GCK3_CAEEL
ID GCK3_CAEEL Reviewed; 596 AA.
AC G5EEN4; B5QSI7; F9UKV1;
DT 01-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Germinal center kinase 3 {ECO:0000303|PubMed:15684092};
DE EC=2.7.11.1 {ECO:0000269|PubMed:18049475, ECO:0000269|PubMed:20595048};
DE AltName: Full=STE20-like serine/threonine kinase {ECO:0000312|EMBL:AAU89102.1};
GN Name=gck-3 {ECO:0000312|WormBase:Y59A8B.23a};
GN ORFNames=Y59A8B.23 {ECO:0000312|WormBase:Y59A8B.23a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAU89102.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, AND INTERACTION WITH
RP CLH-3.
RX PubMed=15684092; DOI=10.1085/jgp.200409215;
RA Denton J., Nehrke K., Yin X., Morrison R., Strange K.;
RT "GCK-3, a newly identified Ste20 kinase, binds to and regulates the
RT activity of a cell cycle-dependent ClC anion channel.";
RL J. Gen. Physiol. 125:113-125(2005).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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 FUNCTION, INTERACTION WITH WNK-1, AND DISRUPTION PHENOTYPE.
RX PubMed=17596296; DOI=10.1152/ajpcell.00126.2007;
RA Choe K.P., Strange K.;
RT "Evolutionarily conserved WNK and Ste20 kinases are essential for acute
RT volume recovery and survival after hypertonic shrinkage in Caenorhabditis
RT elegans.";
RL Am. J. Physiol. 293:C915-927(2007).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH WNK-1, PHOSPHORYLATION AT
RP THR-280 AND SER-419, AND MUTAGENESIS OF THR-280 AND SER-419.
RX PubMed=18049475; DOI=10.1038/sj.embor.7401128;
RA Hisamoto N., Moriguchi T., Urushiyama S., Mitani S., Shibuya H.,
RA Matsumoto K.;
RT "Caenorhabditis elegans WNK-STE20 pathway regulates tube formation by
RT modulating ClC channel activity.";
RL EMBO Rep. 9:70-75(2008).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DISRUPTION PHENOTYPE, PHOSPHORYLATION AT THR-13; THR-32; SER-190 AND
RP SER-405, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF LYS-137.
RX PubMed=20595048; DOI=10.1016/j.ydbio.2010.05.505;
RA Kupinski A.P., Muller-Reichert T., Eckmann C.R.;
RT "The Caenorhabditis elegans Ste20 kinase, GCK-3, is essential for
RT postembryonic developmental timing and regulates meiotic chromosome
RT segregation.";
RL Dev. Biol. 344:758-771(2010).
RN [6]
RP FUNCTION.
RX PubMed=23076791; DOI=10.1152/ajpcell.00294.2012;
RA Lee E.C., Strange K.;
RT "GCN-2 dependent inhibition of protein synthesis activates osmosensitive
RT gene transcription via WNK and Ste20 kinase signaling.";
RL Am. J. Physiol. 303:C1269-1277(2012).
CC -!- FUNCTION: Plays a role in osmotic stress responses by regulating ion
CC homeostasis and by controlling cell volume via the phosphorylation-
CC mediated inhibition of the chloride channel clh-3 (PubMed:15684092,
CC PubMed:17596296). In addition, increases gpdh-1 translation upon
CC osmotic stress, likely downstream of wnk-1 (PubMed:23076791). Involved
CC in several developmental processes including the tubular formation of
CC the excretory canals, the formation of the intestine and the
CC progression through larval stages (PubMed:20595048). In addition,
CC required for germ line development by controlling meiosis and
CC chromosomal segregation during spermatogenesis. By controlling clh-3
CC activity, may regulate the development of the excretory canals and
CC fertility (PubMed:18049475). {ECO:0000269|PubMed:15684092,
CC ECO:0000269|PubMed:17596296, ECO:0000269|PubMed:18049475,
CC ECO:0000269|PubMed:20595048, ECO:0000269|PubMed:23076791}.
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=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:18049475, ECO:0000269|PubMed:20595048};
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=2.7.11.1; Evidence={ECO:0000269|PubMed:18049475,
CC ECO:0000269|PubMed:20595048};
CC -!- SUBUNIT: Interacts (via C-terminus) with clh-3; required for the
CC phosphorylation-mediated inhibition of clh-3 function
CC (PubMed:15684092). Interacts (via C-terminus) with wnk-1; the
CC interaction is direct (PubMed:17596296, PubMed:18049475).
CC {ECO:0000269|PubMed:15684092, ECO:0000269|PubMed:17596296,
CC ECO:0000269|PubMed:18049475}.
CC -!- INTERACTION:
CC G5EEN4; X5M5N0: wnk-1; NbExp=3; IntAct=EBI-7713242, EBI-6540721;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20595048}. Nucleus
CC {ECO:0000269|PubMed:20595048}. Note=Localizes in the nucleus in
CC intestinal cells. {ECO:0000269|PubMed:20595048}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:Y59A8B.23a};
CC IsoId=G5EEN4-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:Y59A8B.23b};
CC IsoId=G5EEN4-2; Sequence=VSP_057536;
CC Name=c {ECO:0000312|WormBase:Y59A8B.23c};
CC IsoId=G5EEN4-3; Sequence=VSP_057537, VSP_057538;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with a higher expression in
CC the excretory cell. Expressed in both male and female germ cells; up-
CC regulated in maturing spermatocytes but absent in mature sperm.
CC {ECO:0000269|PubMed:20595048}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all stages.
CC {ECO:0000269|PubMed:20595048}.
CC -!- PTM: Phosphorylated at Thr-280 and Ser-419 probably by wnk-1;
CC phosphorylation results in weak activation (PubMed:18049475).
CC Predominantly autophosphorylated at Thr-32 and Ser-190 and weakly
CC autophosphorylated at Thr-13 and Ser-405 in vitro (PubMed:20595048).
CC {ECO:0000269|PubMed:18049475, ECO:0000269|PubMed:20595048}.
CC -!- DISRUPTION PHENOTYPE: Hermaphrodites arrest after the first molt and
CC die after at most 6 days. Most animals appear L2-like with morphologies
CC of gonads and vulva that are out of step with the developmental stage.
CC Mutants have a dilated intestinal lumen with extensive internal folding
CC associated with the accumulation of undigested bacteria and a shortened
CC excretory canal. Some animals have adult-type alae and are sterile with
CC vulva and germ line formation defects (PubMed:20595048). In RNAi-
CC mediated knockdown, impaired survival and slower volume recovery upon
CC hypertonic stress (PubMed:17596296). {ECO:0000269|PubMed:17596296,
CC ECO:0000269|PubMed:20595048}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; AY741200; AAU89102.1; -; mRNA.
DR EMBL; AL132898; CAC14417.2; -; Genomic_DNA.
DR EMBL; AL132898; CAR64690.1; -; Genomic_DNA.
DR EMBL; AL132898; CCC42211.1; -; Genomic_DNA.
DR RefSeq; NP_001129918.1; NM_001136446.2. [G5EEN4-2]
DR RefSeq; NP_001256762.1; NM_001269833.1. [G5EEN4-3]
DR RefSeq; NP_507517.2; NM_075116.4. [G5EEN4-1]
DR AlphaFoldDB; G5EEN4; -.
DR SMR; G5EEN4; -.
DR IntAct; G5EEN4; 1.
DR MINT; G5EEN4; -.
DR STRING; 6239.Y59A8B.23a.1; -.
DR iPTMnet; G5EEN4; -.
DR EPD; G5EEN4; -.
DR PaxDb; G5EEN4; -.
DR PeptideAtlas; G5EEN4; -.
DR EnsemblMetazoa; Y59A8B.23a.1; Y59A8B.23a.1; WBGene00013355. [G5EEN4-1]
DR EnsemblMetazoa; Y59A8B.23b.1; Y59A8B.23b.1; WBGene00013355. [G5EEN4-2]
DR EnsemblMetazoa; Y59A8B.23c.1; Y59A8B.23c.1; WBGene00013355. [G5EEN4-3]
DR GeneID; 190400; -.
DR KEGG; cel:CELE_Y59A8B.23; -.
DR CTD; 190400; -.
DR WormBase; Y59A8B.23a; CE38123; WBGene00013355; gck-3. [G5EEN4-1]
DR WormBase; Y59A8B.23b; CE43021; WBGene00013355; gck-3. [G5EEN4-2]
DR WormBase; Y59A8B.23c; CE46529; WBGene00013355; gck-3. [G5EEN4-3]
DR eggNOG; KOG0582; Eukaryota.
DR GeneTree; ENSGT00940000154621; -.
DR HOGENOM; CLU_000288_111_2_1; -.
DR InParanoid; G5EEN4; -.
DR OMA; TSNCKQG; -.
DR OrthoDB; 855861at2759; -.
DR PhylomeDB; G5EEN4; -.
DR PRO; PR:G5EEN4; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00013355; 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; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:WormBase.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0060562; P:epithelial tube morphogenesis; IMP:WormBase.
DR GO; GO:0006972; P:hyperosmotic response; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; IMP:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:WormBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR024678; Kinase_OSR1/WNK_CCT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF12202; OSR1_C; 1.
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.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Developmental protein;
KW Differentiation; Kinase; Meiosis; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Spermatogenesis; Transferase.
FT CHAIN 1..596
FT /note="Germinal center kinase 3"
FT /id="PRO_0000432620"
FT DOMAIN 108..386
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 429..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..64
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 65..79
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 240
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 114..122
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 137
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 13
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20595048"
FT MOD_RES 32
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20595048"
FT MOD_RES 190
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20595048"
FT MOD_RES 280
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18049475"
FT MOD_RES 405
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20595048"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18049475"
FT VAR_SEQ 1..157
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057536"
FT VAR_SEQ 526..541
FT /note="VEGIAHELVTAELIDC -> GTEYFTKSKIYCEARE (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_057537"
FT VAR_SEQ 542..596
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_057538"
FT MUTAGEN 137
FT /note="K->R,M: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18049475,
FT ECO:0000269|PubMed:20595048"
FT MUTAGEN 280
FT /note="T->A: Partial loss of activity."
FT /evidence="ECO:0000269|PubMed:18049475"
FT MUTAGEN 280
FT /note="T->E: Increase in activity."
FT /evidence="ECO:0000269|PubMed:18049475"
FT MUTAGEN 419
FT /note="S->A,D: Abolishes phosphorylation by wnk-1. No
FT effect on activity."
FT /evidence="ECO:0000269|PubMed:18049475"
SQ SEQUENCE 596 AA; 64052 MW; 95FEFB53B7D17A32 CRC64;
MSSSNLAGNT NTTTTSSAAS AAAAHSAANA STITSEYSTT QTTTGTFNTD TLSSIGSTST
LHGSQPSQPP PPPPPQVSSP IAAAAAASAA LVAQLNPADR WPTEPSAYKL DESIGVGATA
TVFTAYCLPR NEKVAIKCIN LEKCQTSVDE LSHEIQAMSQ CNHPNVVSYY TSFIAQEELW
VVMRLLNCGS MLDILKRKVK AIGKEQAQFG VLDEVSIATV LREVLKGLEY FHLNGQIHRD
IKAGNILLAD DGTIQIADFG VSGWLASSGG DLSRQKVRHT FVGTPCWMAP EVMEQVQGYD
FKADIWSLGI LAIELATGTA PYHKYPPMKV LMLTLQNDPP TLETNAERKD QYKAYGKSFK
TLIRDCLQKD PAKRPTASEL LKYSFFKKGK DKKYLVHTLI ENLASVPVVA HHSSKKVASG
KLRKDAHGNW EFEYDSPQES DDDSDLEDEE REKKKKKASA SASGAGAAGA AGGATGGAAS
GAPSAQEGGG ATTPCPETLN MVLRVRNQQR ELNDIKFDYT KSADTVEGIA HELVTAELID
CHDLVIVAAN LQKLIDFAES KSDRRSITFA LNSGVHANEI PDERTLTGFA QISLLD
