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FLASH GENE
Symbol PIAS3 contributors: shn/mct - updated : 04-10-2017
HGNC name protein inhibitor of activated STAT, 3
HGNC id 16861
Location 1q21.1      Physical location : 145.575.987 - 145.586.546
Synonym name
  • zinc finger, MIZ-type containing 5
  • E3 SUMO-protein ligase PIAS3
  • protein inhibitor of activated STAT protein 3E3 SUMO-protein ligase PIAS3
  • protein inhibitor of activated STAT protein 3
    • Synonym symbol(s) FLJ14651, ZMIZ5
    DNA
    TYPE functioning gene
    STRUCTURE 10.56 kb     14 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D1S442 - D1S2344 - PIAS3 - D1S442 - D1S2612 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 2902 - 628 - 2016 26697750
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective    
    cells
    SystemCellPubmedSpeciesStageRna symbol
     mast cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a putative zinc finger binding motif
  • an LXXLL coregulator signature motif located within the N-terminal region requiremed for the interaction with RELA
  • a SAP (SAF-A/B,Acinus and PIAS) domain
  • a MIZ-type zinc finger
  • a conserved domain of 180 residues in PIAS proteins and its 'PINIT' motif as well as other conserved motifs (in the SAP box and in the RING domain), and this conserved proline, isoleucine, asparagine, isoleucine, threonine (PINIT) domain is thought to promote STAT3-PIAS3 interaction
    • HOMOLOGY
    interspecies ortholog to Pias3, Mus musculus
    ortholog to PIAS3, Pan troglodytes
    ortholog to Pias3, Rattus norvegicus
    intraspecies homolog to PIAS1
    homolog to PIASX
    homolog to PIASY
    Homologene
    FAMILY
  • protein inhibitor of activated (PIAS) signal transducer and activator of transcription (STAT) family of transcriptional modulators
  • PIAS family
    • CATEGORY chaperone/stress , regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    basic FUNCTION
  • a specific inhibitor of signal transducer and activator of transcription 3 (STAT3)
  • a key molecule in supressing the transcriptional activity of MITF and a role in mast cell and melanocyte development
  • modulating the ability of NCOA2 to mediate ligand-enhanced transcription activation positively or negatively, for different steroid receptors
  • may function as a modulator in suppressing the transcriptional activity of RELA
  • pias3-mediated SUMOylation of photoreceptor-specific transcription factors as a key mechanism of rod specification
  • acts as a dual-function transcriptional co-regulator to simultaneously coordinate expression of the Opn1mw and Opn1sw genes
  • Pias3-dependent SUMOylation has a role in both developing rods and cones and in regulating cone photoreceptor subtype specification
  • is a novel regulator of ERBB4 receptor tyrosine kinase, controlling its nuclear sequestration and function
  • PIAS3 primes ATR for checkpoint activation by sustaining its basal kinase activity, revealing a new function of the PIAS family in DNA damage signaling
  • functions as a positive regulator of HIF1A-mediated transcription by increasing its protein stability
  • is necessary for dorso-ventral patterning and visual response of retinal cones but is not required for rod photoreceptor differentiation
  • is implicated in guiding specification of rod and cone photoreceptors through post-translational modification of key retinal transcription factors
    • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text small ubiquitin-like modifier-E3 ligase which catalyzes the covalent attachment of a SUMO protein to specific target substrates
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
    protein
  • growth factor independent 1 transcription repressor, GFI1
  • signal transducer and activator of transcription 3 (acute-phase response factor), STAT3
  • high-mobility group (nonhistone chromosomal) protein isoform I-C, HMGI-C
  • transcriptional intermediary factor 2, TIF2
  • microphthalmia transcription factor, MITF
  • AT motif-binding factor 1, ATBF1
  • TRIM8 interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL6-dependent activation of STAT3
  • v-rel reticuloendotheliosis viral oncogene homolog A (avian), RELA
  • mineralocorticoid receptor, MR
  • TATA-binding protein, TBP
  • SERPINE1 mRNA binding protein 1, SERBP1
  • tripartite motif-containing 32, TRIM32
  • interaction between ZMIZ2 and PIAS proteins with higher preference for PIAS3
  • is a novel interaction partner of ERBB4 soluble intracellular domain (ICD)
  • PIAS3-mediated SUMOylation of endogenous RELA was induced by NFKB1 activation thus forming a negative regulatory loop (
  • TP;PIAS3 interaction through the 1-52 amino acid region of TP53, reduces TP53&
    • 8209;MDM2 complex formation, which not only increases the half-life of TP53, but also its transactivation of target genes
  • PIAS3 is a transcriptional corepressor of KLF1 for at least a subset of its target genes during erythropoiesis
  • is the only member of the PIAS family that is indispensable for ATR activation
  • PIAS3 physically associated with HIF1A, and PIAS3 enhances the transcriptional activity of HIF1A by increasing its protein stability
  • is a negative regulator of STAT3 activity
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    significantly lower, in women with endometriosis compared to women without endometriosis, and attenuation of PIAS3 causes likely aberrant activation of STAT3 in endometriosis, leading to inflammatory changes that may impair fertility or cause pain
    tumoral     --low  
    is more negatively correlated with STAT3 activation in the stepwise progress of astrocytomas and would indicate an unfavorable outcome
    tumoral     --low  
    in malignant mesothelioma is associated with increased STAT3 activation and poor patient survival
    Susceptibility
    Variant & Polymorphism
    Candidate gene for thrombocytopenia-absent radius syndrome TAR
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    may represent a promising lung cancer therapeutic target because of its TP53-independent efficacy
    ANIMAL & CELL MODELS