GCK1_CAEEL
ID GCK1_CAEEL Reviewed; 653 AA.
AC H2L099; H2L0A0; H2L0A1; Q6ABW4;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Germinal center kinase 1 {ECO:0000303|PubMed:19826475};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q9P289};
GN Name=gck-1 {ECO:0000312|WormBase:T19A5.2a};
GN ORFNames=T19A5.2 {ECO:0000312|WormBase:T19A5.2a};
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:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, INTERACTION WITH MPK-1,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-55 AND ILE-64.
RX PubMed=19826475; DOI=10.1371/journal.pone.0007450;
RA Schouest K.R., Kurasawa Y., Furuta T., Hisamoto N., Matsumoto K.,
RA Schumacher J.M.;
RT "The germinal center kinase GCK-1 is a negative regulator of MAP kinase
RT activation and apoptosis in the C. elegans germline.";
RL PLoS ONE 4:E7450-E7450(2009).
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 CCM-3, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF LYS-63 AND THR-188.
RX PubMed=25743393; DOI=10.1038/ncomms7449;
RA Lant B., Yu B., Goudreault M., Holmyard D., Knight J.D., Xu P., Zhao L.,
RA Chin K., Wallace E., Zhen M., Gingras A.C., Derry W.B.;
RT "CCM-3/STRIPAK promotes seamless tube extension through endocytic
RT recycling.";
RL Nat. Commun. 6:6449-6449(2015).
CC -!- FUNCTION: Serine/threonine-protein kinase which is required for normal
CC oogenesis and suppression of germline cell apoptosis. Inhibits
CC phosphorylation and thus probably activation of mpk-1 during pachytene
CC stage (PubMed:19826475). Involved in excretory canal elongation during
CC postembryonic development, probably acting downstream of ccm-3
CC (PubMed:25743393). {ECO:0000269|PubMed:19826475,
CC ECO:0000269|PubMed:25743393}.
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:0000250|UniProtKB:Q9P289};
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:0000250|UniProtKB:Q9P289};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9P289};
CC -!- SUBUNIT: Interacts (via N-terminus) with mpk-1 (isoform a)
CC (PubMed:19826475). Interacts with ccm-3 (PubMed:25743393).
CC {ECO:0000269|PubMed:19826475, ECO:0000269|PubMed:25743393}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25743393}. Apical
CC cell membrane {ECO:0000269|PubMed:25743393}; Peripheral membrane
CC protein {ECO:0000269|PubMed:25743393}. Note=Co-localizes with ccm-3 in
CC the apical membrane of the excretory canals.
CC {ECO:0000269|PubMed:25743393}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=a {ECO:0000312|WormBase:T19A5.2a};
CC IsoId=H2L099-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:T19A5.2b};
CC IsoId=H2L099-2; Sequence=VSP_057877;
CC Name=c {ECO:0000312|WormBase:T19A5.2c};
CC IsoId=H2L099-3; Sequence=VSP_057877, VSP_057879;
CC Name=d {ECO:0000312|WormBase:T19A5.2d};
CC IsoId=H2L099-4; Sequence=VSP_057878;
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes sterility
CC resulting from several defects in oogenesis. Proximal ends of the
CC gonads are filled with small germ cells and have a decrease in the
CC number of nuclei in all stages of oogenesis especially at the pachytene
CC stage where there is 60 percent less nuclei. In addition, animals lack
CC a discernible rachis which is a tube-like formation of anucleate
CC cytoplasm between pachytene nuclei, no clear transition into
CC progression from pachytene to diplotene stage and a failure to progress
CC from diplotene into diakinesis. Increased germline cell apoptosis
CC (PubMed:19826475). RNAi-mediated knockdown causes truncated excretory
CC canals associated with the formation of cysts, a reduced distribution
CC of Golgi and ER components along the excretory canals and a decrease in
CC cdc-42 activation (PubMed:25743393). {ECO:0000269|PubMed:19826475,
CC ECO:0000269|PubMed:25743393}.
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; BX284605; CCD72150.1; -; Genomic_DNA.
DR EMBL; BX284605; CCD72151.2; -; Genomic_DNA.
DR EMBL; BX284605; CCD72152.2; -; Genomic_DNA.
DR EMBL; BX284605; CCD72153.1; -; Genomic_DNA.
DR RefSeq; NP_001024141.1; NM_001028970.2. [H2L099-4]
DR RefSeq; NP_505309.1; NM_072908.3.
DR RefSeq; NP_505310.2; NM_072909.2. [H2L099-2]
DR RefSeq; NP_505311.3; NM_072910.5. [H2L099-3]
DR AlphaFoldDB; H2L099; -.
DR SMR; H2L099; -.
DR IntAct; H2L099; 1.
DR STRING; 6239.T19A5.2b; -.
DR EPD; H2L099; -.
DR PaxDb; H2L099; -.
DR PeptideAtlas; H2L099; -.
DR EnsemblMetazoa; T19A5.2a.1; T19A5.2a.1; WBGene00001526. [H2L099-1]
DR EnsemblMetazoa; T19A5.2b.1; T19A5.2b.1; WBGene00001526. [H2L099-2]
DR EnsemblMetazoa; T19A5.2c.1; T19A5.2c.1; WBGene00001526. [H2L099-3]
DR EnsemblMetazoa; T19A5.2d.1; T19A5.2d.1; WBGene00001526. [H2L099-4]
DR GeneID; 179274; -.
DR UCSC; T19A5.2a; c. elegans.
DR CTD; 179274; -.
DR WormBase; T19A5.2a; CE07510; WBGene00001526; gck-1. [H2L099-1]
DR WormBase; T19A5.2b; CE48939; WBGene00001526; gck-1. [H2L099-2]
DR WormBase; T19A5.2c; CE49076; WBGene00001526; gck-1. [H2L099-3]
DR WormBase; T19A5.2d; CE37048; WBGene00001526; gck-1. [H2L099-4]
DR eggNOG; KOG0201; Eukaryota.
DR GeneTree; ENSGT00940000176215; -.
DR InParanoid; H2L099; -.
DR OrthoDB; 967913at2759; -.
DR PhylomeDB; H2L099; -.
DR Reactome; R-CEL-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-CEL-75153; Apoptotic execution phase.
DR SignaLink; H2L099; -.
DR PRO; PR:H2L099; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00001526; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; H2L099; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0098592; C:cytoplasmic side of apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:UniProtKB.
DR GO; GO:0060562; P:epithelial tube morphogenesis; IDA:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:WormBase.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:WormBase.
DR GO; GO:0048477; P:oogenesis; IEA:UniProtKB-KW.
DR GO; GO:2001137; P:positive regulation of endocytic recycling; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:1903358; P:regulation of Golgi organization; IMP:UniProtKB.
DR GO; GO:0060281; P:regulation of oocyte development; IMP:WormBase.
DR Gene3D; 1.10.12.70; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR046409; PDC10_dimerisation_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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; Cell membrane; Cytoplasm;
KW Differentiation; Kinase; Magnesium; Meiosis; Membrane; Metal-binding;
KW Nucleotide-binding; Oogenesis; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..653
FT /note="Germinal center kinase 1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000434013"
FT DOMAIN 34..285
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 309..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..563
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 341..359
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 389..494
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 505..523
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 154
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 40..48
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..26
FT /note="MTTTSSDELPRQADDDSMKWDRIYIQ -> MDDHRFTDTILRTTNVQSAIQR
FT FEKRAPVSAPPYRESEPFREVLKDEPAPPFLQKQNSYDSPLFVNTNIVYPVEQNSYFPQ
FT ITPPREHVTYGIMNDSKMDDSIDSATLNRFETGFKPSNFGKTIQGIYNSTEHPQQTPEV
FT VLPSSLSVDLNVMSPEVSPPKPAERRKVVKPIEDNS (in isoform b and
FT isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_057877"
FT VAR_SEQ 2..26
FT /note="TTTSSDELPRQADDDSMKWDRIYIQ -> DFTNFGSEIE (in isoform
FT d)"
FT /evidence="ECO:0000305"
FT /id="VSP_057878"
FT VAR_SEQ 157..209
FT /note="AANVLVSEHGDVKVADFGVAGQLTETVKKRITFVGSPFWMAPELIKQSSYDY
FT K -> GANVLLDRQTAAVKICDYGVAKPLDTVLKANTFVGTPFFMAPEVVKGEYSIE
FT (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_057879"
FT MUTAGEN 55
FT /note="R->G: Severe loss of interaction with mpk-1 (isoform
FT a)."
FT /evidence="ECO:0000269|PubMed:19826475"
FT MUTAGEN 63
FT /note="K->R: Probable loss of activity. Truncated excretory
FT canals; when associated with A-188."
FT /evidence="ECO:0000269|PubMed:25743393"
FT MUTAGEN 64
FT /note="I->N: Loss of interaction with mpk-1 (isoform a)."
FT /evidence="ECO:0000269|PubMed:19826475"
FT MUTAGEN 188
FT /note="T->A: Probable loss of activity. Truncated excretory
FT canals; when associated with R-63."
FT /evidence="ECO:0000269|PubMed:25743393"
SQ SEQUENCE 653 AA; 71222 MW; 34DEDB17C78F1F88 CRC64;
MTTTSSDELP RQADDDSMKW DRIYIQKLDP EVIFTKQERI GRGSFGEVYK GIDNRTGRVV
AIKIIDLEQA EDEIEDIQQE IQVLSQCDSQ YVTKYFGSFL KGSKLWIIME YLGGGSALDL
TKSGKLDESH IAVILREILK GLEYLHSERK IHRDIKAANV LVSEHGDVKV ADFGVAGQLT
ETVKKRITFV GSPFWMAPEL IKQSSYDYKA DIWSLGITAI ELANGEPPHS DLHPMRVLFL
IPKNPPPVLQ GSQWSKPFKE FVEMCLNKDP ENRPSASTLL KHQFIKRAKK NSILVDLIER
AAEYRLRTGV SSDSDLDEDS DGGGGTSKWD YPTVRGPRVS ADDDGTVRQR TDRPRAQVDR
RSPSGSPGGT IVRGSPQVAA VAEQLRNSSV GSSGYGSGGN SASSQYATSS LPQSHTASSG
GATTITLGSP NGSPTSSLAR TQSMVSPSGQ RSGSAQSWEL ERGNRPMSER VSSQVSPSKY
NQHRTSSSNG VQGGSGGRRE YINGSGSGLN GNSSNQNHSE YSDAVRQRGP GGSGGRLDYR
ESHVPTSSQE NLNHGRMYGY GAPPPSREAN NVPMPRVKGA LDCSLLPAIE HLSRTRHATA
ALDQLRHVFR DVEDSCPGIC NELIEELMQR IAVPQVSQSD LDAAIRRLTT PPS
