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Protein

Mitogen-activated protein kinase 14

Gene

Mapk14

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 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. 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 which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Phosphorylates S100A9 at 'Thr-113' (By similarity).By similarity4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Cofactori

Enzyme regulationi

Activated by cell stresses such as DNA damage, heat shock, osmotic shock, anisomycin and sodium arsenite, as well as pro-inflammatory stimuli such as bacterial lipopolysaccharide (LPS) and interleukin-1. Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6, and potentially also MAP2K4/MKK4, as well as by TAB1-mediated autophosphorylation. MAPK14 phosphorylated on both Thr-180 and Tyr-182 is 10-20-fold more active than MAPK14 phosphorylated only on Thr-180, whereas MAPK14 phosphorylated on Tyr-182 alone is inactive. whereas Thr-180 is necessary for catalysis, Tyr-182 may be required for auto-activation and substrate recognition. Phosphorylated at Tyr-323 by ZAP70 in an alternative activation pathway in response to TCR signaling in T-cells. This alternative pathway is inhibited by GADD45A. Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. Specifically inhibited by the binding of pyridinyl-imidazole compounds, which are cytokine-suppressive anti-inflammatory drugs (CSAID). SB203580 is an inhibitor of MAPK14.3 Publications

Kineticsi

  1. KM=212 µM for ATP (when both Thr-180 and Tyr-182 are phosphorylated)1 Publication
  2. KM=1669 µM for ATP (when only Thr-180 is phosphorylated)1 Publication
  3. KM=656 µM for EGFR peptide as a substrate (when both Thr-180 and Tyr-182 are phosphorylated)1 Publication
  4. KM=2800 µM for EGFR peptide as a substrate (when only Thr-180 is phosphorylated)1 Publication
  5. KM=2.03 µM for ATF2 as a substrate (when both Thr-180 and Tyr-182 are phosphorylated)1 Publication
  6. KM=20.1 µM for ATF2 as a substrate (when only Thr-180 is phosphorylated)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei32Inhibitor2 Publications1
    Binding sitei35Inhibitor2 Publications1
    Binding sitei53ATPPROSITE-ProRule annotation1
    Binding sitei53Inhibitor2 Publications1
    Binding sitei71Inhibitor2 Publications1
    Binding sitei109Inhibitor; via amide nitrogen and carbonyl oxygen2 Publications1
    Binding sitei111Inhibitor; via amide nitrogen2 Publications1
    Active sitei168Proton acceptorPROSITE-ProRule annotation1
    Binding sitei168Inhibitor2 Publications1
    Binding sitei169Inhibitor; via carbonyl oxygen2 Publications1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi30 – 38ATPPROSITE-ProRule annotation9

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • enzyme binding Source: MGI
    • kinase activity Source: MGI
    • MAP kinase activity Source: UniProtKB
    • NFAT protein binding Source: BHF-UCL
    • protein kinase activity Source: MGI
    • protein phosphatase binding Source: MGI
    • protein serine/threonine kinase activity Source: MGI

    GO - Biological processi

    • angiogenesis Source: MGI
    • apoptotic process Source: UniProtKB-KW
    • cartilage condensation Source: AgBase
    • cell morphogenesis Source: MGI
    • cellular response to DNA damage stimulus Source: MGI
    • cellular response to ionizing radiation Source: MGI
    • cellular response to lipopolysaccharide Source: MGI
    • cellular response to vascular endothelial growth factor stimulus Source: MGI
    • cellular response to virus Source: MGI
    • chondrocyte differentiation Source: AgBase
    • DNA damage checkpoint Source: MGI
    • fatty acid oxidation Source: MGI
    • glucose metabolic process Source: MGI
    • intracellular signal transduction Source: UniProtKB
    • lipopolysaccharide-mediated signaling pathway Source: MGI
    • mitochondrion organization Source: Reactome
    • myoblast differentiation involved in skeletal muscle regeneration Source: MGI
    • negative regulation of canonical Wnt signaling pathway Source: AgBase
    • osteoclast differentiation Source: BHF-UCL
    • p38MAPK cascade Source: UniProtKB
    • peptidyl-serine phosphorylation Source: BHF-UCL
    • placenta development Source: MGI
    • positive regulation of brown fat cell differentiation Source: MGI
    • positive regulation of cardiac muscle cell proliferation Source: MGI
    • positive regulation of cyclase activity Source: MGI
    • positive regulation of erythrocyte differentiation Source: MGI
    • positive regulation of gene expression Source: MGI
    • positive regulation of glucose import Source: MGI
    • positive regulation of interleukin-12 secretion Source: MGI
    • positive regulation of muscle cell differentiation Source: Reactome
    • positive regulation of myoblast differentiation Source: UniProtKB
    • positive regulation of myoblast fusion Source: UniProtKB
    • positive regulation of myotube differentiation Source: UniProtKB
    • positive regulation of protein import into nucleus Source: MGI
    • positive regulation of reactive oxygen species metabolic process Source: MGI
    • positive regulation of transcription from RNA polymerase II promoter Source: MGI
    • protein phosphorylation Source: MGI
    • regulation of cytokine production involved in inflammatory response Source: MGI
    • regulation of mRNA stability Source: Reactome
    • regulation of ossification Source: MGI
    • regulation of transcription, DNA-templated Source: MGI
    • regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    • response to lipopolysaccharide Source: MGI
    • response to muramyl dipeptide Source: MGI
    • response to muscle stretch Source: MGI
    • signal transduction in response to DNA damage Source: MGI
    • skeletal muscle tissue development Source: MGI
    • stress-induced premature senescence Source: MGI
    • striated muscle cell differentiation Source: MGI
    • transcription, DNA-templated Source: UniProtKB-KW
    • transmembrane receptor protein serine/threonine kinase signaling pathway Source: MGI
    • vascular endothelial growth factor receptor signaling pathway Source: MGI
    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Stress response, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.24. 3474.
    ReactomeiR-MMU-168638. NOD1/2 Signaling Pathway.
    R-MMU-171007. p38MAPK events.
    R-MMU-198753. ERK/MAPK targets.
    R-MMU-2151209. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
    R-MMU-2559580. Oxidative Stress Induced Senescence.
    R-MMU-375170. CDO in myogenesis.
    R-MMU-376172. DSCAM interactions.
    R-MMU-418592. ADP signalling through P2Y purinoceptor 1.
    R-MMU-432142. Platelet sensitization by LDL.
    R-MMU-4420097. VEGFA-VEGFR2 Pathway.
    R-MMU-450302. activated TAK1 mediates p38 MAPK activation.
    R-MMU-450341. Activation of the AP-1 family of transcription factors.
    R-MMU-450604. KSRP (KHSRP) binds and destabilizes mRNA.
    R-MMU-6798695. Neutrophil degranulation.
    R-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.
    SABIO-RKP47811.
    SIGNORiP47811.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase 14 (EC:2.7.11.242 Publications)
    Short name:
    MAP kinase 14
    Short name:
    MAPK 14
    Alternative name(s):
    CRK1
    Mitogen-activated protein kinase p38 alpha
    Short name:
    MAP kinase p38 alpha
    Gene namesi
    Name:Mapk14
    Synonyms:Crk1, Csbp1, Csbp2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 17

    Organism-specific databases

    MGIiMGI:1346865. Mapk14.

    Subcellular locationi

    • Cytoplasm 1 Publication
    • Nucleus 1 Publication

    GO - Cellular componenti

    • cell Source: MGI
    • cytoplasm Source: UniProtKB
    • cytosol Source: MGI
    • extracellular exosome Source: MGI
    • mitochondrion Source: MGI
    • nucleoplasm Source: MGI
    • nucleus Source: UniProtKB
    • spindle pole Source: MGI
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi180T → A: Phosphorylation blocked. 1 Publication1
    Mutagenesisi182Y → F: Phosphorylation blocked. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL2336.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedBy similarity
    ChainiPRO_00001862922 – 360Mitogen-activated protein kinase 14Add BLAST359

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylserineBy similarity1
    Modified residuei2PhosphoserineBy similarity1
    Modified residuei16PhosphothreonineBy similarity1
    Modified residuei53N6-acetyllysineBy similarity1
    Modified residuei152N6-acetyllysineBy similarity1
    Modified residuei180PhosphothreonineCombined sources1 Publication1
    Modified residuei180Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and autocatalysisBy similarity1
    Modified residuei182PhosphotyrosineCombined sources1 Publication1
    Modified residuei182Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and autocatalysisBy similarity1
    Modified residuei323Phosphotyrosine; by ZAP70By similarity1

    Post-translational modificationi

    Dually phosphorylated on Thr-180 and Tyr-182 by the MAP2Ks MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6 in response to inflammatory cytokines, environmental stress or growth factors, which activates the enzyme. Dual phosphorylation can also be mediated by TAB1-mediated autophosphorylation. TCR engagement in T-cells also leads to Tyr-323 phosphorylation by ZAP70. Dephosphorylated and inactivated by DUPS1, DUSP10 and DUSP16. PPM1D also mediates dephosphorylation and inactivation of MAPK14 (By similarity).By similarity2 Publications
    Acetylated at Lys-53 and Lys-152 by KAT2B and EP300. Acetylation at Lys-53 increases the affinity for ATP and enhances kinase activity. Lys-53 and Lys-152 are deacetylated by HDAC3 (By similarity).By similarity
    Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway (By similarity).By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    EPDiP47811.
    MaxQBiP47811.
    PaxDbiP47811.
    PeptideAtlasiP47811.
    PRIDEiP47811.

    PTM databases

    iPTMnetiP47811.
    PhosphoSitePlusiP47811.

    Expressioni

    Tissue specificityi

    Macrophages, monocytes, T- and B-lymphocytes. Isoform 2 is specifically expressed in kidney and liver.

    Gene expression databases

    BgeeiENSMUSG00000053436.
    CleanExiMM_MAPK14.
    ExpressionAtlasiP47811. baseline and differential.
    GenevisibleiP47811. MM.

    Interactioni

    Subunit structurei

    Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK (By similarity). Binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR (By similarity). This interaction retains MAPK14 in the cytoplasm and prevents nuclear accumulation (By similarity). Interacts with SPAG9 and GADD45A (By similarity). Interacts with CDC25B, CDC25C, DUSP1, DUSP10, DUSP16, NP60, SUPT20H and TAB1. Interacts with casein kinase II subunits CSNK2A1 and CSNK2B. Interacts with PPM1D. Interacts with CDK5RAP3; recruits PPM1D to MAPK14 and may regulate its dephosphorylation (By similarity).By similarity6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    DUSP9Q999562EBI-298727,EBI-3906678From a different organism.
    Lcp1Q612335EBI-298727,EBI-309345
    Mapk11Q9WUI110EBI-298727,EBI-645081
    Mapkapk2P491382EBI-298727,EBI-298776
    PTPN7P352362EBI-298727,EBI-2265723From a different organism.
    Slc12a2P550122EBI-298727,EBI-621078
    Stk39Q9Z1W92EBI-298727,EBI-444764

    GO - Molecular functioni

    • enzyme binding Source: MGI
    • NFAT protein binding Source: BHF-UCL
    • protein phosphatase binding Source: MGI

    Protein-protein interaction databases

    BioGridi204969. 22 interactors.
    DIPiDIP-31073N.
    IntActiP47811. 26 interactors.
    MINTiMINT-1204448.
    STRINGi10090.ENSMUSP00000004990.

    Chemistry databases

    BindingDBiP47811.

    Structurei

    Secondary structure

    1360
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi8 – 13Combined sources6
    Beta strandi16 – 21Combined sources6
    Beta strandi24 – 30Combined sources7
    Helixi31 – 33Combined sources3
    Beta strandi34 – 43Combined sources10
    Turni44 – 46Combined sources3
    Beta strandi49 – 54Combined sources6
    Helixi62 – 77Combined sources16
    Beta strandi87 – 90Combined sources4
    Helixi96 – 98Combined sources3
    Beta strandi103 – 107Combined sources5
    Beta strandi110 – 112Combined sources3
    Helixi113 – 117Combined sources5
    Helixi124 – 143Combined sources20
    Helixi153 – 155Combined sources3
    Beta strandi156 – 158Combined sources3
    Beta strandi164 – 166Combined sources3
    Beta strandi172 – 175Combined sources4
    Helixi176 – 180Combined sources5
    Beta strandi182 – 184Combined sources3
    Helixi185 – 188Combined sources4
    Helixi191 – 194Combined sources4
    Beta strandi197 – 199Combined sources3
    Helixi203 – 218Combined sources16
    Helixi228 – 239Combined sources12
    Helixi244 – 247Combined sources4
    Helixi253 – 261Combined sources9
    Helixi270 – 272Combined sources3
    Turni274 – 276Combined sources3
    Helixi279 – 288Combined sources10
    Helixi293 – 295Combined sources3
    Helixi299 – 303Combined sources5
    Helixi306 – 308Combined sources3
    Turni309 – 311Combined sources3
    Helixi314 – 316Combined sources3
    Helixi326 – 329Combined sources4
    Helixi334 – 346Combined sources13

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1LEWX-ray2.30A13-360[»]
    1LEZX-ray2.30A1-360[»]
    1P38X-ray2.10A1-360[»]
    1YW2X-ray2.01A1-360[»]
    1YWRX-ray1.95A1-360[»]
    2EWAX-ray2.10A1-360[»]
    2GHLX-ray2.10A5-352[»]
    2GHMX-ray2.35A5-352[»]
    2GTMX-ray1.90A5-352[»]
    2GTNX-ray1.80A5-352[»]
    2OZAX-ray2.70B2-360[»]
    2PUUX-ray2.50A5-352[»]
    3P4KX-ray2.30A1-360[»]
    3P5KX-ray2.09A2-360[»]
    3P78X-ray2.30A2-360[»]
    3P79X-ray2.10A2-360[»]
    3P7AX-ray2.31A2-360[»]
    3P7BX-ray1.90A2-360[»]
    3P7CX-ray2.30A2-360[»]
    3PY3X-ray2.10A1-360[»]
    3TG1X-ray2.71A1-360[»]
    4KA3X-ray2.71A1-360[»]
    4LOOX-ray1.95A1-360[»]
    4LOPX-ray2.05A/B/C/D1-360[»]
    4LOQX-ray2.32A/B/C/D1-360[»]
    4TYHX-ray3.00B6-353[»]
    5LARX-ray1.50A1-360[»]
    ProteinModelPortaliP47811.
    SMRiP47811.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP47811.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini24 – 308Protein kinasePROSITE-ProRule annotationAdd BLAST285

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni106 – 111Inhibitor-binding6

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi180 – 182TXY3

    Domaini

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

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiKOG0660. Eukaryota.
    ENOG410XNY0. LUCA.
    GeneTreeiENSGT00550000074271.
    HOVERGENiHBG014652.
    InParanoidiP47811.
    KOiK04441.
    OMAiIQSLAQM.
    OrthoDBiEOG091G08QL.
    PhylomeDBiP47811.
    TreeFamiTF105100.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR003527. MAP_kinase_CS.
    IPR008352. MAPK_p38.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    PRINTSiPR01773. P38MAPKINASE.
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS01351. MAPK. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P47811-1) [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
    MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGHRV
    60 70 80 90 100
    AVKKLSRPFQ SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN
    110 120 130 140 150
    DVYLVTHLMG ADLNNIVKCQ KLTDDHVQFL IYQILRGLKY IHSADIIHRD
    160 170 180 190 200
    LKPSNLAVNE DCELKILDFG LARHTDDEMT GYVATRWYRA PEIMLNWMHY
    210 220 230 240 250
    NQTVDIWSVG CIMAELLTGR TLFPGTDHID QLKLILRLVG TPGAELLKKI
    260 270 280 290 300
    SSESARNYIQ SLAQMPKMNF ANVFIGANPL AVDLLEKMLV LDSDKRITAA
    310 320 330 340 350
    QALAHAYFAQ YHDPDDEPVA DPYDQSFESR DLLIDEWKSL TYDEVISFVP
    360
    PPLDQEEMES
    Length:360
    Mass (Da):41,287
    Last modified:January 23, 2007 - v3
    Checksum:iDFB03EBCE97BB51A
    GO
    Isoform 2 (identifier: P47811-2) [UniParc]FASTAAdd to basket
    Also known as: Piccolo

    The sequence of this isoform differs from the canonical sequence as follows:
         255-278: ARNYIQSLAQMPKMNFANVFIGAN → DAK
         279-360: Missing.

    Show »
    Length:257
    Mass (Da):29,540
    Checksum:iABDF65DC32AF0387
    GO
    Isoform 3 (identifier: P47811-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         230-254: DQLKLILRLVGTPGAELLKKISSES → NQLQQIMRLTGTPPAYLINRMPSHE

    Show »
    Length:360
    Mass (Da):41,487
    Checksum:iF1F20352F76590BD
    GO
    Isoform 4 (identifier: P47811-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-77: Missing.

    Show »
    Length:283
    Mass (Da):32,327
    Checksum:i895D71CB69550519
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti98E → G in AAF06348 (Ref. 7) Curated1
    Sequence conflicti107 – 108HL → LS in AAF06348 (Ref. 7) Curated2
    Sequence conflicti115N → R in AAF06348 (Ref. 7) Curated1
    Sequence conflicti124D → G in AAF06348 (Ref. 7) Curated1
    Sequence conflicti159 – 162NEDC → TQVI in AAF06348 (Ref. 7) Curated4
    Sequence conflicti166I → L in AAF06348 (Ref. 7) Curated1
    Sequence conflicti202Q → R in AAF06348 (Ref. 7) Curated1
    Sequence conflicti211 – 212CI → GF in AAF06348 (Ref. 7) Curated2
    Sequence conflicti224P → L in AAF06348 (Ref. 7) Curated1
    Sequence conflicti271A → P in AAF06348 (Ref. 7) Curated1
    Sequence conflicti299A → V in AAF06348 (Ref. 7) Curated1
    Sequence conflicti315D → Y in AAF06348 (Ref. 7) Curated1
    Isoform 3 (identifier: P47811-3)
    Sequence conflicti238L → M in BAA19741 (Ref. 2) Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0223591 – 77Missing in isoform 4. 1 PublicationAdd BLAST77
    Alternative sequenceiVSP_007544230 – 254DQLKL…ISSES → NQLQQIMRLTGTPPAYLINR MPSHE in isoform 3. 3 PublicationsAdd BLAST25
    Alternative sequenceiVSP_004846255 – 278ARNYI…FIGAN → DAK in isoform 2. 1 PublicationAdd BLAST24
    Alternative sequenceiVSP_007545279 – 360Missing in isoform 2. 1 PublicationAdd BLAST82

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U10871 mRNA. Translation: AAA20888.1.
    D83073 mRNA. Translation: BAA19741.1.
    AF128892 mRNA. Translation: AAF34818.1.
    AK151348 mRNA. Translation: BAE30324.1.
    AK153025 mRNA. Translation: BAE31659.1.
    AK089059 mRNA. Translation: BAC40726.1.
    AK133684 mRNA. Translation: BAE21782.1.
    CT009661 Genomic DNA. Translation: CAQ52036.1.
    CT009661 Genomic DNA. Translation: CAQ52037.1.
    BC012235 mRNA. Translation: AAH12235.1.
    AF195850 mRNA. Translation: AAF06348.1.
    X65067 mRNA. Translation: CAA46200.1.
    CCDSiCCDS28583.1. [P47811-1]
    CCDS50048.1. [P47811-3]
    CCDS50049.1. [P47811-4]
    PIRiI49066.
    RefSeqiNP_001161980.1. NM_001168508.1. [P47811-3]
    NP_001161985.1. NM_001168513.1. [P47811-4]
    NP_001161986.1. NM_001168514.1. [P47811-4]
    NP_036081.1. NM_011951.3. [P47811-1]
    UniGeneiMm.311337.

    Genome annotation databases

    EnsembliENSMUST00000004990; ENSMUSP00000004990; ENSMUSG00000053436. [P47811-3]
    ENSMUST00000062694; ENSMUSP00000061958; ENSMUSG00000053436. [P47811-1]
    ENSMUST00000114752; ENSMUSP00000110400; ENSMUSG00000053436. [P47811-4]
    ENSMUST00000114754; ENSMUSP00000110402; ENSMUSG00000053436. [P47811-4]
    GeneIDi26416.
    KEGGimmu:26416.
    UCSCiuc008brl.2. mouse. [P47811-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U10871 mRNA. Translation: AAA20888.1.
    D83073 mRNA. Translation: BAA19741.1.
    AF128892 mRNA. Translation: AAF34818.1.
    AK151348 mRNA. Translation: BAE30324.1.
    AK153025 mRNA. Translation: BAE31659.1.
    AK089059 mRNA. Translation: BAC40726.1.
    AK133684 mRNA. Translation: BAE21782.1.
    CT009661 Genomic DNA. Translation: CAQ52036.1.
    CT009661 Genomic DNA. Translation: CAQ52037.1.
    BC012235 mRNA. Translation: AAH12235.1.
    AF195850 mRNA. Translation: AAF06348.1.
    X65067 mRNA. Translation: CAA46200.1.
    CCDSiCCDS28583.1. [P47811-1]
    CCDS50048.1. [P47811-3]
    CCDS50049.1. [P47811-4]
    PIRiI49066.
    RefSeqiNP_001161980.1. NM_001168508.1. [P47811-3]
    NP_001161985.1. NM_001168513.1. [P47811-4]
    NP_001161986.1. NM_001168514.1. [P47811-4]
    NP_036081.1. NM_011951.3. [P47811-1]
    UniGeneiMm.311337.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1LEWX-ray2.30A13-360[»]
    1LEZX-ray2.30A1-360[»]
    1P38X-ray2.10A1-360[»]
    1YW2X-ray2.01A1-360[»]
    1YWRX-ray1.95A1-360[»]
    2EWAX-ray2.10A1-360[»]
    2GHLX-ray2.10A5-352[»]
    2GHMX-ray2.35A5-352[»]
    2GTMX-ray1.90A5-352[»]
    2GTNX-ray1.80A5-352[»]
    2OZAX-ray2.70B2-360[»]
    2PUUX-ray2.50A5-352[»]
    3P4KX-ray2.30A1-360[»]
    3P5KX-ray2.09A2-360[»]
    3P78X-ray2.30A2-360[»]
    3P79X-ray2.10A2-360[»]
    3P7AX-ray2.31A2-360[»]
    3P7BX-ray1.90A2-360[»]
    3P7CX-ray2.30A2-360[»]
    3PY3X-ray2.10A1-360[»]
    3TG1X-ray2.71A1-360[»]
    4KA3X-ray2.71A1-360[»]
    4LOOX-ray1.95A1-360[»]
    4LOPX-ray2.05A/B/C/D1-360[»]
    4LOQX-ray2.32A/B/C/D1-360[»]
    4TYHX-ray3.00B6-353[»]
    5LARX-ray1.50A1-360[»]
    ProteinModelPortaliP47811.
    SMRiP47811.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi204969. 22 interactors.
    DIPiDIP-31073N.
    IntActiP47811. 26 interactors.
    MINTiMINT-1204448.
    STRINGi10090.ENSMUSP00000004990.

    Chemistry databases

    BindingDBiP47811.
    ChEMBLiCHEMBL2336.

    PTM databases

    iPTMnetiP47811.
    PhosphoSitePlusiP47811.

    Proteomic databases

    EPDiP47811.
    MaxQBiP47811.
    PaxDbiP47811.
    PeptideAtlasiP47811.
    PRIDEiP47811.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000004990; ENSMUSP00000004990; ENSMUSG00000053436. [P47811-3]
    ENSMUST00000062694; ENSMUSP00000061958; ENSMUSG00000053436. [P47811-1]
    ENSMUST00000114752; ENSMUSP00000110400; ENSMUSG00000053436. [P47811-4]
    ENSMUST00000114754; ENSMUSP00000110402; ENSMUSG00000053436. [P47811-4]
    GeneIDi26416.
    KEGGimmu:26416.
    UCSCiuc008brl.2. mouse. [P47811-1]

    Organism-specific databases

    CTDi1432.
    MGIiMGI:1346865. Mapk14.

    Phylogenomic databases

    eggNOGiKOG0660. Eukaryota.
    ENOG410XNY0. LUCA.
    GeneTreeiENSGT00550000074271.
    HOVERGENiHBG014652.
    InParanoidiP47811.
    KOiK04441.
    OMAiIQSLAQM.
    OrthoDBiEOG091G08QL.
    PhylomeDBiP47811.
    TreeFamiTF105100.

    Enzyme and pathway databases

    BRENDAi2.7.11.24. 3474.
    ReactomeiR-MMU-168638. NOD1/2 Signaling Pathway.
    R-MMU-171007. p38MAPK events.
    R-MMU-198753. ERK/MAPK targets.
    R-MMU-2151209. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
    R-MMU-2559580. Oxidative Stress Induced Senescence.
    R-MMU-375170. CDO in myogenesis.
    R-MMU-376172. DSCAM interactions.
    R-MMU-418592. ADP signalling through P2Y purinoceptor 1.
    R-MMU-432142. Platelet sensitization by LDL.
    R-MMU-4420097. VEGFA-VEGFR2 Pathway.
    R-MMU-450302. activated TAK1 mediates p38 MAPK activation.
    R-MMU-450341. Activation of the AP-1 family of transcription factors.
    R-MMU-450604. KSRP (KHSRP) binds and destabilizes mRNA.
    R-MMU-6798695. Neutrophil degranulation.
    R-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.
    SABIO-RKP47811.
    SIGNORiP47811.

    Miscellaneous databases

    ChiTaRSiMapk14. mouse.
    EvolutionaryTraceiP47811.
    PROiP47811.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000053436.
    CleanExiMM_MAPK14.
    ExpressionAtlasiP47811. baseline and differential.
    GenevisibleiP47811. MM.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR003527. MAP_kinase_CS.
    IPR008352. MAPK_p38.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    PRINTSiPR01773. P38MAPKINASE.
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS01351. MAPK. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiMK14_MOUSE
    AccessioniPrimary (citable) accession number: P47811
    Secondary accession number(s): B2KF37
    , B2KF38, O08666, Q3U6R5, Q3UZS3, Q8C289, Q9JLV8, Q9QZ80
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: January 23, 2007
    Last modified: November 30, 2016
    This is version 191 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.