Aliases for PHLPP2 Gene

Aliases for PHLPP2 Gene

  • PH Domain And Leucine Rich Repeat Protein Phosphatase 2 2 3 5
  • PH Domain Leucine-Rich Repeat-Containing Protein Phosphatase 2 3 4
  • Protein Phosphatase, Mg2+/Mn2+ Dependent 3B 2 3
  • EC 3.1.3.16 4 52
  • 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
  • PPM3B 3

External Ids for PHLPP2 Gene

Previous HGNC Symbols for PHLPP2 Gene

  • PHLPPL

Previous GeneCards Identifiers for PHLPP2 Gene

  • GC16M070236
  • GC16M071674
  • 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 and Bladder Urothelial Carcinoma. Among its related pathways are Downstream signaling events of B Cell Receptor (BCR) and GAB1 signalosome. Gene Ontology (GO) annotations related to this gene include protein serine/threonine phosphatase activity. An important paralog of this gene is PHLPP1.

UniProtKB/Swiss-Prot Summary 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

Additional gene information for PHLPP2 Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PHLPP2 Gene

Genomics for PHLPP2 Gene

GeneHancer (GH) Regulatory Elements for PHLPP2 Gene

Promoters and enhancers for PHLPP2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PHLPP2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PHLPP2

Genomic Locations for PHLPP2 Gene

Genomic Locations for PHLPP2 Gene
chr16:71,637,835-71,724,701
(GRCh38/hg38)
Size:
86,867 bases
Orientation:
Minus strand
chr16:71,671,738-71,758,604
(GRCh37/hg19)
Size:
86,867 bases
Orientation:
Minus strand

Genomic View for PHLPP2 Gene

Genes around PHLPP2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PHLPP2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PHLPP2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence 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;
    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

Selected DME Specific Peptides for PHLPP2 Gene

Q6ZVD8:
  • SDNGLDSDD
  • YNVRKGK
  • SSEVGSTASDE
  • VEVEVDIHC
  • LCGTCLIVSSVKD
  • LAAAKKLCTLAQSYGC
  • KAIITED

Post-translational modifications for PHLPP2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PHLPP2 Gene

Domains & Families for PHLPP2 Gene

Suggested Antigen Peptide Sequences for PHLPP2 Gene

GenScript: Design optimal peptide antigens:
  • PHLPPL protein (A1L3A0_HUMAN)
  • PH domain leucine-rich repeat-containing protein phosphatase-like (PHLP2_HUMAN)
  • PHLPPL protein (Q3ZCW4_HUMAN)
genes like me logo Genes that share domains with PHLPP2: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for PHLPP2 Gene

Function for PHLPP2 Gene

Molecular function for PHLPP2 Gene

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).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, ChEBI:CHEBI:83421; EC=3.1.3.16; Evidence=. ;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, ChEBI:CHEBI:61977; EC=3.1.3.16; Evidence=. ;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by AKT1, AKT2 and AKT3. Activated by oleic acid and arachidonic acid (PubMed:24892992).
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=4.13 mM for p-nitrophenyl phosphate;

Enzyme Numbers (IUBMB) for PHLPP2 Gene

Phenotypes From GWAS Catalog for PHLPP2 Gene

Gene Ontology (GO) - Molecular Function for PHLPP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004721 phosphoprotein phosphatase activity IEA --
GO:0004722 protein serine/threonine phosphatase activity IEA --
GO:0005515 protein binding IEA,IPI 18162466
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with PHLPP2: view
genes like me logo Genes that share phenotypes with PHLPP2: view

Animal Models for PHLPP2 Gene

MGI Knock Outs for PHLPP2:
  • Phlpp2 Phlpp2<tm1d(EUCOMM)Hmgu>

Animal Model Products

  • Taconic Biosciences Mouse Models for PHLPP2

CRISPR Products

miRNA for PHLPP2 Gene

miRTarBase miRNAs that target PHLPP2

Clone Products

No data available for Human Phenotype Ontology , 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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PHLPP2 gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 3
mitochondrion 2
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

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:0016020 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

SIGNOR curated interactions for PHLPP2 Gene

Activates:
Inactivates:

Gene Ontology (GO) - Biological Process for PHLPP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006470 protein dephosphorylation IEA --
GO:0021766 hippocampus development IEA --
GO:0051898 negative regulation of protein kinase B signaling TAS --
genes like me logo Genes that share ontologies with PHLPP2: view

Drugs & Compounds for PHLPP2 Gene

(4) Drugs for PHLPP2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphoric acid Approved Pharma 0
Water Approved Pharma 0
Calcium Approved Nutra 7884
Manganese Approved Nutra 51

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Phosphate
  • [po(OH)3]
  • Acide phosphorique
  • Acidum phosphoricum
  • H3PO4
  • Orthophosphoric acid
14066-19-4, 14265-44-2
genes like me logo Genes that share compounds with PHLPP2: view

Transcripts for PHLPP2 Gene

mRNA/cDNA for PHLPP2 Gene

2 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone 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

Expression for PHLPP2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE 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, MaxQB, and MOPED for PHLPP2 Gene



Protein tissue co-expression partners for PHLPP2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PHLPP2

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).

Evidence on tissue expression from TISSUES for PHLPP2 Gene

  • Nervous system(4.4)
  • Eye(4.1)
genes like me logo Genes that share expression patterns with PHLPP2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer 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 31 30
  • 99.57 (n)
OneToOne
dog
(Canis familiaris)
Mammalia PHLPP2 31 30
  • 89.89 (n)
OneToOne
cow
(Bos Taurus)
Mammalia PHLPP2 31 30
  • 89.64 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Phlpp2 30
  • 87.91 (n)
mouse
(Mus musculus)
Mammalia Phlpp2 17 31 30
  • 86.94 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia PHLPP2 31
  • 86 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia PHLPP2 31
  • 85 (a)
OneToOne
chicken
(Gallus gallus)
Aves PHLPP2 31 30
  • 73.71 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.18314 30
zebrafish
(Danio rerio)
Actinopterygii phlpp2 31
  • 73 (a)
OneToOne
LOC100332895 30
  • 63.38 (n)
fruit fly
(Drosophila melanogaster)
Insecta Phlpp 31
  • 20 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea F43C1.1 31 30
  • 41.24 (n)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CYR1 31
  • 12 (a)
OneToMany
Species where no ortholog for PHLPP2 was found in the sources mined by GeneCards:
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for PHLPP2: view image

Paralogs for PHLPP2 Gene

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

  • PHLP2_HUMAN
  • G3V1T8_HUMAN
  • H3BMS5_HUMAN
  • H3BS75_HUMAN
  • I3L187_HUMAN

Pseudogenes.org Pseudogenes for PHLPP2 Gene

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

Variants for PHLPP2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PHLPP2 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
708147 Likely Benign: not provided 71,649,446(-) G/C MISSENSE_VARIANT
787642 Benign: not provided 71,649,856(-) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for PHLPP2 Gene

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

Variant ID Type Subtype PubMed ID
esv2714680 CNV deletion 23290073
esv29201 CNV loss 19812545
esv3638976 CNV loss 21293372
esv8241 CNV loss 19470904
nsv1063338 CNV gain 25217958
nsv7285 OTHER inversion 18451855
nsv962218 CNV duplication 23825009
nsv984350 CNV duplication 23825009

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)

Additional Variant Information for PHLPP2 Gene

Human Gene Mutation Database (HGMD)
PHLPP2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PHLPP2

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

Disorders for PHLPP2 Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
colorectal cancer
  • crc
bladder urothelial carcinoma
  • bladder transitional cell carcinoma
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for PHLPP2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 AC (Molecular cell 2007) 2 3 4 54
  2. Biochemical characterization of the phosphatase domain of the tumor suppressor PH domain leucine-rich repeat protein phosphatase. (PMID: 24892992) Sierecki E … Newton AC (Biochemistry 2014) 3 4 54
  3. PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma. (PMID: 21804599) Molina JR … Georgescu MM (Oncogene 2012) 3 4 54
  4. PHLPP-mediated dephosphorylation of S6K1 inhibits protein translation and cell growth. (PMID: 21986499) Liu J … Gao T (Molecular and cellular biology 2011) 3 4 54
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54

Products for PHLPP2 Gene

Sources for PHLPP2 Gene