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Aliases for PHLPP1 Gene

Aliases for PHLPP1 Gene

  • PH Domain And Leucine Rich Repeat Protein Phosphatase 1 2 3 5
  • Pleckstrin Homology Domain Containing, Family E (With Leucine Rich Repeats) Member 1 2 3
  • Suprachiasmatic Nucleus Circadian Oscillatory Protein 3 4
  • PH Domain-Containing Family E Member 1 3 4
  • EC 3.1.3.16 4 63
  • PLEKHE1 3 4
  • PHLPP 3 4
  • SCOP 3 4
  • Pleckstrin Homology Domain-Containing Family E Member 1 4
  • PH Domain And Leucine Rich Repeat Protein Phosphatase 2
  • Protein Phosphatase, Mg2+/Mn2+ Dependent 3A 3
  • SCN Circadian Oscillatory Protein 3
  • Mg2+/Mn2+ Dependent 3A 2
  • Protein Phosphatase 2
  • KIAA0606 4
  • PPM3A 3
  • HSCOP 4

External Ids for PHLPP1 Gene

Previous HGNC Symbols for PHLPP1 Gene

  • PLEKHE1
  • PHLPP

Previous GeneCards Identifiers for PHLPP1 Gene

  • GC18P058535
  • GC18P060382
  • GC18P057093

Summaries for PHLPP1 Gene

Entrez Gene Summary for PHLPP1 Gene

  • 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]

GeneCards Summary for PHLPP1 Gene

PHLPP1 (PH Domain And Leucine Rich Repeat Protein Phosphatase 1) is a Protein Coding gene. Diseases associated with PHLPP1 include colorectal cancer. Among its related pathways are Signaling by GPCR and Immune System. GO annotations related to this gene include phosphoprotein phosphatase activity. An important paralog of this gene is PHLPP2.

UniProtKB/Swiss-Prot for PHLPP1 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 AKT2 and AKT3, Ser-660 of PRKCB and Ser-657 of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). 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 suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). 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 (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T cells (By similarity).

Gene Wiki entry for PHLPP1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PHLPP1 Gene

Genomics for PHLPP1 Gene

Regulatory Elements for PHLPP1 Gene

Promoters for PHLPP1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around PHLPP1 on UCSC Golden Path with GeneCards custom track

Genomic Location for PHLPP1 Gene

Chromosome:
18
Start:
62,715,439 bp from pter
End:
62,980,443 bp from pter
Size:
265,005 bases
Orientation:
Plus strand

Genomic View for PHLPP1 Gene

Genes around PHLPP1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PHLPP1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PHLPP1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PHLPP1 Gene

Proteins for PHLPP1 Gene

  • Protein details for PHLPP1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O60346-PHLP1_HUMAN
    Recommended name:
    PH domain leucine-rich repeat-containing protein phosphatase 1
    Protein Accession:
    O60346
    Secondary Accessions:
    • A1A4F5
    • Q641Q7
    • Q6P4C4
    • Q6PJI6
    • Q86TN6
    • Q96FK2
    • Q9NUY1

    Protein attributes for PHLPP1 Gene

    Size:
    1717 amino acids
    Molecular mass:
    184672 Da
    Cofactor:
    Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Quaternary structure:
    • Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats (By similarity). Interacts with AKT2, AKT3, PRKCB isoform beta-II, STK4, RPS6KB1, RAF1 (PubMed:17386267, PubMed:18162466, PubMed:19732725, PubMed:21986499, PubMed:24530606). Isoform 1 (predominantly) and isoform 2 interact with BRAP (PubMed:25820252). Interacts with FKBP5; FKBP5 acts as a scaffold for PHLPP1 and Akt (PubMed:19732725). Interacts with SCRIB; SCRIB acts as a scaffold for PHLPP1 and Akt (PubMed:21701506). Interacts with SLC9A3R1; SLC9A3R1 scaffolds a heterotrimeric complex with PTEN at the plasma membrane (PubMed:21804599).
    SequenceCaution:
    • Sequence=AAH14927.3; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAH82244.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAI26278.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA91980.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for PHLPP1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PHLPP1 Gene

Proteomics data for PHLPP1 Gene at MOPED

Post-translational modifications for PHLPP1 Gene

  • Ubiquitination at Lys 246 and Lys 1146
  • Modification sites at PhosphoSitePlus

Other Protein References for PHLPP1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Domains & Families for PHLPP1 Gene

Suggested Antigen Peptide Sequences for PHLPP1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O60346

UniProtKB/Swiss-Prot:

PHLP1_HUMAN :
  • The PH domain is required for interaction with PRKCB and its dephosphorylation.
  • Contains 21 LRR (leucine-rich) repeats.
Domain:
  • The PH domain is required for interaction with PRKCB and its dephosphorylation.
  • Contains 1 PH domain.
  • Contains 1 PPM-type phosphatase domain.
Similarity:
  • Contains 21 LRR (leucine-rich) repeats.
genes like me logo Genes that share domains with PHLPP1: view

Function for PHLPP1 Gene

Molecular function for PHLPP1 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=1.5 mM for p-nitrophenyl phosphate {ECO:0000269 PubMed:24892992};
UniProtKB/Swiss-Prot CatalyticActivity:
[a protein]-serine/threonine phosphate + H(2)O = [a protein]-serine/threonine + phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Insensitive to okadaic acid.
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 AKT2 and AKT3, Ser-660 of PRKCB and Ser-657 of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). 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 suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). 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 (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T cells (By similarity).

Enzyme Numbers (IUBMB) for PHLPP1 Gene

Gene Ontology (GO) - Molecular Function for PHLPP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA,IPI 18162466
genes like me logo Genes that share ontologies with PHLPP1: view
genes like me logo Genes that share phenotypes with PHLPP1: view

Animal Models for PHLPP1 Gene

MGI Knock Outs for PHLPP1:

Animal Model Products

CRISPR Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PHLPP1 Gene

Localization for PHLPP1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PHLPP1 Gene

Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Note=In colorectal cancer tissue, expression is concentrated at the lateral membrane of epithelial cells.
Isoform 2: Cell membrane.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PHLPP1 Gene COMPARTMENTS Subcellular localization image for PHLPP1 gene
Compartment Confidence
cytosol 5
nucleus 5
plasma membrane 3
cytoskeleton 1
mitochondrion 1
peroxisome 1

No data available for Gene Ontology (GO) - Cellular Components for PHLPP1 Gene

Pathways & Interactions for PHLPP1 Gene

genes like me logo Genes that share pathways with PHLPP1: view

Pathways by source for PHLPP1 Gene

SIGNOR curated interactions for PHLPP1 Gene

Activates:
Inactivates:
Is inactivated by:

Gene Ontology (GO) - Biological Process for PHLPP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process IEA --
GO:0007173 epidermal growth factor receptor signaling pathway TAS --
GO:0008543 fibroblast growth factor receptor signaling pathway TAS --
GO:0009649 entrainment of circadian clock IEA --
GO:0043408 regulation of MAPK cascade IMP 24530606
genes like me logo Genes that share ontologies with PHLPP1: view

Drugs & Compounds for PHLPP1 Gene

(2) Drugs for PHLPP1 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Manganese Pharma 32
calcium Nutra 0

(3) Additional Compounds for PHLPP1 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 PHLPP1: view

Transcripts for PHLPP1 Gene

Unigene Clusters for PHLPP1 Gene

PH domain and leucine rich repeat protein phosphatase 1:
Representative Sequences:

CRISPR Products

miRNA Products

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for PHLPP1 Gene

No ASD Table

Relevant External Links for PHLPP1 Gene

GeneLoc Exon Structure for
PHLPP1
ECgene alternative splicing isoforms for
PHLPP1

Expression for PHLPP1 Gene

mRNA expression in normal human tissues for PHLPP1 Gene

Protein differential expression in normal tissues from HIPED for PHLPP1 Gene

This gene is overexpressed in Monocytes (30.0), Heart (10.8), and Neutrophil (10.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for PHLPP1 Gene



SOURCE GeneReport for Unigene cluster for PHLPP1 Gene Hs.465337

mRNA Expression by UniProt/SwissProt for PHLPP1 Gene

O60346-PHLP1_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 78% of tested tumors (at protein level). Ubiquitously expressed in non-cancerous tissues.
genes like me logo Genes that share expression patterns with PHLPP1: view

Protein tissue co-expression partners for PHLPP1 Gene

Primer Products

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 PHLPP1 Gene

Orthologs for PHLPP1 Gene

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

Orthologs for PHLPP1 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia PHLPP1 35
  • 84.89 (n)
  • 89.34 (a)
PHLPP1 36
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PHLPP1 35
  • 87.39 (n)
  • 90.11 (a)
PHLPP1 36
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Phlpp1 35
  • 86.09 (n)
  • 89.69 (a)
Phlpp1 16
Phlpp1 36
  • 84 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia PHLPP1 35
  • 99.36 (n)
  • 99.24 (a)
PHLPP1 36
  • 96 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Phlpp1 35
  • 85.78 (n)
  • 88.96 (a)
oppossum
(Monodelphis domestica)
Mammalia PHLPP1 36
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PHLPP1 36
  • 70 (a)
OneToOne
chicken
(Gallus gallus)
Aves PHLPP1 35
  • 81.26 (n)
  • 89.92 (a)
PHLPP1 36
  • 90 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PHLPP1 36
  • 86 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100497530 35
  • 72.77 (n)
  • 78.05 (a)
zebrafish
(Danio rerio)
Actinopterygii PHLPP1 36
  • 68 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Phlpp 36
  • 20 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea F43C1.1 36
  • 25 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CYR1 36
  • 12 (a)
OneToMany
CYR1 38
Species with no ortholog for PHLPP1:
  • 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)
  • 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 PHLPP1 Gene

ENSEMBL:
Gene Tree for PHLPP1 (if available)
TreeFam:
Gene Tree for PHLPP1 (if available)

Paralogs for PHLPP1 Gene

Paralogs for PHLPP1 Gene

(4) SIMAP similar genes for PHLPP1 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with PHLPP1: view

Variants for PHLPP1 Gene

Sequence variations from dbSNP and Humsavar for PHLPP1 Gene

SNP ID Clin Chr 18 pos Sequence Context AA Info Type
rs9950585 - 62,958,657(+) GCTAA(C/G)TGAAG reference, missense
rs483712 -- 62,926,685(-) ACTCG(A/G)AGATA intron-variant
rs484380 -- 62,915,305(-) AAGTG(A/G)GCCAA intron-variant
rs484571 -- 62,950,661(-) TATTA(G/T)GTCAA intron-variant
rs485784 -- 62,926,420(-) AGGGC(A/C)TCTTT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for PHLPP1 Gene

Variant ID Type Subtype PubMed ID
esv2717197 CNV Deletion 23290073
esv2384564 CNV Deletion 18987734
esv267732 CNV Insertion 20981092
esv2659096 CNV Deletion 23128226
nsv525821 CNV Loss 19592680
esv2665321 CNV Deletion 23128226

Variation tolerance for PHLPP1 Gene

Residual Variation Intolerance Score: 6.46% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.82; 67.05% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for PHLPP1 Gene

HapMap Linkage Disequilibrium report
PHLPP1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PHLPP1 Gene

Disorders for PHLPP1 Gene

MalaCards: The human disease database

(1) MalaCards diseases for PHLPP1 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 PHLPP1

Genetic Association Database (GAD)
PHLPP1
Human Genome Epidemiology (HuGE) Navigator
PHLPP1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
PHLPP1
genes like me logo Genes that share disorders with PHLPP1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PHLPP1 Gene

Publications for PHLPP1 Gene

  1. PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. (PMID: 15808505) Gao T. … Newton A.C. (Mol. Cell 2005) 2 3 4 23 67
  2. Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis. (PMID: 19079341) Liu J. … Gao T. (Oncogene 2009) 3 23
  3. The phosphatase PHLPP controls the cellular levels of protein kinase C. (PMID: 18162466) Gao T. … Newton A.C. (J. Biol. Chem. 2008) 3 23
  4. 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) 3 23
  5. SCOP, a novel gene product expressed in a circadian manner in rat suprachiasmatic nucleus. (PMID: 10570941) Shimizu K. … Nagai K. (FEBS Lett. 1999) 2 3

Products for PHLPP1 Gene

Sources for PHLPP1 Gene

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