PHLP1_HUMAN
ID PHLP1_HUMAN Reviewed; 1717 AA.
AC O60346; A1A4F5; Q641Q7; Q6P4C4; Q6PJI6; Q86TN6; Q96FK2; Q9NUY1;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 3.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=PH domain leucine-rich repeat-containing protein phosphatase 1;
DE EC=3.1.3.16;
DE AltName: Full=Pleckstrin homology domain-containing family E member 1;
DE Short=PH domain-containing family E member 1;
DE AltName: Full=Suprachiasmatic nucleus circadian oscillatory protein;
DE Short=hSCOP;
GN Name=PHLPP1; Synonyms=KIAA0606, PHLPP, PLEKHE1, SCOP;
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 GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 349-1717.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 475-1717.
RC TISSUE=Cerebellum, Hippocampus, Lymphoma, Melanoma, and Retinoblastoma;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 495-1233.
RC TISSUE=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 [6]
RP FUNCTION, ENZYME ACTIVITY, COFACTOR, ACTIVITY REGULATION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF 1715-THR--LEU-1717.
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).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, AND INTERACTION WITH
RP AKT2 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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
RP INTERACTION WITH SCRIB.
RX PubMed=21701506; DOI=10.1038/embor.2011.106;
RA Li X., Yang H., Liu J., Schmidt M.D., Gao T.;
RT "Scribble-mediated membrane targeting of PHLPP1 is required for its
RT negative regulation of Akt.";
RL EMBO Rep. 12:818-824(2011).
RN [14]
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 [15]
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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [17]
RP INTERACTION WITH WDR48 AND USP12, AND ACTIVITY REGULATION.
RX PubMed=24145035; DOI=10.1074/jbc.m113.503383;
RA Gangula N.R., Maddika S.;
RT "WD repeat protein WDR48 in complex with deubiquitinase USP12 suppresses
RT Akt-dependent cell survival signaling by stabilizing PH domain leucine-rich
RT repeat protein phosphatase 1 (PHLPP1).";
RL J. Biol. Chem. 288:34545-34554(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-317 AND SER-412, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [19]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
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 [20]
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).
RN [21]
RP INTERACTION WITH BRAP.
RX PubMed=25820252; DOI=10.1038/srep09459;
RA Fatima S., Wagstaff K.M., Loveland K.L., Jans D.A.;
RT "Interactome of the negative regulator of nuclear import BRCA1-binding
RT protein 2.";
RL Sci. Rep. 5:9459-9459(2015).
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 AKT2 and AKT3, 'Ser-660' of PRKCB and
CC 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466).
CC Isoform 2 seems to have a major role in regulating Akt signaling in
CC hippocampal neurons (By similarity). Akt regulates the balance between
CC cell 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 suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads
CC to their destabilization and degradation (PubMed:18162466).
CC 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 (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity
CC (PubMed:24530606). May act as a negative regulator of K-Ras signaling
CC in membrane rafts (By similarity). Involved in the hippocampus-
CC dependent long-term memory formation (By similarity). Involved in
CC circadian control by regulating the consolidation of circadian
CC periodicity after resetting (By similarity). Involved in development
CC and function of regulatory T-cells (By similarity).
CC {ECO:0000250|UniProtKB:Q8CHE4, ECO:0000250|UniProtKB:Q9WTR8,
CC ECO:0000269|PubMed:15808505, ECO:0000269|PubMed:17386267,
CC ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341,
CC ECO:0000269|PubMed:21986499, 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:15808505, 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:15808505, 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 (By similarity). Mn(2+) is
CC inhibitory below pH 8 and activating above pH 8 (PubMed:24892992).
CC {ECO:0000250, ECO:0000269|PubMed:24892992};
CC -!- ACTIVITY REGULATION: Insensitive to okadaic acid (PubMed:15808505).
CC Deubiquitination by WDR48-USP12 complex positively regulates PHLPP1
CC stability (PubMed:24145035). {ECO:0000269|PubMed:15808505,
CC ECO:0000269|PubMed:24145035}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.5 mM for p-nitrophenyl phosphate {ECO:0000269|PubMed:24892992};
CC -!- SUBUNIT: Interacts with the nucleotide free form of K-Ras (KRAS) via
CC its LRR repeats (By similarity). Interacts with AKT2, AKT3, PRKCB
CC isoform beta-II, STK4, RPS6KB1, RAF1 (PubMed:17386267, PubMed:18162466,
CC PubMed:19732725, PubMed:21986499, PubMed:24530606). Isoform 1
CC (predominantly) and isoform 2 interact with BRAP (PubMed:25820252).
CC Interacts with FKBP5; FKBP5 acts as a scaffold for PHLPP1 and Akt
CC (PubMed:19732725). Interacts with SCRIB; SCRIB acts as a scaffold for
CC PHLPP1 and Akt (PubMed:21701506). Interacts with SLC9A3R1; SLC9A3R1
CC scaffolds a heterotrimeric complex with PTEN at the plasma membrane
CC (PubMed:21804599). Interacts with WDR48 and USP12 (PubMed:24145035).
CC {ECO:0000250|UniProtKB:Q9WTR8, ECO:0000269|PubMed:17386267,
CC ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19732725,
CC ECO:0000269|PubMed:20513427, ECO:0000269|PubMed:21701506,
CC ECO:0000269|PubMed:21804599, ECO:0000269|PubMed:21986499,
CC ECO:0000269|PubMed:24145035, ECO:0000269|PubMed:24530606,
CC ECO:0000269|PubMed:25820252}.
CC -!- INTERACTION:
CC O60346; P05771-2: PRKCB; NbExp=5; IntAct=EBI-2511516, EBI-5774511;
CC O60346; Q14160: SCRIB; NbExp=2; IntAct=EBI-2511516, EBI-357345;
CC O60346; O14745: SLC9A3R1; NbExp=2; IntAct=EBI-2511516, EBI-349787;
CC O60346; Q80U72: Scrib; Xeno; NbExp=2; IntAct=EBI-2511516, EBI-1766028;
CC O60346-2; O14745: SLC9A3R1; NbExp=5; IntAct=EBI-11165225, EBI-349787;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein.
CC Nucleus. Note=In colorectal cancer tissue, expression is concentrated
CC at the lateral membrane of epithelial cells.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC {ECO:0000269|PubMed:21804599}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=beta;
CC IsoId=O60346-1; Sequence=Displayed;
CC Name=2; Synonyms=alpha;
CC IsoId=O60346-2; Sequence=VSP_057809;
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 78% of tested tumors (at protein
CC level). Ubiquitously expressed in non-cancerous tissues.
CC {ECO:0000269|PubMed:15808505, ECO:0000269|PubMed:19079341}.
CC -!- DOMAIN: The PH domain is required for interaction with PRKCB and its
CC dephosphorylation.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH14927.3; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH82244.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAI26278.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA91980.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PHLPP1ID44544ch18q21.html";
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DR EMBL; AC015989; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022046; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC027553; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB011178; BAA25532.2; -; mRNA.
DR EMBL; BC010706; AAH10706.1; -; mRNA.
DR EMBL; BC014927; AAH14927.3; ALT_INIT; mRNA.
DR EMBL; BC047653; AAH47653.1; -; mRNA.
DR EMBL; BC063519; AAH63519.1; -; mRNA.
DR EMBL; BC082244; AAH82244.1; ALT_SEQ; mRNA.
DR EMBL; BC126277; AAI26278.1; ALT_INIT; mRNA.
DR EMBL; AK001924; BAA91980.1; ALT_INIT; mRNA.
DR CCDS; CCDS45881.2; -. [O60346-1]
DR PIR; T00258; T00258.
DR RefSeq; NP_919431.2; NM_194449.3. [O60346-1]
DR AlphaFoldDB; O60346; -.
DR SMR; O60346; -.
DR BioGRID; 116843; 61.
DR CORUM; O60346; -.
DR IntAct; O60346; 51.
DR MINT; O60346; -.
DR STRING; 9606.ENSP00000262719; -.
DR BindingDB; O60346; -.
DR ChEMBL; CHEMBL3414405; -.
DR DEPOD; PHLPP1; -.
DR GlyGen; O60346; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O60346; -.
DR PhosphoSitePlus; O60346; -.
DR BioMuta; PHLPP1; -.
DR EPD; O60346; -.
DR jPOST; O60346; -.
DR MassIVE; O60346; -.
DR MaxQB; O60346; -.
DR PaxDb; O60346; -.
DR PeptideAtlas; O60346; -.
DR PRIDE; O60346; -.
DR ProteomicsDB; 49376; -.
DR Antibodypedia; 23071; 180 antibodies from 34 providers.
DR DNASU; 23239; -.
DR Ensembl; ENST00000262719.10; ENSP00000262719.4; ENSG00000081913.14. [O60346-1]
DR GeneID; 23239; -.
DR KEGG; hsa:23239; -.
DR MANE-Select; ENST00000262719.10; ENSP00000262719.4; NM_194449.4; NP_919431.2.
DR UCSC; uc021ule.2; human. [O60346-1]
DR CTD; 23239; -.
DR DisGeNET; 23239; -.
DR GeneCards; PHLPP1; -.
DR HGNC; HGNC:20610; PHLPP1.
DR HPA; ENSG00000081913; Tissue enriched (brain).
DR MIM; 609396; gene.
DR neXtProt; NX_O60346; -.
DR OpenTargets; ENSG00000081913; -.
DR PharmGKB; PA165429055; -.
DR VEuPathDB; HostDB:ENSG00000081913; -.
DR eggNOG; KOG0618; Eukaryota.
DR GeneTree; ENSGT00940000158137; -.
DR HOGENOM; CLU_003020_0_0_1; -.
DR InParanoid; O60346; -.
DR OMA; LDICGYF; -.
DR OrthoDB; 172467at2759; -.
DR PhylomeDB; O60346; -.
DR TreeFam; TF315993; -.
DR PathwayCommons; O60346; -.
DR Reactome; R-HSA-199418; Negative regulation of the PI3K/AKT network.
DR SABIO-RK; O60346; -.
DR SignaLink; O60346; -.
DR SIGNOR; O60346; -.
DR BioGRID-ORCS; 23239; 6 hits in 1088 CRISPR screens.
DR ChiTaRS; PHLPP1; human.
DR GeneWiki; PHLPP_(gene); -.
DR GenomeRNAi; 23239; -.
DR Pharos; O60346; Tchem.
DR PRO; PR:O60346; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O60346; protein.
DR Bgee; ENSG00000081913; Expressed in corpus callosum and 188 other tissues.
DR ExpressionAtlas; O60346; baseline and differential.
DR Genevisible; O60346; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0009649; P:entrainment of circadian clock; IEA:Ensembl.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:1900744; P:regulation of p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:0002667; P:regulation of T cell anergy; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00143; PP2Cc; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.60.40.10; -; 1.
DR Gene3D; 3.80.10.10; -; 4.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR036457; PPM-type_dom_sf.
DR InterPro; IPR001932; PPM-type_phosphatase_dom.
DR Pfam; PF13516; LRR_6; 2.
DR Pfam; PF13855; LRR_8; 2.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00481; PP2C; 1.
DR SMART; SM00369; LRR_TYP; 10.
DR SMART; SM00332; PP2Cc; 1.
DR SUPFAM; SSF81606; SSF81606; 1.
DR PROSITE; PS51450; LRR; 17.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS51746; PPM_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Apoptosis; Cell membrane; Cytoplasm;
KW Hydrolase; Leucine-rich repeat; Manganese; Membrane; Metal-binding;
KW Nucleus; Phosphoprotein; Protein phosphatase; Reference proteome; Repeat;
KW Tumor suppressor.
FT CHAIN 1..1717
FT /note="PH domain leucine-rich repeat-containing protein
FT phosphatase 1"
FT /id="PRO_0000057781"
FT DOMAIN 536..636
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REPEAT 638..659
FT /note="LRR 1"
FT REPEAT 661..682
FT /note="LRR 2"
FT REPEAT 692..712
FT /note="LRR 3"
FT REPEAT 715..736
FT /note="LRR 4"
FT REPEAT 738..760
FT /note="LRR 5"
FT REPEAT 761..783
FT /note="LRR 6"
FT REPEAT 784..804
FT /note="LRR 7"
FT REPEAT 808..831
FT /note="LRR 8"
FT REPEAT 832..853
FT /note="LRR 9"
FT REPEAT 873..894
FT /note="LRR 10"
FT REPEAT 895..916
FT /note="LRR 11"
FT REPEAT 918..939
FT /note="LRR 12"
FT REPEAT 941..962
FT /note="LRR 13"
FT REPEAT 963..984
FT /note="LRR 14"
FT REPEAT 987..1008
FT /note="LRR 15"
FT REPEAT 1013..1033
FT /note="LRR 16"
FT REPEAT 1037..1058
FT /note="LRR 17"
FT REPEAT 1061..1082
FT /note="LRR 18"
FT REPEAT 1084..1105
FT /note="LRR 19"
FT REPEAT 1106..1127
FT /note="LRR 20"
FT REPEAT 1129..1150
FT /note="LRR 21"
FT DOMAIN 1175..1422
FT /note="PPM-type phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 41..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 252..470
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1076..1205
FT /note="Interaction with SLC9A3R1"
FT /evidence="ECO:0000269|PubMed:21804599"
FT REGION 1458..1510
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1673..1717
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1715..1717
FT /note="PDZ-binding; required for interaction with SLC9A3R1"
FT /evidence="ECO:0000269|PubMed:21804599"
FT COMPBIAS 258..281
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..305
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..381
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 393..410
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1464..1494
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1210
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 1210
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 1211
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 1374
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT BINDING 1413
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P35813"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..512
FT /note="Missing (in isoform 2)"
FT /id="VSP_057809"
FT VARIANT 1118
FT /note="S -> T (in dbSNP:rs9950585)"
FT /id="VAR_056725"
FT MUTAGEN 1715..1717
FT /note="Missing: Loss of function in vivo, but does not
FT abolishes intrinsic phosphatase activity."
FT /evidence="ECO:0000269|PubMed:15808505"
FT CONFLICT 691
FT /note="T -> A (in Ref. 5; BAA91980)"
FT /evidence="ECO:0000305"
FT CONFLICT 1062
FT /note="L -> F (in Ref. 4; AAH47653)"
FT /evidence="ECO:0000305"
FT CONFLICT 1083
FT /note="R -> S (in Ref. 2; BAA25532)"
FT /evidence="ECO:0000305"
FT CONFLICT 1227
FT /note="D -> V (in Ref. 5; BAA91980)"
FT /evidence="ECO:0000305"
FT CONFLICT 1490
FT /note="V -> M (in Ref. 4; AAH47653)"
FT /evidence="ECO:0000305"
FT CONFLICT 1580
FT /note="Missing (in Ref. 4; AAH63519)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1717 AA; 184672 MW; A4AB53F334EA8AB6 CRC64;
MEPAAAATVQ RLPELGREDR ASAPAAAAAA AAAAAAAAAA LAAAAGGGRS PEPALTPAAP
SGGNGSGSGA REEAPGEAPP GPLPGRAGGA GRRRRRGAPQ PIAGGAAPVP GAGGGANSLL
LRRGRLKRNL SAAAAAASSS SSSSAAAASH SPGAAGLPAS CSASASLCTR SLDRKTLLLK
HRQTLQLQPS DRDWVRHQLQ RGCVHVFDRH MASTYLRPVL CTLDTTAGEV AARLLQLGHK
GGGVVKVLGQ GPGAAAAREP AEPPPEAGPR LAPPEPRDSE VPPARSAPGA FGGPPRAPPA
DLPLPVGGPG GWSRRASPAP SDSSPGEPFV GGPVSSPRAP RPVVSDTESF SLSPSAESVS
DRLDPYSSGG GSSSSSEELE ADAASAPTGV PGQPRRPGHP AQPLPLPQTA SSPQPQQKAP
RAIDSPGGAV REGSCEEKAA AAVAPGGLQS TPGRSGVTAE KAPPPPPPPT LYVQLHGETT
RRLEAEEKPL QIQNDYLFQL GFGELWRVQE EGMDSEIGCL IRFYAGKPHS TGSSERIQLS
GMYNVRKGKM QLPVNRWTRR QVILCGTCLI VSSVKDSLTG KMHVLPLIGG KVEEVKKHQH
CLAFSSSGPQ SQTYYICFDT FTEYLRWLRQ VSKVASQRIS SVDLSCCSLE HLPANLFYSQ
DLTHLNLKQN FLRQNPSLPA ARGLNELQRF TKLKSLNLSN NHLGDFPLAV CSIPTLAELN
VSCNALRSVP AAVGVMHNLQ TFLLDGNFLQ SLPAELENMK QLSYLGLSFN EFTDIPEVLE
KLTAVDKLCM SGNCVETLRL QALRKMPHIK HVDLRLNVIR KLIADEVDFL QHVTQLDLRD
NKLGDLDAMI FNNIEVLHCE RNQLVTLDIC GYFLKALYAS SNELVQLDVY PVPNYLSYMD
VSRNRLENVP EWVCESRKLE VLDIGHNQIC ELPARLFCNS SLRKLLAGHN QLARLPERLE
RTSVEVLDVQ HNQLLELPPN LLMKADSLRF LNASANKLES LPPATLSEET NSILQELYLT
NNSLTDKCVP LLTGHPHLKI LHMAYNRLQS FPASKMAKLE ELEEIDLSGN KLKAIPTTIM
NCRRMHTVIA HSNCIEVFPE VMQLPEIKCV DLSCNELSEV TLPENLPPKL QELDLTGNPR
LVLDHKTLEL LNNIRCFKID QPSTGDASGA PAVWSHGYTE ASGVKNKLCV AALSVNNFCD
NREALYGVFD GDRNVEVPYL LQCTMSDILA EELQKTKNEE EYMVNTFIVM QRKLGTAGQK
LGGAAVLCHI KHDPVDPGGS FTLTSANVGK CQTVLCRNGK PLPLSRSYIM SCEEELKRIK
QHKAIITEDG KVNGVTESTR ILGYTFLHPS VVPRPHVQSV LLTPQDEFFI LGSKGLWDSL
SVEEAVEAVR NVPDALAAAK KLCTLAQSYG CHDSISAVVV QLSVTEDSFC CCELSAGGAV
PPPSPGIFPP SVNMVIKDRP SDGLGVPSSS SGMASEISSE LSTSEMSSEV GSTASDEPPP
GALSENSPAY PSEQRCMLHP ICLSNSFQRQ LSSATFSSAF SDNGLDSDDE EPIEGVFTNG
SRVEVEVDIH CSRAKEKEKQ QHLLQVPAEA SDEGIVISAN EDEPGLPRKA DFSAVGTIGR
RRANGSVAPQ ERSHNVIEVA TDAPLRKPGG YFAAPAQPDP DDQFIIPPEL EEEVKEIMKH
HQEQQQQQQP PPPPQLQPQL PRHYQLDQLP DYYDTPL
