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    PHLPP2 PH domain and leucine rich repeat protein phosphatase 2 [ Homo sapiens (human) ]

    Gene ID: 23035, updated on 14-Nov-2024

    Summary

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    Official Symbol
    PHLPP2provided by HGNC
    Official Full Name
    PH domain and leucine rich repeat protein phosphatase 2provided by HGNC
    Primary source
    HGNC:HGNC:29149
    See related
    Ensembl:ENSG00000040199 MIM:611066; AllianceGenome:HGNC:29149
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PPM3B; PHLPPL
    Summary
    Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Located in several cellular components, including intercellular bridge; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Broad expression in small intestine (RPKM 11.5), colon (RPKM 5.9) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PHLPP2 in Genome Data Viewer
    Location:
    16q22.2
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (71644924..71724701, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (77462088..77541847, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (71678827..71758604, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371334 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7681 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7682 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr16:71671387-71671938 Neighboring gene uncharacterized LOC124903711 Neighboring gene MARVEL domain containing 3 Neighboring gene Sharpr-MPRA regulatory region 2747 Neighboring gene uncharacterized LOC124903712 Neighboring gene RNA, U6 small nuclear 208, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11076 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:71741784-71742412 Neighboring gene small nucleolar RNA, H/ACA box 70D Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:71756941-71757442 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7684 Neighboring gene adaptor related protein complex 1 subunit gamma 1 Neighboring gene small nucleolar RNA, C/D box 71 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:71808874-71809101 Neighboring gene parathymosin-like

    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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    Related articles in PubMed

    1. Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration. Li T, et al. Dis Markers, 2022. PMID 35308140, Free PMC Article
    2. PHLPP2 Downregulation Contributes to Lung Carcinogenesis Following B[a]P/B[a]PDE Exposure. Huang H, et al. Clin Cancer Res, 2015 Aug 15. PMID 25977341, Free PMC Article
    3. PHLPP2 as a novel metastatic and prognostic biomarker in non-small cell lung cancer patients. Wang H, et al. Thorac Cancer, 2019 Nov. PMID 31571378, Free PMC Article
    4. PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer. Wu HK, et al. Aging (Albany NY), 2020 Jul 7. PMID 32633726, Free PMC Article
    5. MicroRNA-27a contributes to the malignant behavior of gastric cancer cells by directly targeting PH domain and leucine-rich repeat protein phosphatase 2. Ding L, et al. J Exp Clin Cancer Res, 2017 Mar 21. PMID 28327189, Free PMC Article

    See all (87) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PHLPP2 gene L1016S (rs61733127) and PIK3R1 gene Met326Ile (rs3730089) polymorphisms are associated with the risk of colon and breast cancers.
      Title: PHLPP2 gene L1016S (rs61733127) and PIK3R1 gene Met326Ile (rs3730089) polymorphisms are associated with the risk of colon and breast cancers.
    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. TRIM22 induces cellular senescence by targeting PHLPP2 in hepatocellular carcinoma.
      Title: TRIM22 induces cellular senescence by targeting PHLPP2 in hepatocellular carcinoma.
    4. 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.
    5. MARCH1 silencing suppresses growth of oral squamous cell carcinoma through regulation of PHLPP2.
      Title: MARCH1 silencing suppresses growth of oral squamous cell carcinoma through regulation of PHLPP2.
    6. Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration.
      Title: Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration.
    7. Mutant p53 achieved Gain-of-Function by promoting tumor growth and immune escape through PHLPP2/AKT/PD-L1 pathway.
      Title: Mutant p53 achieved Gain-of-Function by promoting tumor growth and immune escape through PHLPP2/AKT/PD-L1 pathway.
    8. TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells.
      Title: TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells.
    9. MiR-509-3p is oncogenic, targets the tumor suppressor PHLPP2, and functions as a novel tumor adjacent normal tissue based prognostic biomarker in colorectal cancer.
      Title: MiR-509-3p is oncogenic, targets the tumor suppressor PHLPP2, and functions as a novel tumor adjacent normal tissue based prognostic biomarker in colorectal cancer.
    10. Circular RNA circ_0001017 Sensitizes Cisplatin-Resistant Gastric Cancer Cells to Chemotherapy by the miR-543/PHLPP2 Axis.
      Title: Circular RNA circ_0001017 Sensitizes Cisplatin-Resistant Gastric Cancer Cells to Chemotherapy by the miR-543/PHLPP2 Axis.
    Submit: New GeneRIF Correction See all GeneRIFs (56)

    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

    EBI GWAS Catalog

    Description
    A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
    EBI GWAS Catalog

    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

    • KIAA0931

    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 
    Process Evidence Code Pubs
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in hippocampus development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in intercellular bridge IDA
    Inferred from Direct Assay
    more info
    		  
    located_in mitotic spindle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in photoreceptor inner segment IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in photoreceptor outer segment 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 2
    Names
    protein phosphatase, Mg2+/Mn2+ dependent 3B
    NP_001275932.1
    NP_055835.2

    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.

    mRNA and Protein(s)

    1. NM_001289003.1 → NP_001275932.1  PH domain leucine-rich repeat-containing protein phosphatase 2 isoform 2

      See identical proteins and their annotated locations for NP_001275932.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and lacks an in-frame exon in the central coding region, compared to variant 1. The encoded isoform (2) is shorter, compared to isoform 1.
      Source sequence(s)
      AB023148, AC009097, BC129927
      Consensus CDS
      CCDS73910.1
      UniProtKB/TrEMBL
      H3BMS5
      Related
      ENSP00000377159.2, ENST00000393524.6
      Conserved Domains (5) summary
      cd00116
      Location:444 → 660
      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 ...
      cd00143
      Location:717 → 966
      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 ...
      cd13322
      Location:149 → 243
      PH_PHLPP-like; PH domain leucine-rich repeat protein phosphatase family Pleckstrin homology-like domain
      sd00033
      Location:442 → 461
      LRR_RI; leucine-rich repeat [structural motif]
      pfam13855
      Location:572 → 636
      LRR_8; Leucine rich repeat

    2. NM_015020.3 → NP_055835.2  PH domain leucine-rich repeat-containing protein phosphatase 2 isoform 1

      See identical proteins and their annotated locations for NP_055835.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC009097, BC129927, BX647823
      Consensus CDS
      CCDS32479.1
      UniProtKB/Swiss-Prot
      A1L374, Q6ZVD8, Q9NV17, Q9Y2E3
      UniProtKB/TrEMBL
      H3BMS5
      Related
      ENSP00000457991.1, ENST00000568954.5
      Conserved Domains (6) summary
      cd00116
      Location:313 → 606
      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 ...
      cd00143
      Location:784 → 1033
      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 ...
      cd13322
      Location:149 → 243
      PH_PHLPP-like; PH domain leucine-rich repeat protein phosphatase family Pleckstrin homology-like domain
      sd00033
      Location:482 → 503
      LRR_RI; leucine-rich repeat [structural motif]
      pfam12799
      Location:645 → 685
      LRR_4; Leucine Rich repeats (2 copies)
      pfam13855
      Location:645 → 703
      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_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      71644924..71724701 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      77462088..77541847 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6ZVD8.3 GenPept UniProtKB/Swiss-Prot:Q6ZVD8

    Gene LinkOut

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

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous