MAP kinase-activated protein kinase 5

Details

Name
MAP kinase-activated protein kinase 5
Synonyms
  • 2.7.11.1
  • MAPK-activated protein kinase 5
  • p38-regulated/activated protein kinase
  • PRAK
Gene Name
MAPKAPK5
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051834|MAP kinase-activated protein kinase 5
MSEESDMDKAIKETSILEEYSINWTQKLGAGISGPVRVCVKKSTQERFALKILLDRPKAR
NEVRLHMMCATHPNIVQIIEVFANSVQFPHESSPRARLLIVMEMMEGGELFHRISQHRHF
TEKQASQVTKQIALALRHCHLLNIAHRDLKPENLLFKDNSLDAPVKLCDFGFAKIDQGDL
MTPQFTPYYVAPQVLEAQRRHQKEKSGIIPTSPTPYTYNKSCDLWSLGVIIYVMLCGYPP
FYSKHHSRTIPKDMRRKIMTGSFEFPEEEWSQISEMAKDVVRKLLKVKPEERLTIEGVLD
HPWLNSTEALDNVLPSAQLMMDKAVVAGIQQAHAEQLANMRIQDLKVSLKPLHSVNNPIL
RKRKLLGTKPKDSVYIHDHENGAEDSNVALEKLRDVIAQCILPQAGKGENEDEKLNEVMQ
EAWKYNRECKLLRDTLQSFSWNGRGFTDKVDRLKLAEIVKQVIEEQTTSHESQ
Number of residues
473
Molecular Weight
54220.04
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / calcium-dependent protein serine/threonine kinase activity / calmodulin binding / calmodulin-dependent protein kinase activity / MAP kinase kinase activity / mitogen-activated protein kinase binding / p53 binding / protein serine/threonine kinase activity
Processes
cell surface receptor signaling pathway / negative regulation of TOR signaling / peptidyl-serine phosphorylation / positive regulation of telomerase activity / positive regulation of telomere capping / positive regulation of telomere maintenance via telomerase / protein autophosphorylation / Ras protein signal transduction / regulation of signal transduction by p53 class mediator / regulation of translation / signal transduction / stress-induced premature senescence
Components
cytoplasm / cytosol / nucleoplasm / nucleus
General Function
Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051835|MAP kinase-activated protein kinase 5 (MAPKAPK5)
ATGTCGGAGGAGAGCGACATGGACAAAGCCATCAAGGAAACTTCCATTTTAGAAGAATAC
AGTATCAATTGGACTCAGAAGCTGGGAGCTGGAATTAGTGGTCCAGTTAGAGTCTGTGTA
AAGAAATCTACTCAAGAACGGTTTGCGCTGAAAATTCTTCTTGATCGTCCAAAAGCTAGA
AATGAGGTACGTCTGCACATGATGTGTGCCACACACCCAAACATAGTTCAGATTATTGAA
GTGTTTGCTAACAGTGTCCAGTTTCCCCATGAGTCCAGCCCTAGGGCCCGACTCTTAATT
GTAATGGAGATGATGGAAGGGGGAGAGCTATTTCACAGAATCAGCCAGCACCGGCACTTT
ACAGAGAAGCAAGCCAGCCAAGTAACAAAGCAGATAGCTTTGGCTCTGCGGCACTGTCAC
TTGTTAAACATTGCGCACAGAGACCTCAAGCCTGAAAATCTGCTTTTTAAGGATAACTCT
TTGGATGCCCCAGTGAAGTTGTGTGACTTTGGATTTGCCAAGATTGACCAAGGTGACTTG
ATGACACCCCAGTTCACCCCTTATTATGTAGCACCCCAGGTACTGGAGGCGCAAAGAAGG
CATCAGAAGGAGAAATCTGGCATCATACCTACCTCACCGACGCCCTACACTTACAACAAG
AGCTGTGACTTGTGGTCCCTAGGGGTGATTATCTATGTGATGCTGTGCGGATACCCTCCT
TTTTACTCCAAACACCACAGCCGGACTATCCCAAAGGATATGCGAAGAAAGATCATGACA
GGCAGTTTTGAGTTCCCAGAGGAAGAGTGGAGTCAGATCTCAGAGATGGCCAAAGATGTT
GTGAGGAAGCTCCTGAAGGTCAAACCGGAGGAGAGACTCACCATCGAGGGAGTGCTGGAC
CACCCCTGGCTCAATTCCACCGAGGCCCTGGATAATGTGCTGCCTTCTGCTCAGCTGATG
ATGGACAAGGCAGTGGTTGCAGGAATCCAGCAGGCTCACGCGGAACAGTTGGCCAACATG
AGAATCCAGGATCTGAAAGTCAGCCTCAAACCCCTGCACTCAGTGAACAACCCCATTCTG
CGGAAGAGGAAGTTACTTGGCACCAAGCCAAAGGACAGTGTCTATATCCACGACCATGAG
AATGGAGCCGAGGATTCCAATGTTGCCTTGGAAAAACTCCGAGATGTGATTGCTCAGTGT
ATTCTCCCCCAGGCTGGTAAAGGAGAGAATGAAGATGAGAAACTGAATGAAGTAATGCAG
GAGGCTTGGAAGTATAACCGGGAATGCAAACTCCTAAGAGATACTCTGCAGAGCTTCAGC
TGGAATGGTCGTGGATTCACAGATAAAGTAGATCGACTAAAACTGGCAGAAATTGTGAAG
CAGGTGATAGAAGAGCAAACCACGTCCCACGAATCCCAATAA
Chromosome Location
12
Locus
12q24.12-q24.13
External Identifiers
ResourceLink
UniProtKB IDQ8IW41
UniProtKB Entry NameMAPK5_HUMAN
HGNC IDHGNC:6889
General References
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  4. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
  5. Sudo T, Maruyama M, Osada H: p62 functions as a p38 MAP kinase regulator. Biochem Biophys Res Commun. 2000 Mar 16;269(2):521-5. [Article]
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  7. Tak H, Jang E, Kim SB, Park J, Suk J, Yoon YS, Ahn JK, Lee JH, Joe CO: 14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization. Cell Signal. 2007 Nov;19(11):2379-87. Epub 2007 Jul 31. [Article]
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  9. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
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  15. Kress TR, Cannell IG, Brenkman AB, Samans B, Gaestel M, Roepman P, Burgering BM, Bushell M, Rosenwald A, Eilers M: The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Mol Cell. 2011 Feb 18;41(4):445-57. doi: 10.1016/j.molcel.2011.01.023. [Article]
  16. Shiryaev A, Moens U: Mitogen-activated protein kinase p38 and MK2, MK3 and MK5: menage a trois or menage a quatre? Cell Signal. 2010 Aug;22(8):1185-92. doi: 10.1016/j.cellsig.2010.03.002. Epub 2010 Mar 11. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails