Description: Homo sapiens PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1), mRNA. RefSeq Summary (NM_194449): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data because no single transcript was available for the full length of the gene. The extent of this transcript is supported by transcript alignments and orthologous data. CCDS Note: The coding region has been updated to extend the N-terminus to one that is more supported by available conservation data and publications. There are no publicly available human transcripts that include the extended region. However, the update is supported by homologous transcript data and is consistent with the full-length 190 kDa human isoform described in the literature. This 190 kDa product, known as PHLPP1beta, has been detected in several studies, including PMIDs 17386267, 19079341, 20089132, 20819118 and 20861921. Transcript (Including UTRs) Position: hg19 chr18:60,382,672-60,647,676 Size: 265,005 Total Exon Count: 17 Strand: + Coding Region Position: hg19 chr18:60,382,917-60,646,664 Size: 263,748 Coding Exon Count: 17
ID:PHLP1_HUMAN DESCRIPTION: RecName: Full=PH domain leucine-rich repeat-containing protein phosphatase 1; EC=3.1.3.16; AltName: Full=Pleckstrin homology domain-containing family E member 1; Short=PH domain-containing family E member 1; AltName: Full=Suprachiasmatic nucleus circadian oscillatory protein; Short=hSCOP; 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. CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein + phosphate. COFACTOR: Binds 2 manganese ions per subunit (By similarity). ENZYME REGULATION: Insensitive to okadaic acid. SUBUNIT: Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats (By similarity). Interacts with AKT2, AKT3 and PRKCB isoform beta-II. SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Note=In colorectal cancer tissue, expression is concentrated at the lateral membrane of epithelial cells. 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. DOMAIN: The PH domain is required for interaction with PRKCB and its dephosphorylation. SIMILARITY: Contains 21 LRR (leucine-rich) repeats. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 1 PP2C-like domain. SEQUENCE CAUTION: Sequence=AAH14927.3; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAH82244.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; Sequence=AAI26278.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAA91980.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 50729 - PH domain-like 52047 - RNI-like 52058 - L domain-like 52075 - Outer arm dynein light chain 1 81606 - Protein serine/threonine phosphatase 2C, catalytic domain
ModBase Predicted Comparative 3D Structure on O60346
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002667 regulation of T cell anergy GO:0006470 protein dephosphorylation GO:0006915 apoptotic process GO:0009649 entrainment of circadian clock GO:0042981 regulation of apoptotic process GO:0043408 regulation of MAPK cascade GO:0046328 regulation of JNK cascade GO:0051898 negative regulation of protein kinase B signaling GO:0090036 regulation of protein kinase C signaling GO:1900744 regulation of p38MAPK cascade
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