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PHLPP1 PH domain and leucine rich repeat protein phosphatase 1 [ Homo sapiens (human) ]

Gene ID: 23239, updated on 12-Oct-2019

Summary

Official Symbol
PHLPP1provided by HGNC
Official Full Name
PH domain and leucine rich repeat protein phosphatase 1provided by HGNC
Primary source
HGNC:HGNC:20610
See related
Ensembl:ENSG00000081913 MIM:609396
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SCOP; PHLPP; PPM3A; PLEKHE1
Summary
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]
Expression
Broad expression in brain (RPKM 17.2), testis (RPKM 8.3) and 25 other tissues See more
Orthologs

Genomic context

See PHLPP1 in Genome Data Viewer
Location:
18q21.33
Exon count:
19
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 18 NC_000018.10 (62715445..62980433)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (60382672..60647676)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene zinc finger CCHC-type containing 2 Neighboring gene RNA, 7SL, cytoplasmic 705, pseudogene Neighboring gene RNA, U6 small nuclear 142, pseudogene Neighboring gene uncharacterized LOC105372160 Neighboring gene Sharpr-MPRA regulatory region 4133 Neighboring gene uncharacterized LOC105372161

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Pathways from BioSystems

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
    Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
  • DAP12 interactions, organism-specific biosystem (from REACTOME)
    DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
  • DAP12 signaling, organism-specific biosystem (from REACTOME)
    DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
  • Downstream signal transduction, organism-specific biosystem (from REACTOME)
    Downstream signal transduction, organism-specific biosystemThe role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of aro...
  • Downstream signaling events of B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Downstream signaling events of B Cell Receptor (BCR), organism-specific biosystemSecond messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidyinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RA...
  • Fc epsilon receptor (FCERI) signaling, organism-specific biosystem (from REACTOME)
    Fc epsilon receptor (FCERI) signaling, organism-specific biosystemMast cells (MC) are distributed in tissues throughout the human body and have long been recognized as key cells of type I hypersensitivity reactions. They also play important roles in inflammatory an...
  • GAB1 signalosome, organism-specific biosystem (from REACTOME)
    GAB1 signalosome, organism-specific biosystemGAB1 is recruited to the activated EGFR indirectly, through GRB2. GAB1 acts as an adaptor protein that enables formation of an active PIK3, through recruitment of PIK3 regulatory subunit PIK3R1 (also...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
    NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
  • Negative regulation of the PI3K/AKT network, organism-specific biosystem (from REACTOME)
    Negative regulation of the PI3K/AKT network, organism-specific biosystemThe PI3K/AKT network is negatively regulated by phosphatases that dephosphorylate PIP3, thus hampering AKT activation.
  • PI3K-Akt signaling pathway, organism-specific biosystem (from KEGG)
    PI3K-Akt signaling pathway, organism-specific biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
  • PI3K-Akt signaling pathway, conserved biosystem (from KEGG)
    PI3K-Akt signaling pathway, conserved biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
  • PI3K/AKT activation, organism-specific biosystem (from REACTOME)
    PI3K/AKT activation, organism-specific biosystemPI3K/AKT signalling is a major regulator of neuron survival. It blocks cell death by both impinging on the cytoplasmic cell death machinery and by regulating the expression of genes involved in cell...
  • PIP3 activates AKT signaling, organism-specific biosystem (from REACTOME)
    PIP3 activates AKT signaling, organism-specific biosystemSignaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimula...
  • Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystem (from REACTOME)
    Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystemThe lipid raft resident adaptor molecules LAT1 and Non-T cell activation linker (NTAL), also known as linker for activation of B cells (LAB)/LAT2 are known participants in the regulation of mast cell...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by EGFR, organism-specific biosystem (from REACTOME)
    Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
  • Signaling by PDGF, organism-specific biosystem (from REACTOME)
    Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
  • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
    Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
  • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
  • Signalling by NGF, organism-specific biosystem (from REACTOME)
    Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC161555

Gene Ontology Provided by GOA

Function Evidence Code Pubs
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein serine/threonine phosphatase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
apoptotic process IEA
Inferred from Electronic Annotation
more info
 
entrainment of circadian clock IEA
Inferred from Electronic Annotation
more info
 
negative regulation of protein kinase B signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of protein kinase B signaling TAS
Traceable Author Statement
more info
 
protein dephosphorylation IEA
Inferred from Electronic Annotation
more info
 
regulation of JNK cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of JNK cascade IDA
Inferred from Direct Assay
more info
PubMed 
regulation of MAPK cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of T cell anergy IEA
Inferred from Electronic Annotation
more info
 
regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
regulation of p38MAPK cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of p38MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
nuclear membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
PH domain leucine-rich repeat-containing protein phosphatase 1
Names
PH domain-containing family E member 1
SCN circadian oscillatory protein
pleckstrin homology domain containing, family E (with leucine rich repeats) member 1
protein phosphatase, Mg2+/Mn2+ dependent 3A
suprachiasmatic nucleus circadian oscillatory protein
NP_919431.2
XP_011524188.1
XP_024306873.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_031923.1 RefSeqGene

    Range
    5103..269995
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_194449.4NP_919431.2  PH domain leucine-rich repeat-containing protein phosphatase 1

    See identical proteins and their annotated locations for NP_919431.2

    Status: REVIEWED

    Source sequence(s)
    AC015989, AC022046, AC027553, BC126277
    Consensus CDS
    CCDS45881.2
    UniProtKB/Swiss-Prot
    O60346
    Related
    ENSP00000262719.4, ENST00000262719.10
    Conserved Domains (6) summary
    smart00332
    Location:11681420
    PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain
    cd00116
    Location:625929
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd13322
    Location:535631
    PH_PHLPP-like; PH domain leucine-rich repeat protein phosphatase family Pleckstrin homology-like domain
    sd00033
    Location:833853
    LRR_RI; leucine-rich repeat [structural motif]
    pfam00169
    Location:555636
    PH; PH domain
    pfam13855
    Location:10141072
    LRR_8; Leucine rich repeat

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20190905

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p13 Primary Assembly

    Range
    62715445..62980433
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011525886.1XP_011524188.1  PH domain leucine-rich repeat-containing protein phosphatase 1 isoform X2

    Conserved Domains (6) summary
    COG4886
    Location:6771051
    LRR; Leucine-rich repeat (LRR) protein [Transcription]
    cd00116
    Location:625929
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd13322
    Location:535631
    PH_PHLPP-like; PH domain leucine-rich repeat protein phosphatase family Pleckstrin homology-like domain
    sd00033
    Location:833853
    LRR_RI; leucine-rich repeat [structural motif]
    pfam00169
    Location:555636
    PH; PH domain
    pfam13855
    Location:638703
    LRR_8; Leucine rich repeat
  2. XM_024451105.1XP_024306873.1  PH domain leucine-rich repeat-containing protein phosphatase 1 isoform X1

    Conserved Domains (4) summary
    smart00332
    Location:627879
    PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain
    sd00033
    Location:292312
    LRR_RI; leucine-rich repeat [structural motif]
    cl17171
    Location:190
    PH-like; Pleckstrin homology-like domain
    cl26793
    Location:98585
    PLN00113; leucine-rich repeat receptor-like protein kinase; Provisional
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