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PDCD5 (programmed cell death 5)

Written2014-10Yingyu Chen, Ge Li
Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing, 100191, China

Abstract Programmed Cell Death 5 (PDCD5) was originally identified as an apoptosis-accelerating molecule that was widely expressed and well-conserved in the process of evolution. It has significant homology to the corresponding proteins of species ranging from yeast to mice gene. PDCD5 can accelerate apoptosis in different type of cells in response to different stimuli, and can also induce different types of cell death, including paraptosis-like cell death. In cells undergoing apoptosis, PDCD5 rapidly translocates from the cytoplasm to the nucleus before phosphatidylserine is externalized and genomic DNA undergoes fragmentation. PDCD5 interacts with TIP60 and TP53 and plays an important positive role in TIP60-P53 signaling pathway. PDCD5 also participates in immune regulation through regulating the level of FOXP3 protein and percentage of regulatory T cells. Dysfunction of PDCD5 was associated in many diseases including different tumors, rheumatoid arthritis and presbycusis, etc.

Keywords Programmed Cell Death 5 (PDCD5), Apoptosis, Tumor, Immnuoregulation.

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)TFAR19
MGC9294
Other alias
HGNC (Hugo) PDCD5
LocusID (NCBI) 9141
Atlas_Id 41676
Location 19q13.11  [Link to chromosome band 19q13]
Location_base_pair Starts at 32581188 and ends at 32587452 bp from pter ( according to hg19-Feb_2009)  [Mapping PDCD5.png]
Local_order Orientation: Plus Strand.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CHST8 (19q13.11) / PDCD5 (19q13.11)

DNA/RNA

 
  The DNA sequence of PDCD5.
Description The PDCD5 gene, with 6286 bases in length, consists of 6 exons and 5 intervening introns.
Transcription The PDCD5 gene encodes a 604 bp mRNA transcript. Transcription site is located 75 bp upstream the first ATG of the PDCD5 ORF. The translation start site is located in exon 1.
Pseudogene Pseudogenes have been identified on chromosomes 12p12.3 and 5q13.2.

Protein

Description PDCD5 protein is composed of 125 amino acids, with a calculated molecular mass of 14.285 kDa. In the protein sequence exist six phosphorylation sites, including a cAMP and cGMP depended protein kinase phosphorylation site (Ser100), 4 PKC phosphorylation sites (Ser51, Ser84, Thr103, Thr108), and a casein kinase 2 (CK2) phosphorylation site (Ser118) (Saivi et al., 2009). Five of the phosphorylation sites are located in the C-terminal region.
Expression PDCD5 is widely expressed in different organs and different stages. Decreased expression of PDCD5 has been detected in various human tumors, such as lung cancer, gastric cancer, chronic myelogenous leukemia, prostate cancer, chondrosarcoma and epithelial ovarian carcinomas. The abnormal expression of PDCD5 is also involved in some autoimmune diseases and inflammatory processes, such as lupus nephritis, osteoarthritis, rheumatoid arthritis, hepatitis, sepsis and bronchial asthma. In the patients with rheumatoid arthritis, the levels of PDCD5 in serum and synovial fluid are inversely associated with the expression of inflammatory cytokines IL-17 and TNF- α and disease activity.
Localisation PDCD5 protein has been reported to be localized mainly in the cytoplasm and nucleus, and translocated to the nucleus during apoptosis (Chen et al., 2006).
Function PDCD5 can promote apoptosis in different cell types in response to various stimuli. PDCD5 interacts with the histone acetyltransferase TIP60 and the transcription factor TP53 to promote apoptosis (Xu et al., 2009; Xu et al., 2012). PDCD5 can also interact with other molecules such as NF-kB p65 and CCT in which participate in the regulation of cell apoptosis. It also associates with TAJ/TROY-induced paraptosis-like cell death (Wang et al., 2004), focal cerebral ischemic reperfusion injury (Jiang et al., 2014), virus infections (Li et al., 2014) and cardiac remodeling (An et al., 2012). PDCD5 negatively regulates autoimmunity by enhancing the level of FOXP3 protein, upregulating FOXP3+ regulatory T cells and suppressing Th17 and Th1 responses (Xiao et al., 2013).
Homology PDCD5 gene is highly-conserved among species (from yeast to human).

Mutations

Germinal No data.
Somatic The promoter with -27G/-11A is associated with reduced PDCD5 promoter activity and increased susceptibility to chronic myelogenous leukemia (Ma et al., 2005). A C/G polymorphism (rs1862214) located 35 kb upstream of the PDCD5 gene was associated with lung cancer susceptibility (Spinola et al., 2006).

Implicated in

Note
  
Entity Various cancers
Note Reduced PDCD5 expression has been found in a few types of human tumors and is also associated with the high progression and poor prognosis. Decreased expression of PDCD5 has been reported in various human tumors, such as gastric cancer (Gao et al., 2012), brain tumors (Li et al., 2008), bone tumor (Chen et al., 2010a), ovarian carcinomas (Zhang et al., 2011), leukemia (Ruan et al., 2006), renal tumor (Tan et al., 2006), lung cancer (Spinola et al., 2006), prostate cancer (Du et al., 2009), hepatocellular cancer (Fu et al., 2013), laryngeal cancer (Xu et al., 2013), oral squamous cell carcinoma (Zhao et al., 2013) and cervical cancer (Liu et al., 2013). PDCD5 expression predicts a favorable outcome in patients with hepatocellular carcinoma, epithelial ovarian carcinomas, chondrosarcoma.
PDCD5 may make significance to inhibit tumor malignant transformation and progress. Recombinant human PDCD5 (rhPDCD5) has been shown to enter a variety of cells by clathrin-independent endocytosis and exert biological activities. RhPDCD5 could enhance cell death of tumor cells and enhance the sensitivity to chemotherapeutic, such as cisplatin (Chen et al., 2010b; Shi et al., 2010; Wang et al., 2013c).
  
  
Entity Rheumatoid arthritis
Note PDCD5 is associated with rheumatoid arthritis and osteoarthritis, which can regulate the apoptosis of synoviocytes and chondrocytes (Wang et al., 2007). The levels of PDCD5 in serum, synovial fluid and cartilage are higher in RA and OA than healthy control, which are negatively correlated with IL-17 or TNF-α levels (Wang et al., 2013a). The expression of PDCD5 may be down regulated by Insulin-like growth factor 1 (Yi et al., 2013). Recombinant human PDCD5 has an anti-inflammatory effect in collagen-induced arthritis (CIA) rats (Xiao et al., 2014).
  

Bibliography

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Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo.
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Apoptosis. 2010b Jul;15(7):805-13. doi: 10.1007/s10495-010-0489-5.
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The involvement of programmed cell death 5 (PDCD5) in the regulation of apoptosis in cerebral ischemia/reperfusion injury.
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Chen Y, Sun R, Han W, Zhang Y, Song Q, Di C, Ma D.
FEBS Lett. 2001 Dec 7;509(2):191-6.
PMID 11741587
 
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PMID 20120772
 
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PDCD5 expression predicts a favorable outcome in patients with hepatocellular carcinoma.
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The clinical significance of reduced programmed cell death 5 expression in human gastrointestinal stromal tumors.
Gao F, Ding L, Zhao M, Qu Z, Huang S, Zhang L.
Oncol Rep. 2012 Dec;28(6):2195-9. doi: 10.3892/or.2012.2023. Epub 2012 Sep 11.
PMID 22965478
 
Autophagic effect of programmed cell death 5 (PDCD5) after focal cerebral ischemic reperfusion injury in rats.
Jiang Z, Chen CH, Chen YY, Han JY, Riley J, Zhou CM.
Neurosci Lett. 2014 Apr 30;566:298-303. doi: 10.1016/j.neulet.2014.02.066. Epub 2014 Mar 12.
PMID 24614334
 
Reduced expression of PDCD5 is associated with high-grade astrocytic gliomas.
Li H, Wang Q, Gao F, Zhu F, Wang X, Zhou C, Liu C, Chen Y, Ma C, Sun W, Zhang L.
Oncol Rep. 2008 Sep;20(3):573-9.
PMID 18695908
 
Pretreatment of mice with oligonucleotide prop5 protects them from influenza virus infections.
Li K, Zhou Z, Wang YO, Liu J, Zhao HB, Yang J, Wang SQ.
Viruses. 2014 Feb 6;6(2):573-81. doi: 10.3390/v6020573.
PMID 24509810
 
TFAR19, a novel apoptosis-related gene cloned from human leukemia cell line TF-1, could enhance apoptosis of some tumor cells induced by growth factor withdrawal.
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PMID 9920759
 
Two single-nucleotide polymorphisms with linkage disequilibrium in the human programmed cell death 5 gene 5' regulatory region affect promoter activity and the susceptibility of chronic myelogenous leukemia in Chinese population.
Ma X, Ruan G, Wang Y, Li Q, Zhu P, Qin YZ, Li JL, Liu YR, Ma D, Zhao H.
Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8592-9.
PMID 16361542
 
Programmed cell death protein 5 (PDCD5) is phosphorylated by CK2 in vitro and in 293T cells.
Salvi M, Xu D, Chen Y, Cabrelle A, Sarno S, Pinna LA.
Biochem Biophys Res Commun. 2009 Sep 25;387(3):606-10. doi: 10.1016/j.bbrc.2009.07.067. Epub 2009 Jul 17.
PMID 19616514
 
Potent antitumor activities of recombinant human PDCD5 protein in combination with chemotherapy drugs in K562 cells.
Shi L, Song Q, Zhang Y, Lou Y, Wang Y, Tian L, Zheng Y, Ma D, Ke X, Wang Y.
Biochem Biophys Res Commun. 2010 May 28;396(2):224-30. doi: 10.1016/j.bbrc.2010.04.068. Epub 2010 Apr 14.
PMID 20398626
 
Association of the PDCD5 locus with lung cancer risk and prognosis in smokers.
Spinola M, Meyer P, Kammerer S, Falvella FS, Boettger MB, Hoyal CR, Pignatiello C, Fischer R, Roth RB, Pastorino U, Haeussinger K, Nelson MR, Dierkesmann R, Dragani TA, Braun A.
J Clin Oncol. 2006 Apr 10;24(11):1672-8. Epub 2006 Mar 20.
PMID 16549820
 
Programmed cell death protein 5 interacts with the cytosolic chaperonin containing tailless complex polypeptide 1 (CCT) to regulate β-tubulin folding.
Tracy CM, Gray AJ, Cuellar J, Shaw TS, Howlett AC, Taylor RM, Prince JT, Ahn NG, Valpuesta JM, Willardson BM.
J Biol Chem. 2014 Feb 14;289(7):4490-502. doi: 10.1074/jbc.M113.542159. Epub 2013 Dec 27.
PMID 24375412
 
Plasma and synovial fluid programmed cell death 5 (PDCD5) levels are inversely associated with TNF-α and disease activity in patients with rheumatoid arthritis.
Wang J, Guan Z, Ge Z.
Biomarkers. 2013a Mar;18(2):155-9. doi: 10.3109/1354750X.2012.759277. Epub 2013 Jan 18.
PMID 23327497
 
Programmed cell death 5 correlates with disease activity and interleukin-17 in serum and synovial fluid of rheumatoid arthritis patients.
Wang JF, Guan ZP, Zhang SL, Pei Z, Chen YY, Pan H.
Chin Med J (Engl). 2013b Jan;126(2):296-9.
PMID 23324280
 
Recombinant human PDCD5 protein enhances chemosensitivity of breast cancer in vitro and in vivo.
Wang L, Wang C, Su B, Song Q, Zhang Y, Luo Y, Li Q, Tan W, Ma D, Wang L.
Biochem Cell Biol. 2013c Dec;91(6):526-31. doi: 10.1139/bcb-2013-0052. Epub 2013 Sep 13.
PMID 24219296
 
Involvement of PDCD5 in the regulation of apoptosis in fibroblast-like synoviocytes of rheumatoid arthritis.
Wang N, Lu HS, Guan ZP, Sun TZ, Chen YY, Ruan GR, Chen ZK, Jiang J, Bai CJ.
Apoptosis. 2007 Aug;12(8):1433-41.
PMID 17468978
 
An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression.
Wang Y, Li X, Wang L, Ding P, Zhang Y, Han W, Ma D.
J Cell Sci. 2004 Mar 15;117(Pt 8):1525-32.
PMID 15020679
 
Anti-Inflammatory Effects of Recombinant Human PDCD5 (rhPDCD5) in a Rat Collagen-Induced Model of Arthritis.
Xiao J, Li G, Hu J, Qu L, Ma D, Chen Y.
Inflammation. 2014 Sep 2. [Epub ahead of print]
PMID 25178696
 
PDCD5 negatively regulates autoimmunity by upregulating FOXP3(+) regulatory T cells and suppressing Th17 and Th1 responses.
Xiao J, Liu C, Li G, Peng S, Hu J, Qu L, Lv P, Zhang Y, Ma D, Chen Y.
J Autoimmun. 2013 Dec;47:34-44. doi: 10.1016/j.jaut.2013.08.002. Epub 2013 Sep 5.
PMID 24012345
 
Expression and clinical significance of the programmed cell death 5 gene and protein in laryngeal squamous cell carcinoma.
Xu F, Wu K, Zhao M, Qin Y, Xia M.
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PMID 24265335
 
PDCD5 interacts with Tip60 and functions as a cooperator in acetyltransferase activity and DNA damage-induced apoptosis.
Xu L, Chen Y, Song Q, Xu D, Wang Y, Ma D.
Neoplasia. 2009 Apr;11(4):345-54.
PMID 19308289
 
PDCD5 interacts with p53 and functions as a positive regulator in the p53 pathway.
Xu L, Hu J, Zhao Y, Hu J, Xiao J, Wang Y, Ma D, Chen Y.
Apoptosis. 2012 Nov;17(11):1235-45. doi: 10.1007/s10495-012-0754-x.
PMID 22914926
 
Expression of programmed cell death 5 protein inhibits progression of lung carcinoma in vitro and in vivo via the mitochondrial apoptotic pathway.
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Down-regulation of programmed cell death 5 by insulin-like growth factor 1 in osteoarthritis chondrocytes.
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Clinical and prognostic significance of lost or decreased PDCD5 expression in human epithelial ovarian carcinomas.
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Citation

This paper should be referenced as such :
Yingyu Chen, Ge Li
PDCD5 (programmed cell death 5)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(10):621-624.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PDCD5ID41676ch19q13.html


External links

Nomenclature
HGNC (Hugo)PDCD5   8764
Cards
AtlasPDCD5ID41676ch19q13
Entrez_Gene (NCBI)PDCD5  9141  programmed cell death 5
AliasesTFAR19
GeneCards (Weizmann)PDCD5
Ensembl hg19 (Hinxton)ENSG00000105185 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000105185 [Gene_View]  chr19:32581188-32587452 [Contig_View]  PDCD5 [Vega]
ICGC DataPortalENSG00000105185
TCGA cBioPortalPDCD5
AceView (NCBI)PDCD5
Genatlas (Paris)PDCD5
WikiGenes9141
SOURCE (Princeton)PDCD5
Genetics Home Reference (NIH)PDCD5
Genomic and cartography
GoldenPath hg38 (UCSC)PDCD5  -     chr19:32581188-32587452 +  19q13.11   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PDCD5  -     19q13.11   [Description]    (hg19-Feb_2009)
EnsemblPDCD5 - 19q13.11 [CytoView hg19]  PDCD5 - 19q13.11 [CytoView hg38]
Mapping of homologs : NCBIPDCD5 [Mapview hg19]  PDCD5 [Mapview hg38]
OMIM604583   
Gene and transcription
Genbank (Entrez)AB209040 AF014955 AK124774 AK293486 BC015519
RefSeq transcript (Entrez)NM_004708
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PDCD5
Cluster EST : UnigeneHs.443831 [ NCBI ]
CGAP (NCI)Hs.443831
Alternative Splicing GalleryENSG00000105185
Gene ExpressionPDCD5 [ NCBI-GEO ]   PDCD5 [ EBI - ARRAY_EXPRESS ]   PDCD5 [ SEEK ]   PDCD5 [ MEM ]
Gene Expression Viewer (FireBrowse)PDCD5 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9141
GTEX Portal (Tissue expression)PDCD5
Human Protein AtlasENSG00000105185-PDCD5 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO14737   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO14737  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO14737
Splice isoforms : SwissVarO14737
PhosPhoSitePlusO14737
Domains : Interpro (EBI)PDCD5-related   
Domain families : Pfam (Sanger)dsDNA_bind (PF01984)   
Domain families : Pfam (NCBI)pfam01984   
Conserved Domain (NCBI)PDCD5
DMDM Disease mutations9141
Blocks (Seattle)PDCD5
PDB (SRS)1YYB    2CRU    2K6B   
PDB (PDBSum)1YYB    2CRU    2K6B   
PDB (IMB)1YYB    2CRU    2K6B   
PDB (RSDB)1YYB    2CRU    2K6B   
Structural Biology KnowledgeBase1YYB    2CRU    2K6B   
SCOP (Structural Classification of Proteins)1YYB    2CRU    2K6B   
CATH (Classification of proteins structures)1YYB    2CRU    2K6B   
SuperfamilyO14737
Human Protein Atlas [tissue]ENSG00000105185-PDCD5 [tissue]
Peptide AtlasO14737
HPRD06843
IPIIPI00023640   IPI00908931   IPI00654798   
Protein Interaction databases
DIP (DOE-UCLA)O14737
IntAct (EBI)O14737
FunCoupENSG00000105185
BioGRIDPDCD5
STRING (EMBL)PDCD5
ZODIACPDCD5
Ontologies - Pathways
QuickGOO14737
Ontology : AmiGODNA binding  protein binding  nucleus  cytoplasm  cytosol  apoptotic process  heparin binding  negative regulation of cell proliferation  positive regulation of gene expression  acetyltransferase activator activity  positive regulation of apoptotic process  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  beta-tubulin binding  extracellular exosome  cellular response to transforming growth factor beta stimulus  positive regulation of release of cytochrome c from mitochondria  positive regulation of protein import into mitochondrial outer membrane  negative regulation of chaperone-mediated protein folding  
Ontology : EGO-EBIDNA binding  protein binding  nucleus  cytoplasm  cytosol  apoptotic process  heparin binding  negative regulation of cell proliferation  positive regulation of gene expression  acetyltransferase activator activity  positive regulation of apoptotic process  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  beta-tubulin binding  extracellular exosome  cellular response to transforming growth factor beta stimulus  positive regulation of release of cytochrome c from mitochondria  positive regulation of protein import into mitochondrial outer membrane  negative regulation of chaperone-mediated protein folding  
NDEx NetworkPDCD5
Atlas of Cancer Signalling NetworkPDCD5
Wikipedia pathwaysPDCD5
Orthology - Evolution
OrthoDB9141
GeneTree (enSembl)ENSG00000105185
Phylogenetic Trees/Animal Genes : TreeFamPDCD5
HOVERGENO14737
HOGENOMO14737
Homologs : HomoloGenePDCD5
Homology/Alignments : Family Browser (UCSC)PDCD5
Gene fusions - Rearrangements
Fusion : MitelmanCHST8/PDCD5 [19q13.11/19q13.11]  [t(19;19)(q13;q13)]  
Fusion: TCGA_MDACCCHST8 19q13.11 PDCD5 19q13.11 PRAD
Tumor Fusion PortalPDCD5
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPDCD5 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PDCD5
dbVarPDCD5
ClinVarPDCD5
1000_GenomesPDCD5 
Exome Variant ServerPDCD5
ExAC (Exome Aggregation Consortium)ENSG00000105185
GNOMAD BrowserENSG00000105185
Genetic variants : HAPMAP9141
Genomic Variants (DGV)PDCD5 [DGVbeta]
DECIPHERPDCD5 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPDCD5 
Mutations
ICGC Data PortalPDCD5 
TCGA Data PortalPDCD5 
Broad Tumor PortalPDCD5
OASIS PortalPDCD5 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPDCD5  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPDCD5
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PDCD5
DgiDB (Drug Gene Interaction Database)PDCD5
DoCM (Curated mutations)PDCD5 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PDCD5 (select a term)
intoGenPDCD5
NCG5 (London)PDCD5
Cancer3DPDCD5(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604583   
Orphanet
DisGeNETPDCD5
MedgenPDCD5
Genetic Testing Registry PDCD5
NextProtO14737 [Medical]
TSGene9141
GENETestsPDCD5
Target ValidationPDCD5
Huge Navigator PDCD5 [HugePedia]
snp3D : Map Gene to Disease9141
BioCentury BCIQPDCD5
ClinGenPDCD5
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9141
Chemical/Pharm GKB GenePA33114
Clinical trialPDCD5
Miscellaneous
canSAR (ICR)PDCD5 (select the gene name)
Probes
Litterature
PubMed83 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePDCD5
EVEXPDCD5
GoPubMedPDCD5
iHOPPDCD5
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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