SPOP
Description
The SPOP (speckle type BTB/POZ protein) is a protein-coding gene located on chromosome 17.
Speckle-type POZ protein is a protein that in humans is encoded by the SPOP gene. This gene encodes a protein that may modulate the transcriptional repression activities of death-associated protein 6 (DAXX), which interacts with histone deacetylase, core histones, and other histone-associated proteins. In mouse, the encoded protein binds to the putative leucine zipper domain of macroH2A1.2, a variant H2A histone that is enriched on inactivated X chromosomes. The BTB/POZ domain of this protein has been shown in other proteins to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes. Alternative splicing of this gene results in multiple transcript variants encoding the same protein.
== Clinical relevance == Mutations in SPOP lead to a type of prostate tumor thought to be involved in about 15% of all prostate cancers.
SPOP is a component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. In complex with CUL3, it is involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, it is involved in ubiquitination of MACROH2A1 and BMI1, however, this does not lead to their proteasomal degradation. SPOP inhibits transcriptional activation of PDX1/IPF1 targets, such as insulin, by promoting PDX1/IPF1 degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL. SPOP is involved in the regulation of bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4 stability. It plays an essential role for proper translation, but not for their degradation, of critical DNA replication licensing factors CDT1 and CDC6, thereby participating in DNA synthesis and cell proliferation. SPOP regulates interferon regulatory factor 1/IRF1 proteasomal turnover by targeting S/T-rich degrons in IRF1. It facilitates the lysosome-dependent degradation of enterovirus EV71 protease 2A by inducing its 'Lys-48'-linked polyubiquitination, which ultimately restricts EV71 replication. SPOP acts as an antiviral factor also against hepatitis B virus/HBV by promoting ubiquitination and subsequent degradation of HNF1A. In turn, it inhibits HBV transcription and replication by preventing HNF1A stimulating activity of HBV preS1 promoter and enhancer II. SPOP interacts with GLI2 and GLI3. It forms homodimers and homooligomers. It also forms heterodimers with SPOPL. Each dimer interacts with two CUL3 molecules. SPOP is part of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain CUL3 and homodimeric SPOP, or the heterodimer formed by SPOP and SPOPL, plus a target protein, such as MACROH2A1, PDX1/IPF1, BMI1, BRMS1 and DAXX. It interacts with IRF1; this interaction mediates IRF1 proteasomal degradation. SPOP interacts with HNF1A.
SPOP is also known as BTBD32, NEDMACE, NEDMIDF, NSDVS1, NSDVS2, TEF2.
