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

    Gene ID: 23239, updated on 14-Nov-2024

    Summary

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    Official Symbol
    PHLPP1provided by HGNC
    Official Full Name
    PH domain and leucine rich repeat protein phosphatase 1provided by HGNC
    Primary source
    HGNC:HGNC:20610
    See related
    Ensembl:ENSG00000081913 MIM:609396; AllianceGenome:HGNC:20610
    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; PPM3A; PLEKHE1
    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]
    Expression
    Broad expression in brain (RPKM 17.2), testis (RPKM 8.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PHLPP1 in Genome Data Viewer
    Location:
    18q21.33
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (62715541..62980433)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (62918332..63183249)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (60382774..60647666)

    Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9510 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:60190967-60191540 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9511 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9512 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9513 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9514 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13432 Neighboring gene Sharpr-MPRA regulatory region 3490 Neighboring gene zinc finger CCHC-type containing 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:60278845-60279519 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13434 Neighboring gene RNA, 7SL, cytoplasmic 705, pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_49084 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9515 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13435 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13436 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9516 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:60383195-60384157 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9520 Neighboring gene Sharpr-MPRA regulatory region 7810 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:60418194-60419090 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:60419091-60419986 Neighboring gene uncharacterized LOC105372160 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:60427134-60428104 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:60428105-60429074 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13437 Neighboring gene RNA, U6 small nuclear 142, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:60539365-60539866 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr18:60544855-60545355 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:60546255-60546756 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:60546757-60547256 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_49136 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr18:60565763-60566264 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9521 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:60573152-60573764 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:60573765-60574376 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr18:60609220-60610419 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13438 Neighboring gene Sharpr-MPRA regulatory region 4133 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13439 Neighboring gene uncharacterized LOC105372161 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13440 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13441 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13442 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13443 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13444 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13445 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13446 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:60805026-60805892 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13449 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13448 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:60813108-60813608 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:60813609-60814109 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13450 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13451 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13452 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13455 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13456 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13454 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13453 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13457 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13458 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13459 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13460 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13461 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13462 Neighboring gene uncharacterized LOC124904379 Neighboring gene BCL2 apoptosis regulator

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation.
      Title: Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation.
    2. Pleckstrin Homology Domain Leucine-rich Repeat Protein Phosphatase Acts as a Tumor Suppressor in Oral Squamous Cell Carcinoma.
      Title: Pleckstrin Homology Domain Leucine-rich Repeat Protein Phosphatase Acts as a Tumor Suppressor in Oral Squamous Cell Carcinoma.
    3. PHLPP1 inhibits the growth and aerobic glycolysis activity of human ovarian granular cells through inactivating AKT pathway.
      Title: PHLPP1 inhibits the growth and aerobic glycolysis activity of human ovarian granular cells through inactivating AKT pathway.
    4. NAP1L5 facilitates pancreatic ductal adenocarcinoma progression via TRIM29-mediated ubiquitination of PHLPP1.
      Title: NAP1L5 facilitates pancreatic ductal adenocarcinoma progression via TRIM29-mediated ubiquitination of PHLPP1.
    5. SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma.
      Title: SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma.
    6. PHLPP isoforms differentially regulate Akt isoforms and AS160 affecting neuronal insulin signaling and insulin resistance via Scribble.
      Title: PHLPP isoforms differentially regulate Akt isoforms and AS160 affecting neuronal insulin signaling and insulin resistance via Scribble.
    7. Inhibition of PHLPP1/2 phosphatases rescues pancreatic beta-cells in diabetes.
      Title: Inhibition of PHLPP1/2 phosphatases rescues pancreatic β-cells in diabetes.
    8. Downregulation of PHLPP induced by endoplasmic reticulum stress promotes eIF2alpha phosphorylation and chemoresistance in colon cancer.
      Title: Downregulation of PHLPP induced by endoplasmic reticulum stress promotes eIF2α phosphorylation and chemoresistance in colon cancer.
    9. Heat shock protein 47 promotes tumor survival and therapy resistance by modulating AKT signaling via PHLPP1 in colorectal cancer.
      Title: Heat shock protein 47 promotes tumor survival and therapy resistance by modulating AKT signaling via PHLPP1 in colorectal cancer.
    10. USP46 Inhibits Cell Proliferation in Lung Cancer through PHLPP1/AKT Pathway.
      Title: USP46 Inhibits Cell Proliferation in Lung Cancer through PHLPP1/AKT Pathway.
    Submit: New GeneRIF Correction See all GeneRIFs (70)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC161555

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables MAP kinase serine/threonine phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II CTD heptapeptide repeat T4 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II CTD heptapeptide repeat Y1 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calmodulin-dependent protein phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AXS140 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables myosin phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine/threonine phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine phosphatase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in entrainment of circadian clock IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of JNK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of MAPK cascade IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of T cell anergy IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of p38MAPK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytoplasm IC
    Inferred by Curator
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    PH domain leucine-rich repeat-containing protein phosphatase 1
    Names
    PH domain-containing family E member 1
    SCN circadian oscillatory protein
    pleckstrin homology domain containing, family E (with leucine rich repeats) member 1
    protein phosphatase, Mg2+/Mn2+ dependent 3A
    suprachiasmatic nucleus circadian oscillatory protein
    NP_919431.2

    NCBI Reference Sequences (RefSeq)

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    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
      5103..269995
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_194449.4 → NP_919431.2  PH domain leucine-rich repeat-containing protein phosphatase 1

      See identical proteins and their annotated locations for NP_919431.2

      Status: REVIEWED

      Source sequence(s)
      AC015989, AC022046, AC027553, BC126277
      Consensus CDS
      CCDS45881.2
      UniProtKB/Swiss-Prot
      A1A4F5, O60346, Q641Q7, Q6P4C4, Q6PJI6, Q86TN6, Q96FK2, Q9NUY1
      Related
      ENSP00000262719.4, ENST00000262719.10
      Conserved Domains (6) summary
      smart00332
      Location:1168 → 1420
      PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain
      cd00116
      Location:625 → 929
      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 ...
      cd13322
      Location:535 → 631
      PH_PHLPP-like; PH domain leucine-rich repeat protein phosphatase family Pleckstrin homology-like domain
      sd00033
      Location:833 → 853
      LRR_RI; leucine-rich repeat [structural motif]
      pfam00169
      Location:555 → 636
      PH; PH domain
      pfam13855
      Location:1014 → 1072
      LRR_8; Leucine rich repeat

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

      Range
      62715541..62980433
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060942.1 Alternate T2T-CHM13v2.0

      Range
      62918332..63183249
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O60346.3 GenPept UniProtKB/Swiss-Prot:O60346

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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