CDK2_DROME
ID CDK2_DROME Reviewed; 314 AA.
AC P23573; Q0KI40; Q9TXB2; Q9VDJ4;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Cyclin-dependent kinase 2 {ECO:0000312|FlyBase:FBgn0004107};
DE EC=2.7.11.22;
DE EC=2.7.11.23;
DE AltName: Full=Cell division control protein 2 cognate;
GN Name=Cdk2 {ECO:0000312|FlyBase:FBgn0004107};
GN Synonyms=cdc2c {ECO:0000312|FlyBase:FBgn0004107};
GN ORFNames=CG10498 {ECO:0000312|FlyBase:FBgn0004107};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Oregon-R; TISSUE=Embryo;
RX PubMed=2120045; DOI=10.1002/j.1460-2075.1990.tb07568.x;
RA Lehner C.F., O'Farrell P.H.;
RT "Drosophila cdc2 homologs: a functional homolog is coexpressed with a
RT cognate variant.";
RL EMBO J. 9:3573-3581(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE OF 21-167.
RC TISSUE=Imaginal disk;
RX PubMed=1378625; DOI=10.1073/pnas.89.14.6295;
RA Biggs W.H. III, Zipursky S.L.;
RT "Primary structure, expression, and signal-dependent tyrosine
RT phosphorylation of a Drosophila homolog of extracellular signal-regulated
RT kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:6295-6299(1992).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-162 AND THR-163, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [7]
RP INTERACTION WITH CYCG.
RX PubMed=21311225; DOI=10.4161/cc.10.5.14959;
RA Faradji F., Bloyer S., Dardalhon-Cumenal D., Randsholt N.B., Peronnet F.;
RT "Drosophila melanogaster Cyclin G coordinates cell growth and cell
RT proliferation.";
RL Cell Cycle 10:805-818(2011).
CC -!- FUNCTION: Like Cdk1, could play a key role in the control of the
CC eukaryotic cell cycle.
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 -!- 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;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[DNA-directed RNA polymerase] + ATP = ADP + H(+) + phospho-
CC [DNA-directed RNA polymerase]; Xref=Rhea:RHEA:10216, Rhea:RHEA-
CC COMP:11321, Rhea:RHEA-COMP:11322, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC ChEBI:CHEBI:456216; EC=2.7.11.23;
CC -!- SUBUNIT: Interacts with cyclin CycG. {ECO:0000269|PubMed:21311225}.
CC -!- INTERACTION:
CC P23573; Q24159: CycJ; NbExp=5; IntAct=EBI-95916, EBI-455799;
CC P23573; Q961D1: CycK; NbExp=5; IntAct=EBI-95916, EBI-130995;
CC P23573; P91654: dap; NbExp=3; IntAct=EBI-95916, EBI-868936;
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; X57486; CAA40724.1; -; mRNA.
DR EMBL; AE014297; AAN14363.1; -; Genomic_DNA.
DR EMBL; AY051671; AAK93095.1; -; mRNA.
DR PIR; E46036; E46036.
DR RefSeq; NP_001163666.1; NM_001170195.3.
DR RefSeq; NP_524420.1; NM_079696.6.
DR RefSeq; NP_732544.1; NM_169916.3.
DR AlphaFoldDB; P23573; -.
DR SMR; P23573; -.
DR BioGRID; 67428; 53.
DR DIP; DIP-648N; -.
DR IntAct; P23573; 74.
DR MINT; P23573; -.
DR STRING; 7227.FBpp0289675; -.
DR iPTMnet; P23573; -.
DR PaxDb; P23573; -.
DR EnsemblMetazoa; FBtr0083921; FBpp0083329; FBgn0004107.
DR EnsemblMetazoa; FBtr0083922; FBpp0083330; FBgn0004107.
DR EnsemblMetazoa; FBtr0300447; FBpp0289675; FBgn0004107.
DR GeneID; 42453; -.
DR KEGG; dme:Dmel_CG10498; -.
DR CTD; 1017; -.
DR FlyBase; FBgn0004107; Cdk2.
DR VEuPathDB; VectorBase:FBgn0004107; -.
DR eggNOG; KOG0594; Eukaryota.
DR GeneTree; ENSGT00940000153335; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P23573; -.
DR OMA; FPKWEAT; -.
DR OrthoDB; 1010560at2759; -.
DR PhylomeDB; P23573; -.
DR BRENDA; 2.7.11.22; 1994.
DR Reactome; R-DME-1538133; G0 and Early G1.
DR Reactome; R-DME-176187; Activation of ATR in response to replication stress.
DR Reactome; R-DME-176408; Regulation of APC/C activators between G1/S and early anaphase.
DR Reactome; R-DME-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-DME-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-DME-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-DME-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-DME-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest.
DR Reactome; R-DME-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-DME-68911; G2 Phase.
DR Reactome; R-DME-68949; Orc1 removal from chromatin.
DR Reactome; R-DME-68962; Activation of the pre-replicative complex.
DR Reactome; R-DME-69017; CDK-mediated phosphorylation and removal of Cdc6.
DR Reactome; R-DME-69200; Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
DR Reactome; R-DME-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-DME-69231; Cyclin D associated events in G1.
DR Reactome; R-DME-69563; p53-Dependent G1 DNA Damage Response.
DR Reactome; R-DME-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-DME-9616222; Transcriptional regulation of granulopoiesis.
DR SignaLink; P23573; -.
DR BioGRID-ORCS; 42453; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 42453; -.
DR PRO; PR:P23573; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0004107; Expressed in ovary and 34 other tissues.
DR ExpressionAtlas; P23573; baseline and differential.
DR Genevisible; P23573; DM.
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; ISS:FlyBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISS:FlyBase.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:FlyBase.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IPI:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; ISS:FlyBase.
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: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; Kinase; Mitosis;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..314
FT /note="Cyclin-dependent kinase 2"
FT /id="PRO_0000085744"
FT DOMAIN 8..287
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 130
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 14..22
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 18
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 19
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 162
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 163
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 27
FT /note="S -> T (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="G -> A (in Ref. 5)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 314 AA; 35888 MW; 576A88767F9D35C0 CRC64;
MTTILDNFQR AEKIGEGTYG IVYKARSNST GQDVALKKIR LEGETEGVPS TAIREISLLK
NLKHPNVVQL FDVVISGNNL YMIFEYLNMD LKKLMDKKKD VFTPQLIKSY MHQILDAVGF
CHTNRILHRD LKPQNLLVDT AGKIKLADFG LARAFNVPMR AYTHEVVTLW YRAPEILLGT
KFYSTGVDIW SLGCIFSEMI MRRSLFPGDS EIDQLYRIFR TLSTPDETNW PGVTQLPDFK
TKFPRWEGTN MPQPITEHEA HELIMSMLCY DPNLRISAKD ALQHAYFRNV QHVDHVALPV
DPNAGSASRL TRLV
