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Protein

PH domain leucine-rich repeat-containing protein phosphatase 1

Gene

PHLPP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T cells (By similarity).By similarity6 Publications

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.2 Publications

Cofactori

Mn2+By similarityNote: Binds 2 manganese ions per subunit (By similarity). Mn2+ is inhibitory below pH 8 and activating above pH 8 (PubMed:24892992).By similarity1 Publication

Enzyme regulationi

Insensitive to okadaic acid.1 Publication

Kineticsi

  1. KM=1.5 mM for p-nitrophenyl phosphate1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi1210 – 12101Manganese 1By similarity
    Metal bindingi1210 – 12101Manganese 2By similarity
    Metal bindingi1211 – 12111Manganese 1; via carbonyl oxygenBy similarity
    Metal bindingi1374 – 13741Manganese 2By similarity
    Metal bindingi1413 – 14131Manganese 2By similarity

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Biological processi

    Apoptosis

    Keywords - Ligandi

    Manganese, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_12447. Negative regulation of the PI3K/AKT network.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    PH domain leucine-rich repeat-containing protein phosphatase 1 (EC:3.1.3.16)
    Alternative name(s):
    Pleckstrin homology domain-containing family E member 1
    Short name:
    PH domain-containing family E member 1
    Suprachiasmatic nucleus circadian oscillatory protein
    Short name:
    hSCOP
    Gene namesi
    Name:PHLPP1
    Synonyms:KIAA0606, PHLPP, PLEKHE1, SCOP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 18

    Organism-specific databases

    HGNCiHGNC:20610. PHLPP1.

    Subcellular locationi

    Isoform 2 :

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1715 – 17173Missing : Loss of function in vivo, but does not abolishes intrinsic phosphatase activity. 1 Publication

    Keywords - Diseasei

    Tumor suppressor

    Organism-specific databases

    PharmGKBiPA165429055.

    Polymorphism and mutation databases

    BioMutaiPHLPP1.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 17171717PH domain leucine-rich repeat-containing protein phosphatase 1PRO_0000057781Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiO60346.
    PaxDbiO60346.
    PeptideAtlasiO60346.
    PRIDEiO60346.

    PTM databases

    DEPODiO60346.
    PhosphoSiteiO60346.

    Expressioni

    Tissue specificityi

    In colorectal cancer tissue, expression is highest in the surface epithelium of normal colonic mucosa adjacent to the cancer tissue but is largely excluded from the crypt bases. Expression is lost or significantly decreased in 78% of tested tumors (at protein level). Ubiquitously expressed in non-cancerous tissues.2 Publications

    Gene expression databases

    BgeeiO60346.
    CleanExiHS_PHLPP.
    ExpressionAtlasiO60346. baseline and differential.
    GenevisibleiO60346. HS.

    Organism-specific databases

    HPAiHPA020200.

    Interactioni

    Subunit structurei

    Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats (By similarity). Interacts with AKT2, AKT3, PRKCB isoform beta-II, STK4, RPS6KB1, RAF1 (PubMed:17386267, PubMed:18162466, PubMed:19732725, PubMed:21986499, PubMed:24530606). Isoform 1 (predominantly) and isoform 2 interact with BRAP (PubMed:25820252). Interacts with FKBP5; FKBP5 acts as a scaffold for PHLPP1 and Akt (PubMed:19732725). Interacts with SCRIB; SCRIB acts as a scaffold for PHLPP1 and Akt (PubMed:21701506). Interacts with SLC9A3R1; SLC9A3R1 scaffolds a heterotrimeric complex with PTEN at the plasma membrane (PubMed:21804599).By similarity9 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PRKCBP05771-25EBI-2511516,EBI-5774511
    SCRIBQ141602EBI-2511516,EBI-357345
    ScribQ80U722EBI-2511516,EBI-1766028From a different organism.

    Protein-protein interaction databases

    BioGridi116843. 24 interactions.
    IntActiO60346. 20 interactions.
    MINTiMINT-2796653.
    STRINGi9606.ENSP00000262719.

    Structurei

    3D structure databases

    ProteinModelPortaliO60346.
    SMRiO60346. Positions 626-1160, 1205-1422.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini536 – 636101PHPROSITE-ProRule annotationAdd
    BLAST
    Repeati638 – 65922LRR 1Add
    BLAST
    Repeati661 – 68222LRR 2Add
    BLAST
    Repeati692 – 71221LRR 3Add
    BLAST
    Repeati715 – 73622LRR 4Add
    BLAST
    Repeati738 – 76023LRR 5Add
    BLAST
    Repeati761 – 78323LRR 6Add
    BLAST
    Repeati784 – 80421LRR 7Add
    BLAST
    Repeati808 – 83124LRR 8Add
    BLAST
    Repeati832 – 85322LRR 9Add
    BLAST
    Repeati873 – 89422LRR 10Add
    BLAST
    Repeati895 – 91622LRR 11Add
    BLAST
    Repeati918 – 93922LRR 12Add
    BLAST
    Repeati941 – 96222LRR 13Add
    BLAST
    Repeati963 – 98422LRR 14Add
    BLAST
    Repeati987 – 100822LRR 15Add
    BLAST
    Repeati1013 – 103321LRR 16Add
    BLAST
    Repeati1037 – 105822LRR 17Add
    BLAST
    Repeati1061 – 108222LRR 18Add
    BLAST
    Repeati1084 – 110522LRR 19Add
    BLAST
    Repeati1106 – 112722LRR 20Add
    BLAST
    Repeati1129 – 115022LRR 21Add
    BLAST
    Domaini1175 – 1422248PPM-type phosphatasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1076 – 1205130Interaction with SLC9A3R11 PublicationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi1715 – 17173PDZ-binding; required for interaction with SLC9A3R11 Publication

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi4 – 74Poly-Ala
    Compositional biasi21 – 4525Poly-AlaAdd
    BLAST
    Compositional biasi132 – 1376Poly-Ala
    Compositional biasi138 – 1447Poly-Ser
    Compositional biasi145 – 1484Poly-Ala
    Compositional biasi254 – 2574Poly-Ala
    Compositional biasi463 – 4697Poly-Pro
    Compositional biasi1682 – 16898Poly-Gln

    Domaini

    The PH domain is required for interaction with PRKCB and its dephosphorylation.

    Sequence similaritiesi

    Contains 21 LRR (leucine-rich) repeats.Curated
    Contains 1 PH domain.PROSITE-ProRule annotation
    Contains 1 PPM-type phosphatase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Leucine-rich repeat, Repeat

    Phylogenomic databases

    eggNOGiCOG4886.
    GeneTreeiENSGT00440000037833.
    InParanoidiO60346.
    KOiK16340.
    OMAiFTNGSRV.
    OrthoDBiEOG7RFTGK.
    PhylomeDBiO60346.
    TreeFamiTF315993.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    3.60.40.10. 1 hit.
    InterProiIPR001611. Leu-rich_rpt.
    IPR011993. PH-like_dom.
    IPR001849. PH_domain.
    IPR001932. PPM-type_phosphatase_dom.
    [Graphical view]
    PfamiPF00560. LRR_1. 2 hits.
    PF13855. LRR_8. 2 hits.
    PF00481. PP2C. 1 hit.
    [Graphical view]
    SMARTiSM00233. PH. 1 hit.
    SM00332. PP2Cc. 1 hit.
    [Graphical view]
    SUPFAMiSSF81606. SSF81606. 1 hit.
    PROSITEiPS51450. LRR. 17 hits.
    PS50003. PH_DOMAIN. 1 hit.
    PS51746. PPM_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: O60346-1) [UniParc]FASTAAdd to basket

    Also known as: beta

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MEPAAAATVQ RLPELGREDR ASAPAAAAAA AAAAAAAAAA LAAAAGGGRS
    60 70 80 90 100
    PEPALTPAAP SGGNGSGSGA REEAPGEAPP GPLPGRAGGA GRRRRRGAPQ
    110 120 130 140 150
    PIAGGAAPVP GAGGGANSLL LRRGRLKRNL SAAAAAASSS SSSSAAAASH
    160 170 180 190 200
    SPGAAGLPAS CSASASLCTR SLDRKTLLLK HRQTLQLQPS DRDWVRHQLQ
    210 220 230 240 250
    RGCVHVFDRH MASTYLRPVL CTLDTTAGEV AARLLQLGHK GGGVVKVLGQ
    260 270 280 290 300
    GPGAAAAREP AEPPPEAGPR LAPPEPRDSE VPPARSAPGA FGGPPRAPPA
    310 320 330 340 350
    DLPLPVGGPG GWSRRASPAP SDSSPGEPFV GGPVSSPRAP RPVVSDTESF
    360 370 380 390 400
    SLSPSAESVS DRLDPYSSGG GSSSSSEELE ADAASAPTGV PGQPRRPGHP
    410 420 430 440 450
    AQPLPLPQTA SSPQPQQKAP RAIDSPGGAV REGSCEEKAA AAVAPGGLQS
    460 470 480 490 500
    TPGRSGVTAE KAPPPPPPPT LYVQLHGETT RRLEAEEKPL QIQNDYLFQL
    510 520 530 540 550
    GFGELWRVQE EGMDSEIGCL IRFYAGKPHS TGSSERIQLS GMYNVRKGKM
    560 570 580 590 600
    QLPVNRWTRR QVILCGTCLI VSSVKDSLTG KMHVLPLIGG KVEEVKKHQH
    610 620 630 640 650
    CLAFSSSGPQ SQTYYICFDT FTEYLRWLRQ VSKVASQRIS SVDLSCCSLE
    660 670 680 690 700
    HLPANLFYSQ DLTHLNLKQN FLRQNPSLPA ARGLNELQRF TKLKSLNLSN
    710 720 730 740 750
    NHLGDFPLAV CSIPTLAELN VSCNALRSVP AAVGVMHNLQ TFLLDGNFLQ
    760 770 780 790 800
    SLPAELENMK QLSYLGLSFN EFTDIPEVLE KLTAVDKLCM SGNCVETLRL
    810 820 830 840 850
    QALRKMPHIK HVDLRLNVIR KLIADEVDFL QHVTQLDLRD NKLGDLDAMI
    860 870 880 890 900
    FNNIEVLHCE RNQLVTLDIC GYFLKALYAS SNELVQLDVY PVPNYLSYMD
    910 920 930 940 950
    VSRNRLENVP EWVCESRKLE VLDIGHNQIC ELPARLFCNS SLRKLLAGHN
    960 970 980 990 1000
    QLARLPERLE RTSVEVLDVQ HNQLLELPPN LLMKADSLRF LNASANKLES
    1010 1020 1030 1040 1050
    LPPATLSEET NSILQELYLT NNSLTDKCVP LLTGHPHLKI LHMAYNRLQS
    1060 1070 1080 1090 1100
    FPASKMAKLE ELEEIDLSGN KLKAIPTTIM NCRRMHTVIA HSNCIEVFPE
    1110 1120 1130 1140 1150
    VMQLPEIKCV DLSCNELSEV TLPENLPPKL QELDLTGNPR LVLDHKTLEL
    1160 1170 1180 1190 1200
    LNNIRCFKID QPSTGDASGA PAVWSHGYTE ASGVKNKLCV AALSVNNFCD
    1210 1220 1230 1240 1250
    NREALYGVFD GDRNVEVPYL LQCTMSDILA EELQKTKNEE EYMVNTFIVM
    1260 1270 1280 1290 1300
    QRKLGTAGQK LGGAAVLCHI KHDPVDPGGS FTLTSANVGK CQTVLCRNGK
    1310 1320 1330 1340 1350
    PLPLSRSYIM SCEEELKRIK QHKAIITEDG KVNGVTESTR ILGYTFLHPS
    1360 1370 1380 1390 1400
    VVPRPHVQSV LLTPQDEFFI LGSKGLWDSL SVEEAVEAVR NVPDALAAAK
    1410 1420 1430 1440 1450
    KLCTLAQSYG CHDSISAVVV QLSVTEDSFC CCELSAGGAV PPPSPGIFPP
    1460 1470 1480 1490 1500
    SVNMVIKDRP SDGLGVPSSS SGMASEISSE LSTSEMSSEV GSTASDEPPP
    1510 1520 1530 1540 1550
    GALSENSPAY PSEQRCMLHP ICLSNSFQRQ LSSATFSSAF SDNGLDSDDE
    1560 1570 1580 1590 1600
    EPIEGVFTNG SRVEVEVDIH CSRAKEKEKQ QHLLQVPAEA SDEGIVISAN
    1610 1620 1630 1640 1650
    EDEPGLPRKA DFSAVGTIGR RRANGSVAPQ ERSHNVIEVA TDAPLRKPGG
    1660 1670 1680 1690 1700
    YFAAPAQPDP DDQFIIPPEL EEEVKEIMKH HQEQQQQQQP PPPPQLQPQL
    1710
    PRHYQLDQLP DYYDTPL
    Length:1,717
    Mass (Da):184,672
    Last modified:June 7, 2005 - v3
    Checksum:iA4AB53F334EA8AB6
    GO
    Isoform 2 (identifier: O60346-2) [UniParc]FASTAAdd to basket

    Also known as: alpha

    The sequence of this isoform differs from the canonical sequence as follows:
         1-512: Missing.

    Show »
    Length:1,205
    Mass (Da):133,565
    Checksum:iCDBECB2FDA9C7064
    GO

    Sequence cautioni

    The sequence AAH14927.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence AAH82244.1 differs from that shown.Contaminating sequence. Potential poly-A sequence.Curated
    The sequence AAI26278.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence BAA91980.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti691 – 6911T → A in BAA91980 (PubMed:14702039).Curated
    Sequence conflicti1062 – 10621L → F in AAH47653 (PubMed:15489334).Curated
    Sequence conflicti1083 – 10831R → S in BAA25532 (PubMed:9628581).Curated
    Sequence conflicti1227 – 12271D → V in BAA91980 (PubMed:14702039).Curated
    Sequence conflicti1490 – 14901V → M in AAH47653 (PubMed:15489334).Curated
    Sequence conflicti1580 – 15801Missing in AAH63519 (PubMed:15489334).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti1118 – 11181S → T.
    Corresponds to variant rs9950585 [ dbSNP | Ensembl ].
    VAR_056725

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 512512Missing in isoform 2. VSP_057809Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AC015989 Genomic DNA. No translation available.
    AC022046 Genomic DNA. No translation available.
    AC027553 Genomic DNA. No translation available.
    AB011178 mRNA. Translation: BAA25532.2.
    BC010706 mRNA. Translation: AAH10706.1.
    BC014927 mRNA. Translation: AAH14927.3. Different initiation.
    BC047653 mRNA. Translation: AAH47653.1.
    BC063519 mRNA. Translation: AAH63519.1.
    BC082244 mRNA. Translation: AAH82244.1. Sequence problems.
    BC126277 mRNA. Translation: AAI26278.1. Different initiation.
    AK001924 mRNA. Translation: BAA91980.1. Different initiation.
    CCDSiCCDS45881.2.
    PIRiT00258.
    RefSeqiNP_919431.2. NM_194449.3.
    UniGeneiHs.465337.

    Genome annotation databases

    EnsembliENST00000262719; ENSP00000262719; ENSG00000081913.
    GeneIDi23239.
    KEGGihsa:23239.
    UCSCiuc021ule.1. human.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AC015989 Genomic DNA. No translation available.
    AC022046 Genomic DNA. No translation available.
    AC027553 Genomic DNA. No translation available.
    AB011178 mRNA. Translation: BAA25532.2.
    BC010706 mRNA. Translation: AAH10706.1.
    BC014927 mRNA. Translation: AAH14927.3. Different initiation.
    BC047653 mRNA. Translation: AAH47653.1.
    BC063519 mRNA. Translation: AAH63519.1.
    BC082244 mRNA. Translation: AAH82244.1. Sequence problems.
    BC126277 mRNA. Translation: AAI26278.1. Different initiation.
    AK001924 mRNA. Translation: BAA91980.1. Different initiation.
    CCDSiCCDS45881.2.
    PIRiT00258.
    RefSeqiNP_919431.2. NM_194449.3.
    UniGeneiHs.465337.

    3D structure databases

    ProteinModelPortaliO60346.
    SMRiO60346. Positions 626-1160, 1205-1422.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116843. 24 interactions.
    IntActiO60346. 20 interactions.
    MINTiMINT-2796653.
    STRINGi9606.ENSP00000262719.

    PTM databases

    DEPODiO60346.
    PhosphoSiteiO60346.

    Polymorphism and mutation databases

    BioMutaiPHLPP1.

    Proteomic databases

    MaxQBiO60346.
    PaxDbiO60346.
    PeptideAtlasiO60346.
    PRIDEiO60346.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000262719; ENSP00000262719; ENSG00000081913.
    GeneIDi23239.
    KEGGihsa:23239.
    UCSCiuc021ule.1. human.

    Organism-specific databases

    CTDi23239.
    GeneCardsiGC18P060382.
    H-InvDBHIX0014494.
    HIX0174202.
    HGNCiHGNC:20610. PHLPP1.
    HPAiHPA020200.
    MIMi609396. gene.
    neXtProtiNX_O60346.
    PharmGKBiPA165429055.
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG4886.
    GeneTreeiENSGT00440000037833.
    InParanoidiO60346.
    KOiK16340.
    OMAiFTNGSRV.
    OrthoDBiEOG7RFTGK.
    PhylomeDBiO60346.
    TreeFamiTF315993.

    Enzyme and pathway databases

    ReactomeiREACT_12447. Negative regulation of the PI3K/AKT network.

    Miscellaneous databases

    ChiTaRSiPHLPP1. human.
    GeneWikiiPHLPP_(gene).
    GenomeRNAii23239.
    NextBioi44894.
    PROiO60346.
    SOURCEiSearch...

    Gene expression databases

    BgeeiO60346.
    CleanExiHS_PHLPP.
    ExpressionAtlasiO60346. baseline and differential.
    GenevisibleiO60346. HS.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    3.60.40.10. 1 hit.
    InterProiIPR001611. Leu-rich_rpt.
    IPR011993. PH-like_dom.
    IPR001849. PH_domain.
    IPR001932. PPM-type_phosphatase_dom.
    [Graphical view]
    PfamiPF00560. LRR_1. 2 hits.
    PF13855. LRR_8. 2 hits.
    PF00481. PP2C. 1 hit.
    [Graphical view]
    SMARTiSM00233. PH. 1 hit.
    SM00332. PP2Cc. 1 hit.
    [Graphical view]
    SUPFAMiSSF81606. SSF81606. 1 hit.
    PROSITEiPS51450. LRR. 17 hits.
    PS50003. PH_DOMAIN. 1 hit.
    PS51746. PPM_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    2. "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
      Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 349-1717.
      Tissue: Brain.
    3. "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
      Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
      DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SEQUENCE REVISION.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 475-1717.
      Tissue: Cerebellum, Hippocampus, Lymphoma, Melanoma and Retinoblastoma.
    5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 495-1233.
      Tissue: Placenta.
    6. "PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth."
      Gao T., Furnari F., Newton A.C.
      Mol. Cell 18:13-24(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME ACTIVITY, COFACTOR, ENZYME REGULATION, TISSUE SPECIFICITY, MUTAGENESIS OF 1715-THR--LEU-1717.
    7. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    8. "PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms."
      Brognard J., Sierecki E., Gao T., Newton A.C.
      Mol. Cell 25:917-931(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, INTERACTION WITH AKT2 AND AKT3.
    9. "The phosphatase PHLPP controls the cellular levels of protein kinase C."
      Gao T., Brognard J., Newton A.C.
      J. Biol. Chem. 283:6300-6311(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH PRKCB.
    10. "FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt."
      Pei H., Li L., Fridley B.L., Jenkins G.D., Kalari K.R., Lingle W., Petersen G., Lou Z., Wang L.
      Cancer Cell 16:259-266(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FKBP5; AKT2 AND AKT3.
    11. "Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis."
      Liu J., Weiss H.L., Rychahou P., Jackson L.N., Evers B.M., Gao T.
      Oncogene 28:994-1004(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    12. "Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis."
      Qiao M., Wang Y., Xu X., Lu J., Dong Y., Tao W., Stein J., Stein G.S., Iglehart J.D., Shi Q., Pardee A.B.
      Mol. Cell 38:512-523(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH STK4.
    13. "Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt."
      Li X., Yang H., Liu J., Schmidt M.D., Gao T.
      EMBO Rep. 12:818-824(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SCRIB.
    14. "PHLPP-mediated dephosphorylation of S6K1 inhibits protein translation and cell growth."
      Liu J., Stevens P.D., Li X., Schmidt M.D., Gao T.
      Mol. Cell. Biol. 31:4917-4927(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RPS6KB1.
    15. "PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma."
      Molina J.R., Agarwal N.K., Morales F.C., Hayashi Y., Aldape K.D., Cote G., Georgescu M.M.
      Oncogene 31:1264-1274(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SLC9A3R1.
    16. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    17. "Biochemical characterization of the phosphatase domain of the tumor suppressor PH domain leucine-rich repeat protein phosphatase."
      Sierecki E., Newton A.C.
      Biochemistry 53:3971-3981(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR.
    18. "PHLPP is a negative regulator of RAF1, which reduces colorectal cancer cell motility and prevents tumor progression in mice."
      Li X., Stevens P.D., Liu J., Yang H., Wang W., Wang C., Zeng Z., Schmidt M.D., Yang M., Lee E.Y., Gao T.
      Gastroenterology 146:1301-1310(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RAF1.
    19. "Interactome of the negative regulator of nuclear import BRCA1-binding protein 2."
      Fatima S., Wagstaff K.M., Loveland K.L., Jans D.A.
      Sci. Rep. 5:9459-9459(2015) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH BRAP.

    Entry informationi

    Entry nameiPHLP1_HUMAN
    AccessioniPrimary (citable) accession number: O60346
    Secondary accession number(s): A1A4F5
    , Q641Q7, Q6P4C4, Q6PJI6, Q86TN6, Q96FK2, Q9NUY1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 7, 2005
    Last sequence update: June 7, 2005
    Last modified: July 22, 2015
    This is version 145 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 18
      Human chromosome 18: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.