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P47811 (MK14_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase 14

Short name=MAP kinase 14
Short name=MAPK 14
EC=2.7.11.24
Alternative name(s):
CRK1
Mitogen-activated protein kinase p38 alpha
Short name=MAP kinase p38 alpha
Gene names
Name:Mapk14
Synonyms:Crk1, Csbp1, Csbp2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length360 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.11 Ref.12 Ref.13 Ref.15

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.28

Cofactor

Magnesium.

Enzyme regulation

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. Ref.11 Ref.15 Ref.19

Subunit structure

Binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR. This interaction retains MAPK14 in the cytoplasm and prevents nuclear accumulation. Interacts with SPAG9, SUPT20H and GADD45A. Interacts with CDC25B, CDC25C, DUSP1, DUSP10, DUSP16, NP60 and TAB1 By similarity. Interacts with casein kinase II subunits CSNK2A1 and CSNK2B By similarity. Ref.10 Ref.12 Ref.14 Ref.15 Ref.16 Ref.28

Subcellular location

Cytoplasm. Nucleus Ref.10.

Tissue specificity

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

Domain

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

Post-translational modification

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. Ref.15 Ref.19 Ref.28

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.

Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Contains 1 protein kinase domain.

Biophysicochemical properties

Kinetic parameters:

KM=212 µM for ATP (when both Thr-180 and Tyr-182 are phosphorylated) Ref.19

KM=1669 µM for ATP (when only Thr-180 is phosphorylated)

KM=656 µM for EGFR peptide as a substrate (when both Thr-180 and Tyr-182 are phosphorylated)

KM=2800 µM for EGFR peptide as a substrate (when only Thr-180 is phosphorylated)

KM=2.03 µM for ATF2 as a substrate (when both Thr-180 and Tyr-182 are phosphorylated)

KM=20.1 µM for ATF2 as a substrate (when only Thr-180 is phosphorylated)

Ontologies

Keywords
   Biological processApoptosis
Stress response
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage checkpoint

Inferred from mutant phenotype PubMed 12937170. Source: MGI

angiogenesis

Inferred from mutant phenotype PubMed 10973481. Source: MGI

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cartilage condensation

Inferred from mutant phenotype PubMed 17202865. Source: AgBase

cell morphogenesis

Inferred from genetic interaction PubMed 17686994. Source: MGI

cellular response to DNA damage stimulus

Inferred from direct assay PubMed 20212154. Source: MGI

cellular response to ionizing radiation

Inferred from electronic annotation. Source: Ensembl

cellular response to vascular endothelial growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

chondrocyte differentiation

Inferred from mutant phenotype PubMed 17202865. Source: AgBase

fatty acid oxidation

Inferred from mutant phenotype PubMed 12802337. Source: MGI

glucose metabolic process

Inferred from mutant phenotype PubMed 12802337. Source: MGI

intracellular signal transduction

Inferred from direct assay Ref.1. Source: UniProtKB

lipopolysaccharide-mediated signaling pathway

Inferred from direct assay PubMed 12872135. Source: MGI

negative regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype PubMed 17202865. Source: AgBase

osteoclast differentiation

Inferred from mutant phenotype PubMed 15304486. Source: BHF-UCL

p38MAPK cascade

Inferred from direct assay PubMed 22847234. Source: UniProtKB

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 15304486. Source: BHF-UCL

positive regulation of erythrocyte differentiation

Inferred from mutant phenotype Ref.12. Source: MGI

positive regulation of myoblast differentiation

Inferred from mutant phenotype PubMed 22847234. Source: UniProtKB

positive regulation of myoblast fusion

Inferred from mutant phenotype PubMed 22847234. Source: UniProtKB

positive regulation of myotube differentiation

Inferred from mutant phenotype PubMed 22847234. Source: UniProtKB

positive regulation of protein import into nucleus

Inferred from mutant phenotype PubMed 16954198. Source: MGI

positive regulation of reactive oxygen species metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype Ref.12. Source: MGI

protein phosphorylation

Inferred from direct assay PubMed 15767678PubMed 15937334. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 22847234. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 20212154. Source: MGI

response to lipopolysaccharide

Inferred from direct assay PubMed 12872135. Source: MGI

response to muramyl dipeptide

Inferred from direct assay PubMed 15692051. Source: MGI

signal transduction in response to DNA damage

Inferred from electronic annotation. Source: Ensembl

skeletal muscle tissue development

Inferred from mutant phenotype PubMed 15890335. Source: MGI

stress-induced premature senescence

Inferred from electronic annotation. Source: Ensembl

striated muscle cell differentiation

Inferred from genetic interaction PubMed 20160094. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transmembrane receptor protein serine/threonine kinase signaling pathway

Inferred from genetic interaction PubMed 18363966. Source: MGI

vascular endothelial growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell

Inferred from direct assay PubMed 10973481. Source: MGI

cytoplasm

Inferred from direct assay Ref.10. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 11884367. Source: MGI

mitochondrion

Inferred from direct assay PubMed 11884367. Source: MGI

nucleus

Inferred from direct assay Ref.10. Source: UniProtKB

spindle pole

Inferred from direct assay PubMed 15509711. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

MAP kinase activity

Inferred from direct assay Ref.1. Source: UniProtKB

NFAT protein binding

Inferred from physical interaction PubMed 15304486. Source: BHF-UCL

kinase activity

Inferred from direct assay PubMed 12808090PubMed 15767678. Source: MGI

protein kinase activity

Inferred from direct assay Ref.12. Source: MGI

protein serine/threonine kinase activity

Inferred from direct assay PubMed 18347059. Source: MGI

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P47811-1)

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.
Isoform 2 (identifier: P47811-2)

Also known as: Piccolo;

The sequence of this isoform differs from the canonical sequence as follows:
     255-278: ARNYIQSLAQMPKMNFANVFIGAN → DAK
     279-360: Missing.
Isoform 3 (identifier: P47811-3)

The sequence of this isoform differs from the canonical sequence as follows:
     230-254: DQLKLILRLVGTPGAELLKKISSES → NQLQQIMRLTGTPPAYLINRMPSHE
Isoform 4 (identifier: P47811-4)

The sequence of this isoform differs from the canonical sequence as follows:
     2-77: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 360359Mitogen-activated protein kinase 14
PRO_0000186292

Regions

Domain24 – 308285Protein kinase
Nucleotide binding30 – 389ATP By similarity
Region106 – 1116Inhibitor-binding
Motif180 – 1823TXY

Sites

Active site1681Proton acceptor By similarity
Binding site321Inhibitor
Binding site351Inhibitor
Binding site531ATP By similarity
Binding site531Inhibitor
Binding site711Inhibitor
Binding site1091Inhibitor; via amide nitrogen and carbonyl oxygen
Binding site1111Inhibitor; via amide nitrogen
Binding site1681Inhibitor
Binding site1691Inhibitor; via carbonyl oxygen

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue21Phosphoserine By similarity
Modified residue161Phosphothreonine By similarity
Modified residue531N6-acetyllysine By similarity
Modified residue1521N6-acetyllysine By similarity
Modified residue1801Phosphothreonine; alternate Ref.17 Ref.18 Ref.19 Ref.21
Modified residue1801Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and autocatalysis; alternate By similarity
Modified residue1821Phosphotyrosine; alternate Ref.17 Ref.18 Ref.19 Ref.21
Modified residue1821Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and autocatalysis; alternate By similarity
Modified residue3231Phosphotyrosine; by ZAP70 By similarity

Natural variations

Alternative sequence2 – 7776Missing in isoform 4.
VSP_022359
Alternative sequence230 – 25425DQLKL…ISSES → NQLQQIMRLTGTPPAYLINR MPSHE in isoform 3.
VSP_007544
Alternative sequence255 – 27824ARNYI…FIGAN → DAK in isoform 2.
VSP_004846
Alternative sequence279 – 36082Missing in isoform 2.
VSP_007545

Experimental info

Mutagenesis1801T → A: Phosphorylation blocked.
Mutagenesis1821Y → F: Phosphorylation blocked.
Sequence conflict981E → G in AAF06348. Ref.7
Sequence conflict107 – 1082HL → LS in AAF06348. Ref.7
Sequence conflict1151N → R in AAF06348. Ref.7
Sequence conflict1241D → G in AAF06348. Ref.7
Sequence conflict159 – 1624NEDC → TQVI in AAF06348. Ref.7
Sequence conflict1661I → L in AAF06348. Ref.7
Sequence conflict2021Q → R in AAF06348. Ref.7
Sequence conflict211 – 2122CI → GF in AAF06348. Ref.7
Sequence conflict2241P → L in AAF06348. Ref.7
Sequence conflict2711A → P in AAF06348. Ref.7
Sequence conflict2991A → V in AAF06348. Ref.7
Sequence conflict3151D → Y in AAF06348. Ref.7
Isoform 3:
Sequence conflict2381L → M in BAA19741. Ref.2

Secondary structure

................................................................ 360
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: DFB03EBCE97BB51A

FASTA36041,287
        10         20         30         40         50         60 
MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGHRV AVKKLSRPFQ 

        70         80         90        100        110        120 
SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN DVYLVTHLMG ADLNNIVKCQ 

       130        140        150        160        170        180 
KLTDDHVQFL IYQILRGLKY IHSADIIHRD LKPSNLAVNE DCELKILDFG LARHTDDEMT 

       190        200        210        220        230        240 
GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLTGR TLFPGTDHID QLKLILRLVG 

       250        260        270        280        290        300 
TPGAELLKKI SSESARNYIQ SLAQMPKMNF ANVFIGANPL AVDLLEKMLV LDSDKRITAA 

       310        320        330        340        350        360 
QALAHAYFAQ YHDPDDEPVA DPYDQSFESR DLLIDEWKSL TYDEVISFVP PPLDQEEMES 

« Hide

Isoform 2 (Piccolo) [UniParc].

Checksum: ABDF65DC32AF0387
Show »

FASTA25729,540
Isoform 3 [UniParc].

Checksum: F1F20352F76590BD
Show »

FASTA36041,487
Isoform 4 [UniParc].

Checksum: EF6828D872F4AC30
Show »

FASTA28432,458

References

« Hide 'large scale' references
[1]"A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells."
Han J., Lee J.-D., Bibbs L., Ulevitch R.J.
Science 265:808-811(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
Tissue: Liver.
[2]Higashitsuji H., Fujita J.
Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Strain: C57BL/6.
Tissue: Brain.
[3]"Piccolo, a new alternative spliced form of p38/CSBP1/Mxi2 that is specifically expressed in kidney and liver."
Faccio L., Fusco C., Zervos S.A.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: C57BL/6.
Tissue: Kidney.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
Strain: C57BL/6J.
Tissue: Bone marrow, Pituitary and Thymus.
[5]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Liver.
[7]Yin Z., Li J., Sha J., Zhou Z., Lin M., Wang L.
Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 94-318 (ISOFORM 3).
Tissue: Testis.
[8]"Novel CDC2-related protein kinases produced in murine hematopoietic stem cells."
Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.
Gene 124:305-306(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 154-186.
Strain: CBA.
Tissue: Bone marrow.
[9]"Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms."
Derijard B., Raingeaud J., Barrett T., Wu I.-H., Han J., Ulevitch R.J., Davis R.J.
Science 267:682-685(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[10]"A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine phosphatase."
Blanco-Aparicio C., Torres J., Pulido R.
J. Cell Biol. 147:1129-1136(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPRR, SUBCELLULAR LOCATION.
[11]"Deficiency of the stress kinase p38alpha results in embryonic lethality: characterization of the kinase dependence of stress responses of enzyme-deficient embryonic stem cells."
Allen M., Svensson L., Roach M., Hambor J., McNeish J., Gabel C.A.
J. Exp. Med. 191:859-870(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION.
Tissue: Embryonic stem cell.
[12]"Requirement for p38alpha in erythropoietin expression: a role for stress kinases in erythropoiesis."
Tamura K., Sudo T., Senftleben U., Dadak A.M., Johnson R., Karin M.
Cell 102:221-231(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT.
Strain: C57BL/6J.
[13]"MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts."
Wiggin G.R., Soloaga A., Foster J.M., Murray-Tait V., Cohen P., Arthur J.S.
Mol. Cell. Biol. 22:2871-2881(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION OF RPS6KA5/MSK1 AND RPS6KA4/MSK2.
[14]"JLP: a scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors."
Lee C.M., Onesime D., Reddy C.D., Dhanasekaran N., Reddy E.P.
Proc. Natl. Acad. Sci. U.S.A. 99:14189-14194(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SPAG9.
[15]"The autoimmune suppressor Gadd45alpha inhibits the T cell alternative p38 activation pathway."
Salvador J.M., Mittelstadt P.R., Belova G.I., Fornace A.J. Jr., Ashwell J.D.
Nat. Immunol. 6:396-402(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GADD45A, PHOSPHORYLATION AT TYR-323, AUTOPHOSPHORYLATION, ENZYME REGULATION, FUNCTION.
[16]"p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation."
Zohn I.E., Li Y., Skolnik E.Y., Anderson K.V., Han J., Niswander L.
Cell 125:957-969(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SUPT20H.
[17]"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Mast cell.
[18]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[19]"Enzymatic activity and substrate specificity of mitogen-activated protein kinase p38alpha in different phosphorylation states."
Zhang Y.Y., Mei Z.Q., Wu J.W., Wang Z.X.
J. Biol. Chem. 283:26591-26601(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-180 AND TYR-182, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[20]"In the cellular garden of forking paths: how p38 MAPKs signal for downstream assistance."
Shi Y., Gaestel M.
Biol. Chem. 383:1519-1536(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[21]"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain."
Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.
J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[22]"Mechanisms and functions of p38 MAPK signalling."
Cuadrado A., Nebreda A.R.
Biochem. J. 429:403-417(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ENZYME REGULATION, REVIEW ON FUNCTION.
[23]"The structure of mitogen-activated protein kinase p38 at 2.1-A resolution."
Wang Z., Harkins P.C., Ulevitch R.J., Han J., Cobb M.H., Goldsmith E.J.
Proc. Natl. Acad. Sci. U.S.A. 94:2327-2332(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[24]"Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b."
Chang C.I., Xu B.E., Akella R., Cobb M.H., Goldsmith E.J.
Mol. Cell 9:1241-1249(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH MEF2A AND MAP2K3.
[25]"The development of monocyclic pyrazolone based cytokine synthesis inhibitors."
Golebiowski A., Townes J.A., Laufersweiler M.J., Brugel T.A., Clark M.P., Clark C.M., Djung J.F., Laughlin S.K., Sabat M.P., Bookland R.G., VanRens J.C., De B., Hsieh L.C., Janusz M.J., Walter R.L., Webster M.E., Mekel M.J.
Bioorg. Med. Chem. Lett. 15:2285-2289(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
[26]"The development of new isoxazolone based inhibitors of tumor necrosis factor-alpha (TNF-alpha) production."
Laughlin S.K., Clark M.P., Djung J.F., Golebiowski A., Brugel T.A., Sabat M., Bookland R.G., Laufersweiler M.J., VanRens J.C., Townes J.A., De B., Hsieh L.C., Xu S.C., Walter R.L., Mekel M.J., Janusz M.J.
Bioorg. Med. Chem. Lett. 15:2399-2403(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
[27]"Molecular basis of MAPK-activated protein kinase 2:p38 assembly."
White A., Pargellis C.A., Studts J.M., Werneburg B.G., Farmer B.T. II
Proc. Natl. Acad. Sci. U.S.A. 104:6353-6358(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-360 IN COMPLEX WITH MAPKAPK2.
[28]"A distinct interaction mode revealed by the crystal structure of the kinase p38alpha with the MAPK binding domain of the phosphatase MKP5."
Zhang Y.Y., Wu J.W., Wang Z.X.
Sci. Signal. 4:RA88-RA88(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) IN COMPLEX WITH DUSP10, CATALYTIC ACTIVITY, DEPHOSPHORYLATION BY DUSP10, INTERACTION WITH DUSP10.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRI49066.
RefSeqNP_001161980.1. NM_001168508.1.
NP_001161985.1. NM_001168513.1.
NP_001161986.1. NM_001168514.1.
NP_036081.1. NM_011951.3.
UniGeneMm.311337.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LEWX-ray2.30A1-360[»]
1LEZX-ray2.30A1-360[»]
1P38X-ray2.10A1-360[»]
1YW2X-ray2.01A1-360[»]
1YWRX-ray1.95A1-360[»]
2EWAX-ray2.10A1-360[»]
2GHLX-ray2.10A5-351[»]
2GHMX-ray2.35A5-351[»]
2GTMX-ray1.90A5-351[»]
2GTNX-ray1.80A5-351[»]
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[»]
ProteinModelPortalP47811.
SMRP47811. Positions 5-353.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204969. 20 interactions.
DIPDIP-31073N.
IntActP47811. 26 interactions.
MINTMINT-1204448.
STRING10090.ENSMUSP00000004990.

Chemistry

BindingDBP47811.
ChEMBLCHEMBL2111473.

PTM databases

PhosphoSiteP47811.

Proteomic databases

PaxDbP47811.
PRIDEP47811.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000004990; ENSMUSP00000004990; ENSMUSG00000053436. [P47811-3]
ENSMUST00000062694; ENSMUSP00000061958; ENSMUSG00000053436. [P47811-1]
ENSMUST00000114752; ENSMUSP00000110400; ENSMUSG00000053436.
ENSMUST00000114754; ENSMUSP00000110402; ENSMUSG00000053436.
GeneID26416.
KEGGmmu:26416.
UCSCuc008brl.2. mouse. [P47811-1]

Organism-specific databases

CTD1432.
MGIMGI:1346865. Mapk14.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00550000074271.
HOVERGENHBG014652.
InParanoidB2KF38.
KOK04441.
OMAQALAHGY.
PhylomeDBP47811.
TreeFamTF105100.

Enzyme and pathway databases

BRENDA2.7.11.24. 3474.
ReactomeREACT_188576. Developmental Biology.
REACT_78136. Gene Expression.
SABIO-RKP47811.

Gene expression databases

ArrayExpressP47811.
BgeeP47811.
CleanExMM_MAPK14.
GenevestigatorP47811.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01773. P38MAPKINASE.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP47811.
NextBio304425.
PROP47811.
SOURCESearch...

Entry information

Entry nameMK14_MOUSE
AccessionPrimary (citable) accession number: P47811
Secondary accession number(s): B2KF37 expand/collapse secondary AC list , B2KF38, O08666, Q3U6R5, Q3UZS3, Q8C289, Q9JLV8, Q9QZ80
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 162 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot