MK09_RAT
ID MK09_RAT Reviewed; 423 AA.
AC P49186;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Mitogen-activated protein kinase 9;
DE Short=MAP kinase 9;
DE Short=MAPK 9;
DE EC=2.7.11.24 {ECO:0000269|PubMed:10856240};
DE AltName: Full=SAPK-alpha;
DE AltName: Full=Stress-activated protein kinase JNK2;
DE AltName: Full=c-Jun N-terminal kinase 2;
DE AltName: Full=p54-alpha;
GN Name=Mapk9; Synonyms=Jnk2, Prkm9;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2), AND PARTIAL
RP PROTEIN SEQUENCE.
RC TISSUE=Brain;
RX PubMed=8177321; DOI=10.1038/369156a0;
RA Kyriakis J.M., Banerjee P., Nikolakaki E., Dai T., Rubie E.A., Ahmad M.F.,
RA Avruch J., Woodgett J.R.;
RT "The stress-activated protein kinase subfamily of c-Jun kinases.";
RL Nature 369:156-160(1994).
RN [2]
RP INTERACTION WITH MECOM, AND CATALYTIC ACTIVITY.
RX PubMed=10856240; DOI=10.1093/emboj/19.12.2958;
RA Kurokawa M., Mitani K., Yamagata T., Takahashi T., Izutsu K., Ogawa S.,
RA Moriguchi T., Nishida E., Yazaki Y., Hirai H.;
RT "The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents
RT stress-induced cell death.";
RL EMBO J. 19:2958-2968(2000).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in various processes
CC such as cell proliferation, differentiation, migration, transformation
CC and programmed cell death. Extracellular stimuli such as pro-
CC inflammatory cytokines or physical stress stimulate the stress-
CC activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling
CC pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and
CC MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2
CC phosphorylates a number of transcription factors, primarily components
CC of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional
CC activity. In response to oxidative or ribotoxic stresses, inhibits rRNA
CC synthesis by phosphorylating and inactivating the RNA polymerase 1-
CC specific transcription initiation factor RRN3. Promotes stressed cell
CC apoptosis by phosphorylating key regulatory factors including TP53 and
CC YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized
CC differentiation of T-helper cells into Th1 cells. Upon T-cell receptor
CC (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and
CC MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in
CC the osmotic stress-induced epithelial tight-junctions disruption. When
CC activated, promotes beta-catenin/CTNNB1 degradation and inhibits the
CC canonical Wnt signaling pathway. Participates also in neurite growth in
CC spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1
CC heterodimer and plays a role in the regulation of the circadian clock.
CC Phosphorylates POU5F1, which results in the inhibition of POU5F1's
CC transcriptional activity and enhances its proteosomal degradation.
CC {ECO:0000250|UniProtKB:P45984, ECO:0000250|UniProtKB:Q9WTU6}.
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=2.7.11.24;
CC Evidence={ECO:0000269|PubMed:10856240};
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=2.7.11.24; Evidence={ECO:0000269|PubMed:10856240};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P45984};
CC -!- ACTIVITY REGULATION: Activated by threonine and tyrosine
CC phosphorylation by either of two dual specificity kinases, MAP2K4 and
CC MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7
CC phosphorylates Tyr-183 preferentially. Inhibited by dual specificity
CC phosphatases, such as DUSP1. {ECO:0000250|UniProtKB:P45984}.
CC -!- SUBUNIT: Interacts with MECOM (PubMed:10856240). Binds to at least four
CC scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-
CC 3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other
CC components of the JNK signaling pathway (By similarity). Interacts with
CC NFATC4 (By similarity). Interacts with ATF7; the interaction does not
CC phosphorylate ATF7 but acts as a docking site for ATF7-associated
CC partners such as JUN (By similarity). Interacts with BCL10 (By
CC similarity). Interacts with CTNNB1 and GSK3B (By similarity). Interacts
CC with DCLK2 (By similarity). Interacts with MAPKBP1 (By similarity).
CC Interacts with POU5F1; phosphorylates POU5F1 at 'Ser-347'. Found in a
CC complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and
CC MAPK8/JNK1 (By similarity). {ECO:0000250|UniProtKB:P45984,
CC ECO:0000250|UniProtKB:Q9WTU6, ECO:0000269|PubMed:10856240}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P45984}. Nucleus
CC {ECO:0000250|UniProtKB:Q9WTU6}. Note=Colocalizes with POU5F1 in the
CC nucleus. {ECO:0000250|UniProtKB:Q9WTU6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha-2;
CC IsoId=P49186-1; Sequence=Displayed;
CC Name=Alpha-1;
CC IsoId=P49186-2; Sequence=VSP_004838;
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4,
CC which activates the enzyme. Autophosphorylated in vitro.
CC {ECO:0000250|UniProtKB:P45984}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
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DR EMBL; L27112; AAA42109.1; -; mRNA.
DR EMBL; L27111; AAA42108.1; -; mRNA.
DR PIR; S43968; S43968.
DR RefSeq; NP_001257473.1; NM_001270544.1.
DR RefSeq; NP_059018.1; NM_017322.2. [P49186-1]
DR AlphaFoldDB; P49186; -.
DR SMR; P49186; -.
DR BioGRID; 248408; 1.
DR IntAct; P49186; 2.
DR MINT; P49186; -.
DR STRING; 10116.ENSRNOP00000003987; -.
DR iPTMnet; P49186; -.
DR PhosphoSitePlus; P49186; -.
DR jPOST; P49186; -.
DR PaxDb; P49186; -.
DR PRIDE; P49186; -.
DR GeneID; 50658; -.
DR KEGG; rno:50658; -.
DR UCSC; RGD:628847; rat. [P49186-1]
DR CTD; 5601; -.
DR RGD; 628847; Mapk9.
DR eggNOG; KOG0665; Eukaryota.
DR InParanoid; P49186; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; P49186; -.
DR BRENDA; 2.7.11.24; 5301.
DR Reactome; R-RNO-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-RNO-2871796; FCERI mediated MAPK activation.
DR Reactome; R-RNO-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-RNO-450341; Activation of the AP-1 family of transcription factors.
DR PRO; PR:P49186; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; P49186; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IMP:RGD.
DR GO; GO:0004705; F:JUN kinase activity; IDA:RGD.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; ISO:RGD.
DR GO; GO:0071474; P:cellular hyperosmotic response; IEP:RGD.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEP:RGD.
DR GO; GO:0071276; P:cellular response to cadmium ion; ISO:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0034644; P:cellular response to UV; IMP:RGD.
DR GO; GO:0007417; P:central nervous system development; IEP:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007254; P:JNK cascade; IDA:RGD.
DR GO; GO:0007258; P:JUN phosphorylation; IMP:RGD.
DR GO; GO:0048666; P:neuron development; IEP:RGD.
DR GO; GO:0031175; P:neuron projection development; IMP:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0010770; P:positive regulation of cell morphogenesis involved in differentiation; IMP:RGD.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; ISO:RGD.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:RGD.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IMP:RGD.
DR GO; GO:0071803; P:positive regulation of podosome assembly; ISO:RGD.
DR GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; IMP:RGD.
DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; IMP:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:1901485; P:positive regulation of transcription factor catabolic process; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:RGD.
DR GO; GO:0061833; P:protein localization to tricellular tight junction; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0006626; P:protein targeting to mitochondrion; IEP:RGD.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0046328; P:regulation of JNK cascade; IMP:RGD.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IMP:RGD.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:RGD.
DR GO; GO:0014075; P:response to amine; IEP:RGD.
DR GO; GO:0046686; P:response to cadmium ion; ISO:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:1990089; P:response to nerve growth factor; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0009414; P:response to water deprivation; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:RGD.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008351; MAPK_JNK.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01772; JNKMAPKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01351; MAPK; 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; Biological rhythms; Cytoplasm;
KW Direct protein sequencing; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..423
FT /note="Mitogen-activated protein kinase 9"
FT /id="PRO_0000186275"
FT DOMAIN 26..321
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 366..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 183..185
FT /note="TXY"
FT COMPBIAS 374..415
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 151
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 32..40
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 55
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 183
FT /note="Phosphothreonine; by MAP2K7"
FT /evidence="ECO:0000250|UniProtKB:P45984"
FT MOD_RES 185
FT /note="Phosphotyrosine; by MAP2K4"
FT /evidence="ECO:0000250|UniProtKB:P45984"
FT VAR_SEQ 216..230
FT /note="GELVKGCVIFQGTDH -> AEMVLHKSCSPGRDY (in isoform
FT Alpha-1)"
FT /evidence="ECO:0000303|PubMed:8177321"
FT /id="VSP_004838"
SQ SEQUENCE 423 AA; 48017 MW; EE549B9F4F12F421 CRC64;
MSDSKSDGQF YSVQVADSTF TVLKRYQQLK PIGSGAQGIV CAAFDTVLGI NVAVKKLSRP
FQNQTHAKRA YRELVLLKCV NHKNIISLLN VFTPQKTLEE FQDVYLVMEL MDANLCQVIH
MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTACTNF
MMTPYVVTRY YRAPEVILGM GYKENVDIWS VGCIMGELVK GCVIFQGTDH IDQWNKVIEQ
LGTPSAEFMK KLQPTVRNYV ENRPKYPGIK FEELFPDWIF PSESERDKIK TSQARDLLSK
MLVIDPDKRI SVDEALRHPY ITVWYDPAEA EAPPPQIYDA QLEEREHAIE EWKELIYKEV
MDWEERSKNG VKDQPSDAAV SSKATPSQSS SINDISSMST EHTLASDTDS SLDASTGPLE
GCR
