ID   KP58_DROME              Reviewed;         952 AA.
AC   Q9VPC0; Q5U100; Q8MQR7; Q94889; Q9TXB3;
DT   02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   24-JAN-2024, entry version 170.
DE   RecName: Full=Serine/threonine-protein kinase PITSLRE;
DE            EC=2.7.11.22;
DE   AltName: Full=Cell division cycle 2-like;
GN   Name=Pitslre; ORFNames=CG4268;
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], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC   TISSUE=Embryo;
RX   PubMed=8930898; DOI=10.1091/mbc.7.11.1759;
RA   Sauer K., Weigmann K., Sigrist S., Lehner C.F.;
RT   "Novel members of the cdc2-related kinase family in Drosophila: cdk4/6,
RT   cdk5, PFTAIRE, and PITSLRE kinase.";
RL   Mol. Biol. Cell 7:1759-1769(1996).
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;
RA   Stapleton M., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H., Yu C.,
RA   Celniker S.E.;
RL   Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 22-952.
RC   STRAIN=Berkeley; TISSUE=Head;
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   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 571-722.
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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439; SER-442; TYR-447;
RP   SER-449; SER-881 AND SER-886, AND 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).
CC   -!- FUNCTION: Acts as a negative regulator of the normal cell cycle
CC       progression. May function in regulating proliferation by the
CC       phosphorylation and subsequent plasma membrane targeting of
CC       galactosyltransferase (By similarity). {ECO:0000250}.
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=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC         [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:82620, ChEBI:CHEBI:456216;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Present throughout the early embryo. In late
CC       embryos levels are highest in the CNS. {ECO:0000269|PubMed:8930898}.
CC   -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Highest
CC       levels in early embryogenesis (0-6 hours), low levels during later
CC       embryogenesis, moderate levels in pupae and adults.
CC       {ECO:0000269|PubMed:8930898}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC       protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAM75018.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR   EMBL; X99513; CAA67863.1; -; mRNA.
DR   EMBL; AE014296; AAF51635.1; -; Genomic_DNA.
DR   EMBL; AE014296; AAN12141.1; -; Genomic_DNA.
DR   EMBL; BT016092; AAV36977.1; -; mRNA.
DR   EMBL; AY128425; AAM75018.1; ALT_SEQ; mRNA.
DR   RefSeq; NP_001246851.1; NM_001259922.2.
DR   RefSeq; NP_001246852.1; NM_001259923.2.
DR   RefSeq; NP_001262122.1; NM_001275193.1.
DR   RefSeq; NP_649251.2; NM_140994.4.
DR   RefSeq; NP_730563.1; NM_168869.3.
DR   AlphaFoldDB; Q9VPC0; -.
DR   SMR; Q9VPC0; -.
DR   BioGRID; 65549; 7.
DR   IntAct; Q9VPC0; 10.
DR   STRING; 7227.FBpp0077905; -.
DR   iPTMnet; Q9VPC0; -.
DR   PaxDb; 7227-FBpp0077905; -.
DR   DNASU; 40292; -.
DR   EnsemblMetazoa; FBtr0078247; FBpp0077905; FBgn0016696.
DR   EnsemblMetazoa; FBtr0078250; FBpp0077908; FBgn0016696.
DR   GeneID; 40292; -.
DR   KEGG; dme:Dmel_CG4268; -.
DR   UCSC; CG4268-RC; d. melanogaster.
DR   AGR; FB:FBgn0016696; -.
DR   CTD; 40292; -.
DR   FlyBase; FBgn0016696; Pitslre.
DR   VEuPathDB; VectorBase:FBgn0016696; -.
DR   eggNOG; KOG0663; Eukaryota.
DR   GeneTree; ENSGT00940000158459; -.
DR   InParanoid; Q9VPC0; -.
DR   OMA; HRYEYRN; -.
DR   OrthoDB; 244018at2759; -.
DR   PhylomeDB; Q9VPC0; -.
DR   BRENDA; 2.7.11.22; 1994.
DR   BioGRID-ORCS; 40292; 1 hit in 3 CRISPR screens.
DR   GenomeRNAi; 40292; -.
DR   PRO; PR:Q9VPC0; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0016696; Expressed in egg cell and 62 other cell types or tissues.
DR   ExpressionAtlas; Q9VPC0; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0004674; F:protein serine/threonine kinase activity; ISS:FlyBase.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; IEA:RHEA.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0002225; P:positive regulation of antimicrobial peptide production; IMP:FlyBase.
DR   GO; GO:0045752; P:positive regulation of Toll signaling pathway; IMP:FlyBase.
DR   GO; GO:0006468; P:protein phosphorylation; ISS:FlyBase.
DR   GO; GO:0007346; P:regulation of mitotic cell cycle; IBA:GO_Central.
DR   CDD; cd07843; STKc_CDC2L1; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR045267; CDK11/PITSLRE_STKc.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1.
DR   PANTHER; PTHR24056:SF107; CYCLIN-DEPENDENT KINASE 11A-RELATED; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   Genevisible; Q9VPC0; DM.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell cycle; Kinase; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase.
FT   CHAIN           1..952
FT                   /note="Serine/threonine-protein kinase PITSLRE"
FT                   /id="PRO_0000086160"
FT   DOMAIN          558..851
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..196
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          216..247
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          302..538
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          870..906
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           51..56
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        14..34
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        64..101
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        170..196
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        302..333
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        352..376
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        377..400
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        411..430
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        453..477
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        478..492
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        508..534
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        685
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         564..572
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         587
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         439
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         442
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         447
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         449
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         881
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         886
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   CONFLICT        69
FT                   /note="D -> E (in Ref. 1; CAA67863)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        223
FT                   /note="V -> A (in Ref. 1; CAA67863)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        283
FT                   /note="I -> S (in Ref. 1; CAA67863)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        492
FT                   /note="V -> A (in Ref. 1; CAA67863)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        584
FT                   /note="V -> E (in Ref. 6)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        603
FT                   /note="L -> R (in Ref. 6)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        612
FT                   /note="G -> GG (in Ref. 6)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        670
FT                   /note="Missing (in Ref. 6)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        680
FT                   /note="Missing (in Ref. 6)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        717
FT                   /note="Missing (in Ref. 6)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   952 AA;  108838 MW;  9CBDE8D459D0713D CRC64;
     MVNSSGSEDG QLRSPNDVHY HSRGEEDEHE GDADALYIQP PQASRESGSG PRREKKKHSR
     ERRRHKERDD VGGAALALER DHRYDYRSRE EHYHHHQRER SSNAAAAYAK HHLGHAYHYP
     QPPQQQQQPL PPAPSYAAHH YHHHQHLSGA RAAPREYHSY PSGYHSGSRH GDYPMEEPTR
     RSSKYAESKD AESLEQDLRS RLLKKRHNYV KDYETEENYE HRVERSDRRE GGRKERERTV
     RSTHKQNRHD RVIELLDSPE QEHHHQHQHK SHRSKWREEV EVIRRKVPED LELLARREKL
     LAAERESRQR KQTAREELEA RRELLRERNE HSDALSPTTV AASVTAGLNI HVKRKSKPDN
     YEKEIKLKKR REDDIEVIRD DDDEESEESD SNEEVPEQDS EGSATESGSE DSYASKKKSK
     IKSKSQLEDD DEDLPLPDSP LSVGELYKSP KQRQRSRSVS SKSSSQSSRS SRSRSRSRSQ
     SSLEDEVDRQ DVGADASPSS STRSEERGMT QEQPEEKPEE KLKEKQKSLE EQIPCDDKGI
     PLPNYYPGVQ GCRSVEEFQC LNRIEEGTYG VVYRAKDKRT NEIVALKRLK MEKEKEGFPI
     TSLREINTLL KGQHPNIVTV REIVVGSNMD KIFIVMDYVE HDLKSLMETM KNRKQSFFPG
     EVKCLTQQLL RAVAHLHDNW ILHRDLKTSN LLLSHKGILK VGDFGLAREY GSPIKKYTSL
     VVTLWYRAPE LLLCSPVYST PIDVWSVGCI FAEFLQMLPL FPGKSEIDEL NRIFKELGTP
     NEKIWPGYTE LPAVKNMLSQ NSQFTEYPVS QLRKHFQEKT SEMGLSLLQG LLTYDPKQRL
     SADAALKHGF FKELPLPIDP SMFPTWPAKS ELGARKAQAS SPKPPSGGSQ FKQLGRDEPI
     IVGPGNKLSS GIITGNKKSH GAGGSSASTG FVLNAGITQR QLAMGPGFSL KF
//