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 27-MAR-2024, entry version 176. 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 NHERF1. 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 NHERF1; NHERF1 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; O14745: NHERF1; NbExp=6; IntAct=EBI-2511496, EBI-349787; CC Q6ZVD8; P05771-2: PRKCB; NbExp=2; IntAct=EBI-2511496, EBI-5774511; 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="https://atlasgeneticsoncology.org/gene/44546/PHLPP2"; 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; 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; 31. 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; 9606-ENSP00000457991; -. DR PeptideAtlas; Q6ZVD8; -. DR ProteomicsDB; 68409; -. [Q6ZVD8-1] DR ProteomicsDB; 68410; -. [Q6ZVD8-2] DR ProteomicsDB; 68411; -. [Q6ZVD8-3] DR Pumba; Q6ZVD8; -. DR Antibodypedia; 30102; 176 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 AGR; HGNC:29149; -. 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; 3677323at2759; -. 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 1163 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 176 other cell types or tissues. DR ExpressionAtlas; Q6ZVD8; baseline and differential. 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:0007165; P:signal transduction; IBA:GO_Central. DR CDD; cd13322; PH_PHLPP-like; 1. DR CDD; cd00143; PP2Cc; 1. DR CDD; cd17241; RA_PHLPP2; 1. DR Gene3D; 3.60.40.10; PPM-type phosphatase domain; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 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-like_dom_sf. DR InterPro; IPR001932; PPM-type_phosphatase-like_dom. DR PANTHER; PTHR48051; -; 1. DR PANTHER; PTHR48051:SF37; PH DOMAIN AND LEUCINE-RICH REPEAT PROTEIN PHOSPHATASE 2; 1. DR Pfam; PF00560; LRR_1; 1. DR Pfam; PF13516; LRR_6; 2. DR Pfam; PF13855; LRR_8; 2. DR Pfam; PF00481; PP2C; 1. DR SMART; SM00364; LRR_BAC; 12. DR SMART; SM00369; LRR_TYP; 13. DR SMART; SM00332; PP2Cc; 1. DR SUPFAM; SSF52058; L domain-like; 2. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF81606; PP2C-like; 1. DR PROSITE; PS51450; LRR; 18. DR PROSITE; PS51746; PPM_2; 1. DR Genevisible; Q6ZVD8; HS. 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 //