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FLASH GENE
Symbol PIAS1 contributors: mct/ - updated : 08-03-2019
HGNC name protein inhibitor of activated STAT, 1
HGNC id 2752
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinethyroid   highly
Lymphoid/Immunelymph node   highly
Reproductivemale systemtestis  highly
Visualeye     Homo sapiens
cell lineage spermatogenic cells
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • putative zinc binding motif and a highly acidic region
  • SAP (SAF-A/B,Acinus and PIAS) domain
  • DNA binding (bihelical) motif
  • a chromatin-binding domain that targets PIAS1 to gene promoters to regulate transcription
    • HOMOLOGY
    interspecies homolog to murine Pias1
    Homologene
    FAMILY
  • PIAS family
    • CATEGORY chaperone/stress , enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    text
  • SAE1, UBE2I and PIAS1 are distributed in both nucleus and cytoplasm of ocular cell lines
    • basic FUNCTION
  • involved in androgen receptor initiation, function as a UBL1 (SUMO-E3) ligase or as a tightly bound regulator of it toward activation of TP53
  • regulate MEF2A (promotes sumoylation of MEF2A, and protein sumoylation could play a pivotal role in controlling MEF2 transcriptional activity)
  • confers DNA-binding specificity on the MSX1 homeoprotein by regulating its subnuclear localization and proximity to target genes
  • modulating the AR-dependent transactivation, which, at least in part, can be attributed to their SUMO-E3 activity toward AR
  • silencing transcription factor Sp3 through SUMO modification
  • role in ribosomal RNA biogenesis, editing transport and in general transcription
  • modulates transcriptional activation of smooth muscle cells marker genes through cooperative interactions with both SRF and class I bHLH proteins
  • with AIRE interact functionally to regulate the activities of the target genes of AIRE
  • regulating STAT1 signaling upon PRMT1-mediated arginine methylation
  • promotes myogenic differentiation by specifically inhibiting the JAK1/STAT1/STAT3 pathway
  • recruited to DNA damage sites and needed for the productive association of TP53BP1, BRCA1, RNF168 with these regions of damage
  • promotes double strand breaks repair and confers ionizing radiation resistance
  • required for effective ubiquitin-adduct formation at site of DNA damage
  • acts by binding to the FOXP3 promoter to recruit DNA methyltransferases and heterochromatin protein 1 for epigenetic modifications
  • may be an important cofactor that confers specificity in the DNMT-mediated chromatin methylation
  • recruited to STAT1 target gene promoters in a PRMT1- and methylation-dependent manner
  • PIAS1 may play a crucial role in the regulation of NCOA3 transcriptional activity through sumoylation
  • PIAS1 may serve as a lipogenic regulator by negatively modulating LXRs in a SUMOylation-independent manner
  • PIAS1 may likely play a negative role in the control of lipogenesis by attenuating LXR-dependent up-regulation of the lipogenic gene expression program
  • suppressive action of PIAS1 on NR1H2, NR1H3-activated gene expression programs, particularly in lipogenesis
  • PIAS1 could play a dynamic role in adipogenesis by promoting the SUMOylation of CEBPB (pMID: 24061474)
  • novel role of PIAS1 in maintaining the quiescence of dormant hematopoietic stem cells and in the epigenetic repression of the myeloerythroid program
  • important cell cycle regulator and PIAS1-mediated SUMOylation is essential for DNA repair
  • PIAS1-mediated sumoylation status of TERF2 serves as a molecular switch that controls the level of TERF2 at telomeres
  • PIAS1 acts as a "protein inhibitor of activated MYB" in the absence of SUMOylation while, in its presence, PIAS1 behaves as a "protein activator of repressed MYB"
  • implicated in several biological processes including repression of innate immunity and DNA repair
  • is required for proper embryonic development
  • potential role for the PIAS1-SKIL sumoylation pathway in controlling breast cancer metastasis
  • crucial role of PIAS1-mediated PPARG SUMOylation in protecting against myocardial ischemia-reperfusion injury (IRI)
    • CELLULAR PROCESS cell life, cell death/apoptosis
    protein, degradation
    PHYSIOLOGICAL PROCESS
    text ubiquitin degradation
    PATHWAY
    metabolism
    signaling
    a component
  • non-covalent ternary complex formed by PIAS1, SUMO1, and UBE2I proteins involved in transcriptional regulation
    • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • GU binding
    • protein
  • binding to coactivator of androgen and glucocorticoid receptors, corepressor of progesterone receptor, counteracted by other member of the PIAS family (MIZ1, PIAS3)
  • binding to UBL1, TP53
  • inhibiting STAT1 mediated gene activation in response to interferon
  • binding to ATP dependent RNA helicase
  • interacting with Sp3
  • binding UBC9 the E2 enzyme for SUMO-1, in a RING finger-like domain-dependent manner
  • interacting with ESR1
  • negative regulator of NF-kappaB
  • interacting with GRM8
  • interacting with PRMT1 (arginine methylation of PIAS1 is essential for the repressive function of PRMT1 in IFN-dependent transcription and for the recruitment of PIAS1 to STAT1 target gene promoters in the late phase of the IFN response)
  • enhancing the transcriptional repression activity of ZNF133 through the zinc finger motifs
  • targeting activated STAT1 and prevents its binding to DNA
  • ZMYND11 interacts with PIAS1 (a well-characterized SUMO E3 enzyme) and UBE2I (the only SUMO E2 enzyme so far identified) through its distinct regions
  • associated with DNMT3A and DNMT3B in T cells and is required for their recruitment to the FOXP3 gene promoter
  • is a common partner for two cancer-related nuclear factors, MYB and CASP8AP2 (functional cooperation between CASP8AP2 and PIAS1 in the enhancement of MYB activity in active nuclear foci)
  • PIAS1 was able to interact with NR1H2 and repress its transcriptional activity upon ligand stimulation, which did not require PIAS1-promoted SUMO modification of NR1H2
  • PIAS1 could associate with LXRs and may thereby exert its effect upon LXR-activated gene transcription
  • interacts with PPARGC1B and affects its SUMOylation and co-activation activity
  • direct interaction between STIP1 and PIAS1 is involved in the accumulation of nuclear STIP1, and this retention mechanism could facilitate nuclear chaperone activity
  • PIAS1 functions as a SUMO E3 ligase of CEBPB to regulate adipogenesis
  • SENP1 can deSUMOylate SUMOylated HMGN2, and PIAS1 is the E3 ligase responsible for SUMOylation of HMGN2
  • NDN bound to PIAS1 central domains that are highly conserved among PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates STAT1 and PML
  • RECQL5 helicase promotes TOP1 SUMOylation by facilitating the interaction between PIAS1, SRSF1 and TOP1
  • TERF2 specifically interacts with and is sumoylated by PIAS1 in mammalian cells
  • PIAS1 causes activation or repression of MYB dependent target genes
  • PIAS1 protein regulation of cardiac gene transcription is dependent on transcription factors Myocardin and GATA4
  • PIAS1 is a positive regulator of MYC
  • inhibitor of IFN-activated transcription factor STAT1
  • novel function of CDKN2A to inhibit PIAS1 by enhancing SUMOylation to promote the robust induction of IFNG response
  • PIAS1 is a specific E3 ligase for PPARG SUMOylation
    • cell & other
  • binds to chromatin to repress transcription
    • REGULATION
    Other activating MAPK8 (JNK1-cJUN-NH2 terminal kinase) and inducing apoptosis
    modifying MDM2 (sumoylation)
    methylated by PRMT1 mediation
    PIAS1 function is negatively modulated by SUMO modification and that SUMOylation by CDKN2A is required to inhibit PIAS1 activity
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    caused promoter demethylation, reduced histone H3 methylation at Lys9, and enhanced promoter accessibility
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • PIAS1 is a prognostic biomarker in breast cancer
    • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    PIAS1 is a promising target protein for a combined treatment approach to improve future PCa therapies
    ANIMAL & CELL MODELS
  • Pias1&
    • 8722;/&
    8722; mice displayed an increased natural Treg cell population and were resistant to the development of experimental autoimmune encephalomyelitis