CDK2_CAEEL
ID CDK2_CAEEL Reviewed; 368 AA.
AC O61847;
DT 24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Cyclin-dependent kinase 2 {ECO:0000305};
DE EC=2.7.11.22 {ECO:0000250|UniProtKB:P24941};
DE AltName: Full=Cell division protein kinase 2 {ECO:0000305};
GN Name=cdk-2 {ECO:0000312|WormBase:K03E5.3};
GN ORFNames=K03E5.3 {ECO:0000312|WormBase:K03E5.3};
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|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 [2] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=10207147; DOI=10.1242/dev.126.10.2227;
RA Boxem M., Srinivasan D.G., van den Heuvel S.;
RT "The Caenorhabditis elegans gene ncc-1 encodes a cdc2-related kinase
RT required for M phase in meiotic and mitotic cell divisions, but not for S
RT phase.";
RL Development 126:2227-2239(1999).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17115027; DOI=10.1038/ncb1511;
RA Cowan C.R., Hyman A.A.;
RT "Cyclin E-Cdk2 temporally regulates centrosome assembly and establishment
RT of polarity in Caenorhabditis elegans embryos.";
RL Nat. Cell Biol. 8:1441-1447(2006).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17476329; DOI=10.1371/journal.pone.0000407;
RA Fujita M., Takeshita H., Sawa H.;
RT "Cyclin E and CDK2 repress the terminal differentiation of quiescent cells
RT after asymmetric division in C. elegans.";
RL PLoS ONE 2:E407-E407(2007).
RN [5] {ECO:0000305}
RP FUNCTION, SUBUNIT, AND DISRUPTION PHENOTYPE.
RX PubMed=21455289; DOI=10.1371/journal.pgen.1001348;
RA Jeong J., Verheyden J.M., Kimble J.;
RT "Cyclin E and Cdk2 control GLD-1, the mitosis/meiosis decision, and
RT germline stem cells in Caenorhabditis elegans.";
RL PLoS Genet. 7:E1001348-E1001348(2011).
CC -!- FUNCTION: Serine/threonine-protein kinase which, in association with
CC cye-1, regulates proliferation, quiescent state and cell fate during
CC the development of several cell lineages (PubMed:17115027.
CC PubMed:17476329). In the embryo, initiates the establishment of cell
CC polarity through the recruitment of the centrosomal proteins spd-2 and
CC spd-5 during prophase (PubMed:17115027). Phosphorylation and inhibition
CC of the translational repressor gld-1 by the cdk-2/cye-1 complex
CC regulates the pool of germline stem cells and the size of the mitotic
CC zone in the gonads by preventing entry into meiosis (PubMed:21455289).
CC {ECO:0000269|PubMed:17115027, ECO:0000269|PubMed:17476329,
CC ECO:0000269|PubMed:21455289}.
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=2.7.11.22;
CC Evidence={ECO:0000250|UniProtKB:P24941};
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=2.7.11.22; Evidence={ECO:0000250|UniProtKB:P24941};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P24941};
CC Note=Binds 2 Mg(2+) ions. {ECO:0000250|UniProtKB:P24941};
CC -!- SUBUNIT: Interacts with cye-1 (By similarity); the interaction likely
CC regulates cdk-2 activity and is probably required for gld-1
CC phosphorylation. {ECO:0000250|UniProtKB:P24941,
CC ECO:0000269|PubMed:21455289}.
CC -!- INTERACTION:
CC O61847; O01501: cye-1; NbExp=3; IntAct=EBI-14063070, EBI-6499833;
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes arrest at various
CC developmental stages. The few animals reaching adulthood are sterile
CC and have a protruding vulva (PubMed:10207147). Gonads have an abnormal
CC mitotic zone characterized by an enlargement of the distal germ cell
CC nuclei, a reduction in the number of mitotic germ cells, a reduction in
CC the mitotic region length and abnormal expression of gld-1
CC (PubMed:21455289). Embryos have persistent ruffling throughout the
CC cortex and mislocalization of par-2, which remains cytoplasmic, and
CC par-6, which remains distributed throughout the cortex. In 33 percent
CC of embryos the first division is symmetric (PubMed:17115027).
CC Production of 2 additional distal tip cells (DTC) during larval
CC development (PubMed:17476329). RNAi-mediated knockdown in embryos
CC causes a slight delay in cell cycle progression (PubMed:17115027).
CC {ECO:0000269|PubMed:10207147, ECO:0000269|PubMed:17115027,
CC ECO:0000269|PubMed:17476329, ECO:0000269|PubMed:21455289}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; BX284601; CCD70003.1; -; Genomic_DNA.
DR PIR; T33159; T33159.
DR RefSeq; NP_001021537.1; NM_001026366.1.
DR AlphaFoldDB; O61847; -.
DR SMR; O61847; -.
DR ComplexPortal; CPX-1127; Cyclin cye-1-cdk2 complex.
DR IntAct; O61847; 1.
DR STRING; 6239.K03E5.3; -.
DR EPD; O61847; -.
DR PaxDb; O61847; -.
DR PeptideAtlas; O61847; -.
DR EnsemblMetazoa; K03E5.3a.1; K03E5.3a.1; WBGene00019362.
DR GeneID; 171911; -.
DR KEGG; cel:CELE_K03E5.3; -.
DR UCSC; K03E5.3; c. elegans.
DR CTD; 171911; -.
DR WormBase; K03E5.3; CE36652; WBGene00019362; cdk-2.
DR eggNOG; KOG0594; Eukaryota.
DR GeneTree; ENSGT00940000160805; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; O61847; -.
DR OMA; CHLRRIV; -.
DR OrthoDB; 1010560at2759; -.
DR PhylomeDB; O61847; -.
DR Reactome; R-CEL-1538133; G0 and Early G1.
DR Reactome; R-CEL-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-CEL-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-CEL-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-CEL-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest.
DR Reactome; R-CEL-68949; Orc1 removal from chromatin.
DR Reactome; R-CEL-69017; CDK-mediated phosphorylation and removal of Cdc6.
DR Reactome; R-CEL-69200; Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
DR Reactome; R-CEL-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-CEL-69563; p53-Dependent G1 DNA Damage Response.
DR Reactome; R-CEL-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR PRO; PR:O61847; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00019362; Expressed in adult organism and 3 other tissues.
DR ExpressionAtlas; O61847; baseline.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0097134; C:cyclin E1-CDK2 complex; IPI:ComplexPortal.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030332; F:cyclin binding; IBA:GO_Central.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
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:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:ComplexPortal.
DR GO; GO:0051729; P:germline cell cycle switching, mitotic to meiotic cell cycle; IMP:WormBase.
DR GO; GO:0048815; P:hermaphrodite genitalia morphogenesis; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051782; P:negative regulation of cell division; IMP:UniProtKB.
DR GO; GO:0002119; P:nematode larval development; IMP:UniProtKB.
DR GO; GO:0051081; P:nuclear membrane disassembly; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:1904781; P:positive regulation of protein localization to centrosome; IGI:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IMP:WormBase.
DR GO; GO:0008104; P:protein localization; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:WormBase.
DR GO; GO:0030588; P:pseudocleavage; IMP:UniProtKB.
DR GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0051445; P:regulation of meiotic cell cycle; IMP:UniProtKB.
DR GO; GO:1904776; P:regulation of protein localization to cell cortex; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
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 ATP-binding; Cell cycle; Cell division; Developmental protein; Kinase;
KW Magnesium; Meiosis; Metal-binding; Mitosis; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..368
FT /note="Cyclin-dependent kinase 2"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433387"
FT DOMAIN 45..330
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 170
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 51..59
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 175
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P24941"
FT BINDING 188
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P24941"
SQ SEQUENCE 368 AA; 42616 MW; 96CBD214B704B8D7 CRC64;
MSREIRSLES IISDARENTH EKMLIRKQRD MTTDIAPERD LQGRFCSLRR IGEGTYGVVF
KAIHVRDNVK CALKMIRTDR DEEGIPSTCL REISCIKDLQ HDNIVTLFDI IYANSKLYMV
FEFIDRDLKN LLEMLEPTNS VLPPNYVKSF MWQLLSALSY CHLRRIVHRD LKPQNILVSD
SGVIKIADFG LARNFSFPSR NYTHEVVTLW YRPPEILLGS QRYSTSLDMW SLGCIFSEIA
SNKPLFPGEC EISQLFKIFE IVGTPNIKSW PGVDSFPHYK AVFPQWPVNL KKLEETSCLT
GNGLDVLREI LRYPPERRLT AKGALSHRYF LQNGFTQNRP SVTDLMKDIR AQNRTPPLLN
NHQEKSIF
