MAPK5_MOUSE
ID MAPK5_MOUSE Reviewed; 473 AA.
AC O54992; E9QQ45; Q6QME4; Q6QME5; Q6QME6; Q6QME7;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=MAP kinase-activated protein kinase 5;
DE Short=MAPK-activated protein kinase 5;
DE Short=MAPKAP kinase 5;
DE Short=MAPKAPK-5;
DE EC=2.7.11.1;
GN Name=Mapkapk5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, MUTAGENESIS OF
RP LYS-51, ACTIVITY REGULATION, AND PHOSPHORYLATION BY ERK2/MAPK1 AND MAPK14.
RC TISSUE=Spleen;
RX PubMed=9480836; DOI=10.1006/bbrc.1998.8135;
RA Ni H., Wang X.S., Diener K., Yao Z.;
RT "MAPKAPK5, a novel mitogen-activated protein kinase (MAPK)-activated
RT protein kinase, is a substrate of the extracellular-regulated kinase (ERK)
RT and p38 kinase.";
RL Biochem. Biophys. Res. Commun. 243:492-496(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 5).
RA Benoit M.-J., Moise N., Mamarbachi A.M., Allen B.G.;
RT "Novel splice variants of MK5 from mouse heart.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=14560018; DOI=10.1128/mcb.23.21.7732-7741.2003;
RA Shi Y., Kotlyarov A., Laabeta K., Gruber A.D., Butt E., Marcus K.,
RA Meyer H.E., Friedrich A., Volk H.D., Gaestel M.;
RT "Elimination of protein kinase MK5/PRAK activity by targeted homologous
RT recombination.";
RL Mol. Cell. Biol. 23:7732-7741(2003).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF MAPK6, SUBCELLULAR LOCATION, INTERACTION
RP WITH MAPK6, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT THR-182, MUTAGENESIS OF
RP LYS-51 AND THR-182, AND DISRUPTION PHENOTYPE.
RX PubMed=15538386; DOI=10.1038/sj.emboj.7600467;
RA Schumacher S., Laass K., Kant S., Shi Y., Visel A., Gruber A.D.,
RA Kotlyarov A., Gaestel M.;
RT "Scaffolding by ERK3 regulates MK5 in development.";
RL EMBO J. 23:4770-4779(2004).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF MAPK6, SUBCELLULAR LOCATION, INTERACTION
RP WITH MAPK6, PHOSPHORYLATION AT THR-182, AND MUTAGENESIS OF THR-182.
RX PubMed=15577943; DOI=10.1038/sj.emboj.7600489;
RA Seternes O.M., Mikalsen T., Johansen B., Michaelsen E., Armstrong C.G.,
RA Morrice N.A., Turgeon B., Meloche S., Moens U., Keyse S.M.;
RT "Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel
RT signal transduction pathway.";
RL EMBO J. 23:4780-4791(2004).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF MAPK4, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH MAPK4.
RX PubMed=16973613; DOI=10.1074/jbc.m606693200;
RA Kant S., Schumacher S., Singh M.K., Kispert A., Kotlyarov A., Gaestel M.;
RT "Characterization of the atypical MAPK ERK4 and its activation of the MAPK-
RT activated protein kinase MK5.";
RL J. Biol. Chem. 281:35511-35519(2006).
RN [9]
RP MUTAGENESIS OF LEU-337.
RX PubMed=17997833; DOI=10.1186/1744-9081-3-58;
RA Gerits N., Van Belle W., Moens U.;
RT "Transgenic mice expressing constitutive active MAPKAPK5 display gender-
RT dependent differences in exploration and activity.";
RL Behav. Brain Funct. 3:58-58(2007).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF TP53, DISRUPTION PHENOTYPE, AND MUTAGENESIS
RP OF LYS-51 AND THR-182.
RX PubMed=17254968; DOI=10.1016/j.cell.2006.11.050;
RA Sun P., Yoshizuka N., New L., Moser B.A., Li Y., Liao R., Xie C., Chen J.,
RA Deng Q., Yamout M., Dong M.Q., Frangou C.G., Yates J.R. III, Wright P.E.,
RA Han J.;
RT "PRAK is essential for ras-induced senescence and tumor suppression.";
RL Cell 128:295-308(2007).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=17947239; DOI=10.1074/jbc.m704873200;
RA Gerits N., Mikalsen T., Kostenko S., Shiryaev A., Johannessen M., Moens U.;
RT "Modulation of F-actin rearrangement by the cyclic AMP/cAMP-dependent
RT protein kinase (PKA) pathway is mediated by MAPK-activated protein kinase 5
RT and requires PKA-induced nuclear export of MK5.";
RL J. Biol. Chem. 282:37232-37243(2007).
RN [12]
RP INTERACTION WITH MAPK4.
RX PubMed=18248330; DOI=10.1042/bj20071369;
RA Perander M., Aberg E., Johansen B., Dreyer B., Guldvik I.J., Outzen H.,
RA Keyse S.M., Seternes O.M.;
RT "The Ser(186) phospho-acceptor site within ERK4 is essential for its
RT ability to interact with and activate PRAK/MK5.";
RL Biochem. J. 411:613-622(2008).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=18268017; DOI=10.1074/jbc.m709682200;
RA Li Q., Zhang N., Zhang D., Wang Y., Lin T., Wang Y., Zhou H., Ye Z.,
RA Zhang F., Lin S.C., Han J.;
RT "Determinants that control the distinct subcellular localization of
RT p38alpha-PRAK and p38beta-PRAK complexes.";
RL J. Biol. Chem. 283:11014-11023(2008).
RN [14]
RP INTERACTION WITH MAPK4 AND MAPK6.
RX PubMed=18720373; DOI=10.1002/jcp.21560;
RA Deleris P., Rousseau J., Coulombe P., Rodier G., Tanguay P.L., Meloche S.;
RT "Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4
RT is required for binding, activation and cytoplasmic relocalization of
RT MK5.";
RL J. Cell. Physiol. 217:778-788(2008).
RN [15]
RP INTERACTION WITH MAPK4 AND MAPK6.
RX PubMed=19473979; DOI=10.1074/jbc.m109.023283;
RA Aberg E., Torgersen K.M., Johansen B., Keyse S.M., Perander M.,
RA Seternes O.M.;
RT "Docking of PRAK/MK5 to the atypical MAPKs ERK3 and ERK4 defines a novel
RT MAPK interaction motif.";
RL J. Biol. Chem. 284:19392-19401(2009).
RN [16]
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND
RP MUTAGENESIS OF THR-182.
RX PubMed=20640477; DOI=10.1007/s00018-010-0452-1;
RA Kostenko S., Khan M.T., Sylte I., Moens U.;
RT "The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK)
RT inhibitor.";
RL Cell. Mol. Life Sci. 68:289-301(2011).
RN [17]
RP PHOSPHORYLATION AT SER-115, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP SER-115.
RX PubMed=20734105; DOI=10.1007/s00018-010-0496-2;
RA Kostenko S., Shiryaev A., Gerits N., Dumitriu G., Klenow H.,
RA Johannessen M., Moens U.;
RT "Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its
RT PKA-regulated nuclear export and biological function.";
RL Cell. Mol. Life Sci. 68:847-862(2011).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF HSPB1.
RX PubMed=21575178; DOI=10.1186/1750-2187-6-4;
RA Shiryaev A., Dumitriu G., Moens U.;
RT "Distinct roles of MK2 and MK5 in cAMP/PKA- and stress/p38MAPK-induced heat
RT shock protein 27 phosphorylation.";
RL J. Mol. Signal. 6:4-4(2011).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF RHEB, AND MUTAGENESIS OF LYS-51.
RX PubMed=21336308; DOI=10.1038/ncb2168;
RA Zheng M., Wang Y.H., Wu X.N., Wu S.Q., Lu B.J., Dong M.Q., Zhang H.,
RA Sun P., Lin S.C., Guan K.L., Han J.;
RT "Inactivation of Rheb by PRAK-mediated phosphorylation is essential for
RT energy-depletion-induced suppression of mTORC1.";
RL Nat. Cell Biol. 13:263-272(2011).
CC -!- FUNCTION: Tumor suppressor serine/threonine-protein kinase involved in
CC mTORC1 signaling and post-transcriptional regulation. Phosphorylates
CC FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as
CC a tumor suppressor by mediating Ras-induced senescence and
CC phosphorylating p53/TP53. Involved in post-transcriptional regulation
CC of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3
CC leads to promote nuclear localization of FOXO3, enabling expression of
CC miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind
CC to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a
CC negative regulator of mTORC1 signaling by mediating phosphorylation and
CC inhibition of RHEB. Part of the atypical MAPK signaling via its
CC interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the
CC complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the
CC complex follows a complex set of phosphorylation events: upon
CC interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6
CC (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and
CC activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or
CC ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to
CC PKA/PRKACA stimulation, inducing F-actin rearrangement.
CC {ECO:0000269|PubMed:15538386, ECO:0000269|PubMed:15577943,
CC ECO:0000269|PubMed:16973613, ECO:0000269|PubMed:17254968,
CC ECO:0000269|PubMed:21336308, ECO:0000269|PubMed:21575178}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:20640477};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:20640477};
CC -!- ACTIVITY REGULATION: Activated following phosphorylation at Thr-182 by
CC p38-alpha/MAPK14, p38-beta/MAPK11, ERK2/MAPK1, ERK3/MAPK6, and
CC ERK4/MAPK4. Activated by stress-related extracellular stimuli; such as
CC H(2)O(2), arsenite, anisomycin TNF alpha and also PMA and the calcium
CC ionophore A23187; but to a lesser extent. In vitro, activated by
CC SQSTM1. Inhibited by diterpenoid alkaloid noroxoaconitine.
CC {ECO:0000269|PubMed:20640477, ECO:0000269|PubMed:9480836}.
CC -!- SUBUNIT: Interacts with SQSTM1 (By similarity). Interacts with
CC ERK3/MAPK6 and ERK4/MAPK4 (via FRIEDE motif); the interaction is
CC direct. Interacts with YWHAE; the interaction prevents phosphorylation
CC of HSP27/HSPB1 leading to disrupt F-actin polymerization. {ECO:0000250,
CC ECO:0000269|PubMed:15538386, ECO:0000269|PubMed:15577943,
CC ECO:0000269|PubMed:16973613, ECO:0000269|PubMed:18248330,
CC ECO:0000269|PubMed:18720373, ECO:0000269|PubMed:19473979}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates to the
CC cytoplasm following phosphorylation and activation. Interaction with
CC ERK3/MAPK6 or ERK4/MAPK4 and phosphorylation at Thr-182, activates the
CC protein kinase activity, followed by translocation to the cytoplasm.
CC Phosphorylation by PKA/PRKACA at Ser-115 also induces nuclear export.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=MK-5 type 1;
CC IsoId=O54992-1; Sequence=Displayed;
CC Name=2; Synonyms=MK-5 type 3;
CC IsoId=O54992-2; Sequence=VSP_011600;
CC Name=3; Synonyms=MK-5 type 4;
CC IsoId=O54992-3; Sequence=VSP_011599;
CC Name=4; Synonyms=MK-5 type 5;
CC IsoId=O54992-4; Sequence=VSP_011599, VSP_011598;
CC Name=5; Synonyms=MK-5 type 2;
CC IsoId=O54992-5; Sequence=VSP_011598;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously.
CC {ECO:0000269|PubMed:9480836}.
CC -!- PTM: Phosphorylated on Thr-182 ERK3/MAPK6 or ERK4/MAPK4; which is the
CC regulatory phosphorylation site and is located on the T-loop/loop 12,
CC leading to activation. Phosphorylation at Thr-182 by p38-alpha/MAPK14,
CC p38-beta/MAPK11 is subject to debate. Phosphorylated at Ser-115 by
CC PKA/PRKACA, leading to localization to the cytoplasm.
CC Autophosphorylated. {ECO:0000269|PubMed:15538386,
CC ECO:0000269|PubMed:15577943, ECO:0000269|PubMed:20734105,
CC ECO:0000269|PubMed:9480836}.
CC -!- DISRUPTION PHENOTYPE: Phenotypes are different depending on reports.
CC According to a first report, mice are viable and fertile and do not
CC show changes in tissue morphology and behavior: they exhibit the same
CC susceptibility to LPS-induced endotoxic shock as wild-type animals and
CC do not show the defects in LPS-induced biosynthesis of inflammatory
CC cytokines known to occur with Mapkapk2-deficient animals
CC (PubMed:14560018). According to another report, both homozygous and
CC heterozygous mutant mice are highly susceptible to skin carcinogenesis
CC induced by DMBA (PubMed:17254968). According to a third report, mutant
CC show embryonic lethality around 11 dpc in a C57BL/6 background
CC (PubMed:15538386). {ECO:0000269|PubMed:14560018,
CC ECO:0000269|PubMed:15538386, ECO:0000269|PubMed:17254968}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- CAUTION: The role of p38 MAPK kinases is unclear in phosphorylation and
CC activation of Mapkapk5. According to some reports, it interacts and is
CC phosphorylated by p38-alpha/MAPK14 and p38-beta/MAPK11
CC (PubMed:9480836). According to other reports, it is not activated by
CC p38-alpha/MAPK14 and p38-beta/MAPK11 (PubMed:14560018). An explanation
CC for these discrepancies, might be that the interaction with p38 MAPK
CC kinases is weak and occurs only under specific conditions.
CC {ECO:0000305|PubMed:14560018, ECO:0000305|PubMed:9480836}.
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DR EMBL; AF039840; AAC40047.1; -; mRNA.
DR EMBL; AY533679; AAS22330.1; -; mRNA.
DR EMBL; AY533680; AAS22331.2; -; mRNA.
DR EMBL; AY533681; AAS22332.1; -; mRNA.
DR EMBL; AY533682; AAS22333.1; -; mRNA.
DR EMBL; AC155316; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC019184; AAH19184.1; -; mRNA.
DR CCDS; CCDS39248.1; -. [O54992-1]
DR PIR; JC5952; JC5952.
DR RefSeq; NP_034895.1; NM_010765.2. [O54992-1]
DR AlphaFoldDB; O54992; -.
DR SMR; O54992; -.
DR BioGRID; 201309; 11.
DR IntAct; O54992; 3.
DR STRING; 10090.ENSMUSP00000031410; -.
DR iPTMnet; O54992; -.
DR PhosphoSitePlus; O54992; -.
DR MaxQB; O54992; -.
DR PaxDb; O54992; -.
DR PeptideAtlas; O54992; -.
DR PRIDE; O54992; -.
DR ProteomicsDB; 292019; -. [O54992-1]
DR ProteomicsDB; 292020; -. [O54992-2]
DR ProteomicsDB; 292021; -. [O54992-3]
DR ProteomicsDB; 292022; -. [O54992-4]
DR ProteomicsDB; 292023; -. [O54992-5]
DR DNASU; 17165; -.
DR Ensembl; ENSMUST00000031410; ENSMUSP00000031410; ENSMUSG00000029454. [O54992-1]
DR Ensembl; ENSMUST00000111782; ENSMUSP00000107412; ENSMUSG00000029454. [O54992-4]
DR Ensembl; ENSMUST00000111783; ENSMUSP00000107413; ENSMUSG00000029454. [O54992-5]
DR Ensembl; ENSMUST00000111786; ENSMUSP00000107416; ENSMUSG00000029454. [O54992-3]
DR GeneID; 17165; -.
DR KEGG; mmu:17165; -.
DR UCSC; uc008zjq.1; mouse. [O54992-1]
DR UCSC; uc008zjr.1; mouse. [O54992-3]
DR UCSC; uc008zjs.1; mouse. [O54992-4]
DR CTD; 8550; -.
DR MGI; MGI:1333110; Mapkapk5.
DR VEuPathDB; HostDB:ENSMUSG00000029454; -.
DR VEuPathDB; HostDB:ENSMUSG00000072647; -.
DR eggNOG; KOG0604; Eukaryota.
DR GeneTree; ENSGT00940000154089; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; O54992; -.
DR OMA; QTASHES; -.
DR OrthoDB; 843707at2759; -.
DR PhylomeDB; O54992; -.
DR TreeFam; TF312891; -.
DR Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-MMU-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR BioGRID-ORCS; 17165; 1 hit in 30 CRISPR screens.
DR ChiTaRS; Mapkapk5; mouse.
DR PRO; PR:O54992; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O54992; protein.
DR Bgee; ENSMUSG00000029454; Expressed in zone of skin and 60 other tissues.
DR ExpressionAtlas; O54992; baseline and differential.
DR Genevisible; O54992; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0032156; C:septin cytoskeleton; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:UniProtKB.
DR GO; GO:0002039; F:p53 binding; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; IMP:MGI.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:MGI.
DR GO; GO:1904355; P:positive regulation of telomere capping; ISO:MGI.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; ISS:UniProtKB.
DR GO; GO:0090400; P:stress-induced premature senescence; IMP:UniProtKB.
DR Gene3D; 4.10.1170.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR027442; MAPKAPK_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Coiled coil; Cytoplasm; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tumor suppressor.
FT CHAIN 1..473
FT /note="MAP kinase-activated protein kinase 5"
FT /id="PRO_0000086297"
FT DOMAIN 22..304
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT COILED 409..440
FT /evidence="ECO:0000255"
FT ACT_SITE 148
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 28..36
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 51
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 115
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:20734105"
FT MOD_RES 182
FT /note="Phosphothreonine; by MAPK11, MAPK14, MAPK4, MAPK6
FT and PKA"
FT /evidence="ECO:0000269|PubMed:15538386,
FT ECO:0000269|PubMed:15577943"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IW41"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IW41"
FT VAR_SEQ 13..161
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_011599"
FT VAR_SEQ 344..408
FT /note="DLKVSLKPLHSVNNPILRKRKLLGTKPKDGIYIHDHENGTEDSNVALEKLRD
FT VIAQCILPQAGKG -> E (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_011600"
FT VAR_SEQ 407..408
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_011598"
FT MUTAGEN 51
FT /note="K->E: No p38-alpha/MAPK14-, p38-beta/MAPK11-,
FT ERK3/MAPK6-, ERK4/MAPK4-induced activation."
FT /evidence="ECO:0000269|PubMed:15538386,
FT ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:21336308,
FT ECO:0000269|PubMed:9480836"
FT MUTAGEN 51
FT /note="K->R,M: Kinase defective mutant, abolishes
FT activity."
FT /evidence="ECO:0000269|PubMed:15538386,
FT ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:21336308,
FT ECO:0000269|PubMed:9480836"
FT MUTAGEN 115
FT /note="S->A: Impairs shuttling to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:20734105"
FT MUTAGEN 115
FT /note="S->D: Mimicks phosphorylation state, leading to
FT localization to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:20734105"
FT MUTAGEN 182
FT /note="T->A: Impairs protein kinase activity and shuttling
FT to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:15538386,
FT ECO:0000269|PubMed:15577943, ECO:0000269|PubMed:17254968,
FT ECO:0000269|PubMed:20640477"
FT MUTAGEN 337
FT /note="L->A: Constitutive active mutant. In a knockin
FT model, mouse display increased amounts of head dips and
FT open arm time on the maze, compared to littermate controls.
FT In addition, they also explore further into the open arm on
FT the elevated plus maze and are less active in the closed
FT arm compared to littermate controls. Male knockin mice
FT display no differences in anxiety, but their locomotor
FT activity increases compared to non-transgenic littermates."
FT /evidence="ECO:0000269|PubMed:17997833"
SQ SEQUENCE 473 AA; 54152 MW; 45441A735075B247 CRC64;
MSEDSDMEKA IKETSILEEY SINWTQKLGA GISGPVRVCV KKSTQERFAL KILLDRPKAR
NEVRLHMMCA THPNIVQIIE VFANSVQFPH ESSPRARLLI VMEMMEGGEL FHRISQHRHF
TEKQASQVTK QIALALQHCH LLNIAHRDLK PENLLFKDNS LDAPVKLCDF GFAKVDQGDL
MTPQFTPYYV APQVLEAQRR HQKEKSGIIP TSPTPYTYNK SCDLWSLGVI IYVMLCGYPP
FYSKHHSRTI PKDMRKKIMT GSFEFPEEEW SQISEMAKDV VRKLLKVKPE ERLTIEGVLD
HPWLNSTEAL DNVLPSAQLM MDKAVVAGIQ QAHAEQLANM RIQDLKVSLK PLHSVNNPIL
RKRKLLGTKP KDGIYIHDHE NGTEDSNVAL EKLRDVIAQC ILPQAGKGEN EDEKLNEVMQ
EAWKYNRECK LLRDALQSFS WNGRGFTDKV DRLKLAEVVK QVIEEQTLPH EPQ
