Speckle-type POZ protein (SPOP)
The protein contains 374 amino acids for an estimated molecular weight of 42132 Da.
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, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not lead to their proteasomal degradation. 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. Involved in the regulation of bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4 stability (PubMed:32109420). (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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The reference OMIM entry for this protein is 602650
Speckle-type poz protein; spop
CLONING
Nagai et al. (1997) observed that COS-7 cells immunostained with antiserum from a scleroderma patient showed a rough speckled pattern in nuclei. As the antiserum did not react with known spliceoform antigens, the authors immunoscreened a human HeLa cell cDNA library to identify the antigen. Using expression cloning, Nagai et al. (1997) isolated a novel cDNA, designated SPOP. The SPOP gene encodes a 374-amino acid polypeptide that contains a poxvirus and zinc finger (POZ) domain and an evolutionarily conserved N-terminal region. The protein colocalized with the splicing factor SNRPB (182282). Removal of either domain abolished the intranuclear speckled localization of the protein. By searching for sequences containing TRAF-like domains (see TRAF1, 601711), followed by RT-PCR of Jurkat human T-cell total RNA, Zapata et al. (2001) cloned SPOP. The deduced protein contains an N-terminal TRAF-like domain and a C-terminal POZ domain.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SPOP gene to chromosome 17 (TMAP RH102186).GENE FUNCTION
Zapata et al. (2001) found that the TRAF-like domain of SPOP interacted in vitro with TRAF1 and TRAF6 (602355), but not with other TRAF proteins tested. Liu et al. (2009) identified an ortholog of the human SPOP gene as a component in the Drosophila segmentation pathway. Spop interacted with segmental transcription factors Evx1 (142996), Evx2 (142991), and Ftz (184757), and mediated degeneration of the Drosophila JNK phosphatase Puckered. Overexpression of SPOP in HEK293 cells resulted in increased amounts of phosphorylated JNK. Microarray analysis detected high expression of SPOP was found in up to 99% of human renal cell carcinomas (RCC; 144700), but not in normal kidney tissue. Liu et al. (2009) suggested that SPOP may be a specific tumor marker for renal cell carcinoma. Theurillat et al. (2014) analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK (125264) and TRIM24 (603406) emerged as effector substrates consistently upregulated by SPOP mutants. Theurillat et al. (2014) highlighted DEK as a SPOP substrate that exhibited decreases in ubiquitylation and proteasomal degradation resulting from heteromeric complexes of wildtype and mutant SPOP protein. DEK stabilization promoted prostate epithelial cell invasion, which implicated DEK as an oncogenic effector.MOLECULAR GENETICS
- Serous Tumors Le Gallo et al. (2012) used whole-exome sequencing to comprehensively search for somatic mutations in 13 primary serous endometrial tumors (see 608089), and subsequently resequenced 18 genes that were mutated in more than 1 tumor and/or were components of an enriched functional grouping from 40 additional serous tumors. Le Gallo et al. (2012) identified a high frequency of somatic mutation (8%) in the SPOP gene. - Prostate Cancer Barbieri et al. (2012) sequenced the exomes of 112 prostate tumor (see 176807) and normal tissue pairs. New recurrent mutations were identified in multiple genes, including MED12 (300188) and FOXA1 (602294). SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6 to 15% of tumors across multiple independent cohorts. Prostate tumors with mutant SPOP lacked ETS family (s ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 602650 was added.
March 3, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).