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Q8CHE4

- PHLP1_MOUSE

UniProt

Q8CHE4 - PHLP1_MOUSE

Protein

PH domain leucine-rich repeat-containing protein phosphatase 1

Gene

Phlpp1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 2 (07 Jun 2005)
      Previous versions | rss
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    Functioni

    Protein phosphatase that mediates dephosphorylation of 'Ser-473' of AKT1, 'Ser-660' of PRKCB, 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. May act as a negative regulator of K-Ras signaling in membrane rafts By similarity.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 bindingi1166 – 11661Manganese 1By similarity
    Metal bindingi1166 – 11661Manganese 2By similarity
    Metal bindingi1167 – 11671Manganese 1; via carbonyl oxygenBy similarity
    Metal bindingi1330 – 13301Manganese 2By similarity
    Metal bindingi1369 – 13691Manganese 2By similarity

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. phosphoprotein phosphatase activity Source: UniProtKB-KW

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. entrainment of circadian clock Source: MGI

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Biological processi

    Apoptosis

    Keywords - Ligandi

    Manganese, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_214733. 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
    Gene namesi
    Name:Phlpp1
    Synonyms:Kiaa0606, Phlpp, Plekhe1, Scop
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 1

    Organism-specific databases

    MGIiMGI:2138327. Phlpp1.

    Subcellular locationi

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 16871687PH domain leucine-rich repeat-containing protein phosphatase 1PRO_0000057782Add
    BLAST

    Amino acid modifications

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

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiQ8CHE4.
    PRIDEiQ8CHE4.

    PTM databases

    PhosphoSiteiQ8CHE4.

    Expressioni

    Inductioni

    Up-regulated in the hippocampus upon chronic methamphetamine treatment.1 Publication

    Gene expression databases

    BgeeiQ8CHE4.
    GenevestigatoriQ8CHE4.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    IntActiQ8CHE4. 1 interaction.
    MINTiMINT-4997715.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CHE4.
    SMRiQ8CHE4. Positions 598-1378.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini492 – 592101PHPROSITE-ProRule annotationAdd
    BLAST
    Repeati594 – 61522LRR 1Add
    BLAST
    Repeati617 – 63822LRR 2Add
    BLAST
    Repeati648 – 66922LRR 3Add
    BLAST
    Repeati671 – 69222LRR 4Add
    BLAST
    Repeati694 – 71522LRR 5Add
    BLAST
    Repeati717 – 73923LRR 6Add
    BLAST
    Repeati740 – 76021LRR 7Add
    BLAST
    Repeati764 – 78522LRR 8Add
    BLAST
    Repeati788 – 80922LRR 9Add
    BLAST
    Repeati829 – 85022LRR 10Add
    BLAST
    Repeati851 – 87222LRR 11Add
    BLAST
    Repeati874 – 89522LRR 12Add
    BLAST
    Repeati897 – 91822LRR 13Add
    BLAST
    Repeati919 – 94022LRR 14Add
    BLAST
    Repeati943 – 96422LRR 15Add
    BLAST
    Repeati969 – 98921LRR 16Add
    BLAST
    Repeati993 – 101422LRR 17Add
    BLAST
    Repeati1017 – 103822LRR 18Add
    BLAST
    Repeati1040 – 106122LRR 19Add
    BLAST
    Repeati1062 – 108322LRR 20Add
    BLAST
    Repeati1085 – 110622LRR 21Add
    BLAST
    Domaini1121 – 1376256PP2C-likeAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi1685 – 16873PDZ-binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi4 – 96Poly-Ala
    Compositional biasi21 – 277Poly-Ala
    Compositional biasi112 – 1165Poly-Ala
    Compositional biasi337 – 3404Poly-Gly
    Compositional biasi341 – 3455Poly-Ser
    Compositional biasi399 – 4046Poly-Ala
    Compositional biasi1424 – 14274Poly-Ser
    Compositional biasi1638 – 164811Poly-GlnAdd
    BLAST

    Domaini

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

    Sequence similaritiesi

    Contains 21 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.
    GeneTreeiENSGT00440000037833.
    HOGENOMiHOG000115529.
    InParanoidiQ8CHE4.
    KOiK16340.
    OMAiFTNGSRV.
    OrthoDBiEOG7RFTGK.
    PhylomeDBiQ8CHE4.
    TreeFamiTF315993.

    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. 3 hits.
    PF13855. LRR_8. 1 hit.
    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.

    Q8CHE4-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEPAAAAPAQ RLADPTGEDQ ALAAAAAEGG RCPDPALSAA APSGGNGGAA     50
    REEAPCEAPP GPLPGRAGGT GRRRRRGAPQ PAAGGAAPVP AAGGGANSLL 100
    LKRGRLKRNL SAAAAASSSS SPSSASSAAG GLPASCSASA SLCTRSLDRK 150
    TLLLKHRQLL QLQPSDRDWV RHQLQRGCVH VFDRHMASSY LRPVLCTLDT 200
    TAAEVAARLL QLGHKGGGVV KVLGYGPPPA AAPAASDQTL DGEHGRDVEP 250
    PPSSGTVGAV RGPARAPPAD LPLPGGAWTR CAPRISPAPS DSSPGELFAG 300
    GPGSPPRAPR PASDTESFSL SPSAESVSDR LDPYSSGGGG SSSSSEELEA 350
    DPAMPHRPGR PAQPRPPSPK TSALLQPKAP TGVDSTGVIA GEGPGDDKAM 400
    AAAAPDVPLS TSGRIRETVQ KTSPPSLYVQ LHGETTRRLE ADEKPLQIQN 450
    DYLFQLGFGE LWRVQEEGMD SEIGCLIRFY AGKPHSTGSS ERIQLSGMYN 500
    VRKGKMQLPV NRWTRRQVIL CGTCLIVSSV KDSVSGKMHV LPLIGGKVEE 550
    VKKHQHCLAF SSSGPQSQTY YICFDTFTEY LRWLRQVSKV ASQRISSVDL 600
    SCCSLEHLPA NLFYSQDLTH LNLKQNFLRQ TPTLPAARGL GELQRFTKLK 650
    SLNLSNNHLG AFPSAVCSIP TLAELNVSCN ALREVPAAVG DMQNLQTFLL 700
    DGNFLQSLPA ELESMHQLSY LGLSFNEFTD IPEVLEKLTA VDKLCMAGNC 750
    VETLRLQALR RMPHIKHVDL RLNILRKLMA DEVDFVQHVT QLDLRDNKLG 800
    DLDAMIFNNI EVLHCERNQL VTLNVCGYFL KALYASSNEL AQLDVYPVPN 850
    YLSYMDVSRN CLESVPEWVC ESRKLEVLDI GHNQICELPA RLFCNSSLRK 900
    LLAGHNRLAR LPERLERTSV EVLDVQHNQI TELPPNLLMK ADSLRFLNAS 950
    ANKLETLPPA TLSEETSSIL QELYLTNNCL TDKCVPLLTG HPRLKILHMA 1000
    YNRLQSFPAS KMAKLEELEE IDISGNKLKA IPTTIMNCRR MHTVIAHSNC 1050
    IEVFPEVMQL PEVKCVDLSC NELSEITLPE NLPPKLQELD LTGNPRLALD 1100
    HKSLELLNNI RCFKIDQPSA GDASGAPAVW SHGYTEASGV KNKLCVAALS 1150
    VNNFRDNREA LYGVFDGDRN VEVPYLLQCT MSDILAEELQ KTKNEEEYMV 1200
    NTFIVMQRKL GTAGQKLGGA AVLCHIKPDP VDLGGSFTLT SANVGKCQTV 1250
    LCRNGKPLSL SRSYIMSCEE ERKRIKQHKA IITEDGKVNG VTESTRILGY 1300
    TFLHPSVVPR PHVQSVLLTP QDEFFILGSK GLWDSLSIDE AVEAVRNVPD 1350
    ALAAAKKLCT LAQSYGCHDS ISAVVVQLSV TEDSFCCCEL SAGGSMPPPS 1400
    PGIFPPSVNM VIKDRPSDGL GVPSSSSGMA SEISSELSTS EMSSEVGSTA 1450
    SDEPPSGVLN ESSPAYPNEQ RCMLHPVCLS NSFQRQLSSA TFSSAFSDNG 1500
    LDSDDEEPIE GVFSNGSRVE VEVDIHCSRA KEKERQQHLL QVPAEASDEG 1550
    IVISANEDES GLSKKADFSA VGTIGRRRAN GSVAPQERSH NVIEVAADAP 1600
    LRKPGGYFAA PAQPDPDDQF IIPPELEEEV KEIMKHHQEQ QQQQQQQQLP 1650
    PPPQPPQPQP QPQPQPQPQP QRHFQMDHLP DCYDTPL 1687
    Length:1,687
    Mass (Da):182,367
    Last modified:June 7, 2005 - v2
    Checksum:i32B0809AAB3D2412
    GO

    Sequence cautioni

    The sequence AAH59254.1 differs from that shown. Reason: Frameshift at position 34.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti724 – 7241S → F in AAH59254. (PubMed:15489334)Curated
    Sequence conflicti1506 – 15061E → K in AAH22703. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AC101663 Genomic DNA. No translation available.
    AC124710 Genomic DNA. No translation available.
    AC144773 Genomic DNA. No translation available.
    AB093251 mRNA. Translation: BAC41435.1.
    BC004581 mRNA. Translation: AAH04581.1.
    BC022703 mRNA. Translation: AAH22703.1.
    BC024670 mRNA. Translation: AAH24670.1.
    BC059254 mRNA. Translation: AAH59254.1. Frameshift.
    CCDSiCCDS48337.1.
    RefSeqiNP_598582.3. NM_133821.3.
    UniGeneiMm.24115.

    Genome annotation databases

    EnsembliENSMUST00000061047; ENSMUSP00000056530; ENSMUSG00000044340.
    GeneIDi98432.
    KEGGimmu:98432.
    UCSCiuc007cgv.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AC101663 Genomic DNA. No translation available.
    AC124710 Genomic DNA. No translation available.
    AC144773 Genomic DNA. No translation available.
    AB093251 mRNA. Translation: BAC41435.1 .
    BC004581 mRNA. Translation: AAH04581.1 .
    BC022703 mRNA. Translation: AAH22703.1 .
    BC024670 mRNA. Translation: AAH24670.1 .
    BC059254 mRNA. Translation: AAH59254.1 . Frameshift.
    CCDSi CCDS48337.1.
    RefSeqi NP_598582.3. NM_133821.3.
    UniGenei Mm.24115.

    3D structure databases

    ProteinModelPortali Q8CHE4.
    SMRi Q8CHE4. Positions 598-1378.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q8CHE4. 1 interaction.
    MINTi MINT-4997715.

    PTM databases

    PhosphoSitei Q8CHE4.

    Proteomic databases

    PaxDbi Q8CHE4.
    PRIDEi Q8CHE4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000061047 ; ENSMUSP00000056530 ; ENSMUSG00000044340 .
    GeneIDi 98432.
    KEGGi mmu:98432.
    UCSCi uc007cgv.2. mouse.

    Organism-specific databases

    CTDi 23239.
    MGIi MGI:2138327. Phlpp1.
    Rougei Search...

    Phylogenomic databases

    eggNOGi COG4886.
    GeneTreei ENSGT00440000037833.
    HOGENOMi HOG000115529.
    InParanoidi Q8CHE4.
    KOi K16340.
    OMAi FTNGSRV.
    OrthoDBi EOG7RFTGK.
    PhylomeDBi Q8CHE4.
    TreeFami TF315993.

    Enzyme and pathway databases

    Reactomei REACT_214733. Negative regulation of the PI3K/AKT network.

    Miscellaneous databases

    NextBioi 353478.
    PROi Q8CHE4.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8CHE4.
    Genevestigatori Q8CHE4.

    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. 3 hits.
    PF13855. LRR_8. 1 hit.
    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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    2. "Prediction of the coding sequences of mouse homologues of KIAA gene: I. The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
      Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O., Koga H.
      DNA Res. 9:179-188(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 370-1687.
      Tissue: Brain.
    3. "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 424-1687.
      Strain: C57BL/6, Czech II and FVB/N.
      Tissue: Brain and Mammary tumor.
    4. "Changes in expression of the mouse homologues of KIAA genes after subchronic methamphetamine treatment."
      Yamamoto H., Imai K., Takamatsu Y., Kamegaya E., Hara Y., Shimada K., Yamamoto T., Shen H.W., Hagino Y., Kobayashi H., Ide S., Sora I., Koga H., Ikedaa K.
      Ann. N. Y. Acad. Sci. 1025:92-101(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.

    Entry informationi

    Entry nameiPHLP1_MOUSE
    AccessioniPrimary (citable) accession number: Q8CHE4
    Secondary accession number(s): Q6PCN0
    , Q8QZU8, Q8R5E5, Q99KL6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 7, 2005
    Last sequence update: June 7, 2005
    Last modified: October 1, 2014
    This is version 107 of the entry and version 2 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3