PHLPP_DROME
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 03-AUG-2022, entry version 144.
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.FBpp0080693; -.
DR PaxDb; Q9VJ07; -.
DR EnsemblMetazoa; FBtr0081149; FBpp0080693; FBgn0032749.
DR EnsemblMetazoa; FBtr0336844; FBpp0307805; FBgn0032749.
DR GeneID; 35178; -.
DR KEGG; dme:Dmel_CG10493; -.
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; CDRSNAC; -.
DR OrthoDB; 172467at2759; -.
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 tissue.
DR ExpressionAtlas; Q9VJ07; baseline and differential.
DR Genevisible; Q9VJ07; DM.
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 Gene3D; 3.60.40.10; -; 1.
DR Gene3D; 3.80.10.10; -; 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_dom_sf.
DR InterPro; IPR001932; PPM-type_phosphatase_dom.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF00481; PP2C; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR SUPFAM; SSF81606; SSF81606; 1.
DR PROSITE; PS51450; LRR; 12.
DR PROSITE; PS51746; PPM_2; 1.
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
