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. Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.17
Pathway: Protein modification; protein sumoylation.
Subunit structure: 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 G1 phase. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.11 Ref.14
Subcellular location: Nucleus › PML body. Note: Colocalizes with SUMO1 and TCF7L2/TCF4 and LEF1 in a subset of PML (promyelocytic leukemia) nuclear bodies. Ref.4 Ref.8 Ref.12
Tissue specificity: Highly expressed in testis and, at lower levels, in spleen, prostate, ovary, colon and peripheral blood leukocytes. Ref.5
Domain: The LXXLL motif is a coregulator signature that is essential for transcriptional corepression.
Post-translational modification: Sumoylated. Lys-35 is the main site of sumoylation. Sumoylation is required for TCF4 sumoylation and transcriptional activation. Represses LEF1 transcriptional activity. SUMO1 is the preferred conjugate. Ref.12
Sequence similarities: Belongs to the PIAS family.Contains 1 PINIT domain.Contains 1 SAP domain.Contains 1 SP-RING-type zinc finger.
Sequence caution: The sequence AAD45155.1 differs from that shown. Reason: Erroneous initiation.
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