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Protein

Mitogen-activated protein kinase 12

Gene

MAPK12

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 kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration.7 Publications

<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 PublicationNote: Binds 2 magnesium ions.1 Publication

<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 by phosphorylation on threonine and tyrosine. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK12 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK12 activator in response to TNF-alpha.2 Publications

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=37 µM for ATP1 Publication
  2. KM=313 µM for EGFR substrate peptide1 Publication
  3. KM=254 µM for GST-ATF21 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 sitei56ATPPROSITE-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 sitei153Proton 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 bindingi33 – 41ATPPROSITE-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

    • ATP binding Source: UniProtKB-KW
    • magnesium ion binding Source: UniProtKB
    • MAP kinase activity Source: GO_Central
    • protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionKinase, Serine/threonine-protein kinase, Transferase
    Biological processCell cycle, Stress response, Transcription, Transcription regulation
    LigandATP-binding, Magnesium, Metal-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-168638 NOD1/2 Signaling Pathway
    R-HSA-171007 p38MAPK events
    R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation
    R-HSA-375170 CDO in myogenesis
    R-HSA-376172 DSCAM interactions
    R-HSA-4420097 VEGFA-VEGFR2 Pathway

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

    More...
    SignaLinki
    P53778

    SIGNOR Signaling Network Open Resource

    More...
    SIGNORi
    P53778

    <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 12 (EC:2.7.11.241 Publication)
    Short name:
    MAP kinase 12
    Short name:
    MAPK 12
    Alternative name(s):
    Extracellular signal-regulated kinase 6
    Short name:
    ERK-6
    Mitogen-activated protein kinase p38 gamma
    Short name:
    MAP kinase p38 gamma
    Stress-activated protein kinase 3
    <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:MAPK12
    Synonyms:ERK6, SAPK3
    <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 22

    Organism-specific databases

    Eukaryotic Pathogen Database Resources

    More...
    EuPathDBi
    HostDB:ENSG00000188130.13

    Human Gene Nomenclature Database

    More...
    HGNCi
    HGNC:6874 MAPK12

    Online Mendelian Inheritance in Man (OMIM)

    More...
    MIMi
    602399 gene

    neXtProt; the human protein knowledge platform

    More...
    neXtProti
    NX_P53778

    <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, Mitochondrion, 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 provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

    MAPK is overexpressed in highly metastatic breast cancer cell lines and its expression is preferentially associated with basal-like and metastatic phenotypes of breast tumor samples.

    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>Mutagenesisi179D → A: Emulation of the active state. 1 Publication1
    Mutagenesisi185Y → F: Loss of activity. 1 Publication1
    Mutagenesisi330F → S: No effect. 1 Publication1

    Organism-specific databases

    DisGeNET

    More...
    DisGeNETi
    6300

    Open Targets

    More...
    OpenTargetsi
    ENSG00000188130

    The Pharmacogenetics and Pharmacogenomics Knowledge Base

    More...
    PharmGKBi
    PA30619

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules

    More...
    ChEMBLi
    CHEMBL4674

    Drug and drug target database

    More...
    DrugBanki
    DB05403 CEP-1347
    DB05157 KC706
    DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
    DB02482 Phosphonothreonine

    IUPHAR/BPS Guide to PHARMACOLOGY

    More...
    GuidetoPHARMACOLOGYi
    1501

    Polymorphism and mutation databases

    BioMuta curated single-nucleotide variation and disease association database

    More...
    BioMutai
    MAPK12

    Domain mapping of disease mutations (DMDM)

    More...
    DMDMi
    2851522

    <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_00001862821 – 367Mitogen-activated protein kinase 12Add BLAST367

    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 residuei183Phosphothreonine; by MAP2K3 and MAP2K6By similarity1
    Modified residuei185PhosphotyrosineCombined 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 MAP2K3/MKK3 and MAP2K6/MKK6, which activates the enzyme.2 Publications
    Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    Encyclopedia of Proteome Dynamics

    More...
    EPDi
    P53778

    MaxQB - The MaxQuant DataBase

    More...
    MaxQBi
    P53778

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

    More...
    PaxDbi
    P53778

    PeptideAtlas

    More...
    PeptideAtlasi
    P53778

    PRoteomics IDEntifications database

    More...
    PRIDEi
    P53778

    ProteomicsDB human proteome resource

    More...
    ProteomicsDBi
    56615

    PTM databases

    iPTMnet integrated resource for PTMs in systems biology context

    More...
    iPTMneti
    P53778

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

    More...
    PhosphoSitePlusi
    P53778

    <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

    Highly expressed in skeletal muscle and heart.2 Publications

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

    Expression of MAPK12 is down-regulation by MAPK14 activation.1 Publication

    Gene expression databases

    Bgee dataBase for Gene Expression Evolution

    More...
    Bgeei
    ENSG00000188130 Expressed in 197 organ(s), highest expression level in gastrocnemius

    CleanEx database of gene expression profiles

    More...
    CleanExi
    HS_MAPK12

    ExpressionAtlas, Differential and Baseline Expression

    More...
    ExpressionAtlasi
    P53778 baseline and differential

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...
    Genevisiblei
    P53778 HS

    Organism-specific databases

    Human Protein Atlas

    More...
    HPAi
    CAB025483
    HPA054562

    <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

    Monomer. Interacts with the PDZ domain of the syntrophin SNTA1. Interacts with SH3BP5. Interacts with LIN7C, SCRIB and SYNJ2BP (By similarity).By similarity

    <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

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGrid)

    More...
    BioGridi
    112207, 28 interactors

    CORUM comprehensive resource of mammalian protein complexes

    More...
    CORUMi
    P53778

    Database of interacting proteins

    More...
    DIPi
    DIP-34241N

    Protein interaction database and analysis system

    More...
    IntActi
    P53778, 16 interactors

    Molecular INTeraction database

    More...
    MINTi
    P53778

    STRING: functional protein association networks

    More...
    STRINGi
    9606.ENSP00000215659

    Chemistry databases

    BindingDB database of measured binding affinities

    More...
    BindingDBi
    P53778

    <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

    1367
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

    More...
    ProteinModelPortali
    P53778

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

    More...
    SMRi
    P53778

    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
    P53778

    <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>Domaini27 – 311Protein kinasePROSITE-ProRule annotationAdd BLAST285

    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

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...
    eggNOGi
    KOG0660 Eukaryota
    ENOG410XNY0 LUCA

    Ensembl GeneTree

    More...
    GeneTreei
    ENSGT00940000156189

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...
    HOGENOMi
    HOG000233024

    The HOVERGEN Database of Homologous Vertebrate Genes

    More...
    HOVERGENi
    HBG014652

    InParanoid: Eukaryotic Ortholog Groups

    More...
    InParanoidi
    P53778

    KEGG Orthology (KO)

    More...
    KOi
    K04441

    Identification of Orthologs from Complete Genome Data

    More...
    OMAi
    TVCSAWD

    Database of Orthologous Groups

    More...
    OrthoDBi
    EOG091G08QL

    Database for complete collections of gene phylogenies

    More...
    PhylomeDBi
    P53778

    TreeFam database of animal gene trees

    More...
    TreeFami
    TF105100

    Family and domain databases

    Conserved Domains Database

    More...
    CDDi
    cd07880 STKc_p38gamma, 1 hit

    Integrated resource of protein families, domains and functional sites

    More...
    InterProi
    View protein in InterPro
    IPR011009 Kinase-like_dom_sf
    IPR003527 MAP_kinase_CS
    IPR008352 MAPK_p38-like
    IPR038786 p38gamma
    IPR000719 Prot_kinase_dom
    IPR017441 Protein_kinase_ATP_BS

    Pfam protein domain database

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

    Protein Motif fingerprint database; a protein domain database

    More...
    PRINTSi
    PR01773 P38MAPKINASE

    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
    PS00107 PROTEIN_KINASE_ATP, 1 hit
    PS50011 PROTEIN_KINASE_DOM, 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.

    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 2 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: P53778-1) [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
    MSSPPPARSG FYRQEVTKTA WEVRAVYRDL QPVGSGAYGA VCSAVDGRTG
    60 70 80 90 100
    AKVAIKKLYR PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDETLD
    110 120 130 140 150
    DFTDFYLVMP FMGTDLGKLM KHEKLGEDRI QFLVYQMLKG LRYIHAAGII
    160 170 180 190 200
    HRDLKPGNLA VNEDCELKIL DFGLARQADS EMTGYVVTRW YRAPEVILNW
    210 220 230 240 250
    MRYTQTVDIW SVGCIMAEMI TGKTLFKGSD HLDQLKEIMK VTGTPPAEFV
    260 270 280 290 300
    QRLQSDEAKN YMKGLPELEK KDFASILTNA SPLAVNLLEK MLVLDAEQRV
    310 320 330 340 350
    TAGEALAHPY FESLHDTEDE PQVQKYDDSF DDVDRTLDEW KRVTYKEVLS
    360
    FKPPRQLGAR VSKETPL
    Length:367
    Mass (Da):41,940
    Last modified:July 15, 1998 - v3
    <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:iEF680401D8E40610
    GO
    Isoform 2 (identifier: P53778-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         142-151: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:357
    Mass (Da):40,808
    Checksum:i35F0C4A10EB77B20
    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 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    B5MDL5B5MDL5_HUMAN
    Mitogen-activated protein kinase
    MAPK12 hCG_2039437
    277Annotation score:

    Annotation score:2 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>
    A8MY48A8MY48_HUMAN
    Mitogen-activated protein kinase 12
    MAPK12
    119Annotation 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 conflicti7A → T in CAA55984 (PubMed:8633070).Curated1
    Sequence conflicti70R → L in CAA55984 (PubMed:8633070).Curated1
    Sequence conflicti138L → M in CAA55984 (PubMed:8633070).Curated1
    Sequence conflicti201 – 202MR → IA in CAA55984 (PubMed:8633070).Curated2
    Sequence conflicti261Y → N in AAB40118 (PubMed:8920915).Curated1
    Sequence conflicti297 – 298EQ → DI in CAA55984 (PubMed:8633070).Curated2
    Sequence conflicti300V → L in CAA55984 (PubMed:8633070).Curated1
    Sequence conflicti305A → F in CAA55984 (PubMed:8633070).Curated1
    Sequence conflicti307A → S in CAA55984 (PubMed:8633070).Curated1
    Sequence conflicti332 – 333DV → YF in CAA55984 (PubMed:8633070).Curated2

    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_042265103T → M2 PublicationsCorresponds to variant dbSNP:rs34422484Ensembl.1
    Natural variantiVAR_042266230D → N1 PublicationCorresponds to variant dbSNP:rs35396905Ensembl.1
    Natural variantiVAR_012002244T → M. Corresponds to variant dbSNP:rs2066776Ensembl.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_055224142 – 151Missing in isoform 2. 1 Publication10

    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
    X79483 mRNA Translation: CAA55984.1
    Y10487 mRNA Translation: CAA71511.1
    U66243 mRNA Translation: AAB40118.1
    CR456515 mRNA Translation: CAG30401.1
    AL022328 Genomic DNA No translation available.
    BC015741 mRNA Translation: AAH15741.1

    The Consensus CDS (CCDS) project

    More...
    CCDSi
    CCDS14089.1 [P53778-1]
    CCDS77688.1 [P53778-2]

    Protein sequence database of the Protein Information Resource

    More...
    PIRi
    JC5252
    JC6138

    NCBI Reference Sequences

    More...
    RefSeqi
    NP_001290181.1, NM_001303252.2 [P53778-2]
    NP_002960.2, NM_002969.5 [P53778-1]

    UniGene gene-oriented nucleotide sequence clusters

    More...
    UniGenei
    Hs.432642

    Genome annotation databases

    Ensembl eukaryotic genome annotation project

    More...
    Ensembli
    ENST00000215659; ENSP00000215659; ENSG00000188130 [P53778-1]
    ENST00000622558; ENSP00000479972; ENSG00000188130 [P53778-2]

    Database of genes from NCBI RefSeq genomes

    More...
    GeneIDi
    6300

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...
    KEGGi
    hsa:6300

    UCSC genome browser

    More...
    UCSCi
    uc003bkl.2 human [P53778-1]

    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

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X79483 mRNA Translation: CAA55984.1
    Y10487 mRNA Translation: CAA71511.1
    U66243 mRNA Translation: AAB40118.1
    CR456515 mRNA Translation: CAG30401.1
    AL022328 Genomic DNA No translation available.
    BC015741 mRNA Translation: AAH15741.1
    CCDSiCCDS14089.1 [P53778-1]
    CCDS77688.1 [P53778-2]
    PIRiJC5252
    JC6138
    RefSeqiNP_001290181.1, NM_001303252.2 [P53778-2]
    NP_002960.2, NM_002969.5 [P53778-1]
    UniGeneiHs.432642

    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
    1CM8X-ray2.40A/B1-367[»]
    4QUMX-ray2.52B182-190[»]
    ProteinModelPortaliP53778
    SMRiP53778
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi112207, 28 interactors
    CORUMiP53778
    DIPiDIP-34241N
    IntActiP53778, 16 interactors
    MINTiP53778
    STRINGi9606.ENSP00000215659

    Chemistry databases

    BindingDBiP53778
    ChEMBLiCHEMBL4674
    DrugBankiDB05403 CEP-1347
    DB05157 KC706
    DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
    DB02482 Phosphonothreonine
    GuidetoPHARMACOLOGYi1501

    PTM databases

    iPTMnetiP53778
    PhosphoSitePlusiP53778

    Polymorphism and mutation databases

    BioMutaiMAPK12
    DMDMi2851522

    Proteomic databases

    EPDiP53778
    MaxQBiP53778
    PaxDbiP53778
    PeptideAtlasiP53778
    PRIDEiP53778
    ProteomicsDBi56615

    Protocols and materials databases

    The DNASU plasmid repository

    More...
    DNASUi
    6300
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000215659; ENSP00000215659; ENSG00000188130 [P53778-1]
    ENST00000622558; ENSP00000479972; ENSG00000188130 [P53778-2]
    GeneIDi6300
    KEGGihsa:6300
    UCSCiuc003bkl.2 human [P53778-1]

    Organism-specific databases

    Comparative Toxicogenomics Database

    More...
    CTDi
    6300
    DisGeNETi6300
    EuPathDBiHostDB:ENSG00000188130.13

    GeneCards: human genes, protein and diseases

    More...
    GeneCardsi
    MAPK12
    HGNCiHGNC:6874 MAPK12
    HPAiCAB025483
    HPA054562
    MIMi602399 gene
    neXtProtiNX_P53778
    OpenTargetsiENSG00000188130
    PharmGKBiPA30619

    GenAtlas: human gene database

    More...
    GenAtlasi
    Search...

    Phylogenomic databases

    eggNOGiKOG0660 Eukaryota
    ENOG410XNY0 LUCA
    GeneTreeiENSGT00940000156189
    HOGENOMiHOG000233024
    HOVERGENiHBG014652
    InParanoidiP53778
    KOiK04441
    OMAiTVCSAWD
    OrthoDBiEOG091G08QL
    PhylomeDBiP53778
    TreeFamiTF105100

    Enzyme and pathway databases

    BRENDAi2.7.11.24 2681
    ReactomeiR-HSA-168638 NOD1/2 Signaling Pathway
    R-HSA-171007 p38MAPK events
    R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation
    R-HSA-375170 CDO in myogenesis
    R-HSA-376172 DSCAM interactions
    R-HSA-4420097 VEGFA-VEGFR2 Pathway
    SignaLinkiP53778
    SIGNORiP53778

    Miscellaneous databases

    EvolutionaryTraceiP53778

    The Gene Wiki collection of pages on human genes and proteins

    More...
    GeneWikii
    MAPK12

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

    More...
    GenomeRNAii
    6300

    Protein Ontology

    More...
    PROi
    PR:P53778

    The Stanford Online Universal Resource for Clones and ESTs

    More...
    SOURCEi
    Search...

    Gene expression databases

    BgeeiENSG00000188130 Expressed in 197 organ(s), highest expression level in gastrocnemius
    CleanExiHS_MAPK12
    ExpressionAtlasiP53778 baseline and differential
    GenevisibleiP53778 HS

    Family and domain databases

    CDDicd07880 STKc_p38gamma, 1 hit
    InterProiView protein in InterPro
    IPR011009 Kinase-like_dom_sf
    IPR003527 MAP_kinase_CS
    IPR008352 MAPK_p38-like
    IPR038786 p38gamma
    IPR000719 Prot_kinase_dom
    IPR017441 Protein_kinase_ATP_BS
    PfamiView protein in Pfam
    PF00069 Pkinase, 1 hit
    PRINTSiPR01773 P38MAPKINASE
    SMARTiView protein in SMART
    SM00220 S_TKc, 1 hit
    SUPFAMiSSF56112 SSF56112, 1 hit
    PROSITEiView protein in PROSITE
    PS01351 MAPK, 1 hit
    PS00107 PROTEIN_KINASE_ATP, 1 hit
    PS50011 PROTEIN_KINASE_DOM, 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 nameiMK12_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: P53778
    Secondary accession number(s): Q14260
    , Q6IC53, Q99588, Q99672
    <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: October 1, 1996
    Last sequence update: July 15, 1998
    Last modified: December 5, 2018
    This is version 199 of the entry and version 3 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 22
      Human chromosome 22: 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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