WARTS_DROME
ID WARTS_DROME Reviewed; 1105 AA.
AC Q9VA38;
DT 18-MAY-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Serine/threonine-protein kinase Warts;
DE EC=2.7.11.1;
GN Name=wts; ORFNames=CG12072;
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 [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 [2]
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 [3]
RP FUNCTION, AND INTERACTION WITH YKI.
RX PubMed=16096061; DOI=10.1016/j.cell.2005.06.007;
RA Huang J., Wu S., Barrera J., Matthews K., Pan D.;
RT "The Hippo signaling pathway coordinately regulates cell proliferation and
RT apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP.";
RL Cell 122:421-434(2005).
RN [4]
RP FUNCTION.
RX PubMed=18818081; DOI=10.1016/j.cub.2008.08.052;
RA Dutta S., Baehrecke E.H.;
RT "Warts is required for PI3K-regulated growth arrest, autophagy, and
RT autophagic cell death in Drosophila.";
RL Curr. Biol. 18:1466-1475(2008).
RN [5]
RP FUNCTION.
RX PubMed=18256197; DOI=10.1242/dev.015255;
RA Oh H., Irvine K.D.;
RT "In vivo regulation of Yorkie phosphorylation and localization.";
RL Development 135:1081-1088(2008).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=18245354; DOI=10.1534/genetics.107.081570;
RA Shimizu T., Ho L.L., Lai Z.C.;
RT "The mob as tumor suppressor gene is essential for early development and
RT regulates tissue growth in Drosophila.";
RL Genetics 178:957-965(2008).
RN [7]
RP INTERACTION WITH JUB.
RX PubMed=20303269; DOI=10.1016/j.cub.2010.02.035;
RA Das Thakur M., Feng Y., Jagannathan R., Seppa M.J., Skeath J.B.,
RA Longmore G.D.;
RT "Ajuba LIM proteins are negative regulators of the Hippo signaling
RT pathway.";
RL Curr. Biol. 20:657-662(2010).
CC -!- FUNCTION: Negative regulator of Yorkie (Yki) in the Hippo/SWH
CC (Sav/Wts/Hpo) signaling pathway that plays a pivotal role in organ size
CC control and tumor suppression by restricting proliferation and
CC promoting apoptosis. The core of this pathway is composed of a kinase
CC cascade wherein Hippo (Hpo), in complex with its regulatory protein
CC Salvador (Sav), phosphorylates and activates Warts (Wts) in complex
CC with its regulatory protein Mats, which in turn phosphorylates and
CC inactivates the Yorkie (Yki) oncoprotein. The Hippo/SWH signaling
CC pathway inhibits the activity of the transcriptional complex formed by
CC Scalloped (sd) and Yki and the target genes of this pathway include
CC cyclin-E (cycE), diap1 and bantam. Inhibits nuclear localization of
CC Yki. Regulates salivary gland degradation in a PI3K-dependent manner
CC and Yki- and Sd-independent, mechanism. {ECO:0000269|PubMed:16096061,
CC ECO:0000269|PubMed:18256197, ECO:0000269|PubMed:18818081}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- SUBUNIT: Interacts with yki. Interacts with jub.
CC {ECO:0000269|PubMed:16096061, ECO:0000269|PubMed:20303269}.
CC -!- INTERACTION:
CC Q9VA38; Q24564: Mer; NbExp=8; IntAct=EBI-82717, EBI-180142;
CC Q9VA38; P49657: mnb; NbExp=3; IntAct=EBI-82717, EBI-466373;
CC Q9VA38; Q9VR53: wap; NbExp=2; IntAct=EBI-82717, EBI-92828;
CC Q9VA38; Q9N675: Zyx; NbExp=4; IntAct=EBI-82717, EBI-16223133;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:18245354}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:18245354}. Note=Colocalizes with mats and cyclin E
CC at the centrosome.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AE014297; AAF57085.1; -; Genomic_DNA.
DR RefSeq; NP_733403.1; NM_170524.2.
DR AlphaFoldDB; Q9VA38; -.
DR SMR; Q9VA38; -.
DR BioGRID; 68502; 69.
DR DIP; DIP-20374N; -.
DR ELM; Q9VA38; -.
DR IntAct; Q9VA38; 7.
DR STRING; 7227.FBpp0085082; -.
DR PaxDb; Q9VA38; -.
DR EnsemblMetazoa; FBtr0085720; FBpp0085082; FBgn0011739.
DR GeneID; 43651; -.
DR KEGG; dme:Dmel_CG12072; -.
DR UCSC; CG12072-RA; d. melanogaster.
DR CTD; 43651; -.
DR FlyBase; FBgn0011739; wts.
DR VEuPathDB; VectorBase:FBgn0011739; -.
DR eggNOG; KOG0608; Eukaryota.
DR GeneTree; ENSGT00940000157684; -.
DR HOGENOM; CLU_004885_2_0_1; -.
DR InParanoid; Q9VA38; -.
DR OMA; DSMEPWE; -.
DR OrthoDB; 759391at2759; -.
DR PhylomeDB; Q9VA38; -.
DR Reactome; R-DME-2028269; Signaling by Hippo.
DR Reactome; R-DME-390089; Formation of the Hippo kinase cassette.
DR Reactome; R-DME-390098; Phosphorylation-dependent inhibition of YKI.
DR Reactome; R-DME-390150; DS ligand bound to FT receptor.
DR Reactome; R-DME-390178; DS ligand not bound to FT receptor.
DR Reactome; R-DME-451806; Phosphorylation-independent inhibition of YKI.
DR SignaLink; Q9VA38; -.
DR BioGRID-ORCS; 43651; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 43651; -.
DR PRO; PR:Q9VA38; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0011739; Expressed in crop (Drosophila) and 20 other tissues.
DR ExpressionAtlas; Q9VA38; baseline and differential.
DR Genevisible; Q9VA38; DM.
DR GO; GO:0106037; C:apicomedial cortex; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0004674; F:protein serine/threonine kinase activity; IDA:FlyBase.
DR GO; GO:0007298; P:border follicle cell migration; IMP:FlyBase.
DR GO; GO:0001708; P:cell fate specification; IMP:FlyBase.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0035329; P:hippo signaling; IDA:FlyBase.
DR GO; GO:0007446; P:imaginal disc growth; IMP:FlyBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IGI:FlyBase.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:FlyBase.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IMP:FlyBase.
DR GO; GO:0045571; P:negative regulation of imaginal disc growth; IMP:FlyBase.
DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IMP:FlyBase.
DR GO; GO:0042308; P:negative regulation of protein import into nucleus; IMP:FlyBase.
DR GO; GO:0007424; P:open tracheal system development; HMP:FlyBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IGI:FlyBase.
DR GO; GO:1904504; P:positive regulation of lipophagy; IMP:FlyBase.
DR GO; GO:0045463; P:R8 cell development; IGI:FlyBase.
DR GO; GO:0045464; P:R8 cell fate specification; IMP:FlyBase.
DR GO; GO:0008360; P:regulation of cell shape; IMP:FlyBase.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IGI:FlyBase.
DR GO; GO:0046620; P:regulation of organ growth; IBA:GO_Central.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:FlyBase.
DR GO; GO:0072089; P:stem cell proliferation; IDA:FlyBase.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR028742; LATS2.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24356:SF149; PTHR24356:SF149; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 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; Cytoplasm; Cytoskeleton; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tumor suppressor.
FT CHAIN 1..1105
FT /note="Serine/threonine-protein kinase Warts"
FT /id="PRO_0000394392"
FT DOMAIN 719..1020
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 1021..1091
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 33..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 145..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 273..362
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 383..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 514..643
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 881..900
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1038..1070
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 66..81
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 167..187
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 191..219
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..342
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 383..402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..439
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 514..535
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 548..620
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 622..643
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 886..900
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 843
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 725..733
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 749
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 1105 AA; 122488 MW; 7D09D7AA9BA1A856 CRC64;
MHPAGEKRGG RPNDKYTAEA LESIKQDLTR FEVQNNHRNN QNYTPLRYTA TNGRNDALTP
DYHHAKQPME PPPSASPAPD VVIPPPPAIV GQPGAGSISV SGVGVGVVGV ANGRVPKMMT
ALMPNKLIRK PSIERDTASS HYLRCSPALD SGAGSSRSDS PHSHHTHQPS SRTVGNPGGN
GGFSPSPSGF SEVAPPAPPP RNPTACSAAT PPPPVPPTSQ AYVKRRSPAL NNRPPAIAPP
TQRGNSPVIT QNGLKNPQQQ LTQQLKSLNL YPGGGSGAVV EPPPPYLIQG GAGGAAPPPP
PPSYTASMQS RQSPTQSQQS DYRKSPSSGI YSATSAGSPS PITVSLPPAP LAKPQPRVYQ
ARSQQPIIMQ SVKSTQVQKP VLQTAVAPQS PSSASASNSP VHVLAAPPSY PQKSAAVVQQ
QQQAAAAAHQ QQHQHQQSKP PTPTTPPLVG LNSKPNCLEP PSYAKSMQAK AATVVQQQQQ
QQQQQQQVQQ QQVQQQQQQQ QQQLQALRVL QAQAQRERDQ RERDQRERER DQQKLANGNP
GRQMLPPPPY QSNNNNNSEI KPPSCNNNNI QISNSNLATT PPIPPAKYNN NSSNTGANSS
GGSNGSTGTT ASSSTSCKKI KHASPIPERK KISKEKEEER KEFRIRQYSP QAFKFFMEQH
IENVIKSYRQ RTYRKNQLEK EMHKVGLPDQ TQIEMRKMLN QKESNYIRLK RAKMDKSMFV
KLKPIGVGAF GEVTLVSKID TSNHLYAMKT LRKADVLKRN QVAHVKAERD ILAEADNNWV
VKLYYSFQDK DNLYFVMDYI PGGDLMSLLI KLGIFEEELA RFYIAEVTCA VDSVHKMGFI
HRDIKPDNIL IDRDGHIKLT DFGLCTGFRW THNSKYYQEN GNHSRQDSME PWEEYSENGP
KPTVLERRRM RDHQRVLAHS LVGTPNYIAP EVLERSGYTQ LCDYWSVGVI LYEMLVGQPP
FLANSPLETQ QKVINWEKTL HIPPQAELSR EATDLIRRLC ASADKRLGKS VDEVKSHDFF
KGIDFADMRK QKAPYIPEIK HPTDTSNFDP VDPEKLRSND STMSSGDDVD QNDRTFHGFF
EFTFRRFFDD KQPPDMTDDQ APVYV
