SPOP Gene - Speckle Type BTB/POZ Protein
SPOP: A Key E3 Ubiquitin Ligase Adaptor in Cancer and Development
Gene Information Card
| Symbol | SPOP |
|---|---|
| Full Name | Speckle Type BTB/POZ Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.33 |
| NCBI Gene ID | 8405 ncbi.nlm.nih.gov/gene/8405 |
| Ensembl ID | ENSG00000139926 |
| UniProt ID | O43791 |
| OMIM ID | 602650 |
| HGNC ID | 11254 |
| Aliases | BTBD32, TEF2 |
Description
The SPOP gene encodes the speckle-type POZ protein, a substrate-binding adaptor for Cullin3-RING E3 ubiquitin ligase complexes. SPOP mediates ubiquitination and degradation of various proteins involved in transcriptional regulation, cell proliferation, and apoptosis. It is frequently mutated in several cancers, particularly prostate and endometrial cancers, and plays a critical role in development and cellular homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | Recurrent somatic mutations (e.g., F133V, F102C) in the MATH domain impair substrate binding, leading to accumulation of oncogenic proteins like AR, SRC-3, and DEK. | COSMIC; ClinVar; multiple studies |
| Endometrial Cancer | Recurrent mutations in the MATH domain (e.g., Y87C, S119N) disrupt ubiquitination of substrates, promoting tumorigenesis. | COSMIC; ClinVar |
| Breast Cancer | SPOP mutations or altered expression may affect ERα stability and signaling, contributing to tumor progression. | COSMIC; limited studies |
| Clear Cell Renal Cell Carcinoma | SPOP mutations are less frequent but may contribute to dysregulation of HIF pathway. | COSMIC |
| Neurodevelopmental Disorders | Germline mutations in SPOP have been associated with intellectual disability and developmental delay, though rare. | ClinVar; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | High | High expression in testis, consistent with role in spermatogenesis |
| Brain | Moderate | Widespread expression in brain regions |
| Kidney | Moderate | Expressed in renal tissues |
| Liver | Low | Low expression in liver |
| Prostate | Moderate | Expressed in prostate epithelial cells |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | Moderate | Cervical cancer cell line; used in functional studies |
| HEK293 | Moderate | Embryonic kidney cells; common for overexpression studies |
| LNCaP | High | Prostate cancer cell line; SPOP mutations present in some lines |
| MCF7 | Low | Breast cancer cell line; low endogenous expression |
| HCT116 | Moderate | Colorectal cancer cell line; used in ubiquitination assays |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| F133V | Missense | Recurrent in prostate cancer | Disrupts substrate binding; stabilizes oncogenic substrates |
| F102C | Missense | Recurrent in prostate cancer | Impairs MATH domain function |
| Y87C | Missense | Recurrent in endometrial cancer | Alters substrate specificity |
| S119N | Missense | Recurrent in endometrial cancer | Reduces ubiquitination activity |
| W131G | Missense | Rare in various cancers | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most SPOP mutations in cancer are loss-of-function, impairing substrate binding or ubiquitination, leading to accumulation of oncogenic proteins.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some variants may alter substrate specificity but not enhance activity.
Dominant Negative (DN)
Mutant SPOP can act in a dominant-negative manner by forming inactive complexes with wild-type SPOP, reducing overall ubiquitin ligase activity.
View complete mutation data：
Gene Ontology (GO)
| • Ubiquitin-protein transferase activity | • Protein binding |
| • Cullin family protein binding | • Zinc ion binding |
| • Nucleus | • Cytoplasm |
| • Speckle | • Ubiquitin-dependent protein catabolic process |
| • Proteasome-mediated ubiquitin-dependent protein catabolic process | • Regulation of transcription by RNA polymerase II |
Pathways
• Cullin-RING E3 ubiquitin ligase pathway
• Androgen receptor signaling pathway
• Hedgehog signaling pathway
• p53/TP53 degradation pathway
• Cell cycle regulation
Protein Summary
SPOP is a 374-amino acid protein with an N-terminal MATH domain (substrate binding) and a C-terminal BTB/POZ domain (dimerization and Cullin3 interaction). It functions as a substrate adaptor for CUL3-based E3 ligases, targeting proteins for proteasomal degradation. SPOP regulates key pathways including androgen receptor signaling, hedgehog signaling, and DNA damage response. Mutations in the MATH domain are oncogenic, leading to substrate stabilization and tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPOP Knockout HEK293 Cell Line | EDJ-KQ913 | Human | 8405 | Details Get a Quote |
| SPOPL Knockout HEK293 Cell Line | EDJ-KQ15490 | Human | 339745 | Details Get a Quote |
| SPOPL Knockout HCT 116 Cell Line | EDJ-KQ47184 | Human | 339745 | Details Get a Quote |
| SPOP Knockout HeLa Cell Line | EDJ-KQ18428 | Human | 8405 | Details Get a Quote |
| SPOP Knockout A-549 Cell Line | EDJ-KQ19769 | Human | 8405 | Details Get a Quote |
| SPOP Knockout HCT 116 Cell Line | EDJ-KQ19770 | Human | 8405 | Details Get a Quote |
| SPOPL Knockout HeLa Cell Line | EDJ-KQ45045 | Human | 339745 | Details Get a Quote |
| SPOPL Knockout A-549 Cell Line | EDJ-KQ46280 | Human | 339745 | Details Get a Quote |
| SPOP Knockout 5637 Cell Line | EDJ-KZ49 | Human | 8405 | Details Get a Quote |
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