MK10_MOUSE
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 03-AUG-2022, entry version 192.
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RL Unpublished observations (MAR-1997).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-ARNTL/BMAL1 heterodimer and plays a role in
CC the 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.ENSMUSP00000108468; -.
DR ChEMBL; CHEMBL3885603; -.
DR iPTMnet; Q61831; -.
DR PhosphoSitePlus; Q61831; -.
DR EPD; Q61831; -.
DR MaxQB; Q61831; -.
DR PaxDb; Q61831; -.
DR PeptideAtlas; Q61831; -.
DR PRIDE; 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 CTD; 5602; -.
DR MGI; MGI:1346863; Mapk10.
DR eggNOG; KOG0665; Eukaryota.
DR InParanoid; Q61831; -.
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 75 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:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
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:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0004705; F:JUN kinase activity; IDA:UniProtKB.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
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:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007254; P:JNK cascade; IDA:UniProtKB.
DR GO; GO:0007258; P:JUN phosphorylation; ISO:MGI.
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 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; 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
