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FLASH GENE
Symbol PIAS4 contributors: SGE/npt - updated : 12-10-2009
HGNC name protein inhibitor of activated STAT, 4
HGNC id 17002
Location 19p13.3      Physical location : 4.007.748 - 4.038.065
Synonym name
  • zinc finger, MIZ-type containing 6
  • protein inhibitor of activated STAT protein PIASy
  • Synonym symbol(s) MGC35296, PIASY, Piasg, FLJ12419, PIAS-gamma, ZMIZ6
    DNA
    TYPE functioning gene
    STRUCTURE 30.32 kb     11 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1835 - 510 - Sachdev (2001)
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
     intestinesmall intestine  highly
     pancreas exocrine   moderately
    Lymphoid/Immunespleen   moderately
     thymus   predominantly
    Nervousbrain   moderately
    Reproductivefemale systemplacenta  moderately
     female systemovary  moderately
     female systembreastmammary gland moderately
     female systemuteruscervix moderately
     male systemtestis  highly
     male systemprostate  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES acid
    STRUCTURE
    motifs/domains
  • N-terminal domain of PIAS4 is sufficient for centromeric localization, and interacts with the KNTC1/ZW10 complex
  • a SAP domain
  • a SP-RING-type zinc finger
  • a coregulator signature LXXLL motif, essential for transcriptional corepression
  • a highly acidic region
  • conjugated Other
    HOMOLOGY
    interspecies ortholog to murine Pias4
    Homologene
    FAMILY
  • protein inhibitor of activated STAT protein family (PIAS)
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    text
  • colocalized with promyelocytic leukemia nuclear bodies (PML NBs)
  • redistribution of PIAS4 from the nucleus to the cytoplasm, where it accumulated in cytoplasmic granules that colocalized with TRIM32 (Albor 2006)
  • basic FUNCTION
  • involved in regulation of transcription, DNA-dependent, and in the development
  • binds to nuclear matrix-associated DNA sequences and targets LEF1 to nuclear bodies, suggesting that PIAS4-mediated subnuclear sequestration accounts for the repression of LEF1 activity (Sachdev 2001)
  • involved in the regulation of TGF-beta signaling using
  • the negative feedback loop
  • enhancing the conjugation of SUMO-2 to GATA-2
  • functioning as an E3-type small ubiquitin-like modifier (SUMO) ligase
  • stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor
  • playing a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53 pathway, the wnt pathway and the steroid hormone signaling pathway
  • acting as a transcriptional repressor (involved in gene silencing)
  • having inhibitory action on BMP-regulated SMAD activity due to direct physical interactions between SMADs and PIAS4 through its RING domain
  • stimulates sumoylation and transcriptional activity of TP53 and increases RB-dependent corepression through recruitment to E2F-responsive promoters (Bischof 2006)
  • is a regulator of cellular senescence and apoptosis (Bischof 2006)
  • suppresses TGF-beta signaling by interacting with and sumoylating SMAD3 (regulates TGF-beta/SMAD3-mediated signaling by stimulating sumoylation and nuclear export of SMAD3)(Imoto 2008)
  • negatively regulates ETV4-mediated transcription by both ETV4 sumoylation in a dependent and independent fashion (Nishida 2007)
  • controls ETS1 function, at least in part, by inhibiting ETS1 protein turnover via the ubiquitin-proteasome system (Nishida 2007)
  • recruited to DNA damage sites and needed for the productive association of TP53BP1, BRCA1, RNF168 with these regions of damage (Galanty 2009)
  • promotes double strand breaks repair and confers ionizing radiation resistance (Galanty 2009)
  • required for effective ubiquitin-adduct formation at site of DNA damage (Galanty 2009)
  • SUMO E3 ligase, required for mitotic SUMOylation of chromosomal proteins
  • fundamental mechanism of PIAS4 to localize in the centromeric region of chromosome to execute centromeric SUMOylation during mitosis
  • CELLULAR PROCESS nucleotide, transcription, regulation
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS development
    text Ubl conjugation pathway
    PATHWAY
    metabolism
    signaling
    a component
  • component of the DNA-damage response (Galanty 2009)
  • INTERACTION
    DNA binding to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs)
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • interaction of PIAS4 with GATA-2 can modulate GATA-mediated ET-1 transcription activity in endothelial cells through a RING-like domain-independent mechanism
  • AR (after treatment with IFNG)
  • LEF1 (after treatment with IFNG)
  • TP53 (after treatment with IFNG)
  • STAT1 (after treatment with IFNG)
  • interaction of PIAS4 with TRIM32, an E3-ubiquitin ligase promotes PIAS4 degradation and regulates UVB-induced keratinocyte apoptosis through NFkappaB (Albor 2006)
  • interaction partner of LEF1 (coexpression with LEF1 results in potent repression of LEF1 activity and in covalent modification of LEF1 with SUMO)(Sachdev 2001)
  • RB1CC1 interacting-protein (interaction depends on the integrity of the RING finger of PIAS4 and the C-terminus of RB1CC1)(Martin 2008)
  • cell & other
    REGULATION
    Other
  • sumoylated
  • ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS