ID   PHLPP_DROME             Reviewed;         954 AA.
AC   Q9VJ07;
DT   07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 151.
DE   RecName: Full=Protein phosphatase PHLPP-like protein;
DE            EC=3.1.3.16;
DE   AltName: Full=PH domain leucine-rich repeat protein phosphatase;
DE   AltName: Full=dPHLPP;
GN   Name=Phlpp; ORFNames=CG10493;
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.
RX   PubMed=15808505; DOI=10.1016/j.molcel.2005.03.008;
RA   Gao T., Furnari F., Newton A.C.;
RT   "PHLPP: a phosphatase that directly dephosphorylates Akt, promotes
RT   apoptosis, and suppresses tumor growth.";
RL   Mol. Cell 18:13-24(2005).
CC   -!- FUNCTION: Protein phosphatase that specifically mediates
CC       dephosphorylation of 'Ser-586' of Akt1, a protein that regulates the
CC       balance between cell survival and apoptosis through a cascade that
CC       primarily alters the function of transcription factors that regulate
CC       pro- and antiapoptotic genes. Dephosphorylation of 'Ser-586' of Akt1
CC       triggers apoptosis and suppression of tumor growth.
CC       {ECO:0000269|PubMed:15808505}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:83421; EC=3.1.3.16;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:61977; EC=3.1.3.16;
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
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DR   EMBL; AE014134; AAF53751.1; -; Genomic_DNA.
DR   RefSeq; NP_001260558.1; NM_001273629.1.
DR   RefSeq; NP_609938.1; NM_136094.2.
DR   AlphaFoldDB; Q9VJ07; -.
DR   SMR; Q9VJ07; -.
DR   IntAct; Q9VJ07; 2.
DR   STRING; 7227.FBpp0307805; -.
DR   PaxDb; 7227-FBpp0080693; -.
DR   EnsemblMetazoa; FBtr0081149; FBpp0080693; FBgn0032749.
DR   EnsemblMetazoa; FBtr0336844; FBpp0307805; FBgn0032749.
DR   GeneID; 35178; -.
DR   KEGG; dme:Dmel_CG10493; -.
DR   AGR; FB:FBgn0032749; -.
DR   CTD; 35178; -.
DR   FlyBase; FBgn0032749; Phlpp.
DR   VEuPathDB; VectorBase:FBgn0032749; -.
DR   eggNOG; KOG0618; Eukaryota.
DR   GeneTree; ENSGT00940000161019; -.
DR   HOGENOM; CLU_005692_0_0_1; -.
DR   InParanoid; Q9VJ07; -.
DR   OMA; QFKVCQT; -.
DR   OrthoDB; 3677323at2759; -.
DR   PhylomeDB; Q9VJ07; -.
DR   Reactome; R-DME-199418; Negative regulation of the PI3K/AKT network.
DR   SignaLink; Q9VJ07; -.
DR   BioGRID-ORCS; 35178; 0 hits in 3 CRISPR screens.
DR   GenomeRNAi; 35178; -.
DR   PRO; PR:Q9VJ07; -.
DR   Proteomes; UP000000803; Chromosome 2L.
DR   Bgee; FBgn0032749; Expressed in testis and 1 other cell type or tissue.
DR   ExpressionAtlas; Q9VJ07; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR   GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   Gene3D; 3.60.40.10; PPM-type phosphatase domain; 1.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 2.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   InterPro; IPR036457; PPM-type-like_dom_sf.
DR   InterPro; IPR001932; PPM-type_phosphatase-like_dom.
DR   PANTHER; PTHR48051; -; 1.
DR   PANTHER; PTHR48051:SF43; LEUCINE-RICH REPEAT-CONTAINING PROTEIN 47-LIKE PROTEIN; 1.
DR   Pfam; PF00560; LRR_1; 1.
DR   Pfam; PF13855; LRR_8; 1.
DR   Pfam; PF00481; PP2C; 1.
DR   SMART; SM00364; LRR_BAC; 6.
DR   SMART; SM00369; LRR_TYP; 7.
DR   SUPFAM; SSF52058; L domain-like; 1.
DR   SUPFAM; SSF81606; PP2C-like; 1.
DR   PROSITE; PS51450; LRR; 12.
DR   PROSITE; PS51746; PPM_2; 1.
DR   Genevisible; Q9VJ07; DM.
PE   4: Predicted;
KW   Apoptosis; Hydrolase; Leucine-rich repeat; Manganese; Metal-binding;
KW   Protein phosphatase; Reference proteome; Repeat.
FT   CHAIN           1..954
FT                   /note="Protein phosphatase PHLPP-like protein"
FT                   /id="PRO_0000057787"
FT   REPEAT          69..89
FT                   /note="LRR 1"
FT   REPEAT          90..104
FT                   /note="LRR 2"
FT   REPEAT          110..131
FT                   /note="LRR 3"
FT   REPEAT          135..156
FT                   /note="LRR 4"
FT   REPEAT          158..179
FT                   /note="LRR 5"
FT   REPEAT          183..202
FT                   /note="LRR 6"
FT   REPEAT          206..227
FT                   /note="LRR 7"
FT   REPEAT          231..252
FT                   /note="LRR 8"
FT   REPEAT          255..275
FT                   /note="LRR 9"
FT   REPEAT          279..300
FT                   /note="LRR 10"
FT   REPEAT          303..324
FT                   /note="LRR 11"
FT   REPEAT          326..347
FT                   /note="LRR 12"
FT   REPEAT          348..369
FT                   /note="LRR 13"
FT   REPEAT          372..393
FT                   /note="LRR 14"
FT   DOMAIN          437..655
FT                   /note="PPM-type phosphatase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01082"
FT   REGION          1..28
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   954 AA;  107092 MW;  7ADCF6F54F15957A CRC64;
     MLKATRKQAD PYKSKLKVSA SHSGPHPLPV EVTAAEEEQA ATFGQTSPQK LSLKGSQLGG
     SILIGNYNYL TQLEVCENEM EVLDLSSLAQ LETLKCSRNK LMELIINGTN LQTLVADHNY
     LHNISTTNTH PVPLKLQRID ISHNNFSELP NWVGACASLT AINASHNRLN NVAVLLRNYR
     ITELVSLDLA YNDLKQLDQF PEGFSSIRSL QLQSNELPSL PDNFFAVTHA RLETLNVSCN
     KLSTLPRYEQ NNHAALVNLS LAGNHLNDSI FEPLHNAAKL RVLHLAYNRI GVLPAACVRN
     WPELEILVLS GNMLQQLPEE VATLGQLRVL RCCNNLLLCT PQLAKLAMLK VLDLSHNHLD
     RVNLLALVPS RNLKYLDLSG NLQLQVDEQQ FKVCQSQSQR HWSLVDVSGN NRAALPTTKI
     RQVSAQRNQN KTSGPWTMGF AETPGSGDCR KLSVYQLRAA NYGGSDEALY GMFEALEGRG
     RAAQEMSHLV PDLMKQEQMV KDSAVRDYMK FTLLAAQQQC GSVRSAALFH LTRTRAPSKV
     RPLKSKRYVL RMASTGGLDA YLIRRTSQLR LTKPDVIQKD QIHSMPDPHV LELILSNDDE
     YLVVGNAQLW SVMDIDRAAR EIRKEENSLL AAKRLVDIAQ SFAAAESLSV IVVRFRHLGT
     DVDHLIRELK QSVRKKPQPV SLPLSSGSVC KRTCCDRSNA CRHRAIEQEP LAGRSSPSGQ
     SDRDLLAKDK DDEFVLAHAR VLQEEQQLEM LDETESVSES VLSEEQFKCW EYMLEQNTQL
     LFDKELNTIS KSFTKQRTVP NAIMAATVLP ERNDFTSNLM RTVTNKFIST STPQLPQPIT
     TSVPLGSYHQ VKQAPPGHFG SALSFQQAHS YGYNLFDAKP RPKFHGGTVK RSAGPNSAYF
     GSLQRLMPYN FEYDFAVTQE RERNILDEEE HDDDDFNEHE SRMRKYWGVA TTEL
//