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Q9WTR8

- PHLP1_RAT

UniProt

Q9WTR8 - PHLP1_RAT

Protein

PH domain leucine-rich repeat protein phosphatase 1

Gene

Phlpp1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 101 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
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    Functioni

    Protein phosphatase that mediates dephosphorylation of 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser-657' of PRKCA. AKT1 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 AKT1 triggers apoptosis and suppression of tumor growth. Controls the phosphorylation of AKT2 and AKT3 more efficiently than that of AKT1. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Inhibits cancer cell proliferation and may act as a tumor suppressor By similarity. May act as a negative regulator of K-Ras signaling in membrane rafts.By similarity

    Catalytic activityi

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

    Cofactori

    Binds 2 manganese ions per subunit.By similarity

    Enzyme regulationi

    Insensitive to okadaic acid.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi1173 – 11731Manganese 1By similarity
    Metal bindingi1173 – 11731Manganese 2By similarity
    Metal bindingi1174 – 11741Manganese 1; via carbonyl oxygenBy similarity
    Metal bindingi1337 – 13371Manganese 2By similarity
    Metal bindingi1376 – 13761Manganese 2By similarity

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. protein serine/threonine phosphatase activity Source: RGD

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. circadian rhythm Source: RGD
    3. protein dephosphorylation Source: RGD

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Biological processi

    Apoptosis

    Keywords - Ligandi

    Manganese, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    PH domain leucine-rich repeat 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
    Gene namesi
    Name:Phlpp1
    Synonyms:Phlpp, Plekhe1, Scop
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi621308. Phlpp1.

    Subcellular locationi

    Cytoplasm 1 Publication. Membrane 1 Publication; Peripheral membrane protein 1 Publication. Nucleus By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. membrane Source: UniProtKB-SubCell
    3. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 16961696PH domain leucine-rich repeat protein phosphatase 1PRO_0000057783Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiQ9WTR8.
    PRIDEiQ9WTR8.

    Expressioni

    Tissue specificityi

    Mainly present in brain (at protein level).1 Publication

    Developmental stagei

    In the suprachiasmatic nucleus, it increases during subjective night with a peak at midnight under constant dark conditions. Expressed at a constant level in neurons throughout the brain (at protein level).1 Publication

    Gene expression databases

    GenevestigatoriQ9WTR8.

    Interactioni

    Subunit structurei

    Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats. Interacts with AKT2, AKT3 and PRKCB isoform beta-II By similarity.By similarity

    Protein-protein interaction databases

    BioGridi248740. 1 interaction.
    IntActiQ9WTR8. 2 interactions.
    STRINGi10116.ENSRNOP00000003840.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9WTR8.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini499 – 599101PHPROSITE-ProRule annotationAdd
    BLAST
    Repeati601 – 62222LRR 1Add
    BLAST
    Repeati624 – 64522LRR 2Add
    BLAST
    Repeati655 – 67622LRR 3Add
    BLAST
    Repeati678 – 69922LRR 4Add
    BLAST
    Repeati701 – 72222LRR 5Add
    BLAST
    Repeati724 – 74623LRR 6Add
    BLAST
    Repeati836 – 85722LRR 7Add
    BLAST
    Repeati858 – 87922LRR 8Add
    BLAST
    Repeati881 – 90222LRR 9Add
    BLAST
    Repeati904 – 92522LRR 10Add
    BLAST
    Repeati926 – 94722LRR 11Add
    BLAST
    Repeati950 – 97122LRR 12Add
    BLAST
    Repeati976 – 99621LRR 13Add
    BLAST
    Repeati1000 – 102122LRR 14Add
    BLAST
    Repeati1024 – 104522LRR 15Add
    BLAST
    Repeati1047 – 106822LRR 16Add
    BLAST
    Repeati1069 – 109022LRR 17Add
    BLAST
    Repeati1092 – 111322LRR 18Add
    BLAST
    Domaini1128 – 1383256PP2C-likeAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi1694 – 16963PDZ-binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi4 – 96Poly-Ala
    Compositional biasi21 – 288Poly-Ala
    Compositional biasi116 – 12611Poly-SerAdd
    BLAST
    Compositional biasi339 – 3435Poly-Ser
    Compositional biasi405 – 4106Poly-Ala
    Compositional biasi1431 – 14344Poly-Ser
    Compositional biasi1645 – 166117Poly-GlnAdd
    BLAST
    Compositional biasi1662 – 16698Poly-Pro

    Domaini

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

    Sequence similaritiesi

    Contains 18 LRR (leucine-rich) repeats.Curated
    Contains 1 PH domain.PROSITE-ProRule annotation
    Contains 1 PP2C-like domain.Curated

    Keywords - Domaini

    Leucine-rich repeat, Repeat

    Phylogenomic databases

    eggNOGiCOG4886.
    HOGENOMiHOG000115529.
    InParanoidiQ9WTR8.
    KOiK16340.
    PhylomeDBiQ9WTR8.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    3.60.40.10. 1 hit.
    InterProiIPR001611. Leu-rich_rpt.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR001932. PP2C-like_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.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9WTR8-1 [UniParc]FASTAAdd to Basket

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    MEPAAAAPAQ RLADPTGEDR APAAAAAAEG GRSPDSVLSA AAPSGGNGGA     50
    AREEAPCEAP PGPLPGRAGG TGRRRRRGVP QPAAGGAAPV TAAGGGANSL 100
    LLRRGRLKRN LSAAASSSSS PSSASSAAGG LPASCSASAS LCTRSLDRKT 150
    LLQKHRQLLQ LQPSDRDWVR HQLQRGCVHV FDRHMASSYL RPVLCTLDTT 200
    AAEVAARLLQ LGHKGGGVVK VLGHGPPPAA APAASDQTPA TELGRDVEPP 250
    PSSSTVGAVR GPARAPPADL PLPGGAWTRC APRVNPAPSD SSPGELFAGG 300
    PCSPSRAPRP ASDTESFSLS PSAESVSDRL DPYSSGGGSS SSSEELEADP 350
    ATVLTGPSGP PHHPVRSSQP RPPSPKTSAL LQPKAPTGVD GTGLVVGEGP 400
    GDDKAVAAAA PGVPLWTPGR IRETVQKTSS PPSLYVQLHG ETTRRLEADE 450
    KPLQIQNDYL FQLGFGELWR VQEEGMDSEI GCLIRFYAGK PHSTGSSERI 500
    QLSGMYNVRK GKMQLPVNRW TRRQVILCGT CLIVSSVKDS SSGKMHVLPL 550
    IGGKVEEVKK HQHCLAFSSS GPQSQTYYIC FDTFTEYLRW LRQVSKVASQ 600
    RISSVDLSCC SLEHLPANLF YSQDLTHLNL KQNFLRQNPS LPAARGLGEL 650
    QRFTKLKSLN LSNNHLGAFP SAVCSIPTLA ELNVSCNALQ EVPAAVGAMQ 700
    NLQTFLLDGN FLQSLPAELE NMHQLSYLGL SFNEFTDIPE VLEKLTAVDK 750
    LCMAGNCMET LRLQALRRMP HIKHVDLRLN ILRKLITDEV DFLQHVTQLD 800
    LRDNKLGDLD AMIFNNIEVL HCERNQLVTL NICGYFLKAL YASSNELVQL 850
    DVYPVPNYLS YMDVSRNCLE SVPEWVCESR KLEVLDIGHN QICELPARLF 900
    CNSSLRKLLA GHNRLARLPE RLERTSVEVL DVQHNQIIEL PPNLLMKADS 950
    LRFLNASANK LETLPPATLS EETSSILQEL YLTNNSLTDK CVPLLTGHPR 1000
    LKILHMAYNR LQSFPASKMA KLEELEEIDI SGNKLKAIPT TIMNCRRMHT 1050
    VIAHSNCIEV FPEVMQLPEV KCVDLSCNEL SEITLPENLP PKLQELDLTG 1100
    NPRLALDHKS LELLNNIRCF KIDQPSAGDA SGAPAVWSHG YTEASGVKNK 1150
    LCVAALSVNN FRDNREALYG VFDGDRNVEV PYLLQCTMSD ILAEELQKTK 1200
    NEEEYMVNTF IVMQRKLGTA GQKLGGAAVL CHIRHDPVDL GGSFTLTSAN 1250
    VGKCQTVLCR NGKPLSLSRS YTMSCEEERK RIKQHKAIIT EDGKVNGVTE 1300
    STRILGYTFL HPSVVPRPHV QSVLLTPQDE FFILGSKGLW DSLSIEEAVE 1350
    AVRNVPDALA AAKKLCTLAQ SYGCHDSISA VVVQLSVTED SFCCCELSVG 1400
    GSMPPPSPGI FPPSVSMVIK DRPSDGLGVP SSSSGMASEI SSELSTSEMS 1450
    SEVGSTASDE PPSGALSESS PAYPSEQRCM LHPVCLSNSF QRQLSSATFS 1500
    SAFSDNGLDS DDEEPIEGVF SNGSRVEVEV DIHCSRAKEK ERQQHLLQVP 1550
    AEASDEGIVI SANEDESGLS KKTDISAVGT IGRRRANGSV PPQERSHNVI 1600
    EVATDAPLRK PGGYFAAPAQ PDPDDQFIIP PELEEEVKEI MKHHQEQQQQ 1650
    QQQQQQQQQQ QPPPPPQPPQ AQAQAQAQAQ RPFQMDHLPD CYDTPL 1696
    Length:1,696
    Mass (Da):183,364
    Last modified:November 1, 1999 - v1
    Checksum:iB4C3CC777B8BB6A9
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB023624 mRNA. Translation: BAA77767.1.
    RefSeqiNP_067689.1. NM_021657.1.
    UniGeneiRn.163214.

    Genome annotation databases

    GeneIDi59265.
    KEGGirno:59265.
    UCSCiRGD:621308. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB023624 mRNA. Translation: BAA77767.1 .
    RefSeqi NP_067689.1. NM_021657.1.
    UniGenei Rn.163214.

    3D structure databases

    ProteinModelPortali Q9WTR8.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 248740. 1 interaction.
    IntActi Q9WTR8. 2 interactions.
    STRINGi 10116.ENSRNOP00000003840.

    Proteomic databases

    PaxDbi Q9WTR8.
    PRIDEi Q9WTR8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 59265.
    KEGGi rno:59265.
    UCSCi RGD:621308. rat.

    Organism-specific databases

    CTDi 23239.
    RGDi 621308. Phlpp1.

    Phylogenomic databases

    eggNOGi COG4886.
    HOGENOMi HOG000115529.
    InParanoidi Q9WTR8.
    KOi K16340.
    PhylomeDBi Q9WTR8.

    Miscellaneous databases

    NextBioi 611783.
    PROi Q9WTR8.

    Gene expression databases

    Genevestigatori Q9WTR8.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    3.60.40.10. 1 hit.
    InterProi IPR001611. Leu-rich_rpt.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR001932. PP2C-like_dom.
    [Graphical view ]
    Pfami PF00560. LRR_1. 2 hits.
    PF13855. LRR_8. 2 hits.
    PF00481. PP2C. 1 hit.
    [Graphical view ]
    SMARTi SM00233. PH. 1 hit.
    SM00332. PP2Cc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF81606. SSF81606. 1 hit.
    PROSITEi PS51450. LRR. 17 hits.
    PS50003. PH_DOMAIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "SCOP, a novel gene product expressed in a circadian manner in rat suprachiasmatic nucleus."
      Shimizu K., Okada M., Takano A., Nagai K.
      FEBS Lett. 458:363-369(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
      Tissue: Brain.
    2. "Suprachiasmatic nucleus circadian oscillatory protein, a novel binding partner of K-Ras in the membrane rafts, negatively regulates MAPK pathway."
      Shimizu K., Okada M., Nagai K., Fukada Y.
      J. Biol. Chem. 278:14920-14925(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH KRAS.

    Entry informationi

    Entry nameiPHLP1_RAT
    AccessioniPrimary (citable) accession number: Q9WTR8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 7, 2005
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 101 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3