CMK1_CAEEL
ID CMK1_CAEEL Reviewed; 348 AA.
AC Q9TXJ0; Q6V5R5; Q9UAH6;
DT 13-JUL-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type 1 {ECO:0000303|PubMed:10428833};
DE EC=2.7.11.17 {ECO:0000269|PubMed:10428833, ECO:0000269|PubMed:12231504, ECO:0000269|PubMed:26725111};
DE AltName: Full=CaM kinase I {ECO:0000303|PubMed:10428833};
DE Short=CaM-KI {ECO:0000303|PubMed:10428833};
GN Name=cmk-1 {ECO:0000312|WormBase:K07A9.2};
GN ORFNames=K07A9.2 {ECO:0000312|WormBase:K07A9.2};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAA82674.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, COFACTOR, BINDING TO CALMODULIN,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, PHOSPHORYLATION AT THR-179, AND MUTAGENESIS OF
RP 2-PRO--ARG-7 AND THR-179.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:BAA82674.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:BAA82674.1};
RX PubMed=10428833; DOI=10.1074/jbc.274.32.22556;
RA Eto K., Takahashi N., Kimura Y., Masuho Y., Arai K., Muramatsu M.A.,
RA Tokumitsu H.;
RT "Ca(2+)/Calmodulin-dependent protein kinase cascade in Caenorhabditis
RT elegans. Implication in transcriptional activation.";
RL J. Biol. Chem. 274:22556-22562(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [3] {ECO:0000305, ECO:0000312|EMBL:AAQ54691.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-348, FUNCTION, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF THR-179.
RX PubMed=14711416; DOI=10.1016/j.cub.2003.12.030;
RA Satterlee J.S., Ryu W.S., Sengupta P.;
RT "The CMK-1 CaMKI and the TAX-4 Cyclic nucleotide-gated channel regulate
RT thermosensory neuron gene expression and function in C. elegans.";
RL Curr. Biol. 14:62-68(2004).
RN [4] {ECO:0000305}
RP FUNCTION, COFACTOR, AND TISSUE SPECIFICITY.
RX PubMed=12231504; DOI=10.1093/embo-reports/kvf191;
RA Kimura Y., Corcoran E.E., Eto K., Gengyo-Ando K., Muramatsu M.A.,
RA Kobayashi R., Freedman J.H., Mitani S., Hagiwara M., Means A.R.,
RA Tokumitsu H.;
RT "A CaMK cascade activates CRE-mediated transcription in neurons of
RT Caenorhabditis elegans.";
RL EMBO Rep. 3:962-966(2002).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP THR-179.
RX PubMed=25467978; DOI=10.1016/j.neuron.2014.10.046;
RA Yu Y.V., Bell H.W., Glauser D.A., Van Hooser S.D., Goodman M.B.,
RA Sengupta P.;
RT "CaMKI-dependent regulation of sensory gene expression mediates experience-
RT dependent plasticity in the operating range of a thermosensory neuron.";
RL Neuron 84:919-926(2014).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF LYS-52 AND THR-179.
RX PubMed=25467982; DOI=10.1016/j.neuron.2014.10.039;
RA Schild L.C., Zbinden L., Bell H.W., Yu Y.V., Sengupta P., Goodman M.B.,
RA Glauser D.A.;
RT "The balance between cytoplasmic and nuclear CaM kinase-1 signaling
RT controls the operating range of noxious heat avoidance.";
RL Neuron 84:983-996(2014).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=26335407; DOI=10.7554/elife.10110;
RA Neal S.J., Takeishi A., O'Donnell M.P., Park J., Hong M., Butcher R.A.,
RA Kim K., Sengupta P.;
RT "Feeding state-dependent regulation of developmental plasticity via CaMKI
RT and neuroendocrine signaling.";
RL Elife 4:0-0(2015).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF LYS-52.
RX PubMed=26725111; DOI=10.1016/j.celrep.2015.11.064;
RA Kobayashi K., Nakano S., Amano M., Tsuboi D., Nishioka T., Ikeda S.,
RA Yokoyama G., Kaibuchi K., Mori I.;
RT "Single-cell memory regulates a neural circuit for sensory behavior.";
RL Cell Rep. 14:11-21(2016).
RN [9]
RP FUNCTION.
RX PubMed=27660389; DOI=10.1074/jbc.m116.741132;
RA Zhang C., Zhao N., Chen Y., Zhang D., Yan J., Zou W., Zhang K., Huang X.;
RT "The signaling pathway of Caenorhabditis elegans mediates chemotaxis
RT response to the attractant 2-heptanone in a Trojan horse-like
RT pathogenesis.";
RL J. Biol. Chem. 291:23618-23627(2016).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP LYS-52.
RX PubMed=27462879; DOI=10.1371/journal.pgen.1006180;
RA Moss B.J., Park L., Dahlberg C.L., Juo P.;
RT "The CaM kinase CMK-1 mediates a negative feedback mechanism coupling the
RT C. elegans glutamate receptor GLR-1 with its own transcription.";
RL PLoS Genet. 12:E1006180-E1006180(2016).
RN [11]
RP FUNCTION.
RX PubMed=30779740; DOI=10.1371/journal.pgen.1007945;
RA Peymen K., Watteyne J., Borghgraef C., Van Sinay E., Beets I., Schoofs L.;
RT "Myoinhibitory peptide signaling modulates aversive gustatory learning in
RT Caenorhabditis elegans.";
RL PLoS Genet. 15:E1007945-E1007945(2019).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that operates in
CC the calcium-triggered CaMKK-CaMK1 signaling cascade which results in
CC transcriptional activation (PubMed:10428833, PubMed:12231504,
CC PubMed:26725111). Transcriptional activation occurs at least in part
CC through phosphorylation of crh-1 (PubMed:10428833, PubMed:12231504).
CC Regulates gene expression, sensory morphology, and function of the AFD
CC thermosensory neurons (PubMed:10428833, PubMed:14711416,
CC PubMed:25467978). Involved in long-term adaptation of AFD neurons to
CC temperatures warmer than the initial acclimatized cultivation
CC temperature (PubMed:25467978). Acts in the FLP thermal nociceptors to
CC moderate the responsiveness to noxious heat and controls neuropeptide
CC release from FLP neurons in response to temperature elevations
CC (PubMed:25467982). Regulates the dauer decision, the decision of the
CC larvae to enter into the alternative stress-resistant and long-lived
CC dauer developmental stage, based on the feeding state, primarily in the
CC AWC sensory neurons. Acts non cell-autonomously in the AWC neurons to
CC regulate expression of the daf-28 insulin-like peptide and cell-
CC autonomously in the ASI sensory neurons to regulate expression of the
CC growth promoting daf-7 in a food-regulated manner (PubMed:26335407).
CC Plays a role in memory-based thermal response of an individual AFD
CC neuron cell (PubMed:26725111). Involved in chemotaxis response in AWC
CC neurons to attractant 2-heptanone, a volatile organic compound emitted
CC by the nematode pathogenic bacterium B.nematocida B16
CC (PubMed:27660389). Plays a role in a type of aversive gustatory
CC associated learning called salt avoidance learning via regulation of
CC crh-1 signaling and the promotion of long-term memory formation
CC (PubMed:30779740). Represses transcription of glutamate receptor glr-1
CC in the nucleus basally and in response to change in synaptic activity
CC (PubMed:27462879). {ECO:0000269|PubMed:10428833,
CC ECO:0000269|PubMed:12231504, ECO:0000269|PubMed:14711416,
CC ECO:0000269|PubMed:25467978, ECO:0000269|PubMed:25467982,
CC ECO:0000269|PubMed:26335407, ECO:0000269|PubMed:26725111,
CC ECO:0000269|PubMed:27462879, ECO:0000269|PubMed:27660389,
CC ECO:0000269|PubMed:30779740}.
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=2.7.11.17;
CC Evidence={ECO:0000269|PubMed:10428833, ECO:0000269|PubMed:12231504,
CC ECO:0000269|PubMed:26725111};
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=2.7.11.17; Evidence={ECO:0000269|PubMed:10428833,
CC ECO:0000269|PubMed:12231504, ECO:0000269|PubMed:26725111};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10428833, ECO:0000269|PubMed:12231504};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin (PubMed:10428833,
CC PubMed:26725111). Binding of calmodulin results in a conformational
CC change that generates functional binding sites for both substrate and
CC ATP, and thus relieves autoinhibition and lowers the Km of substrate
CC binding. Must be phosphorylated by ckk-1 to be maximally active but
CC this does not appear to be required for activity in AFD neurons
CC (PubMed:10428833). {ECO:0000269|PubMed:10428833,
CC ECO:0000269|PubMed:26725111}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=657 uM for syntide-2 (when cmk-1 is not phosphorylated on Thr-179)
CC {ECO:0000269|PubMed:10428833};
CC KM=20 uM for syntide-2 (when cmk-1 is phosphorylated on Thr-179)
CC {ECO:0000269|PubMed:10428833};
CC Vmax=0.1 mmol/min/mg enzyme (irrespective of phosphorylation status
CC of Thr-179) {ECO:0000269|PubMed:10428833};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10428833,
CC ECO:0000269|PubMed:25467978, ECO:0000269|PubMed:25467982,
CC ECO:0000269|PubMed:26335407, ECO:0000269|PubMed:27462879}. Cytoplasm
CC {ECO:0000269|PubMed:25467978, ECO:0000269|PubMed:25467982,
CC ECO:0000269|PubMed:26335407, ECO:0000269|PubMed:27462879}.
CC Note=Localization is regulated by temperature in thermosensory neurons
CC (PubMed:25467978, PubMed:25467982). Localizes to the nucleus upon
CC elevated temperature shift (PubMed:25467978). Translocates from
CC cytoplasm to the nucleus of FLP thermal nociceptors during thermal
CC adaptation (PubMed:25467982). Translocates transiently from cytoplasm
CC to the nucleus of AWC sensory neurons in response to food withdrawal.
CC Prolonged starvation results in cytoplasmic enrichment
CC (PubMed:26335407). The distribution between cytoplasm and nucleus is
CC regulated by synaptic glutamate receptor glr-1 levels in PVC neurons,
CC accumulating in the nucleus with increasing glr-1 (PubMed:27462879).
CC {ECO:0000269|PubMed:25467978, ECO:0000269|PubMed:25467982,
CC ECO:0000269|PubMed:26335407, ECO:0000269|PubMed:27462879}.
CC -!- TISSUE SPECIFICITY: Expressed in head and tail neurons and vulval
CC muscles (PubMed:12231504). Throughout the nervous system. Detected in
CC neurites and neuronal cell bodies (PubMed:25467982).
CC {ECO:0000269|PubMed:12231504, ECO:0000269|PubMed:25467982}.
CC -!- DOMAIN: The autoinhibitory domain overlaps with the calmodulin binding
CC region and interacts in the inactive folded state with the catalytic
CC domain as a pseudosubstrate. {ECO:0000250|UniProtKB:Q63450}.
CC -!- DISRUPTION PHENOTYPE: Changes in thermosensory behavior and
CC temperature-dependent defects in AFD-specific gene expression
CC (PubMed:10428833, PubMed:14711416, PubMed:25467978, PubMed:26725111).
CC Decreased threshold for temperature-evoked activity in the AFD neurons.
CC Defects in negative thermotaxis and isothermal tracking behaviors
CC (PubMed:25467978). Defective in thermal avoidance adaptation. Aberrant
CC thermotaxis at innocuous temperatures (PubMed:25467982). Inappropriate
CC dauer formation under well-fed conditions. Reduced expression of growth
CC promoting daf-7 in ASI sensory neurons (PubMed:26335407). Changes in
CC thermosensory response of AIY neurons (PubMed:26725111). Increased
CC transcription of glutamate receptor glr-1 (PubMed:27462879).
CC {ECO:0000269|PubMed:10428833, ECO:0000269|PubMed:14711416,
CC ECO:0000269|PubMed:25467978, ECO:0000269|PubMed:25467982,
CC ECO:0000269|PubMed:26335407, ECO:0000269|PubMed:26725111,
CC ECO:0000269|PubMed:27462879}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000255}.
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DR EMBL; AB021864; BAA82674.1; -; mRNA.
DR EMBL; BX284604; CCD71865.1; -; Genomic_DNA.
DR EMBL; AY350451; AAQ54691.1; -; mRNA.
DR RefSeq; NP_500139.1; NM_067738.6.
DR AlphaFoldDB; Q9TXJ0; -.
DR SMR; Q9TXJ0; -.
DR BioGRID; 42145; 4.
DR DIP; DIP-26403N; -.
DR IntAct; Q9TXJ0; 1.
DR STRING; 6239.K07A9.2; -.
DR iPTMnet; Q9TXJ0; -.
DR EPD; Q9TXJ0; -.
DR PaxDb; Q9TXJ0; -.
DR PeptideAtlas; Q9TXJ0; -.
DR EnsemblMetazoa; K07A9.2.1; K07A9.2.1; WBGene00000553.
DR GeneID; 176989; -.
DR KEGG; cel:CELE_K07A9.2; -.
DR UCSC; K07A9.2; c. elegans.
DR CTD; 176989; -.
DR WormBase; K07A9.2; CE25046; WBGene00000553; cmk-1.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000156378; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q9TXJ0; -.
DR OMA; ADCPEGK; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; Q9TXJ0; -.
DR Reactome; R-CEL-9619229; Activation of RAC1 downstream of NMDARs.
DR SABIO-RK; Q9TXJ0; -.
DR SignaLink; Q9TXJ0; -.
DR PRO; PR:Q9TXJ0; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00000553; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IDA:WormBase.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IDA:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:WormBase.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; IDA:WormBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:WormBase.
DR GO; GO:0040040; P:thermosensory behavior; IMP:WormBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Calmodulin-binding; Cytoplasm;
KW Developmental protein; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..348
FT /note="Calcium/calmodulin-dependent protein kinase type 1"
FT /id="PRO_0000395335"
FT DOMAIN 22..278
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 278..318
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250|UniProtKB:Q63450"
FT REGION 298..319
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q63450"
FT REGION 327..348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 2..7
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:10428833"
FT COMPBIAS 327..342
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 144
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 28..36
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 52
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 179
FT /note="Phosphothreonine; by ckk-1"
FT /evidence="ECO:0000269|PubMed:10428833"
FT MUTAGEN 2..7
FT /note="Missing: Loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:10428833"
FT MUTAGEN 52
FT /note="K->A: Loss of function in cytoplasm and nucleus in
FT FLP thermal nociceptors but no effect on temperature-
FT dependent translocation from cytoplasm to the nucleus.
FT Increased transcription of glutamate receptor glr-1."
FT /evidence="ECO:0000269|PubMed:25467982,
FT ECO:0000269|PubMed:27462879"
FT MUTAGEN 52
FT /note="K->M: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:26725111"
FT MUTAGEN 179
FT /note="T->A: Loss of phosphorylation and activation by ckk-
FT 1. No effect on function in AFD neurons. Strongly enriched
FT in the cytoplasm regardless of cultivation temperature.
FT Fails to rescue the AFD thermosensory neurons defects of
FT cmk-1 null mutant. Loss of temperature-dependent
FT translocation from cytoplasm to the nucleus during heat
FT acclimation in FLP thermal nociceptors."
FT /evidence="ECO:0000269|PubMed:10428833,
FT ECO:0000269|PubMed:14711416, ECO:0000269|PubMed:25467978,
FT ECO:0000269|PubMed:25467982"
FT MUTAGEN 179
FT /note="T->D: Increase in basal kinase activity."
FT /evidence="ECO:0000269|PubMed:10428833,
FT ECO:0000269|PubMed:14711416"
FT CONFLICT 249
FT /note="D -> G (in Ref. 1; BAA82674)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 348 AA; 39124 MW; 88525C390B0A709F CRC64;
MPLFKRRDGS GPAPNATIRE KYDFRDVLGT GAFSKVFLAE SKSDAGQMYA VKCIDKKALK
GKEESLENEI KVLRKLRHNN IVQLFDTYDE KQFVYLVMEL VTGGELFDRI VAKGSYTEQD
ASNLIRQVLE AVGFMHDNGV VHRDLKPENL LYYNQDEDSK IMISDFGLSK TEDSGVMATA
CGTPGYVAPE VLQQKPYGKA VDVWSIGVIA YILLCGYPPF YDESDANLFA QIIKGEYEFD
APYWDQISDS AKDFITHLMC CDPEARFTCQ DALSHPWISG NTAYTHDIHG TVAVHLKKSL
AKRNWKKAYN AAAAIRQLQM LRLSSNSNRL QKQASQQQPE PPTPAFHA
