ID:PIAS3_HUMAN DESCRIPTION: RecName: Full=E3 SUMO-protein ligase PIAS3; EC=6.3.2.-; AltName: Full=Protein inhibitor of activated STAT protein 3; FUNCTION: Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway and the steroid hormone signaling pathway. Involved in regulating STAT3 signaling via inhibiting STAT3 DNA-binding and suppressing cell growth. PATHWAY: Protein modification; protein sumoylation. SUBUNIT: Monomer (By similarity). Binds SUMO1 and UBE2I. Interacts with BCL11A, HMGA2, IRF1, MITF and NCOA2. Interacts with STAT5; the interaction occurs on stimulation by PRL. Interacts with GFI1; the interaction relieves the inhibitory effect of PIAS3 on STAT3- mediated transcriptional activity (By similarity). Interacts with AR, PLAG1 and ZFHX3. Interacts with STAT3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Mainly cytoplasmic but shuttles between the nucleus and cytoplasm. Transported to the nucleus on interaction with phosphorylated STAT3. Colocalizes with GFI1 in nuclear dots (By similarity). TISSUE SPECIFICITY: Isoform 1 is expressed in most tissues except thymus and small intestine. Isoform 3 is expressed only in brain, heart, thymus, muscle, lung, testis, lactating breast and embryonic stem cells. INDUCTION: By dihydrotestosterone (DHT) in prostate cancer cells. DOMAIN: The PINIT domain of PIAS3 is required for STAT3-PIAS3 interaction and for transloaction to the nucleus. DOMAIN: The LXXLL motif is a transcriptional coregulator signature. PTM: Sumoylated (By similarity). SIMILARITY: Belongs to the PIAS family. SIMILARITY: Contains 1 PINIT domain. SIMILARITY: Contains 1 SAP domain. SIMILARITY: Contains 1 SP-RING-type zinc finger. SEQUENCE CAUTION: Sequence=BAA78533.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 68906 - SAP domain 57850 - RING/U-box
ModBase Predicted Comparative 3D Structure on Q9Y6X2
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0009725 response to hormone GO:0010628 positive regulation of gene expression GO:0010629 negative regulation of gene expression GO:0016925 protein sumoylation GO:0033234 negative regulation of protein sumoylation GO:0033235 positive regulation of protein sumoylation GO:0045671 negative regulation of osteoclast differentiation GO:0045838 positive regulation of membrane potential GO:0045892 negative regulation of transcription, DNA-templated GO:0071847 TNFSF11-mediated signaling pathway