SPOP

For the animated series, see She-Ra: Princess of Power and She-Ra and the Princesses of Power.

For the Singaporean singing competition, see SPOP Sing! (season 1) and SPOP Wave.

SPOP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CR2, 3HQH, 3HQI, 3HQL, 3HQM, 3HTM, 3HU6, 3IVB, 3IVQ, 3IVV, 4EOZ, 4HS2, 4J8Z, 4O1V
Identifiers
Aliases	SPOP , BTBD32, TEF2, speckle type BTB/POZ protein, NEDMIDF, NSDVS1, NSDVS2, NEDMACE
External IDs	OMIM: 602650; MGI: 1343085; HomoloGene: 68354; GeneCards: SPOP; OMA:SPOP - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q21.33 Start 49,598,884 bp [1] End 49,678,163 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 D|11 59.01 cM Start 95,304,906 bp [2] End 95,384,232 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in nipple muscle layer of sigmoid colon saphenous vein pylorus seminal vesicula popliteal artery tibial arteries urethra cardia smooth muscle tissue Top expressed in temporal muscle triceps brachii muscle cerebellar vermis ankle lobe of cerebellum sternocleidomastoid muscle neural layer of retina digastric muscle parotid gland blood More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding ubiquitin protein ligase binding Cellular component Cul3-RING ubiquitin ligase complex nuclear speck nucleus nucleoplasm cytoplasm SCF ubiquitin ligase complex Biological process protein ubiquitination regulation of proteolysis negative regulation of transcription by RNA polymerase II glucose homeostasis proteasome-mediated ubiquitin-dependent protein catabolic process negative regulation of DNA-binding transcription factor activity positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway positive regulation of type B pancreatic cell apoptotic process ubiquitin-dependent protein catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8405 20747 Ensembl ENSG00000121067 ENSMUSG00000057522 UniProt O43791 Q6ZWS8 RefSeq (mRNA) NM_001007226 NM_001007227 NM_001007228 NM_001007229 NM_001007230 NM_003563 NM_001370730 NM_001370731 NM_001370732 NM_025287 NM_001359107 RefSeq (protein) NP_001007227 NP_001007228 NP_001007229 NP_001007230 NP_001007231 NP_003554 NP_001357659 NP_001357660 NP_001357661 NP_079563 NP_001346036 Location (UCSC) Chr 17: 49.6 – 49.68 Mb Chr 11: 95.3 – 95.38 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Speckle-type POZ protein is a protein that in humans is encoded by the SPOP gene. ^{[5] [6] [7]}

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. ^[7]

DNA repair

The spop gene is the gene most commonly point mutated in human primary prostate cancers. ^[8] SPOP protein is essential for the repair of DNA-protein crosslinks by removing topoisomerase 2A from the topoisomerase2A-DNA cleavage complex formed during repair. ^[8]

Clinical relevance

Mutations in SPOP lead to a type of prostate tumor thought to be involved in about 15% of all prostate cancers. ^{[9] [10]}

References

1. GRCh38: Ensembl release 89: ENSG00000121067 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000057522 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Nagai Y, Kojima T, Muro Y, Hachiya T, Nishizawa Y, Wakabayashi T, Hagiwara M (Nov 1997). "Identification of a novel nuclear speckle-type protein, SPOP". FEBS Letters. 418 (1–2): 23–6. doi: 10.1016/S0014-5793(97)01340-9 . PMID   9414087. S2CID   32204506.
6. Zapata JM, Pawlowski K, Haas E, Ware CF, Godzik A, Reed JC (Jun 2001). "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains". The Journal of Biological Chemistry. 276 (26): 24242–52. doi: 10.1074/jbc.M100354200 . PMID   11279055.
7. "Entrez Gene: SPOP speckle-type POZ protein".
8. Watanabe R, Maekawa M, Hieda M, Taguchi T, Miura N, Kikugawa T, Saika T, Higashiyama S (March 2020). "SPOP is essential for DNA-protein cross-link repair in prostate cancer cells: SPOP-dependent removal of topoisomerase 2A from the topoisomerase 2A-DNA cleavage complex". Mol Biol Cell. 31 (6): 478–490. doi:10.1091/mbc.E19-08-0456. PMC   7185892 . PMID   31967940.
9. Heidi Evans (20 May 2012). "Scientists find new type of prostate cancer - discovery may lead to tailored treatments". New York Daily News. Retrieved 20 May 2012.
10. Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA (Jun 2012). "Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer". Nature Genetics. 44 (6): 685–9. doi:10.1038/ng.2279. PMC   3673022 . PMID   22610119.

Further reading

• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi: 10.1101/gr.6.9.791 . PMID   8889548.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Wu J, Song Y, Bakker AB, Bauer S, Spies T, Lanier LL, Phillips JH (Jul 1999). "An activating immunoreceptor complex formed by NKG2D and DAP10". Science. 285 (5428): 730–2. doi:10.1126/science.285.5428.730. PMID   10426994.
• Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• Zapata JM, Pawlowski K, Haas E, Ware CF, Godzik A, Reed JC (Jun 2001). "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains". The Journal of Biological Chemistry. 276 (26): 24242–52. doi: 10.1074/jbc.M100354200 . PMID   11279055.
• Takahashi I, Kameoka Y, Hashimoto K (Aug 2002). "MacroH2A1.2 binds the nuclear protein Spop". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1591 (1–3): 63–8. doi: 10.1016/S0167-4889(02)00249-5 . PMID   12183056.
• Gilfillan S, Ho EL, Cella M, Yokoyama WM, Colonna M (Dec 2002). "NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation". Nature Immunology. 3 (12): 1150–5. doi:10.1038/ni857. PMID   12426564. S2CID   5859797.
• Diefenbach A, Tomasello E, Lucas M, Jamieson AM, Hsia JK, Vivier E, Raulet DH (Dec 2002). "Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D". Nature Immunology. 3 (12): 1142–9. doi:10.1038/ni858. PMID   12426565. S2CID   14901451.
• Billadeau DD, Upshaw JL, Schoon RA, Dick CJ, Leibson PJ (Jun 2003). "NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway". Nature Immunology. 4 (6): 557–64. doi:10.1038/ni929. PMID   12740575. S2CID   7699074.
• Liu A, Desai BM, Stoffers DA (May 2004). "Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity". Molecular and Cellular Biology. 24 (10): 4372–83. doi:10.1128/MCB.24.10.4372-4383.2004. PMC   400448 . PMID   15121856.
• La M, Kim K, Park J, Won J, Lee JH, Fu YM, Meadows GG, Joe CO (Jul 2004). "Daxx-mediated transcriptional repression of MMP1 gene is reversed by SPOP". Biochemical and Biophysical Research Communications. 320 (3): 760–5. doi:10.1016/j.bbrc.2004.06.022. hdl: 10203/14362 . PMID   15240113.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC   528930 . PMID   15489336.
• Hernández-Muñoz I, Lund AH, van der Stoop P, Boutsma E, Muijrers I, Verhoeven E, Nusinow DA, Panning B, Marahrens Y, van Lohuizen M (May 2005). "Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase". Proceedings of the National Academy of Sciences of the United States of America. 102 (21): 7635–40. doi: 10.1073/pnas.0408918102 . PMC   1140410 . PMID   15897469.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (Jan 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415-8. doi:10.1093/nar/gkj139. PMC   1347501 . PMID   16381901.