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PDCD10 (Programmed cell death 10)

Written2016-08Urfali-Mamatoglu, Hasan Huseyin Kazan, Ufuk Gunduz
Department of Biological Sciences, Middle East Technical University, Ankara, Turkey. cagri.urfali@metu.edu.tr; hasanhuseyinkazan@gmail.com; ufukg@metu.edu.tr

Abstract PDCD10 is a novel apoptosis regulator which functions in the regulation of cellular proliferation and apoptosis.

(Note : for Links provided by Atlas : click)

Identity

Other namesCCM3 (Cerebral cavernous malformations 3)
TFAR15 (TF-1 cell apoptosis-related protein 15)
HGNC (Hugo) PDCD10
LocusID (NCBI) 11235
Atlas_Id 43399
Location 3q26.1  [Link to chromosome band 3q26]
Location_base_pair Starts at 167401695 and ends at 167452594 bp from pter ( according to hg19-Feb_2009)  [Mapping PDCD10.png]
Local_order From telomere to centromere: LINC01330, MEMO1P3, SERPINI1, PDCD10, HMGN1P8, WDR49, LOC105374197, SERPINI2
 
  Local order of PDCD10 is shown together with leading and subsequent genes on chromosome 3. The direction of arrows indicates transcriptional directions on the chromosome and arrow sizes approximate gene sizes.

DNA/RNA

 
  Boxes are exons and the lines are introns.
Description The PDCD10 gene is 51,688 bp in length, located on the minus strand and spans 9 exons (NCBI, 2016).
Transcription 3 different alternatively spliced mRNAs (1454, 1313 and 1212 bp long, respectively) that differ only in 5'UTRs; 639 bp long open reading frame (NM_007217.3, NM_145859.1, NM_145860.1).
Pseudogene LOC100128686 programmed cell death 10 pseudogene; located on 8q11.21 (NCBI, 2016).

Protein

Description PDCD10 encodes an evolutionarily conserved 212 amino acid long protein (Wang et al, 1999). PDCD10 has an estimated molecular weight of 29 kDa.
Expression PDCD10 is expressed in all tissues including brain, pancreas, breast, ovary, kidney, liver and lungs (The Human Protein Atlas, 2016).
Localisation PDCD10 is localized in cytoplasm, near Golgi apparatus and nucleus (Fidalgo et al, 2010).
Function The PDCD10 protein regulates cell proliferation and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway through interaction with serine/threonine protein kinase STK26 (MST4) (Ma et al, 2007). It also interacts with another serine/threonine kinase, STK25 , and triggers apoptosis under oxidative stress (Zhang et al, 2012). PDCD10 interacts with members of germinal center kinases III subfamily to promote normal Golgi assembly and cell orientation (Fidalgo, 2010). PDCD10 involves in the stabilization of KDR (VEGFR2) signaling and is vital for normal vascular development (He et al, 2010). PDCD10 acts downstream of gamma-protocadherins and regulate neuronal survival (Lin et al, 2010).

Mutations

Germinal Cerebral cavernous malformations are associated with the mutations in 3 loci; one of which is CCM3/PDCD10. Bergametti et al reported a de novo deletion as well as six other deleterious mutations in PDCD10 gene. Three of these mutations were stated as nonsense mutations, two other mutations were reported to generate aberrant splicing in exon 9 with a frameshift and the last one caused an abnormal splicing in exon 5 without frameshift (Bergametti et al, 2005). In a study with 61 families with cerebral caverous malformations, Guclu et al (2005) identified two identical mutations creating a premature stop codon in exon 7, two frameshift mutations in exon 6 and one additional frameshift mutation in exon 9 (Guclu et al, 2005). In patients without KRIT1 (CCM1) and CCM2 mutations, Verlaan et al (2005) identified two mutations in CCM3 which lead to a truncated PDCD10 protein. One of the mutations was a nonsense mutation in exon 7 caused by a transversion o a C to a T that creates a stop codon and the other one was reported to be an invariant splice acceptor site mutation (Verlaan et al, 2005). Riant et al (2013) reported that, in 13 of 54 CCM3-mutated patients, there are deletions in one or several coding exons; 8 of which deletions are whole gene deletions. In 41 patients, several point mutations leading abnormal splicing, nonsense mutations and small insertions and deletions causing frameshifts and premature stop codons were identified. Additionally, they reported deletions in noncoding exons 1-3 in a 5-year old child with cerebral carcinomas (Riant et al, 3013).

Implicated in

Entity Cerebral cavernous malformations
Disease Cerebral cavernous malformations (CCM) is one of the frequently occurring cerebral vascular abnormalities characterized by abnormally enlarged blood vessels that cause brain hemorrhages and seizures which result in focal neurological deficits (Rigamonti et al, 1998; Bergametti et al, 2005). Bergametti et al identified PDCD10 as the CCM3 gene and reported several mutations in this locus (Bergametti et al, 2005). Several other studies also reported different mutations in PDCD10 gene in patients with cerebral cavernous malformations and cerebral carcinomas (see Mutations section above).
  
Entity Prostate cancer
Note PDCD10 is expressed in both benign prostatic hyperplasia and prostate cancer with a stronger staining in prostate cancer cases. Germinal center kinases, MST4 and STK25, are also significantly overexpressed in prostate cancer and associated with the PDCD10 expression (Zhang et al, 2014). miR-103 is reported to regulate PDCD10 in prostate cancer and when overexpressed, it suppresses tumor cell proliferation by targeting PDCD10 (Fu et al, 2016).
  
Entity T cell lymphoma
Note PDCD10 is constitutiely expressed in malignant T cells and cell lines derived from peripheral blood of patients with Sezary syndrome (T cell lymphoma). PDCD10 is found to be constitutively associated with protein phosphatase-2A (PP2A) which is essential in the regulation of cell proliferation and apoptosis in T cell lymphoma. Depletion of PDCD10 was reported to significantly increase apoptosis in various malignant T cells (Lauenborg et al, 2010).
  
Entity Colorectal cancer
Note Zhang et al (2016) reported that PDCD10 expression was down-regulated in drug-resistant colorectal cancer cells. The expression of PDCD10 was regulated by MIR425 (mature sequence miR-425-5p) which directly targets 3'-UTR of PDCD10 (Zhang et al, 2016).
  

Bibliography

Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations
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; Société Française de Neurochirurgie
Am J Hum Genet 2005 Jan;76(1):42-51
PMID 15543491
 
CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation
Fidalgo M, Fraile M, Pires A, Force T, Pombo C, Zalvide J
J Cell Sci 2010 Apr 15;123(Pt 8):1274-84
PMID 20332113
 
MicroRNA-103 suppresses tumor cell proliferation by targeting PDCD10 in prostate cancer
Fu X, Zhang W, Su Y, Lu L, Wang D, Wang H
Prostate 2016 May;76(6):543-51
PMID 26771762
 
Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3
Guclu B, Ozturk AK, Pricola KL, Bilguvar K, Shin D, O'Roak BJ, Gunel M
Neurosurgery 2005 Nov;57(5):1008-13
PMID 16284570
 
Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development
He Y, Zhang H, Yu L, Gunel M, Boggon TJ, Chen H, Min W
Sci Signal 2010 Apr 6;3(116):ra26
PMID 20371769
 
Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis
Lauenborg B, Kopp K, Krejsgaard T, Eriksen KW, Geisler C, Dabelsteen S, Gniadecki R, Zhang Q, Wasik MA, Woetmann A, Odum N
APMIS 2010 Oct;118(10):719-28
PMID 20854465
 
PDCD10/CCM3 acts downstream of {gamma}-protocadherins to regulate neuronal survival
Lin C, Meng S, Zhu T, Wang X
J Biol Chem 2010 Dec 31;285(53):41675-85
 
PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway
Ma X, Zhao H, Shan J, Long F, Chen Y, Chen Y, Zhang Y, Han X, Ma D
Mol Biol Cell 2007 Jun;18(6):1965-78
PMID 17360971
 
CCM3 Mutations Are Associated with Early-Onset Cerebral Hemorrhage and Multiple Meningiomas
Riant F, Bergametti F, Fournier HD, Chapon F, Michalak-Provost S, Cecillon M, Lejeune P, Hosseini H, Choe C, Orth M, Bernreuther C, Boulday G, Denier C, Labauge P, Tournier-Lasserve E
Mol Syndromol 2013 Apr;4(4):165-72
PMID 23801932
 
CCM3 mutations are uncommon in cerebral cavernous malformations
Verlaan DJ, Roussel J, Laurent SB, Elger CE, Siegel AM, Rouleau GA
Neurology 2005 Dec 27;65(12):1982-3
PMID 16380626
 
cDNA cloning and expression of an apoptosis-related gene, humanTFAR15 gene
Wang Y, Liu H, Zhang Y, Ma D
Sci China C Life Sci 1999 Jun;42(3):323-9
PMID 20229348
 
PDCD10 interacts with STK25 to accelerate cell apoptosis under oxidative stress
Zhang H, Ma X, Deng X, Chen Y, Mo X, Zhang Y, Zhao H, Ma D
Front Biosci (Landmark Ed) 2012 Jun 1;17:2295-305
PMID 22652780
 

Citation

This paper should be referenced as such :
Urfali-Mamatoglu C, Kasan HH, Gunduz U
PDCD10 (Programmed cell death 10);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/PDCD10ID43399ch3q26.html


External links

Nomenclature
HGNC (Hugo)PDCD10   8761
Cards
Atlas43399
Entrez_Gene (NCBI)PDCD10  11235  programmed cell death 10
AliasesCCM3; TFAR15
GeneCards (Weizmann)PDCD10
Ensembl hg19 (Hinxton)ENSG00000114209 [Gene_View]  chr3:167401695-167452594 [Contig_View]  PDCD10 [Vega]
Ensembl hg38 (Hinxton)ENSG00000114209 [Gene_View]  chr3:167401695-167452594 [Contig_View]  PDCD10 [Vega]
ICGC DataPortalENSG00000114209
TCGA cBioPortalPDCD10
AceView (NCBI)PDCD10
Genatlas (Paris)PDCD10
WikiGenes11235
SOURCE (Princeton)PDCD10
Genomic and cartography
GoldenPath hg19 (UCSC)PDCD10  -     chr3:167401695-167452594 -  3q26.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)PDCD10  -     3q26.1   [Description]    (hg38-Dec_2013)
EnsemblPDCD10 - 3q26.1 [CytoView hg19]  PDCD10 - 3q26.1 [CytoView hg38]
Mapping of homologs : NCBIPDCD10 [Mapview hg19]  PDCD10 [Mapview hg38]
OMIM603285   609118   
Gene and transcription
Genbank (Entrez)AF022385 AK291130 BC002506 BC016353 CR457107
RefSeq transcript (Entrez)NM_007217 NM_145859 NM_145860
RefSeq genomic (Entrez)NC_000003 NC_018914 NG_008158 NT_005612 NW_004929311
Consensus coding sequences : CCDS (NCBI)PDCD10
Cluster EST : UnigeneHs.478150 [ NCBI ]
CGAP (NCI)Hs.478150
Alternative Splicing GalleryENSG00000114209
Gene ExpressionPDCD10 [ NCBI-GEO ]   PDCD10 [ EBI - ARRAY_EXPRESS ]   PDCD10 [ SEEK ]   PDCD10 [ MEM ]
Gene Expression Viewer (FireBrowse)PDCD10 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)11235
GTEX Portal (Tissue expression)PDCD10
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9BUL8 (Uniprot)
NextProtQ9BUL8  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9BUL8
Splice isoforms : SwissVarQ9BUL8 (Swissvar)
PhosPhoSitePlusQ9BUL8
Domains : Interpro (EBI)PDCD10   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
DMDM Disease mutations11235
Blocks (Seattle)PDCD10
PDB (SRS)3AJM    3L8I    3L8J    3RQE    3RQF    3RQG    3W8H    3W8I    4GEH    4TVQ   
PDB (PDBSum)3AJM    3L8I    3L8J    3RQE    3RQF    3RQG    3W8H    3W8I    4GEH    4TVQ   
PDB (IMB)3AJM    3L8I    3L8J    3RQE    3RQF    3RQG    3W8H    3W8I    4GEH    4TVQ   
PDB (RSDB)3AJM    3L8I    3L8J    3RQE    3RQF    3RQG    3W8H    3W8I    4GEH    4TVQ   
Structural Biology KnowledgeBase3AJM    3L8I    3L8J    3RQE    3RQF    3RQG    3W8H    3W8I    4GEH    4TVQ   
SCOP (Structural Classification of Proteins)3AJM    3L8I    3L8J    3RQE    3RQF    3RQG    3W8H    3W8I    4GEH    4TVQ   
CATH (Classification of proteins structures)3AJM    3L8I    3L8J    3RQE    3RQF    3RQG    3W8H    3W8I    4GEH    4TVQ   
SuperfamilyQ9BUL8
Human Protein AtlasENSG00000114209
Peptide AtlasQ9BUL8
HPRD10141
IPIIPI00298558   IPI00793567   IPI00945696   IPI00790953   IPI00792092   IPI00947286   IPI00946434   IPI00791474   IPI00793671   
Protein Interaction databases
DIP (DOE-UCLA)Q9BUL8
IntAct (EBI)Q9BUL8
FunCoupENSG00000114209
BioGRIDPDCD10
STRING (EMBL)PDCD10
ZODIACPDCD10
Ontologies - Pathways
QuickGOQ9BUL8
Ontology : AmiGOGolgi membrane  angiogenesis  protein binding  cytoplasm  Golgi apparatus  Golgi apparatus  cytosol  plasma membrane  positive regulation of cell proliferation  positive regulation of gene expression  negative regulation of gene expression  protein kinase binding  positive regulation of cell migration  positive regulation of cell migration  positive regulation of stress-activated MAPK cascade  positive regulation of peptidyl-serine phosphorylation  regulation of Rho protein signal transduction  intrinsic apoptotic signaling pathway in response to hydrogen peroxide  response to hydrogen peroxide  protein homodimerization activity  negative regulation of apoptotic process  stress fiber assembly  positive regulation of MAP kinase activity  wound healing, spreading of cells  positive regulation of Notch signaling pathway  protein N-terminus binding  protein stabilization  establishment of Golgi localization  extracellular exosome  positive regulation of protein serine/threonine kinase activity  negative regulation of cell migration involved in sprouting angiogenesis  Golgi reassembly  negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis  
Ontology : EGO-EBIGolgi membrane  angiogenesis  protein binding  cytoplasm  Golgi apparatus  Golgi apparatus  cytosol  plasma membrane  positive regulation of cell proliferation  positive regulation of gene expression  negative regulation of gene expression  protein kinase binding  positive regulation of cell migration  positive regulation of cell migration  positive regulation of stress-activated MAPK cascade  positive regulation of peptidyl-serine phosphorylation  regulation of Rho protein signal transduction  intrinsic apoptotic signaling pathway in response to hydrogen peroxide  response to hydrogen peroxide  protein homodimerization activity  negative regulation of apoptotic process  stress fiber assembly  positive regulation of MAP kinase activity  wound healing, spreading of cells  positive regulation of Notch signaling pathway  protein N-terminus binding  protein stabilization  establishment of Golgi localization  extracellular exosome  positive regulation of protein serine/threonine kinase activity  negative regulation of cell migration involved in sprouting angiogenesis  Golgi reassembly  negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis  
NDEx NetworkPDCD10
Atlas of Cancer Signalling NetworkPDCD10
Wikipedia pathwaysPDCD10
Orthology - Evolution
OrthoDB11235
GeneTree (enSembl)ENSG00000114209
Phylogenetic Trees/Animal Genes : TreeFamPDCD10
Homologs : HomoloGenePDCD10
Homology/Alignments : Family Browser (UCSC)PDCD10
Gene fusions - Rearrangements
Fusion : MitelmanGPR160/PDCD10 [3q26.2/3q26.1]  [t(3;3)(q26;q26)]  
Fusion: TCGAGPR160 3q26.2 PDCD10 3q26.1 PRAD
Polymorphisms : SNP, variants
NCBI Variation ViewerPDCD10 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PDCD10
dbVarPDCD10
ClinVarPDCD10
1000_GenomesPDCD10 
Exome Variant ServerPDCD10
ExAC (Exome Aggregation Consortium)PDCD10 (select the gene name)
Genetic variants : HAPMAP11235
Genomic Variants (DGV)PDCD10 [DGVbeta]
Mutations
ICGC Data PortalPDCD10 
TCGA Data PortalPDCD10 
Broad Tumor PortalPDCD10
OASIS PortalPDCD10 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPDCD10 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Vascular Anomaly and Lymphedema Mutation Database
BioMutasearch PDCD10
DgiDB (Drug Gene Interaction Database)PDCD10
DoCM (Curated mutations)PDCD10 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PDCD10 (select a term)
intoGenPDCD10
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)3:167401695-167452594  ENSG00000114209
CONAN: Copy Number AnalysisPDCD10 
Mutations and Diseases : HGMDPDCD10
OMIM603285    609118   
MedgenPDCD10
Genetic Testing Registry PDCD10
NextProtQ9BUL8 [Medical]
TSGene11235
GENETestsPDCD10
Huge Navigator PDCD10 [HugePedia]
snp3D : Map Gene to Disease11235
BioCentury BCIQPDCD10
ClinGenPDCD10
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD11235
Chemical/Pharm GKB GenePA33111
Clinical trialPDCD10
Miscellaneous
canSAR (ICR)PDCD10 (select the gene name)
Other databasePDCD10 Protein Atlas
Other databasePDCD10 NBCI
Probes
Litterature
PubMed78 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePDCD10
EVEXPDCD10
GoPubMedPDCD10
iHOPPDCD10
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Sep 22 19:59:21 CEST 2016

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