PHLP2_HUMAN
ID PHLP2_HUMAN Reviewed; 1323 AA.
AC Q6ZVD8; A1L374; Q9NV17; Q9Y2E3;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=PH domain leucine-rich repeat-containing protein phosphatase 2;
DE EC=3.1.3.16 {ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:24892992};
DE AltName: Full=PH domain leucine-rich repeat-containing protein phosphatase-like;
DE Short=PHLPP-like;
GN Name=PHLPP2; Synonyms=KIAA0931, PHLPPL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [2]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-423 (ISOFORMS 1/2/3), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 639-1323 (ISOFORM 2).
RC TISSUE=Amygdala, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND INTERACTION WITH
RP AKT1 AND AKT3.
RX PubMed=17386267; DOI=10.1016/j.molcel.2007.02.017;
RA Brognard J., Sierecki E., Gao T., Newton A.C.;
RT "PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude
RT of Akt signaling by regulating distinct Akt isoforms.";
RL Mol. Cell 25:917-931(2007).
RN [8]
RP FUNCTION, AND INTERACTION WITH PRKCB.
RX PubMed=18162466; DOI=10.1074/jbc.m707319200;
RA Gao T., Brognard J., Newton A.C.;
RT "The phosphatase PHLPP controls the cellular levels of protein kinase C.";
RL J. Biol. Chem. 283:6300-6311(2008).
RN [9]
RP INTERACTION WITH FKBP5; AKT2 AND AKT3.
RX PubMed=19732725; DOI=10.1016/j.ccr.2009.07.016;
RA Pei H., Li L., Fridley B.L., Jenkins G.D., Kalari K.R., Lingle W.,
RA Petersen G., Lou Z., Wang L.;
RT "FKBP51 affects cancer cell response to chemotherapy by negatively
RT regulating Akt.";
RL Cancer Cell 16:259-266(2009).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19079341; DOI=10.1038/onc.2008.450;
RA Liu J., Weiss H.L., Rychahou P., Jackson L.N., Evers B.M., Gao T.;
RT "Loss of PHLPP expression in colon cancer: role in proliferation and
RT tumorigenesis.";
RL Oncogene 28:994-1004(2009).
RN [11]
RP FUNCTION, AND INTERACTION WITH STK4.
RX PubMed=20513427; DOI=10.1016/j.molcel.2010.03.017;
RA Qiao M., Wang Y., Xu X., Lu J., Dong Y., Tao W., Stein J., Stein G.S.,
RA Iglehart J.D., Shi Q., Pardee A.B.;
RT "Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis.";
RL Mol. Cell 38:512-523(2010).
RN [12]
RP FUNCTION, AND INTERACTION WITH RPS6KB1.
RX PubMed=21986499; DOI=10.1128/mcb.05799-11;
RA Liu J., Stevens P.D., Li X., Schmidt M.D., Gao T.;
RT "PHLPP-mediated dephosphorylation of S6K1 inhibits protein translation and
RT cell growth.";
RL Mol. Cell. Biol. 31:4917-4927(2011).
RN [13]
RP INTERACTION WITH SLC9A3R1.
RX PubMed=21804599; DOI=10.1038/onc.2011.324;
RA Molina J.R., Agarwal N.K., Morales F.C., Hayashi Y., Aldape K.D., Cote G.,
RA Georgescu M.M.;
RT "PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in
RT glioblastoma.";
RL Oncogene 31:1264-1274(2012).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1210, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP PHE-783; ASP-806; PHE-808; GLU-989 AND ASP-1024.
RX PubMed=24892992; DOI=10.1021/bi500428j;
RA Sierecki E., Newton A.C.;
RT "Biochemical characterization of the phosphatase domain of the tumor
RT suppressor PH domain leucine-rich repeat protein phosphatase.";
RL Biochemistry 53:3971-3981(2014).
RN [16]
RP FUNCTION, AND INTERACTION WITH RAF1.
RX PubMed=24530606; DOI=10.1053/j.gastro.2014.02.003;
RA Li X., Stevens P.D., Liu J., Yang H., Wang W., Wang C., Zeng Z.,
RA Schmidt M.D., Yang M., Lee E.Y., Gao T.;
RT "PHLPP is a negative regulator of RAF1, which reduces colorectal cancer
RT cell motility and prevents tumor progression in mice.";
RL Gastroenterology 146:1301-1310(2014).
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 (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved
CC in regulation of cap-dependent translation (PubMed:21986499). Inhibits
CC cancer cell proliferation and may act as a tumor suppressor.
CC Dephosphorylation of PRKCA and PRKCB leads to their destabilization and
CC degradation. Dephosphorylates RAF1 inhibiting its kinase activity
CC (PubMed:24530606). {ECO:0000269|PubMed:17386267,
CC ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341,
CC ECO:0000269|PubMed:20513427, ECO:0000269|PubMed:21986499,
CC ECO:0000269|PubMed:24530606}.
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 Evidence={ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:24892992};
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 Evidence={ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:24892992};
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 (PubMed:24892992). {ECO:0000250,
CC ECO:0000269|PubMed:24892992};
CC -!- ACTIVITY REGULATION: Inhibited by AKT1, AKT2 and AKT3. Activated by
CC oleic acid and arachidonic acid (PubMed:24892992).
CC {ECO:0000269|PubMed:24892992, ECO:0000305}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.13 mM for p-nitrophenyl phosphate;
CC -!- SUBUNIT: Interacts with AKT1, AKT3 and PRKCB isoform beta-II
CC (PubMed:17386267, PubMed:18162466, PubMed:19732725). Interacts with
CC STK4, RPS6KB1, RAF1 (PubMed:20513427, PubMed:21986499,
CC PubMed:24530606). Interacts with FKBP5; FKBP5 acts as a scaffold for
CC PHLPP2 and Akt (PubMed:19732725). Interacts with SLC9A3R1; SLC9A3R1
CC scaffolds a heterotrimeric complex with PTEN (PubMed:21804599).
CC {ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466,
CC ECO:0000269|PubMed:19732725, ECO:0000269|PubMed:20513427,
CC ECO:0000269|PubMed:21804599, ECO:0000269|PubMed:21986499,
CC ECO:0000269|PubMed:24530606}.
CC -!- INTERACTION:
CC Q6ZVD8; P05771-2: PRKCB; NbExp=2; IntAct=EBI-2511496, EBI-5774511;
CC Q6ZVD8; O14745: SLC9A3R1; NbExp=6; IntAct=EBI-2511496, EBI-349787;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein.
CC Nucleus. Note=In colorectal cancer tissue, expression is concentrated
CC in the cytoplasm and nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6ZVD8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZVD8-2; Sequence=VSP_014056, VSP_014057;
CC Name=3;
CC IsoId=Q6ZVD8-3; Sequence=VSP_017265;
CC -!- TISSUE SPECIFICITY: In colorectal cancer tissue, expression is highest
CC in the surface epithelium of normal colonic mucosa adjacent to the
CC cancer tissue but is largely excluded from the crypt bases. Expression
CC is lost or significantly decreased in 80% of tested tumors (at protein
CC level). {ECO:0000269|PubMed:19079341}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76775.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA91943.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PHLPP2ID44546ch16q22.html";
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DR EMBL; AB023148; BAA76775.2; ALT_INIT; mRNA.
DR EMBL; BX647823; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC009097; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC129927; AAI29928.1; -; mRNA.
DR EMBL; AK001854; BAA91943.1; ALT_INIT; mRNA.
DR EMBL; AK124678; BAC85924.1; -; mRNA.
DR CCDS; CCDS32479.1; -. [Q6ZVD8-1]
DR CCDS; CCDS73910.1; -. [Q6ZVD8-3]
DR RefSeq; NP_001275932.1; NM_001289003.1. [Q6ZVD8-3]
DR RefSeq; NP_055835.2; NM_015020.3. [Q6ZVD8-1]
DR AlphaFoldDB; Q6ZVD8; -.
DR SMR; Q6ZVD8; -.
DR BioGRID; 116674; 27.
DR CORUM; Q6ZVD8; -.
DR DIP; DIP-53556N; -.
DR IntAct; Q6ZVD8; 25.
DR MINT; Q6ZVD8; -.
DR STRING; 9606.ENSP00000457991; -.
DR BindingDB; Q6ZVD8; -.
DR ChEMBL; CHEMBL1275209; -.
DR DEPOD; PHLPP2; -.
DR iPTMnet; Q6ZVD8; -.
DR PhosphoSitePlus; Q6ZVD8; -.
DR BioMuta; PHLPP2; -.
DR DMDM; 116242711; -.
DR EPD; Q6ZVD8; -.
DR jPOST; Q6ZVD8; -.
DR MassIVE; Q6ZVD8; -.
DR MaxQB; Q6ZVD8; -.
DR PaxDb; Q6ZVD8; -.
DR PeptideAtlas; Q6ZVD8; -.
DR PRIDE; Q6ZVD8; -.
DR ProteomicsDB; 68409; -. [Q6ZVD8-1]
DR ProteomicsDB; 68410; -. [Q6ZVD8-2]
DR ProteomicsDB; 68411; -. [Q6ZVD8-3]
DR Antibodypedia; 30102; 159 antibodies from 35 providers.
DR DNASU; 23035; -.
DR Ensembl; ENST00000393524.6; ENSP00000377159.2; ENSG00000040199.18. [Q6ZVD8-3]
DR Ensembl; ENST00000568954.5; ENSP00000457991.1; ENSG00000040199.18. [Q6ZVD8-1]
DR GeneID; 23035; -.
DR KEGG; hsa:23035; -.
DR MANE-Select; ENST00000568954.5; ENSP00000457991.1; NM_015020.3; NP_055835.2.
DR UCSC; uc002fax.5; human. [Q6ZVD8-1]
DR CTD; 23035; -.
DR DisGeNET; 23035; -.
DR GeneCards; PHLPP2; -.
DR HGNC; HGNC:29149; PHLPP2.
DR HPA; ENSG00000040199; Tissue enhanced (intestine, retina).
DR MIM; 611066; gene.
DR neXtProt; NX_Q6ZVD8; -.
DR OpenTargets; ENSG00000040199; -.
DR PharmGKB; PA165450496; -.
DR VEuPathDB; HostDB:ENSG00000040199; -.
DR eggNOG; KOG0618; Eukaryota.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000159841; -.
DR HOGENOM; CLU_003020_0_0_1; -.
DR InParanoid; Q6ZVD8; -.
DR OMA; CPEEHPR; -.
DR OrthoDB; 172467at2759; -.
DR PhylomeDB; Q6ZVD8; -.
DR TreeFam; TF315993; -.
DR PathwayCommons; Q6ZVD8; -.
DR Reactome; R-HSA-199418; Negative regulation of the PI3K/AKT network.
DR SABIO-RK; Q6ZVD8; -.
DR SignaLink; Q6ZVD8; -.
DR SIGNOR; Q6ZVD8; -.
DR BioGRID-ORCS; 23035; 10 hits in 1077 CRISPR screens.
DR ChiTaRS; PHLPP2; human.
DR GeneWiki; PHLPPL; -.
DR GenomeRNAi; 23035; -.
DR Pharos; Q6ZVD8; Tbio.
DR PRO; PR:Q6ZVD8; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q6ZVD8; protein.
DR Bgee; ENSG00000040199; Expressed in ileal mucosa and 175 other tissues.
DR ExpressionAtlas; Q6ZVD8; baseline and differential.
DR Genevisible; Q6ZVD8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0072686; C:mitotic spindle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0001917; C:photoreceptor inner segment; IEA:Ensembl.
DR GO; GO:0042622; C:photoreceptor outer segment membrane; IEA:Ensembl.
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:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:Ensembl.
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; 2.
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; 18.
DR PROSITE; PS51746; PPM_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Hydrolase; Leucine-rich repeat; Manganese;
KW Membrane; Metal-binding; Nucleus; Phosphoprotein; Protein phosphatase;
KW Reference proteome; Repeat; Tumor suppressor.
FT CHAIN 1..1323
FT /note="PH domain leucine-rich repeat-containing protein
FT phosphatase 2"
FT /id="PRO_0000057784"
FT DOMAIN 150..248
FT /note="PH"
FT REPEAT 250..271
FT /note="LRR 1"
FT REPEAT 273..296
FT /note="LRR 2"
FT REPEAT 300..321
FT /note="LRR 3"
FT REPEAT 323..344
FT /note="LRR 4"
FT REPEAT 346..368
FT /note="LRR 5"
FT REPEAT 369..390
FT /note="LRR 6"
FT REPEAT 392..412
FT /note="LRR 7"
FT REPEAT 416..439
FT /note="LRR 8"
FT REPEAT 440..460
FT /note="LRR 9"
FT REPEAT 461..480
FT /note="LRR 10"
FT REPEAT 481..502
FT /note="LRR 11"
FT REPEAT 503..524
FT /note="LRR 12"
FT REPEAT 526..547
FT /note="LRR 13"
FT REPEAT 549..570
FT /note="LRR 14"
FT REPEAT 571..592
FT /note="LRR 15"
FT REPEAT 595..616
FT /note="LRR 16"
FT REPEAT 621..644
FT /note="LRR 17"
FT REPEAT 645..666
FT /note="LRR 18"
FT REPEAT 669..690
FT /note="LRR 19"
FT REPEAT 692..713
FT /note="LRR 20"
FT REPEAT 714..735
FT /note="LRR 21"
FT REPEAT 737..758
FT /note="LRR 22"
FT DOMAIN 785..1033
FT /note="PPM-type phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082"
FT REGION 1060..1157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1285..1323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1062..1102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1123..1148
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 820
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 820
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 821
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 985
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 1024
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT MOD_RES 1210
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 596..662
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10231032"
FT /id="VSP_017265"
FT VAR_SEQ 940..956
FT /note="DNKVNGVTCCTRMLGCT -> NWVLNQKHLQDFPGEDK (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014056"
FT VAR_SEQ 957..1323
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014057"
FT MUTAGEN 783
FT /note="F->V: Decreases activity."
FT /evidence="ECO:0000269|PubMed:24892992"
FT MUTAGEN 806
FT /note="D->N: Decreases activity."
FT /evidence="ECO:0000269|PubMed:24892992"
FT MUTAGEN 808
FT /note="F->V: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:24892992"
FT MUTAGEN 989
FT /note="E->Q: Decreases activity."
FT /evidence="ECO:0000269|PubMed:24892992"
FT MUTAGEN 1024
FT /note="D->N: Decreases activity."
FT /evidence="ECO:0000269|PubMed:24892992"
FT CONFLICT 147
FT /note="R -> C (in Ref. 3; BX647823)"
FT /evidence="ECO:0000305"
FT CONFLICT 542
FT /note="V -> L (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 766
FT /note="K -> E (in Ref. 3; BX647823)"
FT /evidence="ECO:0000305"
FT CONFLICT 896
FT /note="A -> G (in Ref. 6; BAA91943)"
FT /evidence="ECO:0000305"
FT CONFLICT 978
FT /note="E -> G (in Ref. 3; BX647823)"
FT /evidence="ECO:0000305"
FT CONFLICT 1016
FT /note="L -> S (in Ref. 3; BX647823)"
FT /evidence="ECO:0000305"
FT CONFLICT 1312
FT /note="R -> Q (in Ref. 5; AAI29928)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1323 AA; 146751 MW; 04FC8550C2E22A6D CRC64;
MKRNGSRNCL NRRSRFGSRE RDWLREDVKR GCVYLYGADT TTATTTTTTS SSSSSSSSSS
DLHLVLCTVE TPASEICAGE GRESLYLQLH GDLVRRLEPT ERPLQIVYDY LSRLGFDDPV
RIQEEATNPD LGCMIRFYGE KPCHMDRLDR ILLSGIYNVR KGKTQLHKWA ERLVVLCGTC
LIVSSVKDCQ TGKMHILPLV GGKIEEVKRR QYSLAFSSAG AQAQTYHVSF ETLAEYQRWQ
RQASKVVSQR ISTVDLSCYS LEEVPEHLFY SQDITYLNLR HNFMQLERPG GLDTLYKFSQ
LKGLNLSHNK LGLFPILLCE ISTLTELNLS CNGFHDLPSQ IGNLLNLQTL CLDGNFLTTL
PEELGNLQQL SSLGISFNNF SQIPEVYEKL TMLDRVVMAG NCLEVLNLGV LNRMNHIKHV
DLRMNHLKTM VIENLEGNKH ITHVDLRDNR LTDLDLSSLC SLEQLHCGRN QLRELTLSGF
SLRTLYASSN RLTAVNVYPV PSLLTFLDLS RNLLECVPDW ACEAKKIEVL DVSYNLLTEV
PVRILSSLSL RKLMLGHNHV QNLPTLVEHI PLEVLDLQHN ALTRLPDTLF SKALNLRYLN
ASANSLESLP SACTGEESLS MLQLLYLTNN LLTDQCIPVL VGHLHLRILH LANNQLQTFP
ASKLNKLEQL EELNLSGNKL KTIPTTIANC KRLHTLVAHS NNISIFPEIL QLPQIQFVDL
SCNDLTEILI PEALPATLQD LDLTGNTNLV LEHKTLDIFS HITTLKIDQK PLPTTDSTVT
STFWSHGLAE MAGQRNKLCV SALAMDSFAE GVGAVYGMFD GDRNEELPRL LQCTMADVLL
EEVQQSTNDT VFMANTFLVS HRKLGMAGQK LGSSALLCYI RPDTADPASS FSLTVANVGT
CQAVLCRGGK PVPLSKVFSL EQDPEEAQRV KDQKAIITED NKVNGVTCCT RMLGCTYLYP
WILPKPHISS TPLTIQDELL ILGNKALWEH LSYTEAVNAV RHVQDPLAAA KKLCTLAQSY
GCQDNVGAMV VYLNIGEEGC TCEMNGLTLP GPVGFASTTT IKDAPKPATP SSSSGIASEF
SSEMSTSEVS SEVGSTASDE HNAGGLDTAL LPRPERRCSL HPTPTSGLFQ RQPSSATFSS
NQSDNGLDSD DDQPVEGVIT NGSKVEVEVD IHCCRGRDLE NSPPLIESSP TLCSEEHARG
SCFGIRRQNS VNSGMLLPMS KDRMELQKSP STSCLYGKKL SNGSIVPLED SLNLIEVATE
VPKRKTGYFA APTQMEPEDQ FVVPHDLEEE VKEQMKQHQD SRLEPEPHEE DRTEPPEEFD
TAL
