InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PHLPP1

Summary

InnateDB Protein

IDBP-4329.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PHLPP1

Protein Name

PH domain and leucine rich repeat protein phosphatase 1

Synonyms

PHLPP; PLEKHE1; SCOP;

Species

Homo sapiens

Ensembl Protein

ENSP00000262719

InnateDB Gene

IDBG-4327 (PHLPP1)

Protein Structure

UniProt Annotation

Function

Protein phosphatase that mediates dephosphorylation of 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser- 657' of PRKCA. AKT1 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 AKT1 triggers apoptosis and suppression of tumor growth. Controls the phosphorylation of AKT2 and AKT3 more efficiently than that of AKT1. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Inhibits cancer cell proliferation and may act as a tumor suppressor. May act as a negative regulator of K-Ras signaling in membrane rafts. {ECO:0000269PubMed:15808505, ECO:0000269PubMed:17386267, ECO:0000269PubMed:18162466, ECO:0000269PubMed:19079341}.

Subcellular Localization

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

Disease Associations

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. {ECO:0000269PubMed:15808505, ECO:0000269PubMed:19079341}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 31 experimentally validated interaction(s) in this database.

Experimentally validated
Total	31 [view]
Protein-Protein	31 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003824	catalytic activity
GO:0004721	phosphoprotein phosphatase activity
GO:0005515	protein binding
GO:0046872	metal ion binding

Biological Process

GO:0006915	apoptotic process
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0009649	entrainment of circadian clock
GO:0016311	dephosphorylation
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0045087	innate immune response
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling

Cellular Component

GO:0005634	nucleus
GO:0005829	cytosol
GO:0016020	membrane

Protein Structure and Domains

PDB ID

InterPro

IPR001611 Leucine-rich repeat
IPR001849 Pleckstrin homology domain
IPR001932 Protein phosphatase 2C (PP2C)-like domain
IPR003591 Leucine-rich repeat, typical subtype

PFAM

PF00560
PF13504
PF13855
PF00169
PF00481
PF07228

PRINTS

PIRSF

SMART

SM00233
SM00331
SM00332
SM00369

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

O60346