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Q15759 (MK11_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase 11

Short name=MAP kinase 11
Short name=MAPK 11
EC=2.7.11.24
Alternative name(s):
Mitogen-activated protein kinase p38 beta
Short name=MAP kinase p38 beta
Short name=p38b
Stress-activated protein kinase 2b
Short name=SAPK2b
p38-2
Gene names
Name:MAPK11
Synonyms:PRKM11, SAPK2, SAPK2B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length364 AA.
Sequence statusComplete.
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. MAPK11 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. MAPK11 functions are mostly redundant with those of MAPK14. 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. 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. 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. Additional examples of p38 MAPK substrates are the 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. Ref.4 Ref.14 Ref.15 Ref.17 Ref.18

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

Activated by phosphorylation on threonine and tyrosine by MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 induced by environmental stress. HDAC3 interacts directly and selectively with MAPK11 to repress ATF2 transcriptional activity, and regulate TNF gene expression in LPS-stimulated cells. Inhibited by SB203580 and pyridinyl-imidazole related compounds. Ref.4 Ref.5 Ref.16 Ref.18

Subunit structure

Interacts with HDAC3 and DUSP16. Ref.16 Ref.18

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Tissue specificity

Highest levels in the brain and heart. Also expressed in the placenta, lung, liver, skeletal muscle, kidney and pancreas.

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 MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6, which activates the enzyme. Ref.18

Sequence similarities

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

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processStress response
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

RNA metabolic process

Traceable author statement. Source: Reactome

Ras protein signal transduction

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

activation of MAPK activity

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

intracellular signal transduction

Inferred from direct assay Ref.1. Source: UniProtKB

mRNA metabolic process

Traceable author statement. Source: Reactome

muscle cell differentiation

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of muscle cell differentiation

Traceable author statement. Source: Reactome

regulation of sequence-specific DNA binding transcription factor activity

Traceable author statement. Source: Reactome

response to stress

Inferred from direct assay Ref.1. Source: UniProtKB

signal transduction

Traceable author statement Ref.1. Source: ProtInc

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

MAP kinase activity

Inferred from direct assay Ref.15Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 17254968PubMed 17380123. Source: IntAct

protein serine/threonine kinase activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TP53P046372EBI-298304,EBI-366083
ZNHIT1O432572EBI-298304,EBI-347522

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q15759-1)

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: Q15759-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.
     204-321: VDIWSVGCIM...HDPEDEPEAE → GAGGRPWGDE...GYLVRGLHHG
     322-364: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 364364Mitogen-activated protein kinase 11
PRO_0000186280

Regions

Domain24 – 308285Protein kinase
Nucleotide binding30 – 389ATP By similarity
Region106 – 1105Inhibitor-binding
Region168 – 1692Inhibitor-binding
Motif180 – 1823TXY

Sites

Active site1501Proton acceptor By similarity
Binding site531ATP By similarity
Binding site711Nilotinib

Amino acid modifications

Modified residue1801Phosphothreonine; by MAP2K3, MAP2K4 and MAP2K6 Probable
Modified residue1821Phosphotyrosine; by MAP2K3, MAP2K4 and MAP2K6 Probable
Modified residue3231Phosphotyrosine; by ZAP70 By similarity

Natural variations

Alternative sequence1 – 108108Missing in isoform 2.
VSP_055221
Alternative sequence204 – 321118VDIWS…EPEAE → GAGGRPWGDEGQGPRLALDW LCMPGLRGQARSPRMWDPHS KVALQRPLEHDGCWPPLAVQ LWTSPCLGGLGMAEEGVCPS WGLDVTVGLLEEGRGVGTLM EVPSPSHSGYLVRGLHHG in isoform 2.
VSP_055222
Alternative sequence322 – 36443Missing in isoform 2.
VSP_055223
Natural variant2211A → V in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.23
VAR_042264
Natural variant2751R → H. Ref.9 Ref.23
Corresponds to variant rs33932986 [ dbSNP | Ensembl ].
VAR_025176

Experimental info

Mutagenesis1801T → A: Inactivation.
Mutagenesis1821Y → F: Inactivation.
Sequence conflict981D → V in BAF84534. Ref.8
Sequence conflict122 – 1232LS → GAHQGARLAL in AAB05036. Ref.1
Sequence conflict3261S → G in AAB66313. Ref.6

Secondary structure

................................................................. 364
Helix Strand Turn

Details...

Sequences

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

Last modified March 20, 2007. Version 2.
Checksum: 68DA4C7B7C721475

FASTA36441,357
        10         20         30         40         50         60 
MSGPRAGFYR QELNKTVWEV PQRLQGLRPV GSGAYGSVCS AYDARLRQKV AVKKLSRPFQ 

        70         80         90        100        110        120 
SLIHARRTYR ELRLLKHLKH ENVIGLLDVF TPATSIEDFS EVYLVTTLMG ADLNNIVKCQ 

       130        140        150        160        170        180 
ALSDEHVQFL VYQLLRGLKY IHSAGIIHRD LKPSNVAVNE DCELRILDFG LARQADEEMT 

       190        200        210        220        230        240 
GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLQGK ALFPGSDYID QLKRIMEVVG 

       250        260        270        280        290        300 
TPSPEVLAKI SSEHARTYIQ SLPPMPQKDL SSIFRGANPL AIDLLGRMLV LDSDQRVSAA 

       310        320        330        340        350        360 
EALAHAYFSQ YHDPEDEPEA EPYDESVEAK ERTLEEWKEL TYQEVLSFKP PEPPKPPGSL 


EIEQ 

« Hide

Isoform 2 [UniParc].

Checksum: E3466E25BE1D27A3
Show »

FASTA21323,603

References

« Hide 'large scale' references
[1]"Characterization of the structure and function of a new mitogen-activated protein kinase (p38beta)."
Jiang Y., Chen C., Li Z., Guo W., Gegner J.A., Lin S., Han J.
J. Biol. Chem. 271:17920-17926(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[2]Jiang Y., Han J.
Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles."
Kumar S., McDonnell P.C., Gum R.J., Hand A.T., Lee J.C., Young P.R.
Biochem. Biophys. Res. Commun. 235:533-538(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6."
Enslen H., Raingeaud J., Davis R.J.
J. Biol. Chem. 273:1741-1748(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN PHOSPHORYLATION OF ATF2; ELK1 AND MBP, ENZYME REGULATION.
Tissue: Brain.
[5]"Activation of the novel stress-activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases."
Goedert M., Cuenda A., Craxton M., Jakes R., Cohen P.
EMBO J. 16:3563-3571(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME REGULATION.
[6]"p38-2, a novel mitogen-activated protein kinase with distinct properties."
Stein B., Yang M.X., Young D.B., Janknecht R., Hunter T., Murray B.W., Barbosa M.S.
J. Biol. Chem. 272:19509-19517(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[7]"A genome annotation-driven approach to cloning the human ORFeome."
Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain.
[9]NIEHS SNPs program
Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-275.
[10]NHLBI resequencing and genotyping service (RS&G)
Submitted (AUG-2012) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[11]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]"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: Brain.
[14]"Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB."
Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.
EMBO J. 17:4426-4441(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION OF RPS6KA5/MSK1.
[15]"Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors."
Yang S.-H., Galanis A., Sharrocks A.D.
Mol. Cell. Biol. 19:4028-4038(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF MEF2A AND MEF2C.
[16]"A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 alpha and beta MAPKs."
Tanoue T., Yamamoto T., Maeda R., Nishida E.
J. Biol. Chem. 276:26629-26639(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DUSP16, ENZYME REGULATION.
[17]"The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells."
Scheper G.C., Morrice N.A., Kleijn M., Proud C.G.
Mol. Cell. Biol. 21:743-754(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS MKNK2 KINASE.
[18]"Histone deacetylase 3, a class I histone deacetylase, suppresses MAPK11-mediated activating transcription factor-2 activation and represses TNF gene expression."
Mahlknecht U., Will J., Varin A., Hoelzer D., Herbein G.
J. Immunol. 173:3979-3990(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC3, PHOSPHORYLATION, ENZYME REGULATION, FUNCTION IN ATF2 ACTIVATION.
[19]"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.
[20]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"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.
[22]"The three-dimensional structure of MAP kinase p38beta: different features of the ATP-binding site in p38beta compared with p38alpha."
Patel S.B., Cameron P.M., O'Keefe S.J., Frantz-Wattley B., Thompson J., O'Neill E.A., Tennis T., Liu L., Becker J.W., Scapin G.
Acta Crystallogr. D 65:777-785(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
[23]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-221 AND HIS-275.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U53442 mRNA. Translation: AAB05036.1.
AF001008 mRNA. Translation: AAC51250.1.
AF001174 mRNA. Translation: AAC51373.1.
AF031135 mRNA. Translation: AAC12714.1.
Y14440 mRNA. Translation: CAA74792.1.
U92268 mRNA. Translation: AAB66313.1.
CR456514 mRNA. Translation: CAG30400.1.
DQ279722 Genomic DNA. Translation: ABB72677.1.
AK291845 mRNA. Translation: BAF84534.1.
AK299745 mRNA. Translation: BAH13116.1.
EU332851 Genomic DNA. Translation: ABY87540.1.
JX512451 Genomic DNA. Translation: AGC09598.1.
AL022328 Genomic DNA. No translation available.
CH471138 Genomic DNA. Translation: EAW73524.1.
CH471138 Genomic DNA. Translation: EAW73525.1.
CH471138 Genomic DNA. Translation: EAW73526.1.
BC027933 mRNA. Translation: AAH27933.1.
CCDSCCDS14090.1.
PIRG02524.
JC5529.
RefSeqNP_002742.3. NM_002751.6.
UniGeneHs.57732.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3GC8X-ray2.40A/B1-364[»]
3GC9X-ray2.05A/B1-364[»]
3GP0X-ray1.90A5-350[»]
ProteinModelPortalQ15759.
SMRQ15759. Positions 3-349.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111586. 28 interactions.
IntActQ15759. 20 interactions.
MINTMINT-3032032.
STRING9606.ENSP00000333685.

Chemistry

BindingDBQ15759.
ChEMBLCHEMBL3961.
GuidetoPHARMACOLOGY1500.

PTM databases

PhosphoSiteQ15759.

Polymorphism databases

DMDM134047835.

Proteomic databases

PaxDbQ15759.
PRIDEQ15759.

Protocols and materials databases

DNASU5600.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330651; ENSP00000333685; ENSG00000185386.
ENST00000395764; ENSP00000379113; ENSG00000185386.
ENST00000449719; ENSP00000406921; ENSG00000185386.
GeneID5600.
KEGGhsa:5600.
UCSCuc003bkr.3. human.

Organism-specific databases

CTD5600.
GeneCardsGC22M050702.
HGNCHGNC:6873. MAPK11.
HPACAB012961.
MIM602898. gene.
neXtProtNX_Q15759.
PharmGKBPA30618.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidQ15759.
KOK04441.
OMAETIGGCE.
OrthoDBEOG7PCJGV.
PhylomeDBQ15759.
TreeFamTF105100.

Enzyme and pathway databases

BRENDA2.7.11.24. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_120956. Cellular responses to stress.
REACT_200751. Organelle biogenesis and maintenance.
REACT_21257. Metabolism of RNA.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
REACT_71. Gene Expression.
SignaLinkQ15759.

Gene expression databases

ArrayExpressQ15759.
BgeeQ15759.
CleanExHS_MAPK11.
GenevestigatorQ15759.

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

EvolutionaryTraceQ15759.
GeneWikiMAPK11.
GenomeRNAi5600.
NextBio21748.
PROQ15759.
SOURCESearch...

Entry information

Entry nameMK11_HUMAN
AccessionPrimary (citable) accession number: Q15759
Secondary accession number(s): A8K730 expand/collapse secondary AC list , B0LPG1, B7Z630, E7ETQ1, L7RT27, O00284, O15472, Q2XNF2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 20, 2007
Last modified: July 9, 2014
This is version 157 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

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

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM