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Aliases for PHLPP2 Gene

Aliases for PHLPP2 Gene

  • PH Domain And Leucine Rich Repeat Protein Phosphatase 2 2 3
  • EC 3.1.3.16 4 63
  • PHLPPL 3 4
  • PH Domain Leucine-Rich Repeat-Containing Protein Phosphatase-Like 4
  • PH Domain And Leucine Rich Repeat Protein Phosphatase-Like 2
  • PHLPP-Like 4
  • KIAA0931 4

External Ids for PHLPP2 Gene

Previous HGNC Symbols for PHLPP2 Gene

  • PHLPPL

Previous GeneCards Identifiers for PHLPP2 Gene

  • GC16M070236
  • GC16M057446

Summaries for PHLPP2 Gene

GeneCards Summary for PHLPP2 Gene

PHLPP2 (PH Domain And Leucine Rich Repeat Protein Phosphatase 2) is a Protein Coding gene. Diseases associated with PHLPP2 include colorectal cancer. Among its related pathways are PI3K-Akt signaling pathway and PI3K/AKT Signaling in Cancer. GO annotations related to this gene include protein serine/threonine phosphatase activity. An important paralog of this gene is PHLPP1.

UniProtKB/Swiss-Prot for PHLPP2 Gene

  • Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on Ser-473 of AKT1, Ser-660 of PRKCB isoform beta-II and Ser-657 of PRKCA. Akt 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 Akt triggers apoptosis and decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylates STK4 on Thr-387 leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606).

Gene Wiki entry for PHLPP2 Gene

No data available for Entrez Gene Summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PHLPP2 Gene

Genomics for PHLPP2 Gene

Genomic Location for PHLPP2 Gene

Chromosome:
16
Start:
71,637,835 bp from pter
End:
71,724,701 bp from pter
Size:
86,867 bases
Orientation:
Minus strand

Genomic View for PHLPP2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for PHLPP2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PHLPP2 Gene

No data available for Regulatory Elements for PHLPP2 Gene

Proteins for PHLPP2 Gene

  • Protein details for PHLPP2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6ZVD8-PHLP2_HUMAN
    Recommended name:
    PH domain leucine-rich repeat-containing protein phosphatase 2
    Protein Accession:
    Q6ZVD8
    Secondary Accessions:
    • A1L374
    • Q9NV17
    • Q9Y2E3

    Protein attributes for PHLPP2 Gene

    Size:
    1323 amino acids
    Molecular mass:
    146751 Da
    Cofactor:
    Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Note=Binds 2 manganese ions per subunit. Mn(2+) is inhibitory below pH 8 and activating above pH 8 (PubMed:24892992).;
    Quaternary structure:
    • Interacts with AKT1, AKT3 and PRKCB isoform beta-II (PubMed:17386267, PubMed:18162466, PubMed:19732725). Interacts with STK4, RPS6KB1, RAF1 (PubMed:20513427, PubMed:21986499, PubMed:24530606). Interacts with FKBP5; FKBP5 acts as a scaffold for PHLPP2 and Akt (PubMed:19732725). Interacts with SLC9A3R1; SLC9A3R1 scaffolds a heterotrimeric complex with PTEN (PubMed:21804599).
    SequenceCaution:
    • Sequence=BAA76775.2; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAA91943.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for PHLPP2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PHLPP2 Gene

Proteomics data for PHLPP2 Gene at MOPED

Selected DME Specific Peptides for PHLPP2 Gene

Post-translational modifications for PHLPP2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PHLPP2 Gene

Antibody Products

Domains & Families for PHLPP2 Gene

Protein Domains for PHLPP2 Gene

Suggested Antigen Peptide Sequences for PHLPP2 Gene

Graphical View of Domain Structure for InterPro Entry

Q6ZVD8

UniProtKB/Swiss-Prot:

PHLP2_HUMAN :
  • Contains 1 PH domain.
  • Contains 22 LRR (leucine-rich) repeats.
Domain:
  • Contains 1 PH domain.
  • Contains 1 PPM-type phosphatase domain.
Similarity:
  • Contains 22 LRR (leucine-rich) repeats.
genes like me logo Genes that share domains with PHLPP2: view

Function for PHLPP2 Gene

Molecular function for PHLPP2 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=4.13 mM for p-nitrophenyl phosphate;
UniProtKB/Swiss-Prot CatalyticActivity:
[a protein]-serine/threonine phosphate + H(2)O = [a protein]-serine/threonine + phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by AKT1, AKT2 and AKT3. Activated by oleic acid and arachidonic acid (PubMed:24892992).
UniProtKB/Swiss-Prot Function:
Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on Ser-473 of AKT1, Ser-660 of PRKCB isoform beta-II and Ser-657 of PRKCA. Akt 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 Akt triggers apoptosis and decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylates STK4 on Thr-387 leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606).

Enzyme Numbers (IUBMB) for PHLPP2 Gene

Gene Ontology (GO) - Molecular Function for PHLPP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity --
GO:0004722 protein serine/threonine phosphatase activity IEA --
GO:0005515 protein binding --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with PHLPP2: view

Phenotypes for PHLPP2 Gene

genes like me logo Genes that share phenotypes with PHLPP2: view

Animal Model Products

miRNA for PHLPP2 Gene

miRTarBase miRNAs that target PHLPP2

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PHLPP2

In Situ Assay Products

Flow Cytometry Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for PHLPP2 Gene

Localization for PHLPP2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PHLPP2 Gene

Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Note=In colorectal cancer tissue, expression is concentrated in the cytoplasm and nucleus.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PHLPP2 Gene COMPARTMENTS Subcellular localization image for PHLPP2 gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 2

Gene Ontology (GO) - Cellular Components for PHLPP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001917 photoreceptor inner segment IEA --
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
GO:0042622 photoreceptor outer segment membrane IEA --
genes like me logo Genes that share ontologies with PHLPP2: view

Pathways & Interactions for PHLPP2 Gene

genes like me logo Genes that share pathways with PHLPP2: view

Pathways by source for PHLPP2 Gene

Interacting Proteins for PHLPP2 Gene

Selected Interacting proteins: Q6ZVD8-PHLP2_HUMAN for PHLPP2 Gene via I2D MINT

SIGNOR curated interactions for PHLPP2 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for PHLPP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006470 protein dephosphorylation IEA --
GO:0007173 epidermal growth factor receptor signaling pathway TAS --
GO:0008152 metabolic process --
GO:0008543 fibroblast growth factor receptor signaling pathway TAS --
GO:0021766 hippocampus development IEA --
genes like me logo Genes that share ontologies with PHLPP2: view

Drugs & Compounds for PHLPP2 Gene

(2) Drugs for PHLPP2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Manganese Pharma 30
Calcium Nutra 0

(3) Additional Compounds for PHLPP2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Phosphate
  • NFB Orthophosphate
  • O-Phosphoric acid
  • Ortho-phosphate
  • Orthophosphate (PO43-)
  • Orthophosphate(3-)
14265-44-2
phosphoric acid
  • Acide phosphorique (FRENCH)
  • Acido fosforico [Italian]
  • Acidum phosphoricum
  • Diphosphate tetrasodium
  • Fosforzuuroplossingen [Dutch]
7664-38-2
Water
  • Dihydrogen oxide
  • Steam
7732-18-5
genes like me logo Genes that share compounds with PHLPP2: view

Transcripts for PHLPP2 Gene

Unigene Clusters for PHLPP2 Gene

PH domain and leucine rich repeat protein phosphatase 2:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PHLPP2

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for PHLPP2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18
SP1:
SP2: -

Relevant External Links for PHLPP2 Gene

GeneLoc Exon Structure for
PHLPP2
ECgene alternative splicing isoforms for
PHLPP2

Expression for PHLPP2 Gene

mRNA expression in normal human tissues for PHLPP2 Gene

Protein differential expression in normal tissues from HIPED for PHLPP2 Gene

This gene is overexpressed in Fetal gut (53.2) and Retina (15.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MOPED, and MaxQB for PHLPP2 Gene



SOURCE GeneReport for Unigene cluster for PHLPP2 Gene Hs.709458

mRNA Expression by UniProt/SwissProt for PHLPP2 Gene

Q6ZVD8-PHLP2_HUMAN
Tissue specificity: In colorectal cancer tissue, expression is highest in the surface epithelium of normal colonic mucosa adjacent to the cancer tissue but is largely excluded from the crypt bases. Expression is lost or significantly decreased in 80% of tested tumors (at protein level).
genes like me logo Genes that share expression patterns with PHLPP2: view

Protein tissue co-expression partners for PHLPP2 Gene

Primer Products

  • QuantiTect SYBR Green Assays in human,mouse,rat
  • Pre-validated RT² qPCR Primer Assay in human,mouse,rat
  • QuantiFast Probe-based Assays in human,mouse,rat

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for PHLPP2 Gene

Orthologs for PHLPP2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PHLPP2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PHLPP2 36
  • 99 (a)
OneToOne
PHLPP2 35
  • 99.57 (n)
  • 99.24 (a)
platypus
(Ornithorhynchus anatinus)
Mammalia PHLPP2 36
  • 86 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Phlpp2 36
  • 88 (a)
OneToOne
Phlpp2 16
Phlpp2 35
  • 86.94 (n)
  • 90.76 (a)
oppossum
(Monodelphis domestica)
Mammalia PHLPP2 36
  • 85 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PHLPP2 36
  • 94 (a)
OneToOne
PHLPP2 35
  • 89.89 (n)
  • 93.77 (a)
cow
(Bos Taurus)
Mammalia PHLPP2 36
  • 93 (a)
OneToOne
PHLPP2 35
  • 89.64 (n)
  • 93.56 (a)
rat
(Rattus norvegicus)
Mammalia Phlpp2 35
  • 87.91 (n)
  • 92.67 (a)
chicken
(Gallus gallus)
Aves PHLPP2 36
  • 72 (a)
OneToOne
PHLPP2 35
  • 73.71 (n)
  • 79.02 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.18314 35
zebrafish
(Danio rerio)
Actinopterygii phlpp2 36
  • 73 (a)
OneToOne
LOC100332895 35
  • 63.38 (n)
  • 63.9 (a)
fruit fly
(Drosophila melanogaster)
Insecta Phlpp 36
  • 20 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea F43C1.1 36
  • 30 (a)
OneToMany
F43C1.1 35
  • 41.24 (n)
  • 33.45 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CYR1 36
  • 12 (a)
OneToMany
Species with no ortholog for PHLPP2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for PHLPP2 Gene

ENSEMBL:
Gene Tree for PHLPP2 (if available)
TreeFam:
Gene Tree for PHLPP2 (if available)

Paralogs for PHLPP2 Gene

Paralogs for PHLPP2 Gene

(4) SIMAP similar genes for PHLPP2 Gene using alignment to 5 proteins:

Pseudogenes.org Pseudogenes for PHLPP2 Gene

genes like me logo Genes that share paralogs with PHLPP2: view

Variants for PHLPP2 Gene

Sequence variations from dbSNP and Humsavar for PHLPP2 Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type MAF
rs74881934 -- 71,718,579(+) TATCT(A/C)AAAAA intron-variant
rs74773912 -- 71,665,636(+) TTGTG(C/T)TGTGG intron-variant
rs74750149 -- 71,691,507(+) AATAA(-/ATAAATAA)GGAAT intron-variant
rs74714254 -- 71,651,338(+) TGCCT(A/C)AAAAA intron-variant
rs74552141 -- 71,719,457(+) ATCGC(C/T)TGAAC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for PHLPP2 Gene

Variant ID Type Subtype PubMed ID
nsv7285 OTHER Inversion 18451855

Variation tolerance for PHLPP2 Gene

Residual Variation Intolerance Score: 6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.35; 81.60% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for PHLPP2 Gene

HapMap Linkage Disequilibrium report
PHLPP2
Human Gene Mutation Database (HGMD)
PHLPP2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PHLPP2 Gene

Disorders for PHLPP2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for PHLPP2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
colorectal cancer
  • colorectal cancer, somatic
- elite association

Relevant External Links for PHLPP2

Genetic Association Database (GAD)
PHLPP2
Human Genome Epidemiology (HuGE) Navigator
PHLPP2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
PHLPP2
genes like me logo Genes that share disorders with PHLPP2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PHLPP2 Gene

Publications for PHLPP2 Gene

  1. PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. (PMID: 17386267) Brognard J. … Newton A.C. (Mol. Cell 2007) 2 67
  2. The BioPlex Network: A Systematic Exploration of the Human Interactome. (PMID: 26186194) Huttlin E.L. … Gygi S.P. (Cell 2015) 67
  3. miR-372 regulates glioma cell proliferation and invasion by directly targeting PHLPP2. (PMID: 25160587) Chen X. … Liu J. (J. Cell. Biochem. 2015) 67
  4. Biochemical characterization of the phosphatase domain of the tumor suppressor PH domain leucine-rich repeat protein phosphatase. (PMID: 24892992) Sierecki E. … Newton A.C. (Biochemistry 2014) 67
  5. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. (PMID: 25217961) Al Olama A.A. … Haiman C.A. (Nat. Genet. 2014) 67

Products for PHLPP2 Gene

Sources for PHLPP2 Gene

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