| Tag | Content |
|---|
| EKPD ID | EKS-HOS-00467 |
| Classification | | Group/Family | Score | E-Value | Start | End | Domain Length |
|---|
| CMGC/MAPK | 438.7 | 4.4E-131 | 26 | 308 | 283 |
|
| Status | Reviewed |
| Ensembl Protein | ENSP00000333685 |
| UniProt Accession | Q15759; B0LPG1; O00284; O15472; Q2XNF2; |
| Protein Name | Mitogen-activated protein kinase 11 |
| Protein Synonyms/Alias | MAP kinase 11; MAPK 11; Mitogen-activated protein kinase p38 beta; MAP kinase p38 beta; p38b; Stress-activated protein kinase 2b; SAPK2b; p38-2; |
| Gene Name | MAPK11 |
| Gene Synonyms/Alias | MAPK11; PRKM11, SAPK2, SAPK2B; |
| Ensembl Information | |
| Organism | Homo sapiens |
| Functional Description | Serine/threonine kinase which acts as an essentialcomponent 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. |
| Protein Length | 364 |
Protein Sequence
(FASTA) | | MSGPRAGFYR QELNKTVWEV PQRLQGLRPV GSGAYGSVCS AYDARLRQKV AVKKLSRPFQ 60 | | SLIHARRTYR ELRLLKHLKH ENVIGLLDVF TPATSIEDFS EVYLVTTLMG ADLNNIVKCQ 120 | | ALSDEHVQFL VYQLLRGLKY IHSAGIIHRD LKPSNVAVNE DCELRILDFG LARQADEEMT 180 | | GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLQGK ALFPGSDYID QLKRIMEVVG 240 | | TPSPEVLAKI SSEHARTYIQ SLPPMPQKDL SSIFRGANPL AIDLLGRMLV LDSDQRVSAA 300 | | EALAHAYFSQ YHDPEDEPEA EPYDESVEAK ERTLEEWKEL TYQEVLSFKP PEPPKPPGSL 360 | | EIEQ 364 |
|
Nucleotide Sequence
(FASTA) | | ATGTCGGGCC CTCGCGCCGG CTTCTACCGG CAGGAGCTGA ACAAGACCGT GTGGGAGGTG 60 | | CCGCAGCGGC TGCAGGGGCT GCGCCCGGTG GGCTCCGGCG CCTACGGCTC CGTCTGTTCG 120 | | GCCTACGACG CCCGGCTGCG CCAGAAGGTG GCGGTGAAGA AGCTGTCGCG CCCCTTCCAG 180 | | TCGCTGATCC ACGCGCGCAG AACGTACCGG GAGCTGCGGC TGCTCAAGCA CCTGAAGCAC 240 | | GAGAACGTCA TCGGGCTTCT GGACGTCTTC ACGCCGGCCA CGTCCATCGA GGACTTCAGC 300 | | GAAGTGTACT TGGTGACCAC CCTGATGGGC GCCGACCTGA ACAACATCGT CAAGTGCCAG 360 | | GCGCTGAGCG ACGAGCACGT TCAATTCCTG GTTTACCAGC TGCTGCGCGG GCTGAAGTAC 420 | | ATCCACTCGG CCGGGATCAT CCACCGGGAC CTGAAGCCCA GCAACGTGGC TGTGAACGAG 480 | | GACTGTGAGC TCAGGATCCT GGATTTTGGG CTGGCGCGCC AGGCGGACGA GGAGATGACC 540 | | GGCTATGTGG CCACGCGCTG GTACCGGGCA CCTGAGATCA TGCTCAACTG GATGCATTAC 600 | | AACCAAACAG TGGATATCTG GTCCGTGGGC TGCATCATGG CTGAGCTGCT CCAGGGCAAG 660 | | GCCCTCTTCC CGGGAAGCGA CTACATTGAC CAGCTGAAGC GCATCATGGA AGTGGTGGGC 720 | | ACACCCAGCC CTGAGGTTCT GGCAAAAATC TCCTCAGAAC ACGCCCGGAC ATATATCCAG 780 | | TCCCTGCCCC CCATGCCCCA GAAGGACCTG AGCAGCATCT TCCGTGGAGC CAACCCCCTG 840 | | GCCATAGACC TCCTTGGAAG GATGCTGGTG CTGGACAGTG ACCAGAGGGT CAGTGCAGCT 900 | | GAGGCACTGG CCCACGCCTA CTTCAGCCAG TACCACGACC CCGAGGATGA GCCAGAGGCC 960 | | GAGCCATATG ATGAGAGCGT TGAGGCCAAG GAGCGCACGC TGGAGGAGTG GAAGGAGCTC 1020 | | ACTTACCAGG AAGTCCTCAG CTTCAAGCCC CCAGAGCCAC CGAAGCCACC TGGCAGCCTG 1080 | | GAGATTGAGC AGTGA 1095 |
|
| Domain Profile | S: 3 slkplgeGaygvvvsavdkrteervaikklsrpfqketsakrtlRElkllkelkheNiik 62 | l+p+g+Gayg v+sa+d+r +++va+kklsrpfq+ ++a+rt+REl+llk+lkheN+i | Q: 26 GLRPVGSGAYGSVCSAYDARLRQKVAVKKLSRPFQSLIHARRTYRELRLLKHLKHENVIG 85 | 5799******************************************************** |
| S: 63 lldvftpeeeleelkdvYlvtelmetdLkkviksqklsdehiklllyqilrglkylHsan 122 | lldvftp++++e++++vYlvt+lm++dL++++k q lsdeh+++l+yq+lrglky+Hsa+ | Q: 86 LLDVFTPATSIEDFSEVYLVTTLMGADLNNIVKCQALSDEHVQFLVYQLLRGLKYIHSAG 145 | ************************************************************ |
| S: 123 viHrDlKPsNllvnedcelkildFGlarsadkekekklteyvatrwYraPeillslkeyt 182 | +iHrDlKPsN++vnedcel+ildFGlar+ad+e +t+yvatrwYraPei+l++++y+ | Q: 146 IIHRDLKPSNVAVNEDCELRILDFGLARQADEE----MTGYVATRWYRAPEIMLNWMHYN 201 | ********************************9....*********************** |
| S: 183 kavDiWsvGCIlaElltgkplfpgkdeidqlekilevlgtpseeflkkieseearnyiks 242 | ++vDiWsvGCI+aEll+gk lfpg+d+idql++i+ev+gtps e+l+ki+se+ar+yi+s | Q: 202 QTVDIWSVGCIMAELLQGKALFPGSDYIDQLKRIMEVVGTPSPEVLAKISSEHARTYIQS 261 | ************************************************************ |
| S: 243 lpkkkkkdfeelfpkaseealdLleklLvldpdkRisveeaLehpYl 289 | lp++++kd++++f a++ a+dLl ++Lvld+d+R+s++eaL+h Y+ | Q: 262 LPPMPQKDLSSIFRGANPLAIDLLGRMLVLDSDQRVSAAEALAHAYF 308 | *********************************************96 |
|
Domain Sequence
(FASTA) | | GLRPVGSGAY GSVCSAYDAR LRQKVAVKKL SRPFQSLIHA RRTYRELRLL KHLKHENVIG 60 | | LLDVFTPATS IEDFSEVYLV TTLMGADLNN IVKCQALSDE HVQFLVYQLL RGLKYIHSAG 120 | | IIHRDLKPSN VAVNEDCELR ILDFGLARQA DEEMTGYVAT RWYRAPEIML NWMHYNQTVD 180 | | IWSVGCIMAE LLQGKALFPG SDYIDQLKRI MEVVGTPSPE VLAKISSEHA RTYIQSLPPM 240 | | PQKDLSSIFR GANPLAIDLL GRMLVLDSDQ RVSAAEALAH AYF 283 |
|
| Keyword | 3D-structure; ATP-binding; Complete proteome; Cytoplasm; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Stress response; Transcription; Transcription regulation; Transferase. |
| Sequence Source | Ensembl |
| Orthology | |
| Gene Ontology | |
| KEGG | |
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| Prints | |
| Created Date | 20-Feb-2013 |