PHLP2_MOUSE
ID PHLP2_MOUSE Reviewed; 1320 AA.
AC Q8BXA7; Q148U6; Q8BX96;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=PH domain leucine-rich repeat-containing protein phosphatase 2;
DE EC=3.1.3.16;
DE AltName: Full=PH domain leucine-rich repeat-containing protein phosphatase-like;
DE Short=PHLPP-like;
GN Name=Phlpp2; Synonyms=Phlppl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1259.
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1207, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=20089132; DOI=10.1111/j.1471-4159.2010.06609.x;
RA Kanan Y., Matsumoto H., Song H., Sokolov M., Anderson R.E., Rajala R.V.;
RT "Serine/threonine kinase akt activation regulates the activity of retinal
RT serine/threonine phosphatases, PHLPP and PHLPPL.";
RL J. Neurochem. 113:477-488(2010).
CC -!- FUNCTION: Protein phosphatase involved in regulation of Akt and PKC
CC signaling. Mediates dephosphorylation in the C-terminal domain
CC hydrophobic motif of members of the AGC Ser/Thr protein kinase family;
CC specifically acts on 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform
CC beta-II and 'Ser-657' of PRKCA. Akt regulates the balance between cell
CC survival and apoptosis through a cascade that primarily alters the
CC function of transcription factors that regulate pro- and antiapoptotic
CC genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and
CC decreases cell proliferation. Also controls the phosphorylation of
CC AKT3. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and
CC apoptosis. Dephosphorylates RPS6KB1 and is involved in regulation of
CC cap-dependent translation. Inhibits cancer cell proliferation and may
CC act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads
CC to their destabilization and degradation. Dephosphorylates RAF1
CC inhibiting its kinase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q6ZVD8}.
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};
CC Note=Binds 2 manganese ions per subunit. Mn(2+) is inhibitory below pH
CC 8 and activating above pH 8 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q6ZVD8};
CC -!- ACTIVITY REGULATION: Inhibited by AKT1, AKT2 and AKT3. Activated by
CC oleic acid and arachidonic acid. {ECO:0000250|UniProtKB:Q6ZVD8}.
CC -!- SUBUNIT: Interacts with AKT1, AKT3 and PRKCB. Interacts with STK4,
CC RPS6KB1, RAF1. Interacts with FKBP5; FKBP5 acts as a scaffold for
CC PHLPP2 and Akt. Interacts with SLC9A3R1; SLC9A3R1 scaffolds a
CC heterotrimeric complex with PTEN (By similarity).
CC {ECO:0000250|UniProtKB:Q6ZVD8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6ZVD8}.
CC Membrane; Peripheral membrane protein {ECO:0000250|UniProtKB:Q6ZVD8}.
CC Nucleus {ECO:0000250|UniProtKB:Q6ZVD8}.
CC -!- TISSUE SPECIFICITY: Expressed in the retina.
CC {ECO:0000269|PubMed:20089132}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC33347.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AC122807; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117961; AAI17962.1; -; mRNA.
DR EMBL; BC117962; AAI17963.1; -; mRNA.
DR EMBL; AK048260; BAC33288.1; -; mRNA.
DR EMBL; AK048472; BAC33347.2; ALT_INIT; mRNA.
DR RefSeq; NP_001116066.2; NM_001122594.2.
DR AlphaFoldDB; Q8BXA7; -.
DR SMR; Q8BXA7; -.
DR BioGRID; 232671; 1.
DR STRING; 10090.ENSMUSP00000136166; -.
DR iPTMnet; Q8BXA7; -.
DR PhosphoSitePlus; Q8BXA7; -.
DR jPOST; Q8BXA7; -.
DR MaxQB; Q8BXA7; -.
DR PaxDb; Q8BXA7; -.
DR PRIDE; Q8BXA7; -.
DR ProteomicsDB; 288144; -.
DR Antibodypedia; 30102; 159 antibodies from 35 providers.
DR DNASU; 244650; -.
DR Ensembl; ENSMUST00000034175; ENSMUSP00000034175; ENSMUSG00000031732.
DR GeneID; 244650; -.
DR KEGG; mmu:244650; -.
DR CTD; 23035; -.
DR MGI; MGI:2444928; Phlpp2.
DR VEuPathDB; HostDB:ENSMUSG00000031732; -.
DR eggNOG; KOG0618; Eukaryota.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000159841; -.
DR HOGENOM; CLU_003020_0_0_1; -.
DR InParanoid; Q8BXA7; -.
DR OMA; CPEEHPR; -.
DR OrthoDB; 172467at2759; -.
DR Reactome; R-MMU-199418; Negative regulation of the PI3K/AKT network.
DR BioGRID-ORCS; 244650; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Phlpp2; mouse.
DR PRO; PR:Q8BXA7; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8BXA7; protein.
DR Bgee; ENSMUSG00000031732; Expressed in pigmented layer of retina and 210 other tissues.
DR ExpressionAtlas; Q8BXA7; baseline and differential.
DR Genevisible; Q8BXA7; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0072686; C:mitotic spindle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00143; PP2Cc; 1.
DR Gene3D; 3.60.40.10; -; 1.
DR Gene3D; 3.80.10.10; -; 3.
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; 4.
DR Pfam; PF00481; PP2C; 1.
DR SMART; SM00369; LRR_TYP; 13.
DR SMART; SM00332; PP2Cc; 1.
DR SUPFAM; SSF81606; SSF81606; 1.
DR PROSITE; PS51450; LRR; 17.
DR PROSITE; PS51746; PPM_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Leucine-rich repeat; Manganese; Membrane;
KW Metal-binding; Nucleus; Phosphoprotein; Protein phosphatase;
KW Reference proteome; Repeat; Tumor suppressor.
FT CHAIN 1..1320
FT /note="PH domain leucine-rich repeat-containing protein
FT phosphatase 2"
FT /id="PRO_0000057785"
FT DOMAIN 147..245
FT /note="PH"
FT REPEAT 247..268
FT /note="LRR 1"
FT REPEAT 270..293
FT /note="LRR 2"
FT REPEAT 297..318
FT /note="LRR 3"
FT REPEAT 320..341
FT /note="LRR 4"
FT REPEAT 343..364
FT /note="LRR 5"
FT REPEAT 366..388
FT /note="LRR 6"
FT REPEAT 389..409
FT /note="LRR 7"
FT REPEAT 413..434
FT /note="LRR 8"
FT REPEAT 437..457
FT /note="LRR 9"
FT REPEAT 458..477
FT /note="LRR 10"
FT REPEAT 478..499
FT /note="LRR 11"
FT REPEAT 500..521
FT /note="LRR 12"
FT REPEAT 523..544
FT /note="LRR 13"
FT REPEAT 546..567
FT /note="LRR 14"
FT REPEAT 568..589
FT /note="LRR 15"
FT REPEAT 592..613
FT /note="LRR 16"
FT REPEAT 618..641
FT /note="LRR 17"
FT REPEAT 642..663
FT /note="LRR 18"
FT REPEAT 666..687
FT /note="LRR 19"
FT REPEAT 689..710
FT /note="LRR 20"
FT REPEAT 711..732
FT /note="LRR 21"
FT REPEAT 734..755
FT /note="LRR 22"
FT DOMAIN 782..1030
FT /note="PPM-type phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082"
FT REGION 1057..1100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1265..1320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1059..1100
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1278..1320
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 817
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 817
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 818
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 982
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 1021
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT MOD_RES 1207
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 67
FT /note="E -> Q (in Ref. 3; BAC33288)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1320 AA; 145947 MW; 302407C231BD539B CRC64;
MKHNGSRTCL NRRSRFGSRE RDWLREDVKR GCVYLYGADT TTATTTTSSS SSSSSSSDLH
LVLCTVETPA SEICAGEGRE SLYLQLHGDL VRRLEPSERP LQIVYDYLSR LGFEDPVRIQ
EEATNPDLSC MIRFYGEKPC QMDHLDRILL SGIYNVRKGK TQLHKWAERL VVLCGTCLIV
SSVKDCQTGK MHILPLVGGK IEEVKRRQHS LAFSSAGAQA QTYHVSFETL AEYQRWQRQA
SKVVSQRMST VDLSCYSLEE VPEHLFYSQD ITYLNLRHNF MQLERPGGLD TLHKFSQLKG
LNLSHNKLGL FPVLLCEIST LTELSLSCNG FHDLPSQIGK LLNLQTLSLD GNGLTALPDE
LGNLRQLTSL GISFNDFRHI PEVLEKLTML DKVAMAGNRL EVLNLGALTR MSQVKHVDLR
MNHLKTVITE NMEGNKHITH MDLRDNQLTD LDLSSLCSLE QLHCERNQLR ELTLSGFSLR
TLYASWNRLT AVNVYPVPSL LTSLELSQNL LECVPDWACE AKKLEILDIS HNLLTEVPMR
ILSSLSLRKL MVGHNHIHVL PALVEHIPLE VLDIQHNTLS RLPDTLFSKA LNLRYLNASA
NSLESLPSAC AGEESLSVLQ LLYLTSNLLT DQCIPVLVGH PHLRVLHLAN NQLQTFPASK
LNKLEQLEEL NLSGNKLTAI PTTIANCKRL HTLVAHANNI SIFPEILQLP QIQFVDLSCN
DLTEILIPEA LPATLQDLDL TGNTNLVLEH KTLDMFSHIT ALKIDQKPLP ATDSAVTSTF
WSHGLAEMAG QRNKLCVSAL AMDNFAEGVG AVYGMFDGDR NEELPRLLQC TMADVLLEEV
QHSTNDTVFM TNTFLVSHRK LGMAGQKLGS SALLCYIRPD TADPTSSFSL TVANVGMCQA
VLCRGGKPVP LSKVFSLEHD PEEAQRVKDQ KAIITEDNKV NGVTCCTRLL GCTYLYPWIL
PKPHIASTPL TIQDELLILG NKALWEHLSY LEAVNAVRHV QDPLAAAKKL CTLAQSYGCQ
DNVGAMVVYL NIGEEGCTCE MNGLTLPGPV GFASTAALKD TPKPTTPSSS SGIASEFSSE
MSTSEVSSEV GSTASDEHNT VGLEASLLPR PERRCSLHPA SSAGVFQRQP SCATFSSNQS
DNGLDSDDDQ PVEGVITNGS RVEVEVDIHC CRGREPESSP PLPKNSSNAC SEERARGAGF
GIRRQNSVNS GILLPANRDK MELQKSPSTS CLYGKKLSNG SIVPLEDSLN LIEVATEAPK
RKTGYFAAPT QLEPEDQFVV PRDLEEEVKE QMKQHQEGRP EPEPRGEERT EPLEEFDTAL
