GeneID: 262


Common Name: SPOP Type: Gene
Chromosome: 17 (NC_000017.11) Locus: NG_041815.1 (SPOP)
HUGO Symbol: SPOP Full Name: speckle type BTB/POZ protein
Exons: 11 Introns: 10

Speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) is an E3 ubiquitin ligase adaptor protein. E3 ubiquitin ligases catalyze ubiquitin transfer to target substrates, therefore playing essential roles in diverse biological pathways. CRLs (Cullin-RING Ligases) are the largest group of E3 ligases, constructed around a Cullin family of scaffold proteins (CUL1 to CUL7). SPOP binds to CUL3 via the BTB domain to form a complex for ubiquitinating target proteins, leading most often to their proteasomal degradation. SPOP is expressed across a broad range of tissues. It is highly enriched in erythroid cells and its mRNA levels are comparable between adult and foetal erythroblasts. SPOP modulates the transcriptional repression activities of death-associated protein 6 (DAXX), which interacts with histone deacetylase, core histones, and other histone-associated proteins. SPOP is frequently mutated or has altered expression in various cancers, including prostate, renal and endometrial. Protein domain-focused CRISPR-Cas screening in HUDEP-2 cells identified SPOP as a potential HbF repressor. The repressive role of SPOP on γ-globin gene expression is dependent on the CUL3 ubiquitin ligase complex and appears to use a mechanism that does not involve the direct HbF repressors BCL11A and LRF.

Synonyms: TEF2 , BTBD32


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Publications / Origin

  1. Kwon JE, La M, Oh KH, Oh YM, Kim GR, Seol JH, Baek SH, Chiba T, Tanaka K, Bang OS, Joe CO, Chung CH, BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase., J. Biol. Chem., 281(18), 12664-72, 2006 PubMed
  2. Sarikas A, Hartmann T, Pan ZQ, The cullin protein family., Genome Biol., 12(4), 220, 2011 PubMed
  3. Wei X, Fried J, Li Y, Hu L, Gao M, Zhang S, Xu B, Functional roles of Speckle-Type Poz (SPOP) Protein in Genomic stability., J Cancer, 9(18), 3257-3262, 2018 PubMed
  4. Lan X, Khandros E, Huang P, Peslak SA, Bhardwaj SK, Grevet JD, Abdulmalik O, Wang H, Keller CA, Giardine B, Baeza J, Duffner ER, El Demerdash O, Wu XS, Vakoc CR, Garcia BA, Hardison RC, Shi J, Blobel GA, The E3 ligase adaptor molecule SPOP regulates fetal hemoglobin levels in adult erythroid cells., Blood Adv, 3(10), 1586-1597, 2019 PubMed
Created on 2019-06-26 09:36:37, Last reviewed on (Show full history)

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