PDCD2

Programmed cell death 2
Identifiers
Symbols	PDCD2 ; RP8; ZMYND7
External IDs	OMIM: 600866 MGI: 104643 HomoloGene: 1951 GeneCards: PDCD2 Gene
Gene ontology Molecular function • DNA binding • protein binding • enzyme binding • metal ion binding Cellular component • nucleus • cytoplasm • extracellular exosome Biological process • apoptotic process • activation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of apoptotic process • regulation of hematopoietic progenitor cell differentiation • positive regulation of hematopoietic stem cell proliferation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5134	18567
Ensembl	ENSG00000071994	ENSMUSG00000014771
UniProt	Q16342	P46718
RefSeq (mRNA)	NM_001199461	NM_008799
RefSeq (protein)	NP_001186390	NP_032825
Location (UCSC)	Chr 6: 170.58 – 170.58 Mb	Chr 17: 15.52 – 15.53 Mb
PubMed search

Programmed cell death protein 2 is a protein that in humans is encoded by the PDCD2 gene.^[1][2]

Function

This gene encodes a nuclear protein expressed in a variety of tissues. The rat homolog, Rp8, is transiently expressed in immature thymocytes and is thought to be involved in programmed cell death. Expression of the human gene has been shown to be repressed by BCL6, a transcriptional repressor required for lymph node germinal center development, suggesting that BCL6 regulates apoptosis by its effects on PDCD2. This gene is closely linked on chromosome 6 to the gene for TBP, the TATA binding protein. Six transcripts encoding different proteins have been identified.^[2]

Interactions

PDCD2 has been shown to interact with Host cell factor C1^[3] and Parkin (ligase).^[4]

Model organisms

Model organisms have been used in the study of PDCD2 function. A conditional knockout mouse line called Pdcd2^{tm1b(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.^[5] Male and female animals underwent a standardized phenotypic screen^[6] to determine the effects of deletion.^{[7][8][9][10]} Additional screens performed: - In-depth immunological phenotyping^[11]

Pdcd2 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[6][11]
Insulin	Normal
Homozygous viability at P14	Abnormal
Recessive lethal study	Abnormal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal

References

1. Kawakami T, Furukawa Y, Sudo K, Saito H, Takami S, Takahashi E, Nakamura Y (Aug 1995). "Isolation and mapping of a human gene (PDCD2) that is highly homologous to Rp8, a rat gene associated with programmed cell death". Cytogenetics and Cell Genetics 71 (1): 41–3. doi:10.1159/000134058. PMID 7606924.
2. "Entrez Gene: PDCD2 programmed cell death 2".
3. Scarr RB, Sharp PA (Aug 2002). "PDCD2 is a negative regulator of HCF-1 (C1)". Oncogene 21 (34): 5245–54. doi:10.1038/sj.onc.1205647. PMID 12149646.
4. Fukae J, Sato S, Shiba K, Sato K, Mori H, Sharp PA, Mizuno Y, Hattori N (Feb 2009). "Programmed cell death-2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson's disease". FEBS Letters 583 (3): 521–5. doi:10.1016/j.febslet.2008.12.055. PMID 19146857.
5. 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.
6. "International Mouse Phenotyping Consortium".
7. 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.
8. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
9. 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.
10. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
11. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

• Baron BW, Anastasi J, Thirman MJ, Furukawa Y, Fears S, Kim DC, Simone F, Birkenbach M, Montag A, Sadhu A, Zeleznik-Le N, McKeithan TW (Mar 2002). "The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: implications for a role of BCL6 in the down-regulation of apoptosis". Proceedings of the National Academy of Sciences of the United States of America 99 (5): 2860–5. doi:10.1073/pnas.042702599. PMC 122438. PMID 11854457.
• Scarr RB, Sharp PA (Aug 2002). "PDCD2 is a negative regulator of HCF-1 (C1)". Oncogene 21 (34): 5245–54. doi:10.1038/sj.onc.1205647. PMID 12149646.
• Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (Feb 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
• Lehner B, Sanderson CM (Jul 2004). "A protein interaction framework for human mRNA degradation". Genome Research 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747.
• Chen Q, Qian K, Yan C (Dec 2005). "Cloning of cDNAs with PDCD2(C) domain and their expressions during apoptosis of HEK293T cells". Molecular and Cellular Biochemistry 280 (1-2): 185–91. doi:10.1007/s11010-005-8910-z. PMID 16311922.
• Baron BW, Zeleznik-Le N, Baron MJ, Theisler C, Huo D, Krasowski MD, Thirman MJ, Baron RM, Baron JM (May 2007). "Repression of the PDCD2 gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas". Proceedings of the National Academy of Sciences of the United States of America 104 (18): 7449–54. doi:10.1073/pnas.0701770104. PMC 1863460. PMID 17468402.