Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol PELP1 contributors: mct/npt/pgu - updated : 10-10-2017
HGNC name proline, glutamate and leucine rich protein 1
HGNC id 30134
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal leucine-abundant region interacting with HDAC2 and exhibited repressive activity when tethered to the chromatin
  • one zinc finger
  • ten nuclear receptor-interacting boxes (LXXLL motifs), which allow it to interact with ER and other nuclear hormone receptors
  • a glutamic acid-rich domain, and two proline-rich domains
  • a histone-binding domain, and recognizes histone modifications and interacts with several chromatin-modifying complexes
  • C-terminal glutamic acid-abundant region bound to the hypoacetylated histones H3 and H4 and prevented them from becoming substrates of histone acetyltransferase
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY storage , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text
  • located within nucleus, cytoplasm, dendritic/synaptic terminals, and astrocytic processes
  • highly localized in the cell nucleus of neurons, with some cytoplasm localization as well, and PELP1 is also localized at synaptic sites
  • basic FUNCTION
  • major keratinocyte cell envelope protein, playing a role in breast cancer tumorigenesis
  • participating in chromatin remodeling activity via displacement of histone 1 in cancer cells
  • promoting and maintaining the hypoacetylated state of histones at the target genomic site, and ER binding reverses its role to hyperacetylate histones through an as yet unidentified mechanism
  • scaffold protein/coactivator which may modulate glucocorticoid actions in the brain (
  • inhibited transactivation of glucocorticoid receptor (GR) by the ligand-independent activation function (AF)1 but potentiated the COOH-terminal AF2 domain, and likely mediating important cell variation in glucocorticoid responsiveness, in a c-Src-independent mechanism
  • implicated to be important for mediation of both the genomic and nongenomic signaling of 17beta-estradiol (E2)
  • critical for nongenomic and genomic signaling by E2
  • is a reader of H3 methylation marks and has a crucial role in modulating the histone code at the ESR1 target genes
  • proto-oncogene that functions as an ESR1 co-regulator
  • proto-oncogene PELP1 plays a vital role in rDNA transcription. PELP1 modulation of rRNA transcription, a key step in ribosomal biogenesis may have implications in PELP1-mediated oncogenic functions
  • central role for PELP1 in nonandrogenic activation of the androgen receptor in prostate cancer
  • is a reader of histone arginine methyl modifications and deregulation promotes tumor proliferation via epigenetic alterations at ESR1 target promoters
  • modulates several pathways including the molecular mechanisms of cancer, estrogen signaling, and breast cancer progression
  • is a scaffolding oncogenic protein that functions as a coregulator for a number of nuclear receptors
  • is a novel coregulator of nuclear hormone receptors and is implicated in playing a role in driving breast cancer and enhancing metastatic potential
  • essential role for PELP1 in E2-mediated rapid extranuclear signaling, neuroprotection, and cognitive function in the brain
  • scaffolding protein that functions as a coregulator of several transcription factors and nuclear receptors
  • plays essential roles in several pathways including hormonal signaling, cell cycle progression, ribosomal biogenesis, and the DNA damage response
  • cytoplasmic localization of PELP1 up-regulates pro-tumorigenic IKBKE and secreted inflammatory signals, which through paracrine macrophage activation regulates the migratory phenotype associated with breast cancer initiation
  • is a scaffold protein that interacts with ERs, kinase signaling factors, as well as proteins involved in chromatin remodeling and DNA repair
  • functions as a critical ESR1 coregulator in the brain to mediate E2 signaling and actions
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ESR1 (coactivator of ESR1), ESR target gene
  • interacting with histone 1 and 3, with more preference toward histone 1
  • interact with multiple steroid receptors, including androgen and glucocorticoid receptors (
  • interacts with GR in the nucleus but not cytoplasm and regulates GR transactivation in a complex manner depending on cell type
  • interacts with KDM1A (PELP1 has a role in defining KDM1A substrate specificity and has the potential to modulate histone methyl code at ESR1 target genes)
  • PELP1 and the PELP1-associated factor LAS1L are SENP3-sensitive targets of SUMO
  • LAS1L interacts with PELP1 and WDR18, the mammalian homologues of the budding yeast Rix1 complex, along with NOL9 and SENP3, to form a novel nucleolar complex that cofractionates with the 60S preribosomal subunit
  • ESR1 coregulator PELP1 plays an important role in ESR1 signaling and is a proto-oncogene with aberrant expression in breast cancer
  • PELP1-CARM1 interactions synergistically enhance ESR1 transactivation
  • interacts with the arginine methyltransferase PRMT6 and modifies PRMT6 functions
  • unexpected role for PELP1 in modulating TP53-mediated DNA damage response (DDR)
  • modification of PELP1 promotes the recruitment of MDN1 to pre-60S particles, while deSUMOylation is needed to release both MDN1 and PELP1 from pre-ribosomes
  • is an estrogen receptor (ESR1) coregulator protein
  • cell & other
    REGULATION
    activated by by both ESR1 and ESR2 and differentially regulated by selective estrogen receptor modulators
    Phosphorylated by ATM, ATR at Serine1033 by various DDR kinases like ATM and ATR
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast tumors
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is a much more sensitive marker than GATA3 for triple negative cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    is a much more sensitive marker than GATA3 for triple negative cancer
    ANIMAL & CELL MODELS