EGL4_CAEBR
ID EGL4_CAEBR Reviewed; 749 AA.
AC A8X6H1;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=cGMP-dependent protein kinase egl-4 {ECO:0000250|UniProtKB:O76360};
DE EC=2.7.11.12 {ECO:0000250|UniProtKB:O76360};
DE AltName: Full=Egg-laying defective protein 4 {ECO:0000250|UniProtKB:O76360};
GN Name=egl-4 {ECO:0000312|EMBL:CAP28232.2};
GN ORFNames=CBG08401 {ECO:0000312|WormBase:CBG08401a};
OS Caenorhabditis briggsae.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6238;
RN [1] {ECO:0000312|EMBL:CAP28232.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AF16 {ECO:0000312|EMBL:CAP28232.2};
RX PubMed=14624247; DOI=10.1371/journal.pbio.0000045;
RA Stein L.D., Bao Z., Blasiar D., Blumenthal T., Brent M.R., Chen N.,
RA Chinwalla A., Clarke L., Clee C., Coghlan A., Coulson A., D'Eustachio P.,
RA Fitch D.H.A., Fulton L.A., Fulton R.E., Griffiths-Jones S., Harris T.W.,
RA Hillier L.W., Kamath R., Kuwabara P.E., Mardis E.R., Marra M.A.,
RA Miner T.L., Minx P., Mullikin J.C., Plumb R.W., Rogers J., Schein J.E.,
RA Sohrmann M., Spieth J., Stajich J.E., Wei C., Willey D., Wilson R.K.,
RA Durbin R.M., Waterston R.H.;
RT "The genome sequence of Caenorhabditis briggsae: a platform for comparative
RT genomics.";
RL PLoS Biol. 1:166-192(2003).
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. Regulates
CC gene expression via recruitment of a histone deacetylase complex
CC containing hda-2, saeg-1 and saeg-2. Represses body size and lifespan
CC through the dbl-1 and insulin pathways, respectively. May also signal
CC through daf-3 and/or daf-5. Role in egg-laying, dauer formation and
CC motility. Regulates behavioral responses to various chemosensory
CC stimuli in sensory neurons. Required for the initiation of long term
CC adaptation to prolonged odor exposure which results in a decrease in
CC odor seeking behavior. May regulate this process by phosphorylating
CC tax-2, a subunit of cyclic nucleotide-gated channel tax-2/tax-4. In ASH
CC sensory neurons, negatively regulates avoidance behavior to some bitter
CC tastants, such as quinine, probably by phosphorylating rgs-2 and rgs-3
CC which are 2 regulator of G-protein signaling proteins. In AWB sensory
CC neurons, involved in avoidance behavior to some repellent odors. In ASE
CC left (ASEL) sensory neuron, involved in the sensing of environmental
CC alkalinity downstream of receptor-type guanylate cyclase gcy-14. In
CC sensory neurons, involved in the signaling pathway downstream of
CC insulin, TGF-beta and receptor-type guanylate cyclase responsible for
CC inducing quiescence after food intake. 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. Probably by regulating neuronal transmission downstream of
CC lin-3 and receptor lin-23 and phospholipase plc-3 in ALA neurons,
CC involved in the decrease in locomotion during the quiescent state that
CC precedes each larval molt. {ECO:0000250|UniProtKB:O76360}.
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:0000250|UniProtKB:O76360};
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:0000250|UniProtKB:O76360};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O76360};
CC -!- ACTIVITY REGULATION: Binding of cGMP results in enzyme activation.
CC {ECO:0000250|UniProtKB:O76360}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O76360}. Nucleus
CC {ECO:0000250|UniProtKB:O76360}. Note=In resting AWC sensory neurons,
CC localizes in cytoplasm. Prolonged exposure to attractive odorants
CC sensed by AWC neurons results in nuclear translocation. Nuclear
CC translocation is required for the adaptation to prolonged odor exposure
CC and is controlled by G(o)-alpha subunit protein goa-1. Localization is
CC regulated by cGMP levels: high cGMP levels result in cytoplasmic
CC localization whereas low cGMP levels result in nuclear localization.
CC Nuclear localization in AWC neurons is dependent on age-1. In addition,
CC an intact sensory cilia structure is required for cytoplasmic
CC localization in resting AWC neurons. In resting AWB sensory neurons,
CC constitutive nuclear localization is dependent on goa-1. In resting ASH
CC sensory neurons, localizes in both cytoplasm and nucleus. Cytoplasmic
CC localization is important for negative regulation of quinine
CC sensitivity in ASH neurons. {ECO:0000250|UniProtKB:O76360}.
CC -!- PTM: Autophosphorylated. {ECO:0000250|UniProtKB:O76360}.
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; HE601100; CAP28232.2; -; Genomic_DNA.
DR AlphaFoldDB; A8X6H1; -.
DR SMR; A8X6H1; -.
DR STRING; 6238.CBG08401; -.
DR EnsemblMetazoa; CBG08401a.1; CBG08401a.1; WBGene00030199.
DR WormBase; CBG08401a; CBP30576; WBGene00030199; Cbr-egl-4.
DR eggNOG; KOG0614; Eukaryota.
DR HOGENOM; CLU_000288_73_2_1; -.
DR InParanoid; A8X6H1; -.
DR OMA; WIVKLYK; -.
DR OrthoDB; 401933at2759; -.
DR Proteomes; UP000008549; Chromosome IV.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
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:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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; 1.
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 3: Inferred from homology;
KW ATP-binding; cGMP; cGMP-binding; Chemotaxis; Coiled coil; Cytoplasm;
KW Developmental protein; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..749
FT /note="cGMP-dependent protein kinase egl-4"
FT /id="PRO_0000390490"
FT DOMAIN 438..698
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 699..749
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 87..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 723..749
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 30..96
FT /evidence="ECO:0000255"
FT MOTIF 461..473
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 562
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 234..237
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 244..245
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 349
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 358..361
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 368..369
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 403
FT /ligand="3',5'-cyclic GMP"
FT /ligand_id="ChEBI:CHEBI:57746"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q13976"
FT BINDING 444..452
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 468
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 749 AA; 84587 MW; 683926102A334C33 CRC64;
MYGSSRHHLD SFSSNDGNAF LVQVGSRTFE AHELQKLIPQ LEEAISRKDA QLRQQQSIVE
GHIKRISELE GEVTTLQREC DKLRSVLEQK AQSAASPGQP PSPSPRTDQL GNDLQQKAVF
PADGTQQRAK KIAVSAEPTN FENKPATLQH YNKTVAAKQM IRDAVQKNDF LKQLAKEQII
ELVNCMYEMR ARAGQWVIQE GEPGDRLFVV AEGELQVSRE GATLGKMRAG TVMGELAILY
NCTRTASVQA LTDVQLWVLD RSVFQMITQR LGMERHSQII NFLSKVSIFA NLTEDRISKI
ADVMDQDYYD GGHYILRQGE KGDAFFVINS GQVKVTQQIE GEKEAREIRI LNQGDFFGER
ALLGDEVRTA NIIAQAPGVE VLTLDRESFT KLIGDLDTLR KDYGDKERVA TLVREPPSPV
KIVDDFREEF ANVTLKNVKR LATLGVGGFG RVELVCVNGD KSKTYALKAL KKKHIVDTRQ
QEHIFAERNI MMETSTDWIV KLYKTFRDQK FVYMLLEVCL GGELWTTLRD RGHFDDYTAR
FYVACVLEGL EYLHRKNIVY RDLKPENCLL ANSGYLKLVD FGFAKKLASG RKTWTFCGTP
EYVSPEIILN KGHDQAADYW ALGIYICELM LGRPPFQASD PMKTYTLILK GVDALEIPNR
RIGKTATALV KKLCRDNPGE RLGSGSGGVN DIRKHRWFMG FDWEGLRTKT LKPPILPKVN
NPADVTNFDN YPPDNDVPPD EFSGWDEGF
