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    PHLPP1 PH domain and leucine rich repeat protein phosphatase 1 [ Homo sapiens ]

    Gene ID: 23239, updated on 19-May-2012

    Summary

    Official Symbol
    PHLPP1provided by HGNC
    Official Full Name
    PH domain and leucine rich repeat protein phosphatase 1provided by HGNC
    Primary source
    HGNC:20610
    See related
    Ensembl:ENSG00000081913; HPRD:15145; MIM:609396; Vega:OTTHUMG00000150629
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SCOP; PHLPP; PLEKHE1; MGC161555
    Summary
    This gene encodes a member of the serine/threonine phosphatase family. The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. Increased expression of this gene may also play a role in obesity and type 2 diabetes by interfering with Akt-mediated insulin signaling. [provided by RefSeq, Dec 2011]

    Genomic context

    Location :
    18q21.33
    Sequence :
    Chromosome: 18; NC_000018.9 (60382672..60647666)
    See PHLPP1 in Epigenomics, MapViewer

    Chromosome 18 - NC_000018.9Genomic Context describing neighboring genes Neighboring gene actin, beta pseudogene 9 Neighboring gene uncharacterized LOC100505657 Neighboring gene zinc finger, CCHC domain containing 2 Neighboring gene B-cell CLL/lymphoma 2 Neighboring gene 3-ketodihydrosphingosine reductase

    Genomic regions, transcripts, and products

    Bibliography

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_919431.1 NP_005154.2 AKT1    BIND  PubMed PHLPP interacts with Akt. This interaction was modelled on a demonstrated interaction between human PHLPP and Akt from an unspecified species. 
    BioGRID:116843 BioGRID:106710 AKT1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:116843 BioGRID:114457 BTRC    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:116843 BioGRID:107836 CSNK1A1    BioGRID  PubMed Biochemical Activity 
    BioGRID:116843 BioGRID:108102 DMWD    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:108579 FKBP5    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:109187 GSK3B    BioGRID  PubMed Biochemical Activity 
    BioGRID:116843 BioGRID:108326 MARK2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:116674 PHLPP2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:111528 PPP5C    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:122293 RBM15    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:117060 SCRIB    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:114754 SLC9A3R2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:123546 SNX27    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:116115 SUGT1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:116843 BioGRID:113241 USP1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:128522 USP12    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:122327 USP46    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:124884 WDR20    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:116843 BioGRID:121649 WDR48    BioGRID  PubMed Affinity Capture-MS 

    General gene information

    Markers

    Homology

    Pathways from BioSystems

    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Downstream Signaling Events Of B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
      Downstream Signaling Events Of B Cell Receptor (BCR), organism-specific biosystemSecond messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidyinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RA...
    • Downstream signal transduction, organism-specific biosystem (from REACTOME)
      Downstream signal transduction, organism-specific biosystemThe role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of aro...
    • Downstream signaling of activated FGFR, organism-specific biosystem (from REACTOME)
      Downstream signaling of activated FGFR, organism-specific biosystemSignaling via FGFRs is mediated via direct recruitment of signaling proteins that bind to tyrosine auto-phosphorylation sites on the activated receptor and via closely linked docking proteins that be...
    • GAB1 signalosome, organism-specific biosystem (from REACTOME)
      GAB1 signalosome, organism-specific biosystemGAB1 is recruited to the activated EGFR indirectly, through GRB2. GAB1 acts as an adaptor protein that enables formation of an active PIK3, through recruitment of PIK3 regulatory subunit PIK3R1 (also...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
      NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
    • Negative regulation of the PI3K/AKT network, organism-specific biosystem (from REACTOME)
      Negative regulation of the PI3K/AKT network, organism-specific biosystemThe PI3K/AKT network is negatively regulated by phosphatases that dephosphorylate PIP3, thus hampering AKT activation.
    • PI-3K cascade, organism-specific biosystem (from REACTOME)
      PI-3K cascade, organism-specific biosystemThe ability of growth factors to protect from apoptosis is primarily due to the activation of the AKT survival pathway. P-I-3-kinase dependent activation of PDK leads to the activation of AKT which i...
    • PI3K events in ERBB2 signaling, organism-specific biosystem (from REACTOME)
      PI3K events in ERBB2 signaling, organism-specific biosystemERBB2:ERBB3 and ERBB2:ERBB4cyt1 heterodimers activate PI3K signaling by direct binding of PI3K regulatory subunit p85 (Yang et al. 2007, Cohen et al. 1996, Kaushansky et al. 2008) to phosphorylated t...
    • PI3K events in ERBB4 signaling, organism-specific biosystem (from REACTOME)
      PI3K events in ERBB4 signaling, organism-specific biosystemThe CYT1 isoforms of ERBB4 possess a C-tail tyrosine residue that, upon trans-autophosphorylation, serves as a docking site for the p85 alpha subunit of PI3K - PIK3R1 (Kaushansky et al. 2008, Cohen e...
    • PI3K/AKT activation, organism-specific biosystem (from REACTOME)
      PI3K/AKT activation, organism-specific biosystemPI3K/AKT signalling is a major regulator of neuron survival. It blocks cell death by both impinging on the cytoplasmic cell death machinery and by regulating the expression of genes involved in cell...
    • PIP3 activates AKT signaling, organism-specific biosystem (from REACTOME)
      PIP3 activates AKT signaling, organism-specific biosystemSignaling by AKT is one of the key outcomes of activation of receptor tyrosine kinases (RTKs). Following ligand binding and autophosphorylation, RTKs recruit the 85 kDa regulatory subunit of PI3K (PI...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by EGFR, organism-specific biosystem (from REACTOME)
      Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
    • Signaling by EGFR in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by EGFR in Cancer, organism-specific biosystemThe pathway "Signaling by EGFR in Cancer" shows "Signaling by constitutively active EGFR" in parallel with "Signaling by EGFR". This allows users to compare signaling by constitutively active EGFR ca...
    • Signaling by ERBB2, organism-specific biosystem (from REACTOME)
      Signaling by ERBB2, organism-specific biosystemERBB2, also known as HER2 or NEU, is a receptor tyrosine kinase (RTK) belonging to the EGFR family. ERBB2 possesses an extracellular domain that does not bind any known ligand, contrary to other EGFR...
    • Signaling by ERBB4, organism-specific biosystem (from REACTOME)
      Signaling by ERBB4, organism-specific biosystemERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular lig...
    • Signaling by FGFR, organism-specific biosystem (from REACTOME)
      Signaling by FGFR, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
    • Signaling by PDGF, organism-specific biosystem (from REACTOME)
      Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
    • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
      Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
    • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
      Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    hydrolase activity IEA
    Inferred from Electronic Annotation
    more info
     
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein serine/threonine phosphatase activity TAS
    Traceable Author Statement
    more info
     
    Process Evidence Code Pubs
    apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    circadian rhythm IEA
    Inferred from Electronic Annotation
    more info
     
    epidermal growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    fibroblast growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    nerve growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    phosphatidylinositol-mediated signaling TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
     
    cytosol TAS
    Traceable Author Statement
    more info
     
    membrane IEA
    Inferred from Electronic Annotation
    more info
     
    nucleus IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    PH domain leucine-rich repeat-containing protein phosphatase 1
    Names
    PH domain leucine-rich repeat-containing protein phosphatase 1
    SCN circadian oscillatory protein
    PH domain-containing family E member 1
    suprachiasmatic nucleus circadian oscillatory protein
    pleckstrin homology domain containing, family E (with leucine rich repeats) member 1
    NP_919431.2

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_031923.1 RefSeqGene

      Range
      5001..270005
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_194449.3NP_919431.2  PH domain leucine-rich repeat-containing protein phosphatase 1

      Status: REVIEWED

      Source sequence(s)
      AC015989, AC022046, AC027553, BC126277
      Consensus CDS
      CCDS45881.2
      UniProtKB/Swiss-Prot
      O60346
      Related
      ENSP00000262719, OTTHUMP00000198060, ENST00000262719, OTTHUMT00000319249
      Conserved Domains (6) summary
      cd00143
      Location:11741422
      Blast Score: 419
      PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...
      PRK07764
      Location:381459
      Blast Score: 94
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      cl15309
      Location:8141074
      Blast Score: 137
      LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
      pfam00481
      Location:11941415
      Blast Score: 266
      PP2C; Protein phosphatase 2C
      pfam13855
      Location:10141072
      Blast Score: 114
      LRR_8; Leucine rich repeat
      cl00273
      Location:556636
      Blast Score: 105
      PH-like; Pleckstrin homology-like domain

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000018.9 Reference GRCh37.p5 Primary Assembly

      Range
      60382672..60647666
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000150.1 Alternate HuRef

      Range
      57093040..57356428
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC015989.11 (6119..184091) None
    genomic AC022046.11 (124674..169552) None
    genomic AC027553.6 (51321..93473) None
    genomic CH471096.1 EAW63135.1
    mRNA AB011178.2 BAA25532.2
    mRNA AF130097.1 AAG35522.1
    mRNA AK001924.1 BAA91980.1
    mRNA AK124714.1 None
    mRNA AL079409.1 None
    mRNA BC010706.1 AAH10706.1
    mRNA BC014927.2 AAH14927.3
    mRNA BC047653.1 AAH47653.1
    mRNA BC063519.1 AAH63519.1
    mRNA BC082244.1 AAH82244.1
    mRNA BC126277.1 AAI26278.1
    mRNA BG110729.1 None
    Protein Accession Links
    GenPept Link UniProtKB Link
    O60346.3 GenPept UniProtKB/Swiss-Prot:O60346
    Q9H380 GenPept UniProtKB/TrEMBL:Q9H380

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