ID   MK10_MOUSE              Reviewed;         464 AA.
AC   Q61831; Q9R0U6;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 2.
DT   24-JAN-2024, entry version 199.
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=MAP kinase p49 3F12;
DE   AltName: Full=Stress-activated protein kinase JNK3;
DE   AltName: Full=c-Jun N-terminal kinase 3;
GN   Name=Mapk10; Synonyms=Jnk3, Prkm10, Serk2;
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].
RC   STRAIN=BALB/cJ; TISSUE=Brain;
RX   PubMed=8717339; DOI=10.1016/0169-328x(95)00181-q;
RA   Martin J.H., Mohit A.A., Miller C.A.;
RT   "Developmental expression in the mouse nervous system of the p493F12 SAP
RT   kinase.";
RL   Brain Res. Mol. Brain Res. 35:47-57(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 39-464.
RC   TISSUE=Brain;
RX   PubMed=10523642; DOI=10.1128/mcb.19.11.7539;
RA   Ito M., Yoshioka K., Akechi M., Yamashita S., Takamatsu N., Sugiyama K.,
RA   Hibi M., Nakabeppu Y., Shiba T., Yamamoto K.;
RT   "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that
RT   functions as a scaffold factor in the JNK signaling pathway.";
RL   Mol. Cell. Biol. 19:7539-7548(1999).
RN   [3]
RP   IDENTIFICATION OF LONG FORM (ALPHA-2).
RA   Hulo-Demole C., Braconi-Quintaje S.;
RL   Unpublished observations (MAR-1997).
RN   [4]
RP   FUNCTION, AND COFACTOR.
RC   TISSUE=Hippocampus;
RX   PubMed=9349820; DOI=10.1038/39899;
RA   Yang D.D., Kuan C.-Y., Whitmarsh A.J., Rincon M., Zheng T.S., Davis R.J.,
RA   Rakic P., Flavell R.A.;
RT   "Absence of excitotoxicity-induced apoptosis in the hippocampus of mice
RT   lacking the Jnk3 gene.";
RL   Nature 389:865-870(1997).
RN   [5]
RP   INTERACTION WITH MAPKBP1.
RX   PubMed=10471813; DOI=10.1016/s0014-5793(99)01084-4;
RA   Koyano S., Ito M., Takamatsu N., Shiba T., Yamamoto K., Yoshioka K.;
RT   "A novel Jun N-terminal kinase (JNK)-binding protein that enhances the
RT   activation of JNK by MEK kinase 1 and TGF-beta-activated kinase 1.";
RL   FEBS Lett. 457:385-388(1999).
RN   [6]
RP   INTERACTION WITH HDAC9, AND ACTIVITY REGULATION.
RX   PubMed=16611996; DOI=10.1128/mcb.26.9.3550-3564.2006;
RA   Morrison B.E., Majdzadeh N., Zhang X., Lyles A., Bassel-Duby R.,
RA   Olson E.N., D'Mello S.R.;
RT   "Neuroprotection by histone deacetylase-related protein.";
RL   Mol. Cell. Biol. 26:3550-3564(2006).
RN   [7]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH SARM1.
RX   PubMed=17724133; DOI=10.1084/jem.20070868;
RA   Kim Y., Zhou P., Qian L., Chuang J.Z., Lee J., Li C., Iadecola C.,
RA   Nathan C., Ding A.;
RT   "MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and
RT   regulates neuronal survival.";
RL   J. Exp. Med. 204:2063-2074(2007).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [9]
RP   FUNCTION IN NEURONAL APOPTOSIS.
RX   PubMed=20418776; DOI=10.1097/nen.0b013e3181db8100;
RA   Choi W.S., Abel G., Klintworth H., Flavell R.A., Xia Z.;
RT   "JNK3 mediates paraquat- and rotenone-induced dopaminergic neuron death.";
RL   J. Neuropathol. Exp. Neurol. 69:511-520(2010).
RN   [10]
RP   FUNCTION IN NEURITE GROWTH.
RX   PubMed=21554942; DOI=10.1016/j.heares.2011.04.011;
RA   Atkinson P.J., Cho C.H., Hansen M.R., Green S.H.;
RT   "Activity of all JNK isoforms contributes to neurite growth in spiral
RT   ganglion neurons.";
RL   Hear. Res. 278:77-85(2011).
RN   [11]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=22441692; DOI=10.1038/embor.2012.37;
RA   Yoshitane H., Honma S., Imamura K., Nakajima H., Nishide S.Y., Ono D.,
RA   Kiyota H., Shinozaki N., Matsuki H., Wada N., Doi H., Hamada T., Honma K.,
RA   Fukada Y.;
RT   "JNK regulates the photic response of the mammalian circadian clock.";
RL   EMBO Rep. 13:455-461(2012).
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 (PubMed:22441692).
CC       Phosphorylates JUND and this phosphorylation is inhibited in the
CC       presence of MEN1 (By similarity). {ECO:0000250|UniProtKB:P53779,
CC       ECO:0000269|PubMed:20418776, ECO:0000269|PubMed:21554942,
CC       ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:9349820}.
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;
CC         Evidence={ECO:0000269|PubMed:9349820};
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 (By similarity). Inhibited by
CC       HDAC9. {ECO:0000250, ECO:0000269|PubMed:16611996}.
CC   -!- SUBUNIT: Interacts with MAPK8IP1/JIP-1, MAPK8IP3/JIP-3/JSAP1 and
CC       SPAG9/MAPK8IP4/JIP4 (By similarity). Interacts with HDAC9 and MAPKBP1
CC       (PubMed:10471813, PubMed:16611996). Interacts with ARRB2; the
CC       interaction enhances MAPK10 activation by MAP3K5 (By similarity).
CC       Interacts with SARM1 (PubMed:17724133). Interacts with JUND;
CC       interaction is inhibited in the presence of MEN1 (By similarity).
CC       {ECO:0000250|UniProtKB:P49187, ECO:0000250|UniProtKB:P53779,
CC       ECO:0000269|PubMed:10471813, ECO:0000269|PubMed:16611996,
CC       ECO:0000269|PubMed:17724133}.
CC   -!- INTERACTION:
CC       Q61831; Q9ESN9-2: Mapk8ip3; NbExp=4; IntAct=EBI-400741, EBI-9549291;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17724133}. Membrane
CC       {ECO:0000269|PubMed:17724133}; Lipid-anchor
CC       {ECO:0000269|PubMed:17724133}. Nucleus {ECO:0000269|PubMed:17724133}.
CC       Mitochondrion {ECO:0000269|PubMed:17724133}. Note=Palmitoylation
CC       regulates MAPK10 trafficking to cytoskeleton (By similarity). Recruited
CC       to the mitochondria in the presence of SARM1. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Alpha-2;
CC         IsoId=Q61831-1; Sequence=Displayed;
CC       Name=Alpha-1;
CC         IsoId=Q61831-2; Sequence=VSP_004840;
CC   -!- TISSUE SPECIFICITY: Brain (at protein level). Expressed specifically in
CC       neurons of the hippocampus, cortex, cerebellum, brainstem, and spinal
CC       cord. Seems to be also found in testis, and very weakly in the heart.
CC       {ECO:0000269|PubMed:22441692}.
CC   -!- DEVELOPMENTAL STAGE: Expression begins in day 11.5 dpc embryos, and is
CC       localized in both the rostral spinal cord and rhombencephalon. In 12.5-
CC       13 dpc embryos, it is found throughout the telencephalon. By day 17.5,
CC       JNK3 is also expressed in neurons of dorsal root and sensory ganglia
CC       and at lower levels in neurons of the myenteric plexus and the
CC       developing heart.
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}.
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DR   EMBL; L35236; AAB37741.1; -; mRNA.
DR   EMBL; AB005665; BAA85877.1; -; mRNA.
DR   RefSeq; NP_001297615.1; NM_001310686.2.
DR   RefSeq; XP_017176379.1; XM_017320890.1.
DR   RefSeq; XP_017176380.1; XM_017320891.1.
DR   AlphaFoldDB; Q61831; -.
DR   SMR; Q61831; -.
DR   BioGRID; 204967; 14.
DR   ELM; Q61831; -.
DR   IntAct; Q61831; 1.
DR   MINT; Q61831; -.
DR   STRING; 10090.ENSMUSP00000127193; -.
DR   ChEMBL; CHEMBL3885603; -.
DR   ChEMBL; CHEMBL4888451; -.
DR   iPTMnet; Q61831; -.
DR   PhosphoSitePlus; Q61831; -.
DR   EPD; Q61831; -.
DR   MaxQB; Q61831; -.
DR   PaxDb; 10090-ENSMUSP00000108468; -.
DR   PeptideAtlas; Q61831; -.
DR   ProteomicsDB; 291463; -. [Q61831-1]
DR   ProteomicsDB; 291464; -. [Q61831-2]
DR   DNASU; 26414; -.
DR   GeneID; 26414; -.
DR   KEGG; mmu:26414; -.
DR   UCSC; uc008yjg.1; mouse. [Q61831-1]
DR   AGR; MGI:1346863; -.
DR   CTD; 5602; -.
DR   MGI; MGI:1346863; Mapk10.
DR   eggNOG; KOG0665; Eukaryota.
DR   InParanoid; Q61831; -.
DR   OrthoDB; 158564at2759; -.
DR   PhylomeDB; Q61831; -.
DR   BRENDA; 2.7.11.24; 3474.
DR   Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
DR   Reactome; R-MMU-2871796; FCERI mediated MAPK activation.
DR   Reactome; R-MMU-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR   Reactome; R-MMU-450341; Activation of the AP-1 family of transcription factors.
DR   BioGRID-ORCS; 26414; 1 hit in 80 CRISPR screens.
DR   ChiTaRS; Mapk10; mouse.
DR   PRO; PR:Q61831; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q61831; Protein.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0043204; C:perikaryon; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR   GO; GO:0150051; C:postsynaptic Golgi apparatus; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; ISO:MGI.
DR   GO; GO:0004705; F:JUN kinase activity; IDA:UniProtKB.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0007254; P:JNK cascade; IDA:UniProtKB.
DR   GO; GO:0045475; P:locomotor rhythm; IMP:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR   GO; GO:0098969; P:neurotransmitter receptor transport to postsynaptic membrane; ISO:MGI.
DR   GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR   GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR   GO; GO:0009416; P:response to light stimulus; IMP:UniProtKB.
DR   GO; GO:0099003; P:vesicle-mediated transport in synapse; ISO:MGI.
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_0000186278"
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        405..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         418..464
FT                   /note="GAAVNSSESLPPSSAVNDISSMSTDQTLASDTDSSLEASAGPLGCCR -> A
FT                   QVQQ (in isoform Alpha-1)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_004840"
FT   CONFLICT        267
FT                   /note="S -> D (in Ref. 2; BAA85877)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        345
FT                   /note="V -> A (in Ref. 2; BAA85877)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        412
FT                   /note="S -> G (in Ref. 2; BAA85877)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        418..423
FT                   /note="GAAVNS -> AQVQQ (in Ref. 2)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   464 AA;  52532 MW;  4313335AC2E9D2E6 CRC64;
     MSLHFLYYCS EPTLDVKIAF CQGFDKHVDV SSIAKHYNMS KSKVDNQFYS VEVGDSTFTV
     LKRYQNLKPI GSGAQGIVCA AYDAVLDRNV AIKKLSRPFQ NQTHAKRAYR ELVLMKCVNH
     KNIISLLNVF TPQKTLEEFQ DVYLVMELMD ANLCQVIQME LDHERMSYLL YQMLCGIKHL
     HSAGIIHRDL KPSNIVVKSD CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY
     KENVDIWSVG CIMGEMVRHK ILFPGRSYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN
     RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPVKRISV DDALQHPYIN
     VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN SEEKTKNGVV KSQPSPSGAA
     VNSSESLPPS SAVNDISSMS TDQTLASDTD SSLEASAGPL GCCR
//