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 24-JAN-2024, entry version 183. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyGen; O54992; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O54992; -. DR PhosphoSitePlus; O54992; -. DR MaxQB; O54992; -. DR PaxDb; 10090-ENSMUSP00000031410; -. DR PeptideAtlas; 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; ENSMUST00000031410.14; ENSMUSP00000031410.8; ENSMUSG00000029454.16. [O54992-1] DR Ensembl; ENSMUST00000111782.8; ENSMUSP00000107412.2; ENSMUSG00000029454.16. [O54992-4] DR Ensembl; ENSMUST00000111783.8; ENSMUSP00000107413.2; ENSMUSG00000029454.16. [O54992-5] DR Ensembl; ENSMUST00000111786.9; ENSMUSP00000107416.3; ENSMUSG00000029454.16. [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 AGR; MGI:1333110; -. 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; 1121238at2759; -. 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 33 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 63 other cell types or tissues. DR ExpressionAtlas; O54992; baseline and differential. 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:0032007; P:negative regulation of TOR signaling; IDA:UniProtKB. DR GO; GO:0060999; P:positive regulation of dendritic spine development; IMP: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 CDD; cd14171; STKc_MAPKAPK5; 1. DR Gene3D; 4.10.1170.10; MAP kinase activated protein kinase 2; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24349:SF179; MAP KINASE-ACTIVATED PROTEIN KINASE 5; 1. DR PANTHER; PTHR24349; SERINE/THREONINE-PROTEIN KINASE; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; O54992; MM. 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 //