Modified residuei90PhosphoserineCombined sources1
Modified residuei257Phosphoserine; by MAP3KCombined sources1
Modified residuei261Phosphothreonine; by MAP3K1 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

Activated by phosphorylation on Ser-257 and Thr-261 by MAP kinase kinase kinases (MAP3Ks).1 Publication

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>Sitei45 – 46Cleavage; by anthrax lethal factor2
Sitei58 – 59Cleavage; by anthrax lethal factor2

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P45985

MaxQB - The MaxQuant DataBase

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MaxQBi
P45985

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

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PaxDbi
P45985

PeptideAtlas

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PeptideAtlasi
P45985

PRoteomics IDEntifications database

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PRIDEi
P45985

ProteomicsDB human proteome resource

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ProteomicsDBi
55703
55704 [P45985-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P45985

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

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PhosphoSitePlusi
P45985

Miscellaneous databases

CutDB - Proteolytic event database

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PMAP-CutDBi
P45985

<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

Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000065559 Expressed in 227 organ(s), highest expression level in frontal cortex

CleanEx database of gene expression profiles

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CleanExi
HS_MAP2K4

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P45985 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P45985 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB007751
HPA060074

<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

Interacts with SPAG9 (By similarity). Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAPK11 and MAPK14. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with ARRB1, ARRB2 and MAPK8IP3/JIP3.By similarity5 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

WithEntry#Exp.IntActNotes
MAP3K1Q132333EBI-447868,EBI-49776

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
112315, 43 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
P45985

Protein interaction database and analysis system

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IntActi
P45985, 17 interactors

Molecular INTeraction database

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MINTi
P45985

STRING: functional protein association networks

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STRINGi
9606.ENSP00000262445

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P45985

<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

1399
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P45985

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

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SMRi
P45985

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P45985

<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>Domaini102 – 367Protein kinasePROSITE-ProRule annotationAdd BLAST266

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>Regioni37 – 52D domainAdd BLAST16
Regioni364 – 387DVD domainAdd BLAST24

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi5 – 19Gly/Ser-richAdd BLAST15

<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 DVD domain (residues 364-387) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.
The D domain (residues 34-52) contains a conserved docking site and is required for the binding to MAPK substrates.

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

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0984 Eukaryota
ENOG410XT3F LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000154744

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG108518

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P45985

KEGG Orthology (KO)

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KOi
K04430

Identification of Orthologs from Complete Genome Data

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OMAi
TCLIKDE

Database of Orthologous Groups

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OrthoDBi
EOG091G0A9H

Database for complete collections of gene phylogenies

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PhylomeDBi
P45985

TreeFam database of animal gene trees

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TreeFami
TF350701

Family and domain databases

Integrated resource of protein families, domains and functional sites

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

Pfam protein domain database

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Pfami
View protein in Pfam
PF00069 Pkinase, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00220 S_TKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

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

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)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.

<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 in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <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 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P45985-1) [UniParc]FASTAAdd to basket

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
MAAPSPSGGG GSGGGSGSGT PGPVGSPAPG HPAVSSMQGK RKALKLNFAN
60 70 80 90 100
PPFKSTARFT LNPNPTGVQN PHIERLRTHS IESSGKLKIS PEQHWDFTAE
110 120 130 140 150
DLKDLGEIGR GAYGSVNKMV HKPSGQIMAV KRIRSTVDEK EQKQLLMDLD
160 170 180 190 200
VVMRSSDCPY IVQFYGALFR EGDCWICMEL MSTSFDKFYK YVYSVLDDVI
210 220 230 240 250
PEEILGKITL ATVKALNHLK ENLKIIHRDI KPSNILLDRS GNIKLCDFGI
260 270 280 290 300
SGQLVDSIAK TRDAGCRPYM APERIDPSAS RQGYDVRSDV WSLGITLYEL
310 320 330 340 350
ATGRFPYPKW NSVFDQLTQV VKGDPPQLSN SEEREFSPSF INFVNLCLTK
360 370 380 390
DESKRPKYKE LLKHPFILMY EERAVEVACY VCKILDQMPA TPSSPMYVD
Length:399
Mass (Da):44,288
Last modified:November 1, 1995 - 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:iA472537F2F26770B
GO
Isoform 2 (identifier: P45985-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     39-39: G → GFQINFCEKAQS

Note: No experimental confirmation available.
Show »
Length:410
Mass (Da):45,584
Checksum:i097F8966398DD6C0
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 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
R4GN37R4GN37_HUMAN
Dual-specificity mitogen-activated ...
MAP2K4
92Annotation 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>
J3QLE2J3QLE2_HUMAN
Dual-specificity mitogen-activated ...
MAP2K4
45Annotation 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>
R4GN68R4GN68_HUMAN
Dual-specificity mitogen-activated ...
MAP2K4
41Annotation 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>
K7EP58K7EP58_HUMAN
Dual-specificity mitogen-activated ...
MAP2K4
16Annotation 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 conflicti118K → R in CAG38801 (Ref. 4) Curated1
Sequence conflicti179E → G in BAG35884 (PubMed:14702039).Curated1
Sequence conflicti356P → L in AAH60764 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_06296316S → R1 PublicationCorresponds to variant dbSNP:rs17855590Ensembl.1
Natural variantiVAR_040818142Q → L in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040819154R → W in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040820234N → I in an ovarian serous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040821251S → N in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040822279A → T in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs753665559Ensembl.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. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_03883839G → GFQINFCEKAQS in isoform 2. 1 Publication1

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
L36870 mRNA Translation: AAC41719.1
U17743 mRNA Translation: AAC50127.1
AF070090
, AF070080, AF070081, AF070082, AF070083, AF070084, AF070085, AF070086, AF070087, AF070088, AF070089 Genomic DNA Translation: AAC24130.1
CR536564 mRNA Translation: CAG38801.1
BT019676 mRNA Translation: AAV38482.1
AK131544 mRNA Translation: BAG54774.1
AK313053 mRNA Translation: BAG35884.1
DQ015703 Genomic DNA Translation: AAY22176.1
AC005244 Genomic DNA No translation available.
AC005410 Genomic DNA No translation available.
CH471108 Genomic DNA Translation: EAW89975.1
CH471108 Genomic DNA Translation: EAW89974.1
CH471108 Genomic DNA Translation: EAW89976.1
BC036032 mRNA Translation: AAH36032.1
BC060764 mRNA Translation: AAH60764.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS11162.1 [P45985-1]
CCDS62095.1 [P45985-2]

Protein sequence database of the Protein Information Resource

More...
PIRi
I38901

NCBI Reference Sequences

More...
RefSeqi
NP_001268364.1, NM_001281435.1 [P45985-2]
NP_003001.1, NM_003010.3 [P45985-1]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.514681

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000353533; ENSP00000262445; ENSG00000065559 [P45985-1]
ENST00000415385; ENSP00000410402; ENSG00000065559 [P45985-2]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
6416

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:6416

UCSC genome browser

More...
UCSCi
uc002gnj.5 human [P45985-1]

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

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36870 mRNA Translation: AAC41719.1
U17743 mRNA Translation: AAC50127.1
AF070090
, AF070080, AF070081, AF070082, AF070083, AF070084, AF070085, AF070086, AF070087, AF070088, AF070089 Genomic DNA Translation: AAC24130.1
CR536564 mRNA Translation: CAG38801.1
BT019676 mRNA Translation: AAV38482.1
AK131544 mRNA Translation: BAG54774.1
AK313053 mRNA Translation: BAG35884.1
DQ015703 Genomic DNA Translation: AAY22176.1
AC005244 Genomic DNA No translation available.
AC005410 Genomic DNA No translation available.
CH471108 Genomic DNA Translation: EAW89975.1
CH471108 Genomic DNA Translation: EAW89974.1
CH471108 Genomic DNA Translation: EAW89976.1
BC036032 mRNA Translation: AAH36032.1
BC060764 mRNA Translation: AAH60764.1
CCDSiCCDS11162.1 [P45985-1]
CCDS62095.1 [P45985-2]
PIRiI38901
RefSeqiNP_001268364.1, NM_001281435.1 [P45985-2]
NP_003001.1, NM_003010.3 [P45985-1]
UniGeneiHs.514681

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
3ALNX-ray2.30A/B/C80-399[»]
3ALOX-ray2.60A80-399[»]
3VUTX-ray3.50A/B80-399[»]
ProteinModelPortaliP45985
SMRiP45985
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112315, 43 interactors
CORUMiP45985
IntActiP45985, 17 interactors
MINTiP45985
STRINGi9606.ENSP00000262445

Chemistry databases

BindingDBiP45985
ChEMBLiCHEMBL2897
GuidetoPHARMACOLOGYi2065

PTM databases

iPTMnetiP45985
PhosphoSitePlusiP45985

Polymorphism and mutation databases

BioMutaiMAP2K4
DMDMi1170596

Proteomic databases

EPDiP45985
MaxQBiP45985
PaxDbiP45985
PeptideAtlasiP45985
PRIDEiP45985
ProteomicsDBi55703
55704 [P45985-2]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
6416
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000353533; ENSP00000262445; ENSG00000065559 [P45985-1]
ENST00000415385; ENSP00000410402; ENSG00000065559 [P45985-2]
GeneIDi6416
KEGGihsa:6416
UCSCiuc002gnj.5 human [P45985-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
6416
DisGeNETi6416
EuPathDBiHostDB:ENSG00000065559.14

GeneCards: human genes, protein and diseases

More...
GeneCardsi
MAP2K4
HGNCiHGNC:6844 MAP2K4
HPAiCAB007751
HPA060074
MIMi601335 gene
neXtProtiNX_P45985
OpenTargetsiENSG00000065559
PharmGKBiPA30589

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG0984 Eukaryota
ENOG410XT3F LUCA
GeneTreeiENSGT00940000154744
HOVERGENiHBG108518
InParanoidiP45985
KOiK04430
OMAiTCLIKDE
OrthoDBiEOG091G0A9H
PhylomeDBiP45985
TreeFamiTF350701

Enzyme and pathway databases

BRENDAi2.7.12.2 2681
ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-5210891 Uptake and function of anthrax toxins
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
SignaLinkiP45985
SIGNORiP45985

Miscellaneous databases

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

More...
ChiTaRSi
MAP2K4 human
EvolutionaryTraceiP45985

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
MAP2K4

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

More...
GenomeRNAii
6416
PMAP-CutDBiP45985

Protein Ontology

More...
PROi
PR:P45985

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000065559 Expressed in 227 organ(s), highest expression level in frontal cortex
CleanExiHS_MAP2K4
ExpressionAtlasiP45985 baseline and differential
GenevisibleiP45985 HS

Family and domain databases

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

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 nameiMP2K4_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: P45985
Secondary accession number(s): B2R7N7
, B3KYB2, D3DTS5, Q5U0B8, Q6FHX4, Q6P9H2, Q6PIE6
<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, 1995
Last modified: December 5, 2018
This is version 190 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
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 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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