JNK1_CAEEL
ID JNK1_CAEEL Reviewed; 463 AA.
AC Q8WQG9; Q17507; Q9UAH2;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Stress-activated protein kinase jnk-1;
DE EC=2.7.11.24 {ECO:0000269|PubMed:10393177, ECO:0000269|PubMed:11566876, ECO:0000269|PubMed:11738026, ECO:0000269|PubMed:15767565};
GN Name=jnk-1; ORFNames=B0478.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10393177; DOI=10.1093/emboj/18.13.3604;
RA Kawasaki M., Hisamoto N., Iino Y., Yamamoto M., Ninomiya-Tsuji J.,
RA Matsumoto K.;
RT "A Caenorhabditis elegans JNK signal transduction pathway regulates
RT coordinated movement via type-D GABAergic motor neurons.";
RL EMBO J. 18:3604-3615(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), FUNCTION, CATALYTIC
RP ACTIVITY, COFACTOR, ACTIVITY REGULATION, PHOSPHORYLATION AT THR-276 AND
RP TYR-278, AND MUTAGENESIS OF THR-276 AND TYR-278.
RX PubMed=11566876; DOI=10.1093/emboj/20.18.5114;
RA Villanueva A., Lozano J., Morales A., Lin X., Deng X., Hengartner M.O.,
RA Kolesnick R.N.;
RT "jkk-1 and mek-1 regulate body movement coordination and response to heavy
RT metals through jnk-1 in Caenorhabditis elegans.";
RL EMBO J. 20:5114-5128(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND INTERACTION WITH UNC-16.
RX PubMed=11738026; DOI=10.1016/s0896-6273(01)00532-3;
RA Byrd D.T., Kawasaki M., Walcoff M., Hisamoto N., Matsumoto K., Jin Y.;
RT "UNC-16, a JNK-signaling scaffold protein, regulates vesicle transport in
RT C. elegans.";
RL Neuron 32:787-800(2001).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH DAF-16,
RP PHOSPHORYLATION AT THR-276 AND TYR-278, AND MUTAGENESIS OF THR-276 AND
RP TYR-278.
RX PubMed=15767565; DOI=10.1073/pnas.0500749102;
RA Oh S.W., Mukhopadhyay A., Svrzikapa N., Jiang F., Davis R.J.,
RA Tissenbaum H.A.;
RT "JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear
RT translocation of forkhead transcription factor/DAF-16.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:4494-4499(2005).
RN [6]
RP FUNCTION.
RX PubMed=18597494; DOI=10.1021/tx800074e;
RA Pei B., Wang S., Guo X., Wang J., Yang G., Hang H., Wu L.;
RT "Arsenite-induced germline apoptosis through a MAPK-dependent, p53-
RT independent pathway in Caenorhabditis elegans.";
RL Chem. Res. Toxicol. 21:1530-1535(2008).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND PHOSPHORYLATION AT THR-276 AND TYR-278.
RX PubMed=17894411; DOI=10.1002/jcp.21269;
RA Wolf M., Nunes F., Henkel A., Heinick A., Paul R.J.;
RT "The MAP kinase JNK-1 of Caenorhabditis elegans: location, activation, and
RT influences over temperature-dependent insulin-like signaling, stress
RT responses, and fitness.";
RL J. Cell. Physiol. 214:721-729(2008).
RN [8]
RP FUNCTION.
RX PubMed=19497412; DOI=10.1016/j.cbi.2009.03.012;
RA Wang S., Wu L., Wang Y., Luo X., Lu Y.;
RT "Copper-induced germline apoptosis in Caenorhabditis elegans: the
RT independent roles of DNA damage response signaling and the dependent roles
RT of MAPK cascades.";
RL Chem. Biol. Interact. 180:151-157(2009).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23721876; DOI=10.1016/j.neuro.2013.05.014;
RA Settivari R., VanDuyn N., LeVora J., Nass R.;
RT "The Nrf2/SKN-1-dependent glutathione S-transferase pi homologue GST-1
RT inhibits dopamine neuron degeneration in a Caenorhabditis elegans model of
RT manganism.";
RL NeuroToxicology 38:51-60(2013).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29523076; DOI=10.1186/s12868-018-0408-1;
RA Bennett H.L., Khoruzhik Y., Hayden D., Huang H., Sanders J., Walsh M.B.,
RA Biron D., Hart A.C.;
RT "Normal sleep bouts are not essential for C. elegans survival and FoxO is
RT important for compensatory changes in sleep.";
RL BMC Neurosci. 19:10-10(2018).
CC -!- FUNCTION: Serine/threonine-protein kinase which responds to activation
CC by environmental stress by phosphorylating a number of transcription
CC factors such as daf-16, and thus regulates transcriptional activity. By
CC phosphorylating daf-16, plays a role in daf-16 nuclear translocation in
CC intestinal cells in response to environmental stresses such as heat and
CC oxidative stresses (PubMed:17894411). Downstream of jkk-1, may
CC coordinate locomotion via type-D GABAergic motoneurons and regulates
CC synaptic vesicle transport in conjunction with unc-16. Independently of
CC jkk-1, may regulate some mechanosensory responses, such as response to
CC touch (PubMed:11566876). Independently of jkk-1 and downstream of mek-
CC 1, plays a role in resistance to heavy metals, such as Cu(2+) or Cd(2+)
CC (PubMed:11566876). Regulates germline cell apoptosis in response to
CC heavy metals such as Cu(2+) and arsenite (PubMed:18597494,
CC PubMed:19497412). Required for dopaminergic CEP neuron degeneration in
CC response to Mn(2+) (PubMed:23721876). Required for normal sleep bout
CC quantity and arousal thresholds during the transition from the last
CC larval stage to adulthood in well-fed animals (PubMed:29523076).
CC Downstream of jkk-1 but independently of mek-1, positively regulates
CC lifespan (PubMed:15767565). {ECO:0000269|PubMed:10393177,
CC ECO:0000269|PubMed:11566876, ECO:0000269|PubMed:11738026,
CC ECO:0000269|PubMed:17894411, ECO:0000269|PubMed:18597494,
CC ECO:0000269|PubMed:19497412, ECO:0000269|PubMed:23721876,
CC ECO:0000269|PubMed:29523076}.
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:10393177, ECO:0000269|PubMed:11566876,
CC ECO:0000269|PubMed:11738026, ECO:0000269|PubMed:15767565};
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:10393177,
CC ECO:0000269|PubMed:11566876, ECO:0000269|PubMed:11738026,
CC ECO:0000269|PubMed:15767565};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10393177, ECO:0000269|PubMed:11566876,
CC ECO:0000269|PubMed:11738026, ECO:0000269|PubMed:15767565};
CC -!- ACTIVITY REGULATION: Activated by threonine and tyrosine
CC phosphorylation by either of the dual specificity kinases, jkk-1 and
CC mek-1. {ECO:0000269|PubMed:10393177, ECO:0000269|PubMed:11566876,
CC ECO:0000269|PubMed:11738026}.
CC -!- SUBUNIT: Binds to the scaffolding protein, unc-16. Unc-16 also binds
CC other components of the JNK signaling pathway (PubMed:11738026).
CC Interacts with daf-16 (PubMed:15767565). {ECO:0000269|PubMed:11738026,
CC ECO:0000269|PubMed:15767565}.
CC -!- INTERACTION:
CC Q8WQG9; P05412: JUN; Xeno; NbExp=3; IntAct=EBI-321822, EBI-852823;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10393177}.
CC Perikaryon {ECO:0000269|PubMed:10393177}. Cell projection, axon
CC {ECO:0000269|PubMed:10393177}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=Q8WQG9-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q8WQG9-2; Sequence=VSP_050269;
CC -!- TISSUE SPECIFICITY: Expressed in most neurons, including nerve ring,
CC head ganglions, dorsal and ventral nerve cords and tail ganglions
CC (PubMed:10393177). The Thr-276/Tyr-278 phosphorylated form is present
CC in the nerve ring upon heat exposure (PubMed:17894411).
CC {ECO:0000269|PubMed:10393177, ECO:0000269|PubMed:17894411}.
CC -!- DEVELOPMENTAL STAGE: Isoform a and isoform b are expressed in embryo
CC and in all larval stages. {ECO:0000269|PubMed:11566876}.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC {ECO:0000305|PubMed:11566876, ECO:0000305|PubMed:15767565}.
CC -!- PTM: Dually phosphorylated on Thr-276 and Tyr-278, which activates the
CC enzyme. {ECO:0000305|PubMed:11566876, ECO:0000305|PubMed:15767565}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown prevents Mn(2+)-induced
CC dopaminergic CEP neuron degeneration (PubMed:23721876). RNAi-mediated
CC knockdown targeted to neurons results in increased total time in sleep
CC bouts (PubMed:29523076). {ECO:0000269|PubMed:23721876,
CC ECO:0000269|PubMed:29523076}.
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; AB024085; BAA82640.1; -; mRNA.
DR EMBL; FO080209; CCD62004.1; -; Genomic_DNA.
DR EMBL; FO080209; CCD62005.1; -; Genomic_DNA.
DR PIR; T30031; T30031.
DR PIR; T37323; T37323.
DR RefSeq; NP_001021270.1; NM_001026099.3. [Q8WQG9-1]
DR RefSeq; NP_741434.2; NM_171371.4.
DR AlphaFoldDB; Q8WQG9; -.
DR SMR; Q8WQG9; -.
DR BioGRID; 42580; 6.
DR DIP; DIP-26951N; -.
DR IntAct; Q8WQG9; 4.
DR STRING; 6239.B0478.1a; -.
DR iPTMnet; Q8WQG9; -.
DR EPD; Q8WQG9; -.
DR PaxDb; Q8WQG9; -.
DR PeptideAtlas; Q8WQG9; -.
DR EnsemblMetazoa; B0478.1a.1; B0478.1a.1; WBGene00002178. [Q8WQG9-1]
DR EnsemblMetazoa; B0478.1b.1; B0478.1b.1; WBGene00002178. [Q8WQG9-2]
DR GeneID; 177460; -.
DR KEGG; cel:CELE_B0478.1; -.
DR UCSC; B0478.1a; c. elegans. [Q8WQG9-1]
DR CTD; 177460; -.
DR WormBase; B0478.1a; CE27574; WBGene00002178; jnk-1. [Q8WQG9-1]
DR WormBase; B0478.1b; CE30123; WBGene00002178; jnk-1. [Q8WQG9-2]
DR eggNOG; KOG0665; Eukaryota.
DR GeneTree; ENSGT00940000169409; -.
DR InParanoid; Q8WQG9; -.
DR OMA; IESVGNW; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; Q8WQG9; -.
DR BRENDA; 2.7.11.24; 1045.
DR Reactome; R-CEL-193648; NRAGE signals death through JNK.
DR Reactome; R-CEL-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-CEL-2871796; FCERI mediated MAPK activation.
DR Reactome; R-CEL-376172; DSCAM interactions.
DR Reactome; R-CEL-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-CEL-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-CEL-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-CEL-9007892; Interleukin-38 signaling.
DR SignaLink; Q8WQG9; -.
DR PRO; PR:Q8WQG9; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00002178; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004705; F:JUN kinase activity; IDA:WormBase.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:WormBase.
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:0008134; F:transcription factor binding; IPI:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0006972; P:hyperosmotic response; IGI:WormBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007254; P:JNK cascade; ISS:UniProtKB.
DR GO; GO:0007258; P:JUN phosphorylation; IDA:WormBase.
DR GO; GO:0000165; P:MAPK cascade; IGI:WormBase.
DR GO; GO:0048681; P:negative regulation of axon regeneration; IMP:WormBase.
DR GO; GO:1905803; P:negative regulation of cellular response to manganese ion; IMP:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0009408; P:response to heat; IMP:WormBase.
DR GO; GO:0030431; P:sleep; IMP:UniProtKB.
DR GO; GO:0030050; P:vesicle transport along actin filament; IDA:UniProtKB.
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; Cell projection; Cytoplasm; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..463
FT /note="Stress-activated protein kinase jnk-1"
FT /id="PRO_0000186270"
FT DOMAIN 119..412
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 276..278
FT /note="TXY"
FT /evidence="ECO:0000305"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 244
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 126..131
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 148
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 276
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11566876,
FT ECO:0000269|PubMed:15767565, ECO:0000269|PubMed:17894411"
FT MOD_RES 278
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11566876,
FT ECO:0000269|PubMed:15767565, ECO:0000269|PubMed:17894411"
FT VAR_SEQ 1..91
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_050269"
FT MUTAGEN 276
FT /note="T->A: Abolishes phosphorylation. Loss of kinase
FT activity; when associated with F-278."
FT /evidence="ECO:0000269|PubMed:11566876,
FT ECO:0000269|PubMed:15767565"
FT MUTAGEN 278
FT /note="Y->F: Abolishes phosphorylation. Loss of kinase
FT activity; when associated with A-276."
FT /evidence="ECO:0000269|PubMed:11566876,
FT ECO:0000269|PubMed:15767565"
SQ SEQUENCE 463 AA; 52885 MW; E12495B45B052BC7 CRC64;
MEERLSTTSS YPSHPGRSVE EDHNTLLASS SISSIIRGTR GHLNNFIESV GNWLVPSSSG
RDDDAVSLDS CQSVYSPVRH HINSGTGGGI LMEPSSIHVP ENYYSVTIGE AQMVVLKRYQ
NLRLIGSGAQ GIVCSAFDTV RNEQVAIKKL SRPFQNVTHA KRAYRELKLM SLVNHKNIIG
ILNCFTPQKK LDEFNDLYIV MELMDANLCQ VIQMDLDHER LSYLLYQMLC GIRHLHSAGI
IHRDLKPSNI VVRSDCTLKI LDFGLARTAI EAFMMTPYVV TRYYRAPEVI LGMGYKENVD
VWSIGCIFGE LIRGRVLFPG GDHIDQWTRI IEQLGTPDRS FLERLQPTVR NYVENRPRYQ
ATPFEVLFSD NMFPMTADSS RLTGAQARDL LSRMLVIDPE RRISVDDALR HPYVNVWFDE
IEVYAPPPLP YDHNMDVEQN VDSWREHIFR ELTDYARTHD IYS
