ID MK10_RAT Reviewed; 464 AA.
AC P49187; B0VXR6; D3ZQ33;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 3.
DT 24-JAN-2024, entry version 187.
DE RecName: Full=Mitogen-activated protein kinase 10;
DE Short=MAP kinase 10;
DE Short=MAPK 10;
DE EC=2.7.11.24;
DE AltName: Full=SAPK-beta;
DE AltName: Full=Stress-activated protein kinase JNK3;
DE AltName: Full=c-Jun N-terminal kinase 3;
DE AltName: Full=p54-beta;
GN Name=Mapk10; Synonyms=Jnk3, Prkm10;
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] (ISOFORM 1).
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 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH MAPK8IP1 AND
RP MAPK8IP3.
RC STRAIN=Sprague-Dawley; TISSUE=Heart;
RX PubMed=21076496; DOI=10.1139/y10-088;
RA Xu B., Zhou Y., Karmin O., Choy P.C., Pierce G.N., Siow Y.L.;
RT "Regulation of stress-associated scaffold proteins JIP1 and JIP3 on the c-
RT Jun NH2-terminal kinase in ischemia-reperfusion.";
RL Can. J. Physiol. Pharmacol. 88:1084-1092(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP IDENTIFICATION OF PROBABLE FRAMESHIFT.
RA Hulo-Demole C., Braconi-Quintaje S.;
RL Unpublished observations (MAR-1997).
RN [6]
RP INTERACTION WITH ARRB2.
RX PubMed=11090355; DOI=10.1126/science.290.5496.1574;
RA McDonald P.H., Chow C.W., Miller W.E., Laporte S.A., Field M.E., Lin F.-T.,
RA Davis R.J., Lefkowitz R.J.;
RT "Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of
RT JNK3.";
RL Science 290:1574-1577(2000).
RN [7]
RP FUNCTION.
RX PubMed=12424734; DOI=10.1002/jnr.10437;
RA Bruckner S.R., Estus S.;
RT "JNK3 contributes to c-jun induction and apoptosis in 4-hydroxynonenal-
RT treated sympathetic neurons.";
RL J. Neurosci. Res. 70:665-670(2002).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF APP.
RX PubMed=15944381; DOI=10.1523/jneurosci.4883-04.2005;
RA Kimberly W.T., Zheng J.B., Town T., Flavell R.A., Selkoe D.J.;
RT "Physiological regulation of the beta-amyloid precursor protein signaling
RT domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation.";
RL J. Neurosci. 25:5533-5543(2005).
RN [9]
RP INTERACTION WITH ARRB2.
RX PubMed=18408005; DOI=10.1074/jbc.m710006200;
RA Guo C., Whitmarsh A.J.;
RT "The beta-arrestin-2 scaffold protein promotes c-Jun N-terminal kinase-3
RT activation by binding to its nonconserved N terminus.";
RL J. Biol. Chem. 283:15903-15911(2008).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in various processes
CC such as neuronal proliferation, differentiation, migration and
CC programmed cell death. Extracellular stimuli such as pro-inflammatory
CC cytokines or physical stress stimulate the stress-activated protein
CC kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this
CC cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7
CC phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3
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. Plays regulatory roles in the signaling pathways during
CC neuronal apoptosis. Phosphorylates the neuronal microtubule regulator
CC STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP
CC signaling during neuronal differentiation by phosphorylating APP.
CC Participates also in neurite growth in spiral ganglion neurons.
CC Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the
CC photic regulation of the circadian clock (By similarity).
CC Phosphorylates JUND and this phosphorylation is inhibited in the
CC presence of MEN1 (By similarity). {ECO:0000250|UniProtKB:Q61831,
CC ECO:0000269|PubMed:12424734, ECO:0000269|PubMed:15944381}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by threonine and tyrosine
CC phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7.
CC MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change
CC and a large increase in Vmax for the enzyme. MAP2K4 then phosphorylates
CC Tyr-223 resulting in a further increase in Vmax. Inhibited by dual
CC specificity phosphatases, such as DUSP1. Inhibited by HDAC9 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with MAPK8IP1/JIP-1 and MAPK8IP3/JIP-3/JSAP1
CC (PubMed:21076496). Interacts with SPAG9/MAPK8IP4/JIP4 (By similarity).
CC Interacts with HDAC9 and MAPKBP1 (By similarity). Interacts with ARRB2;
CC the interaction enhances MAPK10 activation by MAP3K5 (By similarity).
CC Interacts with SARM1 (By similarity). Interacts with JUND; interaction
CC is inhibited in the presence of MEN1 (By similarity).
CC {ECO:0000250|UniProtKB:P53779, ECO:0000250|UniProtKB:Q61831,
CC ECO:0000269|PubMed:21076496}.
CC -!- INTERACTION:
CC P49187; P50232: Syt4; NbExp=2; IntAct=EBI-7155513, EBI-540118;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Lipid-anchor. Nucleus.
CC Mitochondrion. Note=Palmitoylation regulates MAPK10 trafficking to
CC cytoskeleton. Recruited to the mitochondria in the presence of SARM1.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49187-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49187-2; Sequence=VSP_059665;
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-221 and Tyr-223 by MAP2K4 and MAP2K7,
CC which activates the enzyme. MAP2K7 shows a strong preference for Thr-
CC 221 while MAP2K4 phosphorylates Tyr-223 preferentially. Weakly
CC autophosphorylated on threonine and tyrosine residues in vitro (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Palmitoylation regulates subcellular location and axonal
CC development. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA42110.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L27128; AAA42110.1; ALT_FRAME; mRNA.
DR EMBL; DQ377224; ABD24063.1; -; mRNA.
DR EMBL; AABR07014301; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07072369; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC141145; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474022; EDL99527.1; -; Genomic_DNA.
DR PIR; S43969; S43969.
DR RefSeq; NP_036938.2; NM_012806.2. [P49187-2]
DR RefSeq; XP_017454572.1; XM_017599083.1. [P49187-2]
DR AlphaFoldDB; P49187; -.
DR SMR; P49187; -.
DR BioGRID; 247312; 1.
DR ELM; P49187; -.
DR IntAct; P49187; 1.
DR MINT; P49187; -.
DR STRING; 10116.ENSRNOP00000075846; -.
DR BindingDB; P49187; -.
DR ChEMBL; CHEMBL4092; -.
DR iPTMnet; P49187; -.
DR PhosphoSitePlus; P49187; -.
DR SwissPalm; P49187; -.
DR jPOST; P49187; -.
DR PaxDb; 10116-ENSRNOP00000060904; -.
DR GeneID; 25272; -.
DR KEGG; rno:25272; -.
DR AGR; RGD:3663; -.
DR CTD; 5602; -.
DR RGD; 3663; Mapk10.
DR VEuPathDB; HostDB:ENSRNOG00000002079; -.
DR eggNOG; KOG0665; Eukaryota.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P49187; -.
DR PhylomeDB; P49187; -.
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:P49187; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Proteomes; UP000234681; Chromosome 14.
DR Bgee; ENSRNOG00000002079; Expressed in frontal cortex and 15 other cell types or tissues.
DR ExpressionAtlas; P49187; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0150051; C:postsynaptic Golgi apparatus; IDA:SynGO.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0004705; F:JUN kinase activity; IDA:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0071474; P:cellular hyperosmotic response; IEP:RGD.
DR GO; GO:0007254; P:JNK cascade; IDA:RGD.
DR GO; GO:0045475; P:locomotor rhythm; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL.
DR GO; GO:0098969; P:neurotransmitter receptor transport to postsynaptic membrane; IDA:SynGO.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0009416; P:response to light stimulus; ISS:UniProtKB.
DR GO; GO:0099003; P:vesicle-mediated transport in synapse; IDA:SynGO.
DR CDD; cd07850; STKc_JNK; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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 PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1.
DR PANTHER; PTHR24055:SF162; MITOGEN-ACTIVATED PROTEIN KINASE 10; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01772; JNKMAPKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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; Kinase;
KW Lipoprotein; Membrane; Mitochondrion; Nucleotide-binding; Nucleus;
KW Palmitate; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..464
FT /note="Mitogen-activated protein kinase 10"
FT /id="PRO_0000186279"
FT DOMAIN 64..359
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 405..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 221..223
FT /note="TXY"
FT COMPBIAS 406..454
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 189
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 70..78
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 221
FT /note="Phosphothreonine; by MAP2K7"
FT /evidence="ECO:0000250|UniProtKB:P53779"
FT MOD_RES 223
FT /note="Phosphotyrosine; by MAP2K4"
FT /evidence="ECO:0000250|UniProtKB:P53779"
FT LIPID 462
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 463
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..38
FT /note="Missing (in isoform 2)"
FT /id="VSP_059665"
FT CONFLICT 175..176
FT /note="CG -> SA (in Ref. 1; AAA42110)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 464 AA; 52532 MW; 1B08210326F4EEDD CRC64;
MSLHFLYYCS EPTLDVKIAF CQGFDKHVDV SSVVKHYNMS KSKVDNQFYS VEVGDSTFTV
LKRYQNLKPI GSGAQGIVCA AYDAVLDRNV AIKKLSRPFQ NQTHAKRAYR ELVLMKCVNH
KNIISLLNVF TPQKTLEEFQ DVYLVMELMD ANLCQVIQME LDHERMSYLL YQMLCGIKHL
HSAGIIHRDL KPSNIVVKSD CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY
KENVDIWSVG CIMGEMVRHK ILFPGRDYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN
RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPAKRISV DDALQHPYIN
VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN SEEKTKNGVV KGQPSPSGAA
VNSSESLPPS SSVNDISSMS TDQTLASDTD SSLEASAGPL GCCR
//
