PDCD10

Programmed cell death 10

Rendering based on PDB 3AJM.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsPDCD10 ; CCM3; TFAR15
External IDsOMIM: 609118 MGI: 1928396 HomoloGene: 10505 GeneCards: PDCD10 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez1123556426
EnsemblENSG00000114209ENSMUSG00000027835
UniProtQ9BUL8Q8VE70
RefSeq (mRNA)NM_007217NM_019745
RefSeq (protein)NP_009148NP_062719
Location (UCSC)Chr 3:
167.4 – 167.45 Mb		Chr 3:
75.52 – 75.56 Mb
PubMed search

Programmed cell death protein 10 is a protein that in humans is encoded by the PDCD10 gene.[1][2]

This gene encodes a protein, originally identified in a premyeloid cell line, with similarity to proteins that participate in apoptosis. Three alternative transcripts encoding the same protein, differing only in their 5' UTRs, have been identified for this gene.[2]

Gene

Loss of function mutations in PDCD10 result in the onset of Cerebral Cavernous Malformations (CCM) illness.[1] Therefore, this gene is also called CCM3. Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.

Interactions

CCM3 encodes a protein called Programmed Cell Death 10 (PDCD10). The function of this protein has only recently begun to be understood. PDCD10 has roles in vascular development and VEGF signaling1,[3] apoptosis[4] and functions as part of a larger signaling complex that includes germinal center kinase III,.[5][6] Specifically, PDCD10 has been shown to interact with RP6-213H19.1,[7] STK25,[7][8] STRN,[7] STRN3,[7] MOBKL3,[7] CTTNBP2NL,[7] STK24[7][8][9] and FAM40A.[7]

Model organisms

Model organisms have been used in the study of PDCD10 function. A conditional knockout mouse line, called Pdcd10tm1a(KOMP)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[12] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.[12]

References

  1. ↑ 1.0 1.1 Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, Coubes P, Echenne B, Ibrahim R, Irthum B, Jacquet G, Lonjon M, Moreau JJ, Neau JP, Parker F, Tremoulet M, Tournier-Lasserve E (Dec 2004). "Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations". Am J Hum Genet 76 (1): 42–51. doi:10.1086/426952. PMC 1196432. PMID 15543491.
  2. ↑ 2.0 2.1 "Entrez Gene: PDCD10 programmed cell death 10".
  3. ↑ He, Y.; Zhang, H.; Yu, L.; Gunel, M.; Boggon, T. J.; Chen, H.; Min, W. (2010). "Cerebral cavernous malformation gene CCM3 is critical for vascular development by regulating VEGFR2 signaling". Science Signaling 3 (116): ra26. doi:10.1126/scisignal.2000722. PMC 3052863. PMID 20371769.
  4. ↑ Guclu, B.; Ozturk, A. K.; Pricola, K. L.; Bilguvar, K.; Shin, D.; O'Roak, B. J.; Gunel, M. (2005). "Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3". Neurosurgery 57 (5): 1008–1013. doi:10.1227/01.NEU.0000180811.56157.E1. PMID 16284570.
  5. ↑ Fidalgo, M.; Fraile, M.; Pires, A.; Force, T.; Pombo, C.; Zalvide, J. (2010). "CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation". Journal of Cell Science 123 (8): 1274–1284. doi:10.1242/jcs.061341. PMID 20332113.
  6. ↑ Ceccarelli, D. F.; Laister, R. C.; Mulligan, V. K.; Kean, M. J.; Goudreault, M.; Scott, I. C.; Derry, W. B.; Chakrabartty, A.; Gingras, A. -C.; Sicheri, F. (2011). "CCM3/PDCD10 Heterodimerizes with Germinal Center Kinase III (GCKIII) Proteins Using a Mechanism Analogous to CCM3 Homodimerization". Journal of Biological Chemistry 286 (28): 25056–25064. doi:10.1074/jbc.M110.213777. PMC 3137079. PMID 21561863.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 Goudreault, Marilyn; D'Ambrosio Lisa M, Kean Michelle J, Mullin Michael J, Larsen Brett G, Sanchez Amy, Chaudhry Sidharth, Chen Ginny I, Sicheri Frank, Nesvizhskii Alexey I, Aebersold Ruedi, Raught Brian, Gingras Anne-Claude (Jan 2009). "A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein". Mol. Cell Proteomics (United States) 8 (1): 157–71. doi:10.1074/mcp.M800266-MCP200. PMC 2621004. PMID 18782753.
  8. ↑ 8.0 8.1 Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
  9. ↑ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  10. ↑ "Salmonella infection data for Pdcd10". Wellcome Trust Sanger Institute.
  11. ↑ "Citrobacter infection data for Pdcd10". Wellcome Trust Sanger Institute.
  12. ↑ 12.0 12.1 12.2 12.3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  13. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  14. ↑ "International Knockout Mouse Consortium".
  15. ↑ "Mouse Genome Informatics".
  16. ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  17. ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  18. ↑ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  19. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

External links