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Aliases for PHLPP2 Gene

Aliases for PHLPP2 Gene

  • PH Domain And Leucine Rich Repeat Protein Phosphatase 2 2 3 5
  • Protein Phosphatase, Mg2+/Mn2+ Dependent 3B 2 3
  • EC 3.1.3.16 4 61
  • PHLPPL 3 4
  • PH Domain Leucine-Rich Repeat-Containing Protein Phosphatase-Like 4
  • PH Domain Leucine-Rich Repeat-Containing Protein Phosphatase 2 3
  • 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
  • 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 RET signaling and Immune System. 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

Regulatory Elements for PHLPP2 Gene

Enhancers for PHLPP2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH16F071625 1.2 Ensembl ENCODE 31.9 +97.2 97246 3.7 ZFP64 ARID4B SIN3A DMAP1 RAD21 ZNF2 SLC30A9 ZNF121 SCRT2 ZNF391 PHLPP2 RNU6-208P TAT SNORA70D MARVELD3 HPR LOC105371336 ENSG00000260593
GH16F071707 1.3 FANTOM5 Ensembl ENCODE 21.3 +15.8 15848 3.3 MAX RAD21 ZNF121 ZNF664 ZNF316 GATA3 SMC3 FOS MAFK TCF7L2 ZNF19 PMFBP1 PHLPP2 MARVELD3 RNU6-208P HPR HYDIN ENSG00000261513 SNORA70D
GH16F071669 0.8 ENCODE 32.6 +54.2 54178 2.0 ELF3 CTCF SOX13 TBP TFAP4 MXI1 ATF1 SAP130 ARID4B ZNF384 PHLPP2 SNORA70D TAT HPR RNU6-208P
GH16F071563 1.1 ENCODE 19.3 +159.6 159570 3.3 HDGF PKNOX1 ARNT MLX ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 DHX38 ENSG00000247324 PHLPP2 ZNF23 TAT-AS1 DHODH HPR ZNF19 TAT
GH16F071807 1.2 ENCODE 17.4 -84.9 -84939 4.8 MLX CREB3L1 FEZF1 DMAP1 YY1 SLC30A9 ZNF143 ZNF263 SP3 NFYC PHLPP2 TAT-AS1 AP1G1 ATXN1L MARVELD3 ENSG00000247324 LINC01572 ZNF23 LOC100420489
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around PHLPP2 on UCSC Golden Path with GeneCards custom track

Promoters for PHLPP2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000273048 1301 2401 HDGF PKNOX1 MLX ZFP64 ARID4B SIN3A YBX1 DMAP1 ZNF2 SLC30A9

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

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

Antibody Products

  • Abcam antibodies for PHLPP2

Domains & Families 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 IEA --
GO:0004721 phosphoprotein phosphatase activity IEA --
GO:0004722 protein serine/threonine phosphatase activity IEA --
GO:0005515 protein binding IPI 19615732
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:

Animal Model Products

  • Taconic Biosciences Mouse Models for PHLPP2

miRNA for PHLPP2 Gene

miRTarBase miRNAs that target PHLPP2

Inhibitory RNA Products

Clone Products

Flow Cytometry 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 5
plasma membrane 3
mitochondrion 1

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

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 --
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
Manganese Approved Nutra 34
calcium Nutra 0

(1) 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
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:

Inhibitory RNA Products

Clone Products

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 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

NURSA nuclear receptor signaling pathways regulating expression of PHLPP2 Gene:

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).
genes like me logo Genes that share expression patterns with PHLPP2: view

Primer 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 34 35
  • 99.57 (n)
dog
(Canis familiaris)
Mammalia PHLPP2 34 35
  • 89.89 (n)
cow
(Bos Taurus)
Mammalia PHLPP2 34 35
  • 89.64 (n)
rat
(Rattus norvegicus)
Mammalia Phlpp2 34
  • 87.91 (n)
mouse
(Mus musculus)
Mammalia Phlpp2 34 16 35
  • 86.94 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia PHLPP2 35
  • 86 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia PHLPP2 35
  • 85 (a)
OneToOne
chicken
(Gallus gallus)
Aves PHLPP2 34 35
  • 73.71 (n)
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.18314 34
zebrafish
(Danio rerio)
Actinopterygii phlpp2 35
  • 73 (a)
OneToOne
LOC100332895 34
  • 63.38 (n)
fruit fly
(Drosophila melanogaster)
Insecta Phlpp 35
  • 20 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea F43C1.1 34 35
  • 41.24 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CYR1 35
  • 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)

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
rs1035545 -- 71,663,849(+) AAATA(C/T)AGAAT intron-variant
rs10500559 -- 71,659,190(-) ATTAA(A/G)GACTG intron-variant
rs10500560 -- 71,647,250(-) TTTTC(C/T)ATTGG utr-variant-3-prime
rs10568400 -- 71,725,717(+) TCTCC(-/CAA)CAAGA upstream-variant-2KB
rs10571368 -- 71,694,198(+) AAAAT(-/AATAA)AATAA intron-variant

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

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

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

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

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

Disorder Aliases PubMed IDs
colorectal cancer
  • colorectal cancer, somatic
- elite association - COSMIC cancer census association via MalaCards

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 3 4 64
  2. 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) 3 4 64
  3. PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma. (PMID: 21804599) Molina J.R. … Georgescu M.M. (Oncogene 2012) 3 4 64
  4. PHLPP-mediated dephosphorylation of S6K1 inhibits protein translation and cell growth. (PMID: 21986499) Liu J. … Gao T. (Mol. Cell. Biol. 2011) 3 4 64
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose J.E. … Uhl G.R. (Mol. Med. 2010) 3 46 64

Products for PHLPP2 Gene

Sources for PHLPP2 Gene

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