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   27-MAR-2024, entry version 207.
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; 7227-FBpp0289675; -.
DR   EnsemblMetazoa; FBtr0083921; FBpp0083329; FBgn0004107.
DR   EnsemblMetazoa; FBtr0083922; FBpp0083330; FBgn0004107.
DR   EnsemblMetazoa; FBtr0300447; FBpp0289675; FBgn0004107.
DR   GeneID; 42453; -.
DR   KEGG; dme:Dmel_CG10498; -.
DR   AGR; FB:FBgn0004107; -.
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; PDETKWP; -.
DR   OrthoDB; 244018at2759; -.
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 cell types or tissues.
DR   ExpressionAtlas; P23573; baseline and differential.
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: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:0010033; P:response to organic substance; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   CDD; cd07835; STKc_CDK1_CdkB_like; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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   PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1.
DR   PANTHER; PTHR24056:SF254; CYCLIN-DEPENDENT KINASE 2; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   Genevisible; P23573; DM.
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
//