EGL4_CAEEL
ID EGL4_CAEEL Reviewed; 780 AA.
AC O76360; Q688A8; Q688A9; Q7KPJ2; Q8MXG6; Q8MXG7;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=cGMP-dependent protein kinase egl-4 {ECO:0000303|PubMed:10978280, ECO:0000303|PubMed:11181837};
DE EC=2.7.11.12 {ECO:0000269|PubMed:11181837, ECO:0000269|PubMed:12571101, ECO:0000269|PubMed:21573134};
DE AltName: Full=Egg-laying defective protein 4;
GN Name=egl-4 {ECO:0000312|WormBase:F55A8.2a};
GN Synonyms=cgk-1 {ECO:0000303|PubMed:11181837},
GN odr-9 {ECO:0000303|PubMed:10978280};
GN ORFNames=F55A8.2 {ECO:0000312|WormBase:F55A8.2a};
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}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), FUNCTION, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AUTOPHOSPHORYLATION, AND DISRUPTION PHENOTYPE.
RX PubMed=11181837; DOI=10.1046/j.1471-4159.2001.00131.x;
RA Stansberry J., Baude E.J., Taylor M.K., Chen P.J., Jin S.W., Ellis R.E.,
RA Uhler M.D.;
RT "A cGMP-dependent protein kinase is implicated in wild-type motility in C.
RT elegans.";
RL J. Neurochem. 76:1177-1187(2001).
RN [2] {ECO:0000305}
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 [3] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=10978280; DOI=10.1093/genetics/156.1.123;
RA Daniels S.A., Ailion M., Thomas J.H., Sengupta P.;
RT "egl-4 acts through a transforming growth factor-beta/SMAD pathway in
RT Caenorhabditis elegans to regulate multiple neuronal circuits in response
RT to sensory cues.";
RL Genetics 156:123-141(2000).
RN [4]
RP FUNCTION, NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF LYS-502.
RX PubMed=12495623; DOI=10.1016/s0896-6273(02)01066-8;
RA L'Etoile N.D., Coburn C.M., Eastham J., Kistler A., Gallegos G.,
RA Bargmann C.I.;
RT "The cyclic GMP-dependent protein kinase EGL-4 regulates olfactory
RT adaptation in C. elegans.";
RL Neuron 36:1079-1089(2002).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=12571101; DOI=10.1242/dev.00330;
RA Hirose T., Nakano Y., Nagamatsu Y., Misumi T., Ohta H., Ohshima Y.;
RT "Cyclic GMP-dependent protein kinase EGL-4 controls body size and lifespan
RT in C elegans.";
RL Development 130:1089-1099(2003).
RN [6]
RP FUNCTION, ACTIVITY REGULATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15330854; DOI=10.1111/j.1365-2443.2004.00771.x;
RA Nakano Y., Nagamatsu Y., Ohshima Y.;
RT "cGMP and a germ-line signal control body size in C. elegans through cGMP-
RT dependent protein kinase EGL-4.";
RL Genes Cells 9:773-779(2004).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF GLY-362.
RX PubMed=16547093; DOI=10.1534/genetics.106.057380;
RA Raizen D.M., Cullison K.M., Pack A.I., Sundaram M.V.;
RT "A novel gain-of-function mutant of the cyclic GMP-dependent protein kinase
RT egl-4 affects multiple physiological processes in Caenorhabditis elegans.";
RL Genetics 173:177-187(2006).
RN [8]
RP FUNCTION.
RX PubMed=17891142; DOI=10.1038/nn1981;
RA Van Buskirk C., Sternberg P.W.;
RT "Epidermal growth factor signaling induces behavioral quiescence in
RT Caenorhabditis elegans.";
RL Nat. Neurosci. 10:1300-1307(2007).
RN [9]
RP FUNCTION.
RX PubMed=18316030; DOI=10.1016/j.cmet.2008.01.005;
RA You Y.J., Kim J., Raizen D.M., Avery L.;
RT "Insulin, cGMP, and TGF-beta signals regulate food intake and quiescence in
RT C. elegans: a model for satiety.";
RL Cell Metab. 7:249-257(2008).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18832350; DOI=10.1534/genetics.108.094771;
RA van der Linden A.M., Wiener S., You Y.J., Kim K., Avery L., Sengupta P.;
RT "The EGL-4 PKG acts with KIN-29 salt-inducible kinase and protein kinase A
RT to regulate chemoreceptor gene expression and sensory behaviors in
RT Caenorhabditis elegans.";
RL Genetics 180:1475-1491(2008).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF THR-276 AND ASP-611.
RX PubMed=20220099; DOI=10.1073/pnas.1000866107;
RA Lee J.I., O'Halloran D.M., Eastham-Anderson J., Juang B.T., Kaye J.A.,
RA Scott Hamilton O., Lesch B., Goga A., L'Etoile N.D.;
RT "Nuclear entry of a cGMP-dependent kinase converts transient into long-
RT lasting olfactory adaptation.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:6016-6021(2010).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-162; ALA-497; LYS-499
RP AND GLY-682.
RX PubMed=21573134; DOI=10.1371/journal.pgen.1002065;
RA Hao Y., Xu N., Box A.C., Schaefer L., Kannan K., Zhang Y., Florens L.,
RA Seidel C., Washburn M.P., Wiegraebe W., Mak H.Y.;
RT "Nuclear cGMP-dependent kinase regulates gene expression via activity-
RT dependent recruitment of a conserved histone deacetylase complex.";
RL PLoS Genet. 7:E1002065-E1002065(2011).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF THR-276.
RX PubMed=22319638; DOI=10.1371/journal.pone.0031614;
RA O'Halloran D.M., Hamilton O.S., Lee J.I., Gallegos M., L'Etoile N.D.;
RT "Changes in cGMP levels affect the localization of EGL-4 in AWC in
RT Caenorhabditis elegans.";
RL PLoS ONE 7:E31614-E31614(2012).
RN [14]
RP FUNCTION.
RX PubMed=23664973; DOI=10.1016/j.cub.2013.04.052;
RA Murayama T., Takayama J., Fujiwara M., Maruyama I.N.;
RT "Environmental alkalinity sensing mediated by the transmembrane guanylyl
RT cyclase GCY-14 in C. elegans.";
RL Curr. Biol. 23:1007-1012(2013).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23954825; DOI=10.1016/j.neulet.2013.08.011;
RA He C., O'Halloran D.M.;
RT "Nuclear PKG localization is regulated by G(0) alpha and is necessary in
RT the AWB neurons to mediate avoidance in Caenorhabditis elegans.";
RL Neurosci. Lett. 553:35-39(2013).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23874221; DOI=10.1371/journal.pgen.1003619;
RA Krzyzanowski M.C., Brueggemann C., Ezak M.J., Wood J.F., Michaels K.L.,
RA Jackson C.A., Juang B.T., Collins K.D., Yu M.C., L'etoile N.D.,
RA Ferkey D.M.;
RT "The C. elegans cGMP-dependent protein kinase EGL-4 regulates nociceptive
RT behavioral sensitivity.";
RL PLoS Genet. 9:E1003619-E1003619(2013).
RN [17]
RP DISRUPTION PHENOTYPE.
RX PubMed=24015261; DOI=10.1371/journal.pone.0072569;
RA Beckert U., Aw W.Y., Burhenne H., Forsterling L., Kaever V., Timmons L.,
RA Seifert R.;
RT "The receptor-bound guanylyl cyclase DAF-11 is the mediator of hydrogen
RT peroxide-induced cGMP increase in Caenorhabditis elegans.";
RL PLoS ONE 8:E72569-E72569(2013).
RN [18]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26434723; DOI=10.1534/genetics.115.177543;
RA Fujiwara M., Hino T., Miyamoto R., Inada H., Mori I., Koga M., Miyahara K.,
RA Ohshima Y., Ishihara T.;
RT "The importance of cGMP signaling in sensory cilia for body size regulation
RT in Caenorhabditis elegans.";
RL Genetics 201:1497-1510(2015).
RN [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27383131; DOI=10.7554/elife.14000;
RA Cho C.E., Brueggemann C., L'Etoile N.D., Bargmann C.I.;
RT "Parallel encoding of sensory history and behavioral preference during
RT Caenorhabditis elegans olfactory learning.";
RL Elife 5:14000-14000(2016).
CC -!- FUNCTION: Promotes chemoreceptor gene expression in response to
CC increased cGMP levels by antagonizing the gene repression functions of
CC the class II HDAC hda-4 and the mef-2 transcription factor
CC (PubMed:18832350). Regulates gene expression via recruitment of a
CC histone deacetylase complex containing hda-2, saeg-1 and saeg-2
CC (PubMed:21573134). Represses body size and lifespan through the dbl-1
CC and insulin pathways, respectively (PubMed:12571101, PubMed:15330854,
CC PubMed:26434723). May also signal through daf-3 and/or daf-5. Role in
CC egg-laying, dauer formation and motility (PubMed:12571101,
CC PubMed:11181837, PubMed:21573134). Regulates behavioral responses to
CC various chemosensory stimuli in sensory neurons (PubMed:10978280,
CC PubMed:22319638, PubMed:23874221, PubMed:26434723). Required for the
CC initiation of long term adaptation to prolonged odor exposure which
CC results in a decrease in odor seeking behavior (PubMed:12495623,
CC PubMed:20220099, PubMed:26434723). May regulate this process by
CC phosphorylating tax-2, a subunit of cyclic nucleotide-gated channel
CC tax-2/tax-4 (PubMed:12495623). In ASH sensory neurons, negatively
CC regulates avoidance behavior to some bitter tastants, such as quinine,
CC probably by phosphorylating rgs-2 and rgs-3 which are 2 regulator of G-
CC protein signaling proteins (PubMed:23874221). In AWB sensory neurons,
CC involved in avoidance behavior to some repellent odors
CC (PubMed:23954825). In ASE left (ASEL) sensory neuron, involved in the
CC sensing of environmental alkalinity downstream of receptor-type
CC guanylate cyclase gcy-14 (PubMed:23664973). In sensory neurons,
CC involved in the signaling pathway downstream of insulin, TGF-beta and
CC receptor-type guanylate cyclase responsible for inducing quiescence
CC after food intake (PubMed:18316030). Might play a role in aversive
CC olfactory learning in AWC neurons when an odor is associated with food
CC deprivation, depending on the ins-1/age-1 signal from the AIA to the
CC AWC neurons (PubMed:27383131). Probably by regulating neuronal
CC transmission downstream of lin-3 and receptor lin-23 and phospholipase
CC plc-3 in ALA neurons, involved in the decrease in locomotion during the
CC quiescent state that precedes each larval molt (PubMed:17891142).
CC {ECO:0000269|PubMed:11181837, ECO:0000269|PubMed:12571101,
CC ECO:0000269|PubMed:15330854, ECO:0000269|PubMed:16547093,
CC ECO:0000269|PubMed:17891142, ECO:0000269|PubMed:18316030,
CC ECO:0000269|PubMed:18832350, ECO:0000269|PubMed:20220099,
CC ECO:0000269|PubMed:21573134, ECO:0000269|PubMed:22319638,
CC ECO:0000269|PubMed:23664973, ECO:0000269|PubMed:23874221,
CC ECO:0000269|PubMed:23954825, ECO:0000269|PubMed:26434723,
CC ECO:0000269|PubMed:27383131, ECO:0000305|PubMed:12495623}.
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=2.7.11.12;
CC Evidence={ECO:0000269|PubMed:11181837, ECO:0000269|PubMed:12571101,
CC ECO:0000269|PubMed:21573134};
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=2.7.11.12; Evidence={ECO:0000269|PubMed:11181837,
CC ECO:0000269|PubMed:12571101, ECO:0000269|PubMed:21573134};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11181837, ECO:0000269|PubMed:12571101};
CC -!- ACTIVITY REGULATION: Binding of cGMP results in enzyme activation.
CC {ECO:0000269|PubMed:11181837, ECO:0000269|PubMed:15330854}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=2.1 umol/min/mg enzyme towards cGMP (Isoform c at pH 6.8 and 30
CC degrees Celsius) {ECO:0000269|PubMed:11181837};
CC -!- SUBUNIT: When phosphorylated, interacts with saeg-2. May interact with
CC saeg-1. {ECO:0000269|PubMed:21573134}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20220099,
CC ECO:0000269|PubMed:22319638, ECO:0000269|PubMed:23874221,
CC ECO:0000269|PubMed:23954825, ECO:0000269|PubMed:27383131}. Nucleus
CC {ECO:0000269|PubMed:20220099, ECO:0000269|PubMed:21573134,
CC ECO:0000269|PubMed:22319638, ECO:0000269|PubMed:23874221,
CC ECO:0000269|PubMed:23954825, ECO:0000269|PubMed:27383131}. Note=In
CC resting AWC sensory neurons, localizes in cytoplasm (PubMed:20220099,
CC PubMed:23954825, PubMed:27383131). Prolonged exposure to attractive
CC odorants sensed by AWC neurons results in nuclear translocation
CC (PubMed:20220099, PubMed:23954825, PubMed:27383131). Nuclear
CC translocation is required for the adaptation to prolonged odor exposure
CC and is controlled by G(o)-alpha subunit protein goa-1 (PubMed:23954825,
CC PubMed:20220099, PubMed:27383131). Localization is regulated by cGMP
CC levels: high cGMP levels result in cytoplasmic localization whereas low
CC cGMP levels result in nuclear localization (PubMed:20220099,
CC PubMed:22319638). Nuclear localization in AWC neurons is dependent on
CC age-1 (PubMed:27383131). In addition, an intact sensory cilia structure
CC is required for cytoplasmic localization in resting AWC neurons
CC (PubMed:22319638). In resting AWB sensory neurons, constitutive nuclear
CC localization is dependent on goa-1 (PubMed:23954825). In resting ASH
CC sensory neurons, localizes in both cytoplasm and nucleus
CC (PubMed:23874221). Cytoplasmic localization is important for negative
CC regulation of quinine sensitivity in ASH neurons (PubMed:23874221).
CC {ECO:0000269|PubMed:20220099, ECO:0000269|PubMed:22319638,
CC ECO:0000269|PubMed:23874221, ECO:0000269|PubMed:23954825,
CC ECO:0000269|PubMed:27383131}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=a {ECO:0000269|PubMed:11181837, ECO:0000269|PubMed:9851916};
CC IsoId=O76360-1; Sequence=Displayed;
CC Name=b {ECO:0000269|PubMed:11181837, ECO:0000269|PubMed:9851916};
CC IsoId=O76360-2; Sequence=VSP_053172, VSP_053177;
CC Name=c {ECO:0000269|PubMed:11181837, ECO:0000269|PubMed:9851916};
CC IsoId=O76360-3; Sequence=VSP_053174, VSP_053175;
CC Name=d {ECO:0000269|PubMed:9851916};
CC IsoId=O76360-4; Sequence=VSP_053171, VSP_053178, VSP_053180;
CC Name=e {ECO:0000269|PubMed:9851916};
CC IsoId=O76360-5; Sequence=VSP_053173, VSP_053176;
CC Name=f {ECO:0000269|PubMed:9851916};
CC IsoId=O76360-6; Sequence=VSP_053170, VSP_053179;
CC -!- TISSUE SPECIFICITY: Expressed in AWC sensory neurons (at protein level)
CC (PubMed:20220099). Mainly expressed in head neurons, hypodermis,
CC intestine and body wall muscles. L2 and L3 larvae show extensive
CC expression, lower levels are observed in L4 larvae, later embryos and
CC adults. Isoform c is expressed in a subset of neurons in the head,
CC nerve ring, and ventral nerve cord including some motor neurons, also
CC in several neurons in the tail, the pharyngeal marginal cells, body
CC muscle, intestine, vulval muscles, and spermatheca (PubMed:11181837,
CC PubMed:12571101, PubMed:15330854). {ECO:0000269|PubMed:11181837,
CC ECO:0000269|PubMed:12571101, ECO:0000269|PubMed:15330854,
CC ECO:0000269|PubMed:20220099}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:11181837}.
CC -!- DISRUPTION PHENOTYPE: Increased size and extended lifespan
CC (PubMed:11181837, PubMed:12571101, PubMed:18832350, PubMed:26434723).
CC Defects in chemosensory behavior, egg-laying, synaptic transmission,
CC and dauer formation (PubMed:11181837, PubMed:12571101, PubMed:18832350,
CC PubMed:26434723). Impaired movement of adult animals in response to
CC sensory stimuli (PubMed:10978280). Loss of adaptive behavior to long
CC lasting exposure to attractive odorants (PubMed:20220099). Normal
CC initial chemotaxis response during a first and short exposure to
CC attractive odorants (PubMed:20220099). Loss of chemotaxis response to
CC the repellent odor 2-nonanone (PubMed:23954825). Defective chemotaxis
CC in response to diacetyl and isoamylalcohol (PubMed:26434723). High
CC sensitivity to benzaldehyde, which is retained following pre-exposure
CC in contrast to wild-type animals (PubMed:26434723). Increased basal
CC cGMP levels (PubMed:24015261). {ECO:0000269|PubMed:10978280,
CC ECO:0000269|PubMed:11181837, ECO:0000269|PubMed:12571101,
CC ECO:0000269|PubMed:15330854, ECO:0000269|PubMed:18832350,
CC ECO:0000269|PubMed:20220099, ECO:0000269|PubMed:24015261,
CC ECO:0000269|PubMed:26434723}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. cGMP subfamily. {ECO:0000255}.
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DR EMBL; FO081473; CCD71859.1; -; Genomic_DNA.
DR EMBL; FO081473; CCD71860.1; -; Genomic_DNA.
DR EMBL; FO081473; CCD71861.1; -; Genomic_DNA.
DR EMBL; FO081473; CCD71862.1; -; Genomic_DNA.
DR EMBL; FO081473; CCD71863.1; -; Genomic_DNA.
DR EMBL; FO081473; CCD71864.1; -; Genomic_DNA.
DR RefSeq; NP_001023223.1; NM_001028052.2. [O76360-5]
DR RefSeq; NP_001023224.1; NM_001028053.2. [O76360-6]
DR RefSeq; NP_500141.1; NM_067740.4. [O76360-1]
DR RefSeq; NP_500142.1; NM_067741.3. [O76360-2]
DR RefSeq; NP_741329.1; NM_171279.3. [O76360-3]
DR RefSeq; NP_741330.2; NM_171280.2. [O76360-4]
DR AlphaFoldDB; O76360; -.
DR SMR; O76360; -.
DR BioGRID; 42146; 6.
DR STRING; 6239.F55A8.2h.1; -.
DR EPD; O76360; -.
DR PaxDb; O76360; -.
DR PeptideAtlas; O76360; -.
DR EnsemblMetazoa; F55A8.2a.1; F55A8.2a.1; WBGene00001173. [O76360-1]
DR EnsemblMetazoa; F55A8.2a.2; F55A8.2a.2; WBGene00001173. [O76360-1]
DR EnsemblMetazoa; F55A8.2b.1; F55A8.2b.1; WBGene00001173. [O76360-2]
DR EnsemblMetazoa; F55A8.2c.1; F55A8.2c.1; WBGene00001173. [O76360-3]
DR EnsemblMetazoa; F55A8.2d.1; F55A8.2d.1; WBGene00001173. [O76360-4]
DR EnsemblMetazoa; F55A8.2e.1; F55A8.2e.1; WBGene00001173. [O76360-5]
DR EnsemblMetazoa; F55A8.2f.1; F55A8.2f.1; WBGene00001173. [O76360-6]
DR GeneID; 176991; -.
DR UCSC; F55A8.2a.1; c. elegans.
DR CTD; 176991; -.
DR WormBase; F55A8.2a; CE19897; WBGene00001173; egl-4. [O76360-1]
DR WormBase; F55A8.2b; CE19898; WBGene00001173; egl-4. [O76360-2]
DR WormBase; F55A8.2c; CE31541; WBGene00001173; egl-4. [O76360-3]
DR WormBase; F55A8.2d; CE37718; WBGene00001173; egl-4. [O76360-4]
DR WormBase; F55A8.2e; CE37241; WBGene00001173; egl-4. [O76360-5]
DR WormBase; F55A8.2f; CE37242; WBGene00001173; egl-4. [O76360-6]
DR eggNOG; KOG0614; Eukaryota.
DR InParanoid; O76360; -.
DR PhylomeDB; O76360; -.
DR SABIO-RK; O76360; -.
DR PRO; PR:O76360; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00001173; Expressed in adult organism and 4 other tissues.
DR ExpressionAtlas; O76360; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030553; F:cGMP binding; IEA:UniProtKB-KW.
DR GO; GO:0004692; F:cGMP-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:0007635; P:chemosensory behavior; IMP:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0043577; P:chemotropism; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IGI:WormBase.
DR GO; GO:0030536; P:larval feeding behavior; IGI:UniProtKB.
DR GO; GO:0050849; P:negative regulation of calcium-mediated signaling; IMP:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:WormBase.
DR GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; IMP:UniProtKB.
DR GO; GO:1902160; P:negative regulation of cyclic nucleotide-gated ion channel activity; IGI:WormBase.
DR GO; GO:0061067; P:negative regulation of dauer larval development; IMP:UniProtKB.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; IMP:UniProtKB.
DR GO; GO:0046621; P:negative regulation of organ growth; IMP:WormBase.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IGI:WormBase.
DR GO; GO:0008355; P:olfactory learning; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:1905959; P:positive regulation of cellular response to alcohol; IMP:UniProtKB.
DR GO; GO:0010753; P:positive regulation of cGMP-mediated signaling; IMP:WormBase.
DR GO; GO:0050921; P:positive regulation of chemotaxis; IMP:UniProtKB.
DR GO; GO:0051343; P:positive regulation of cyclic-nucleotide phosphodiesterase activity; IGI:WormBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:1901046; P:positive regulation of oviposition; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IMP:UniProtKB.
DR GO; GO:1903998; P:regulation of eating behavior; IGI:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IGI:UniProtKB.
DR GO; GO:0046662; P:regulation of oviposition; IMP:WormBase.
DR GO; GO:0097305; P:response to alcohol; IMP:UniProtKB.
DR GO; GO:0042542; P:response to hydrogen peroxide; IMP:UniProtKB.
DR GO; GO:1990834; P:response to odorant; IMP:UniProtKB.
DR GO; GO:0070482; P:response to oxygen levels; IMP:WormBase.
DR GO; GO:0050913; P:sensory perception of bitter taste; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR GO; GO:0030431; P:sleep; IMP:WormBase.
DR CDD; cd00038; CAP_ED; 2.
DR CDD; cd05572; STKc_cGK; 1.
DR Gene3D; 2.60.120.10; -; 2.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR002374; cGMP_dep_kinase.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR018488; cNMP-bd_CS.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR035014; STKc_cGK.
DR Pfam; PF00027; cNMP_binding; 2.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF000559; cGMP-dep_kinase; 1.
DR PRINTS; PR00104; CGMPKINASE.
DR SMART; SM00100; cNMP; 2.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF51206; SSF51206; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00888; CNMP_BINDING_1; 2.
DR PROSITE; PS00889; CNMP_BINDING_2; 2.
DR PROSITE; PS50042; CNMP_BINDING_3; 2.
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 Alternative splicing; ATP-binding; cGMP; cGMP-binding; Chemotaxis;
KW Coiled coil; Cytoplasm; Developmental protein; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..780
FT /note="cGMP-dependent protein kinase egl-4"
FT /id="PRO_0000390491"
FT DOMAIN 469..729
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 730..780
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 757..780
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 61..127
FT /evidence="ECO:0000255"
FT MOTIF 492..504
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 593
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 265..268
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 275..276
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 380
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 389..392
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 399..400
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 434
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 475..483
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 499
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..310
FT /note="Missing (in isoform f)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_053170"
FT VAR_SEQ 1..188
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_053171"
FT VAR_SEQ 1..43
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:11181837,
FT ECO:0000303|PubMed:9851916"
FT /id="VSP_053172"
FT VAR_SEQ 1..37
FT /note="Missing (in isoform e)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_053173"
FT VAR_SEQ 1..20
FT /note="MSSGSRPSSGGGGGGGGASG -> MYGSSRHHMDSFSSNDGGAFL (in
FT isoform c)"
FT /evidence="ECO:0000303|PubMed:11181837,
FT ECO:0000303|PubMed:9851916"
FT /id="VSP_053174"
FT VAR_SEQ 21..52
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000303|PubMed:11181837,
FT ECO:0000303|PubMed:9851916"
FT /id="VSP_053175"
FT VAR_SEQ 38..52
FT /note="FSKLRKPSDQPNGNQ -> MCWKFNPLKALRVVE (in isoform e)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_053176"
FT VAR_SEQ 44..52
FT /note="PSDQPNGNQ -> MKQQPPRIY (in isoform b)"
FT /evidence="ECO:0000303|PubMed:11181837,
FT ECO:0000303|PubMed:9851916"
FT /id="VSP_053177"
FT VAR_SEQ 189..275
FT /note="KQMIRDAVQKNDFLKQLAKEQIIELVNCMYEMRARAGQWVIQEGEPGDRLFV
FT VAEGELQVSREGALLGKMRAGTVMGELAILYNCTR -> MLTCSTTTCQISPAYPKFIE
FT KLRRMIWGREPSTSYEFDELAQQVALKSHRRNVDDGYYVEEIHFEPPQVVRKKQPTRNL
FT FYKRSHKK (in isoform d)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_053178"
FT VAR_SEQ 311..316
FT /note="MNFLTK -> MKKVYV (in isoform f)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_053179"
FT VAR_SEQ 353..749
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_053180"
FT MUTAGEN 162
FT /note="K->N: Constitutively active. Undergoes
FT autophosphorylation in vitro."
FT /evidence="ECO:0000269|PubMed:21573134"
FT MUTAGEN 276
FT /note="T->A: Loss of nuclear translocation mediated by
FT cGMP. Loss of nuclear translocation upon prolonged exposure
FT to attractive odorants."
FT /evidence="ECO:0000269|PubMed:20220099,
FT ECO:0000269|PubMed:22319638"
FT MUTAGEN 362
FT /note="G->R: Loss of body size, reduced locomotion in the
FT presence of food, a pale intestine, increased intestinal
FT fat storage, and a decreased propensity to form dauer
FT larvae."
FT /evidence="ECO:0000269|PubMed:16547093"
FT MUTAGEN 497
FT /note="A->T: No obvious phenotype. May cause partial loss
FT of kinase activity."
FT /evidence="ECO:0000269|PubMed:21573134"
FT MUTAGEN 499
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:21573134"
FT MUTAGEN 502
FT /note="K->E: Loss of adaptive behavior upon prolonged
FT exposure to attractive odorants."
FT /evidence="ECO:0000269|PubMed:12495623"
FT MUTAGEN 611
FT /note="D->N: Loss of nuclear translocation upon prolonged
FT exposure to attractive odorants."
FT /evidence="ECO:0000269|PubMed:20220099"
FT MUTAGEN 682
FT /note="G->R: No obvious phenotype. May cause partial loss
FT of kinase activity."
FT /evidence="ECO:0000269|PubMed:21573134"
SQ SEQUENCE 780 AA; 86742 MW; 55E036AF50626DD2 CRC64;
MSSGSRPSSG GGGGGGGASG GAGGGAPGGG GGGIRGFFSK LRKPSDQPNG NQVQVGTRTF
EAHELQKLIP QLEEAISRKD AQLRQQQTIV EGHIKRISEL EGEVTTLQRE CDKLRSVLEQ
KAQSAASPGG QPPSPSPRTD QLGNDLQQKA VLPADGVQRA KKIAVSAEPT NFENKPATLQ
HYNKTVGAKQ MIRDAVQKND FLKQLAKEQI IELVNCMYEM RARAGQWVIQ EGEPGDRLFV
VAEGELQVSR EGALLGKMRA GTVMGELAIL YNCTRTASVQ ALTDVQLWVL DRSVFQMITQ
RLGMERHSQL MNFLTKVSIF QNLSEDRISK MADVMDQDYY DGGHYIIRQG EKGDAFFVIN
SGQVKVTQQI EGETEPREIR VLNQGDFFGE RALLGEEVRT ANIIAQAPGV EVLTLDRESF
GKLIGDLESL KKDYGDKERL AQVVREPPSP VKIVDDFREE FAQVTLKNVK RLATLGVGGF
GRVELVCVNG DKAKTFALKA LKKKHIVDTR QQEHIFAERN IMMETSTDWI VKLYKTFRDQ
KFVYMLLEVC LGGELWTTLR DRGHFDDYTA RFYVACVLEG LEYLHRKNIV YRDLKPENCL
LANTGYLKLV DFGFAKKLAS GRKTWTFCGT PEYVSPEIIL NKGHDQAADY WALGIYICEL
MLGRPPFQAS DPMKTYTLIL KGVDALEIPN RRIGKTATAL VKKLCRDNPG ERLGSGSGGV
NDIRKHRWFM GFDWEGLRSR TLKPPILPKV SNPADVTNFD NYPPDNDVPP DEFSGWDEGF
