MAPK2_CRILO
ID MAPK2_CRILO Reviewed; 329 AA.
AC P49136;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=MAP kinase-activated protein kinase 2;
DE Short=MAPK-activated protein kinase 2;
DE Short=MAPKAP kinase 2;
DE Short=MAPKAP-K2;
DE Short=MAPKAPK-2;
DE Short=MK-2;
DE Short=MK2;
DE EC=2.7.11.1;
DE AltName: Full=P45-54 HSP27 kinase;
DE Flags: Fragment;
GN Name=MAPKAPK2;
OS Cricetulus longicaudatus (Long-tailed dwarf hamster) (Chinese hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10030;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=7851416; DOI=10.1111/j.1432-1033.1995.tb20404.x;
RA Huot J., Lambert H., Lavoie J.N., Guimond A., Houle F., Landry J.;
RT "Characterization of 45-kDa/54-kDa HSP27 kinase, a stress-sensitive kinase
RT which may activate the phosphorylation-dependent protective function of
RT mammalian 27-kDa heat-shock protein HSP27.";
RL Eur. J. Biochem. 227:416-427(1995).
CC -!- FUNCTION: Stress-activated serine/threonine-protein kinase involved in
CC cytokine production, endocytosis, reorganization of the cytoskeleton,
CC cell migration, cell cycle control, chromatin remodeling, DNA damage
CC response and transcriptional regulation. Following stress, it is
CC phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to
CC phosphorylation of substrates. Phosphorylates serine in the peptide
CC sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue.
CC Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0,
CC HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1,
CC RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the
CC interaction with HSP90 proteins and inhibiting HSF1 homotrimerization,
CC DNA-binding and transactivation activities. Mediates phosphorylation of
CC HSP27/HSPB1 in response to stress, leading to the dissociation of
CC HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and
CC impairment of their chaperone activities and ability to protect against
CC oxidative stress effectively. Involved in inflammatory response by
CC regulating tumor necrosis factor (TNF) and IL6 production post-
CC transcriptionally: acts by phosphorylating AU-rich elements (AREs)-
CC binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to
CC regulation of the stability and translation of TNF and IL6 mRNAs.
CC Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of
CC TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA
CC affinity, leading to inhibition of dependent degradation of ARE-
CC containing transcripts. Phosphorylates CEP131 in response to cellular
CC stress following ultraviolet irradiation which promotes binding of
CC CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar
CC satellites. Also involved in late G2/M checkpoint following DNA damage
CC through a process of post-transcriptional mRNA stabilization: following
CC DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates
CC HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in
CC toll-like receptor signaling pathway (TLR) in dendritic cells: required
CC for acute TLR-induced macropinocytosis by phosphorylating and
CC activating RPS6KA3. {ECO:0000250|UniProtKB:P49137}.
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 -!- 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;
CC -!- ACTIVITY REGULATION: Activated following phosphorylation by p38-
CC alpha/MAPK14 following various stresses. Inhibited following
CC sumoylation. Specifically inhibited by pyrrolopyridine inhibitors (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer with p38-alpha/MAPK14; this heterodimer forms a
CC stable complex: molecules are positioned 'face to face' so that the
CC ATP-binding sites of both kinases are at the heterodimer interface.
CC Interacts with PHC2. Interacts with HSF1.
CC {ECO:0000250|UniProtKB:P49137}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P49137}. Nucleus
CC {ECO:0000250|UniProtKB:P49137}. Note=Phosphorylation and subsequent
CC activation releases the autoinhibitory helix, resulting in the export
CC from the nucleus into the cytoplasm. {ECO:0000250|UniProtKB:P49137}.
CC -!- PTM: Sumoylation inhibits the protein kinase activity.
CC {ECO:0000250|UniProtKB:P49137}.
CC -!- PTM: Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at
CC Thr-151, Ser-201 and Thr-263. {ECO:0000250|UniProtKB:P49137}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; X82220; CAA57700.1; -; mRNA.
DR PIR; S49490; S49490.
DR AlphaFoldDB; P49136; -.
DR BMRB; P49136; -.
DR SMR; P49136; -.
DR PRIDE; P49136; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0044351; P:macropinocytosis; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0032675; P:regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0034097; P:response to cytokine; ISS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISS: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 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; DNA damage; Isopeptide bond; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN <1..329
FT /note="MAP kinase-activated protein kinase 2"
FT /id="PRO_0000086287"
FT DOMAIN <1..254
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 257..293
FT /note="Autoinhibitory helix"
FT /evidence="ECO:0000250"
FT REGION 295..319
FT /note="p38 MAPK-binding site"
FT /evidence="ECO:0000250"
FT MOTIF 285..294
FT /note="Nuclear export signal (NES)"
FT /evidence="ECO:0000250"
FT MOTIF 300..303
FT /note="Bipartite nuclear localization signal 1"
FT /evidence="ECO:0000250"
FT MOTIF 314..318
FT /note="Bipartite nuclear localization signal 2"
FT /evidence="ECO:0000250"
FT ACT_SITE 115
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING <1..7
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 22
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 68..70
FT /ligand="staurosporine"
FT /ligand_id="ChEBI:CHEBI:57491"
FT /evidence="ECO:0000250"
FT MOD_RES 151
FT /note="Phosphothreonine; by MAPK14"
FT /evidence="ECO:0000250|UniProtKB:P49137"
FT MOD_RES 201
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000250|UniProtKB:P49137"
FT MOD_RES 257
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 263
FT /note="Phosphothreonine; by MAPK14"
FT /evidence="ECO:0000250|UniProtKB:P49137"
FT CROSSLNK 282
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 329 AA; 38014 MW; A61F67DAA05EB88F CRC64;
LGINGKVLRI FDKRTQQKFA LKMLQDCPKA RREVELHWRA SQCPHIVDIV DVYENLYAGR
KCLLIVMECL DGGELFSRIQ DRGDQAFTER EASEIMKSIG EAIQYLHSIN IAHRDVKPEN
LLYTSKRPNA ILKLTDFGFA KETTSHNSLT TPCYTPYYVA PEVLGPEKYD KSCDMWSLGV
IMYILLCGYP PFYSNHGLAI SPGMKTRIRM GQYEFPNPEW SEVSEEVKML IRNLLKTEPT
QRMTITEFMN HPWIMQSTKV PQTPLHTSRV LKEDKERWED VKEEMTSALA TMRVDYEQIK
IKKIEDASNP LLLKRRKKAR AVEAAALAH
