Top PHLPP2
Localization (UniProt annotation) Cytoplasm Membrane; Peripheral membraneprotein Nucleus Note=In colorectal cancer tissue, expression isconcentrated in the cytoplasm and nucleus Function (UniProt annotation) Protein phosphatase involved in regulation of Akt andPKC signaling Mediates dephosphorylation in the C-terminal domainhydrophobic motif of members of the AGC Ser/Thr protein kinasefamily; specifically acts on 'Ser-473' of AKT1, 'Ser-660' of PRKCBisoform beta-II and 'Ser-657' of PRKCA Akt regulates the balancebetween cell survival and apoptosis through a cascade thatprimarily alters the function of transcription factors thatregulate pro- and antiapoptotic genes Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and decreases cell proliferationAlso controls the phosphorylation of AKT3 Dephosphorylates STK4on 'Thr-387' leading to STK4 activation and apoptosis(PubMed:20513427) Dephosphorylates RPS6KB1 and is involved inregulation of cap-dependent translation (PubMed:21986499)Inhibits cancer cell proliferation and may act as a tumorsuppressor Dephosphorylation of PRKCA and PRKCB leads to theirdestabilization and degradation Dephosphorylates RAF1 inhibitingits kinase activity (PubMed:24530606) Catalytic Activity (UniProt annotation) [a protein]-serine/threonine phosphate + H(2)O= [a protein]-serine/threonine + phosphate Protein Sequence MKRNGSRNCLNRRSRFGSRERDWLREDVKRGCVYLYGADTTTATTTTTTSSSSSSSSSSSDLHLVLCTVETPASEICAGE
GRESLYLQLHGDLVRRLEPTERPLQIVYDYLSRLGFDDPVRIQEEATNPDLGCMIRFYGEKPCHMDRLDRILLSGIYNVR
KGKTQLHKWAERLVVLCGTCLIVSSVKDCQTGKMHILPLVGGKIEEVKRRQYSLAFSSAGAQAQTYHVSFETLAEYQRWQ
RQASKVVSQRISTVDLSCYSLEEVPEHLFYSQDITYLNLRHNFMQLERPGGLDTLYKFSQLKGLNLSHNKLGLFPILLCE
ISTLTELNLSCNGFHDLPSQIGNLLNLQTLCLDGNFLTTLPEELGNLQQLSSLGISFNNFSQIPEVYEKLTMLDRVVMAG
NCLEVLNLGVLNRMNHIKHVDLRMNHLKTMVIENLEGNKHITHVDLRDNRLTDLDLSSLCSLEQLHCGRNQLRELTLSGF
SLRTLYASSNRLTAVNVYPVPSLLTFLDLSRNLLECVPDWACEAKKIEVLDVSYNLLTEVPVRILSSLSLRKLMLGHNHV
QNLPTLVEHIPLEVLDLQHNALTRLPDTLFSKALNLRYLNASANSLESLPSACTGEESLSMLQLLYLTNNLLTDQCIPVL
VGHLHLRILHLANNQLQTFPASKLNKLEQLEELNLSGNKLKTIPTTIANCKRLHTLVAHSNNISIFPEILQLPQIQFVDL
SCNDLTEILIPEALPATLQDLDLTGNTNLVLEHKTLDIFSHITTLKIDQKPLPTTDSTVTSTFWSHGLAEMAGQRNKLCV
SALAMDSFAEGVGAVYGMFDGDRNEELPRLLQCTMADVLLEEVQQSTNDTVFMANTFLVSHRKLGMAGQKLGSSALLCYI
RPDTADPASSFSLTVANVGTCQAVLCRGGKPVPLSKVFSLEQDPEEAQRVKDQKAIITEDNKVNGVTCCTRMLGCTYLYP
WILPKPHISSTPLTIQDELLILGNKALWEHLSYTEAVNAVRHVQDPLAAAKKLCTLAQSYGCQDNVGAMVVYLNIGEEGC
TCEMNGLTLPGPVGFASTTTIKDAPKPATPSSSSGIASEFSSEMSTSEVSSEVGSTASDEHNAGGLDTALLPRPERRCSL
HPTPTSGLFQRQPSSATFSSNQSDNGLDSDDDQPVEGVITNGSKVEVEVDIHCCRGRDLENSPPLIESSPTLCSEEHARG
SCFGIRRQNSVNSGMLLPMSKDRMELQKSPSTSCLYGKKLSNGSIVPLEDSLNLIEVATEVPKRKTGYFAAPTQMEPEDQ
FVVPHDLEEEVKEQMKQHQDSRLEPEPHEEDRTEPPEEFDTAL
ELM Motif Motif Instance Description Motif Regex NA NA NA NA
Download FASTA sequences of PHLPP2-substrates in HumansSubstrate Gene Name Substrate UniProt_AC DephosphoSite and sequence (+/-5) Bioassay Type PubMed ID View in Europe PMC Reliability of the interaction AKT3 Q9Y243 Ser-472 _HFPQFsYSASG , In vitro and in vivo 17386267 , 19261608 , Europe PMC AKT1 P31749 Ser-473_HFPQFsYSASG , In vitro and in vivo 17386267 , 19261608 , Europe PMC AKT2 P31751 Ser-474 _HFPQFsYSASI , In vitro and in vivo 17386267 , 19261608 , Europe PMC PRKCA P17252 Ser-657_DFEGFsYVNPQ , In vitro and in vivo 18162466 , Europe PMC STK4 Q13043 Thr-387_KRRDEtMQPAK , In vitro and in vivo 20513427 , Europe PMC PRKCB P05771 Ser-660 in Isoform Beta-II _EFEGFsFVNSE , In vitro and in vivo 18162466 , Europe PMC RPS6KB1 P23443 Thr-252_GTVTHtFCGTI, , Thr-412_VFLGFtYVAPS , In vitro 21986499 , Europe PMC
Pathway ID Pathway Name Pathway Description (KEGG) hsa04151 PI3K-Akt signaling pathway The phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, translation, proliferation, growth, and survival. The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) stimulates class Ia and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5-triphosphate (PIP3) at the cell membrane. PIP3 in turn serves as a second messenger that helps to activate Akt. Once active, Akt can control key cellular processes by phosphorylating substrates involved in apoptosis, protein synthesis, metabolism, and cell cycle.
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source DMWD Affinity Capture-MS physical 27880917 , (Europe PMC )NA BioGRID EZR Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , (Europe PMC )0.40 BioGRID, IntAct FANCI Affinity Capture-Western physical 27097374 , (Europe PMC )NA BioGRID FKBP5 Affinity Capture-Western physical 28363942 , (Europe PMC )NA BioGRID LRRC6 Affinity Capture-MS physical 28514442 , (Europe PMC )NA BioGRID PHLPP1 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct PPP3CA Affinity Capture-Western physical 20605778 , (Europe PMC )NA BioGRID RDX Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , (Europe PMC )0.40 BioGRID, IntAct SLC9A3R1 Affinity Capture-MS, Affinity Capture-Western, Far Western, Reconstituted Complex, anti tag coimmunoprecipitation, filter binding, pull down direct interaction, physical, physical association 19615732 , 21804599 , 27880917 , (Europe PMC )0.70 BioGRID, IntAct SLC9A3R2 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct SNX27 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct SUGT1 Affinity Capture-MS physical 27880917 , (Europe PMC )NA BioGRID USP1 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27463890 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct USP12 Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 19615732 , 25216524 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct USP46 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 26186194 , 27880917 , 28514442 , (Europe PMC )0.40 BioGRID, IntAct VAT1 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct WDR20 Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 19615732 , 25216524 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct WDR48 Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation, pull down association, physical, physical association 19615732 , 25216524 , 27463890 , 27880917 , 28330616 , (Europe PMC )0.56 BioGRID, IntAct
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source EZR Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , (Europe PMC )0.40 BioGRID, IntAct GRN pull down association 28330616 , (Europe PMC )0.35 IntAct HSPA4 pull down association 28330616 , (Europe PMC )0.35 IntAct HSPH1 pull down association 28330616 , (Europe PMC )0.35 IntAct PHLPP1 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct PRKCB anti tag coimmunoprecipitation, cosedimentation physical association 18162466 , (Europe PMC )0.52 IntAct, MINT PTEN filter binding physical association 21804599 , (Europe PMC )0.40 IntAct RDX Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , (Europe PMC )0.40 BioGRID, IntAct RPL3 pull down association 28330616 , (Europe PMC )0.35 IntAct RPS11 pull down physical association 28330616 , (Europe PMC )0.40 IntAct RPS6KB1 anti bait coimmunoprecipitation association 21986499 , (Europe PMC )0.35 IntAct SLC9A3R1 Affinity Capture-MS, Affinity Capture-Western, Far Western, Reconstituted Complex, anti tag coimmunoprecipitation, filter binding, pull down direct interaction, physical, physical association 19615732 , 21804599 , 27880917 , (Europe PMC )0.70 BioGRID, IntAct SLC9A3R2 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct SNX27 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct USP1 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27463890 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct USP12 Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 19615732 , 25216524 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct USP46 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 26186194 , 27880917 , 28514442 , (Europe PMC )0.40 BioGRID, IntAct VAT1 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct WDR20 Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 19615732 , 25216524 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct WDR48 Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation, pull down association, physical, physical association 19615732 , 25216524 , 27463890 , 27880917 , 28330616 , (Europe PMC )0.56 BioGRID, IntAct
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source CUL3 Affinity Capture-Western physical 28859855 , (Europe PMC )NA BioGRID DMWD Affinity Capture-MS physical 27880917 , (Europe PMC )NA BioGRID EZR Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , (Europe PMC )0.40 BioGRID, IntAct FANCI Affinity Capture-Western physical 27097374 , (Europe PMC )NA BioGRID FKBP5 Affinity Capture-Western physical 28363942 , (Europe PMC )NA BioGRID GRN pull down association 28330616 , (Europe PMC )0.35 IntAct HSPA4 pull down association 28330616 , (Europe PMC )0.35 IntAct HSPH1 pull down association 28330616 , (Europe PMC )0.35 IntAct LRRC6 Affinity Capture-MS physical 28514442 , (Europe PMC )NA BioGRID PHLPP1 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct PPP3CA Affinity Capture-Western physical 20605778 , (Europe PMC )NA BioGRID PRKCB anti tag coimmunoprecipitation, cosedimentation physical association 18162466 , (Europe PMC )0.52 IntAct, MINT PTEN filter binding physical association 21804599 , (Europe PMC )0.40 IntAct RDX Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , (Europe PMC )0.40 BioGRID, IntAct RPL3 pull down association 28330616 , (Europe PMC )0.35 IntAct RPS11 pull down physical association 28330616 , (Europe PMC )0.40 IntAct RPS6KB1 anti bait coimmunoprecipitation association 21986499 , (Europe PMC )0.35 IntAct SLC9A3R1 Affinity Capture-MS, Affinity Capture-Western, Far Western, Reconstituted Complex, anti tag coimmunoprecipitation, filter binding, pull down direct interaction, physical, physical association 19615732 , 21804599 , 27880917 , (Europe PMC )0.70 BioGRID, IntAct SLC9A3R2 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct SNX27 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct SUGT1 Affinity Capture-MS physical 27880917 , (Europe PMC )NA BioGRID USP1 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27463890 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct USP12 Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 19615732 , 25216524 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct USP46 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 26186194 , 27880917 , 28514442 , (Europe PMC )0.40 BioGRID, IntAct VAT1 Affinity Capture-MS, anti tag coimmunoprecipitation physical, physical association 19615732 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct WDR20 Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation physical, physical association 19615732 , 25216524 , 27880917 , (Europe PMC )0.40 BioGRID, IntAct WDR48 Affinity Capture-MS, Affinity Capture-Western, anti tag coimmunoprecipitation, pull down association, physical, physical association 19615732 , 25216524 , 27463890 , 27880917 , 28330616 , (Europe PMC )0.56 BioGRID, IntAct
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