ID:PIAS4_HUMAN DESCRIPTION: RecName: Full=E3 SUMO-protein ligase PIAS4; EC=6.3.2.-; AltName: Full=PIASy; AltName: Full=Protein inhibitor of activated STAT protein 4; AltName: Full=Protein inhibitor of activated STAT protein gamma; Short=PIAS-gamma; 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, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. PATHWAY: Protein modification; protein sumoylation. SUBUNIT: Interacts with AR, AXIN1, GATA2, LEF1, TP53 and STAT1 (IFNG-induced). Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (By similarity). Interacts with TICAM1. Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G(1) phase. INTERACTION: Q16665:HIF1A; NbExp=3; IntAct=EBI-473160, EBI-447269; P42858:HTT; NbExp=3; IntAct=EBI-473160, EBI-466029; P61956:SUMO2; NbExp=3; IntAct=EBI-473160, EBI-473220; O75528:TADA3; NbExp=2; IntAct=EBI-473160, EBI-473249; P04637:TP53; NbExp=2; IntAct=EBI-473160, EBI-366083; SUBCELLULAR LOCATION: Nucleus, PML body. Note=Colocalizes with SUMO1 and TCF7L2/TCF4 and LEF1 in a subset of PML (promyelocytic leukemia) nuclear bodies. TISSUE SPECIFICITY: Highly expressed in testis and, at lower levels, in spleen, prostate, ovary, colon and peripheral blood leukocytes. DOMAIN: The LXXLL motif is a coregulator signature that is essential for transcriptional corepression. PTM: Sumoylated. Lys-35 is the main site of sumoylation. Sumoylation is required for TCF4 sumoylation and transcriptional activitation. Represses LEF1 transcriptional activity. SUMO1 is the preferred conjugate. 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=AAD45155.1; 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.
ModBase Predicted Comparative 3D Structure on Q8N2W9
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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:0006303 double-strand break repair via nonhomologous end joining GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway GO:0016055 Wnt signaling pathway GO:0016925 protein sumoylation GO:0032088 negative regulation of NF-kappaB transcription factor activity GO:0033235 positive regulation of protein sumoylation GO:0042359 vitamin D metabolic process GO:0045892 negative regulation of transcription, DNA-templated GO:1902174 positive regulation of keratinocyte apoptotic process GO:1902231 positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage