PDCD10

Programmed cell death protein 10 is a protein that in humans is encoded by the PDCD10 gene.[5][6]

PDCD10
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPDCD10, CCM3, TFAR15, programmed cell death 10
External IDsOMIM: 609118 MGI: 1928396 HomoloGene: 10505 GeneCards: PDCD10
Gene location (Human)
Chr.Chromosome 3 (human)[1]
Band3q26.1Start167,683,298 bp[1]
End167,734,939 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

11235

56426

Ensembl

ENSG00000114209

ENSMUSG00000027835

UniProt

Q9BUL8

Q8VE70

RefSeq (mRNA)

NM_007217
NM_145859
NM_145860

NM_019745

RefSeq (protein)

NP_009148
NP_665858
NP_665859

NP_062719

Location (UCSC)Chr 3: 167.68 – 167.73 MbChr 3: 75.52 – 75.56 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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.[6]

Gene

Loss of function mutations in PDCD10 result in the onset of Cerebral Cavernous Malformations (CCM) illness.[5] 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,[7] apoptosis[8] and functions as part of a larger signaling complex that includes germinal center kinase III,.[9][10] Specifically, PDCD10 has been shown to interact with RP6-213H19.1,[11] STK25,[11][12] STRN,[11] STRN3,[11] MOBKL3,[11] CTTNBP2NL,[11] STK24[11][12][13] and FAM40A.[11]

Model organisms

Model organisms have been used in the study of PDCD10 function. A conditional knockout mouse line, called Pdcd10tm1a(KOMP)Wtsi[18][19] 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.[20][21][22]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[16][23] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[16] 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.[16]

References
  1. GRCh38: Ensembl release 89: ENSG00000114209 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000027835 - 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. 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 (Jan 2005). "Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations". American Journal of Human Genetics. 76 (1): 42–51. doi:10.1086/426952. PMC 1196432. PMID 15543491.
  6. "Entrez Gene: PDCD10 programmed cell death 10".
  7. He Y, Zhang H, Yu L, Gunel M, Boggon TJ, Chen H, Min W (2010). "Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development". Science Signaling. 3 (116): ra26. doi:10.1126/scisignal.2000722. PMC 3052863. PMID 20371769.
  8. Guclu B, Ozturk AK, Pricola KL, Bilguvar K, Shin D, O'Roak BJ, Gunel M (Nov 2005). "Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3". Neurosurgery. 57 (5): 1008–13. doi:10.1227/01.NEU.0000180811.56157.E1. PMID 16284570. S2CID 10303325.
  9. Fidalgo M, Fraile M, Pires A, Force T, Pombo C, Zalvide J (Apr 2010). "CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation". Journal of Cell Science. 123 (Pt 8): 1274–84. doi:10.1242/jcs.061341. PMID 20332113.
  10. Ceccarelli DF, Laister RC, Mulligan VK, Kean MJ, Goudreault M, Scott IC, Derry WB, Chakrabartty A, Gingras AC, Sicheri F (Jul 2011). "CCM3/PDCD10 heterodimerizes with germinal center kinase III (GCKIII) proteins using a mechanism analogous to CCM3 homodimerization". The Journal of Biological Chemistry. 286 (28): 25056–64. doi:10.1074/jbc.M110.213777. PMC 3137079. PMID 21561863.
  11. Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, Chaudhry S, Chen GI, Sicheri F, Nesvizhskii AI, Aebersold R, Raught B, Gingras AC (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". Molecular & Cellular Proteomics. 8 (1): 157–71. doi:10.1074/mcp.M800266-MCP200. PMC 2621004. PMID 18782753.
  12. 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. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
  13. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  14. "Salmonella infection data for Pdcd10". Wellcome Trust Sanger Institute.
  15. "Citrobacter infection data for Pdcd10". Wellcome Trust Sanger Institute.
  16. 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. S2CID 85911512.
  17. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  18. "International Knockout Mouse Consortium".
  19. "Mouse Genome Informatics".
  20. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  21. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  22. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  23. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading
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