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YPEL3 (yippee-like 3 (Drosophila))

Written2014-04Gizem Güpür, Mesut Muyan
Department of Biological Sciences, Middle East Technical University, Ankara, Turkey

(Note : for Links provided by Atlas : click)

Identity

Alias_namesyippee-like 3 (Drosophila)
Alias_symbol (synonym)MGC10500
HGNC (Hugo) YPEL3
LocusID (NCBI) 83719
Atlas_Id 51528
Location 16p11.2  [Link to chromosome band 16p11]
Location_base_pair Starts at 30103637 and ends at 30107537 bp from pter ( according to hg19-Feb_2009)  [Mapping YPEL3.png]
Local_order From telomere to centromere: MAPK3-GDPD3-LOC101928595-YPEL3-TBX6-PPP4C-ALDOA-FAM57B-C16orf92-DOC2A.
 
  Local order of YPEL3 is shown together with leading and subsequent genes on chromosome 16.

DNA/RNA

 
  Boxes show exons; filled boxes correspond to coding exons, empty boxes indicate noncoding exons. Lines connecting the boxes represent introns. Arrows indicate the translation initiation codon.
Description YPEL3 has 4 exons.
Transcription YPEL3 has 2 transcript variants, resulting from the differential processing of the exon 1.
Transcript variant 1: 1588 bp mRNA (NCBI RefSeq NM_031477.4).
Transcript variant 2: 940 bp mRNA (NCBI RefSeq NM_001145524.1).

Protein

Note Two transcript variants encode two protein isoforms differing at their amino-termini.
Protein yippee-like 3 isoform 1; 157 aa protein (NCBI RefSeq NP_113665.3).
Protein yippee-like 3 isoform 2; 119 aa protein (NCBI RefSeq NP_001138996.1).
Expression In human, YPEL3 is expressed in the brain, heart, kidney, lung, pancreas, placenta, skeletal muscle, colon, ovary, leukocyte, prostate, small intestine, spleen, testis, thymus, bone marrow, leukocyte, tonsil, fetal brain, fetal heart, fetal kidney, fetal liver, fetal lung, fetal skeletal muscle, fetal spleen and fetal thymus (Hosono et al., 2004).
Localisation Immunofluorescence staining with an antibody recognizing Ypel1, 2, 3 and 4 proteins suggests that Ypel1-4 are nuclear proteins. In interphase cells, Ypel1-4 are localized in nucleoli and the centrosome. In the mitotic phase, Ypel1-4 become localized on or close to the mitotic apparatus rather than in the centrosome (Hosono et al., 2004).
Function Studies show that the expression of YPEL3 gene is up-regulated during DNA damage, reflected as an increase in YPEL protein levels, likely through two functional p53 binding sites present on the YPEL3 gene promoter (Kelley et al., 2010).
When YPEL3 is expressed by a tetracycline inducible system at levels comparable to endogenous mRNA levels detected upon DNA damage, both MCF7 and U2OS cells showed fewer colonies compared to uninduced cells. YPEL3 expressing U2OS and MCF7 cells also showed an increase in cellular senescence as shown by increases β-galactosidase activity and the appearance of foci within the nuclei of senescent cells (SAHF) (Kelley et al., 2010).
Homology In human, YPEL3 has 4 paralogs; YPEL1, YPEL2, YPEL4 and YPEL5. Ypel3 has 88.2% aminoacid sequence identity with Ypel1; 89.1% with Ypel2; 83.9% with Ypel4 and 43.8% with Ypel5 (Hosono et al., 2004).
Ypel3 is an ortholog of Drosophila Yippee protein and has 45.5% aminoacid sequence identity to Yippee. There are 100 YPEL family genes in 68 species including mammal, bird, amphibia, fish, protochordate, insect, nematode, coelenterate, echinoderm, protozoan, plant, and fungi. In this diverge range of organisms, YPEL family proteins show a high level of homology with many identical residues. Thus, a consensus sequence is deduced as follows: C-X2-C-X19-G-X3-L-X5-N-X13-G-X8-C-X2-C-X4-GWXY-X10-K-X6-E. In the consensus sequence, the number of non-consensus residues, designated as X, is identical for all species examined (Hosono et al., 2004).

Implicated in

Note
Entity Colon cancer
Note YPEL3 is found to be down-regulated in 9 commercial colon tumor samples and in 22 patient colon adenocarcinoma (Tuttle et al., 2011).
  
Entity Ovarian cancer
Note A significant decrease in YPEL3 mRNA levels was detected in 9 commercial and 30 patient ovarian tumors. In Cp70 ovarian cells, hypermethylation of a CpG island immediately upstream of the YPEL3 promoter is suggested to be the basis for the observed down-regulation (Kelley et al., 2010).
  
Entity Lung cancer
Note YPEL3 mRNA is shown to be down-regulated in 8 of 9 commercial lung tumor samples (Tuttle et al., 2011).
  
Entity Breast cancer
Note YPEL3 is observed to be down-regulated in breast cancer cell models. Decrease in YPEL3 mRNA levels by siRNA causes an increase in the growth of estrogen receptor positive (ER+) MCF7 cells while YPEL3 over-expression decreases cell number. Moreover, YPEL3 mRNA as well as Ypel protein levels show an increase in MCF7 cells when 17β-estradiol (E2) is withdrawn. In contrast, the addition of E2 at a circulating level (1nM) decreases the expression of YPEL3. The down-regulation of YPEL3 by E2 can be reversed by the addition of selective estrogen receptor modulator, tamoxifen, TMX (Tuttle et al., 2012).
In addition to p53, E2-ER signaling plays a role in the regulation of YPEL3 gene expression based on the observations that the reduction of intracellular ERa levels in MCF7 cells by ERa knockdown increases the expression of YPEL3 gene (Tuttle et al., 2012).
Studies also showed that when grown in the absence of E2, MCF7 cells undergo cellular senescence, whereas the silencing of YPEL3 rescues cells from senescence. Further evidence that YPEL3 is involved in E2-ER mediated cellular senescence was obtained from studies showing that the treatment of MCF7 cells with TMX increases the expression of the YPEL3 gene and that TMX-induced cellular senescence is not observed when YPEL3 is silenced. Importantly, cellular senescence induced by removal of E2 and/or over-expression of YPEL3 is independent of p53 expression. Thus, it appears that YPEL3 plays a role in E2-ER signaling dependent cellular growth and senescence in MCF7 cells. This in turn implies that Ypel3 is a tumor suppressor protein (Tuttle et al., 2012).
  

Bibliography

Identification and characterization of a novel gene family YPEL in a wide spectrum of eukaryotic species.
Hosono K, Sasaki T, Minoshima S, Shimizu N.
Gene. 2004 Sep 29;340(1):31-43.
PMID 15556292
 
YPEL3, a p53-regulated gene that induces cellular senescence.
Kelley KD, Miller KR, Todd A, Kelley AR, Tuttle R, Berberich SJ.
Cancer Res. 2010 May 1;70(9):3566-75. doi: 10.1158/0008-5472.CAN-09-3219. Epub 2010 Apr 13.
PMID 20388804
 
Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence.
Tuttle R, Miller KR, Maiorano JN, Termuhlen PM, Gao Y, Berberich SJ.
Int J Cancer. 2012 May 15;130(10):2291-9. doi: 10.1002/ijc.26239. Epub 2011 Aug 9.
PMID 21671470
 
Senescence-associated gene YPEL3 is downregulated in human colon tumors.
Tuttle R, Simon M, Hitch DC, Maiorano JN, Hellan M, Ouellette J, Termuhlen P, Berberich SJ.
Ann Surg Oncol. 2011 Jun;18(6):1791-6. doi: 10.1245/s10434-011-1558-x. Epub 2011 Jan 26.
PMID 21267786
 

Citation

This paper should be referenced as such :
G Güpür, M Muyan
YPEL3 (yippee-like 3 (Drosophila))
Atlas Genet Cytogenet Oncol Haematol. 2015;19(1):38-40.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/YPEL3ID51528ch16p11.html


External links

Nomenclature
HGNC (Hugo)YPEL3   18327
Cards
AtlasYPEL3ID51528ch16p11
Entrez_Gene (NCBI)YPEL3  83719  yippee like 3
Aliases
GeneCards (Weizmann)YPEL3
Ensembl hg19 (Hinxton)ENSG00000090238 [Gene_View]  chr16:30103637-30107537 [Contig_View]  YPEL3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000090238 [Gene_View]  chr16:30103637-30107537 [Contig_View]  YPEL3 [Vega]
ICGC DataPortalENSG00000090238
TCGA cBioPortalYPEL3
AceView (NCBI)YPEL3
Genatlas (Paris)YPEL3
WikiGenes83719
SOURCE (Princeton)YPEL3
Genetics Home Reference (NIH)YPEL3
Genomic and cartography
GoldenPath hg19 (UCSC)YPEL3  -     chr16:30103637-30107537 -  16p11.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)YPEL3  -     16p11.2   [Description]    (hg38-Dec_2013)
EnsemblYPEL3 - 16p11.2 [CytoView hg19]  YPEL3 - 16p11.2 [CytoView hg38]
Mapping of homologs : NCBIYPEL3 [Mapview hg19]  YPEL3 [Mapview hg38]
OMIM609724   
Gene and transcription
Genbank (Entrez)AB098737 AF305622 AK022409 AK026047 BC005009
RefSeq transcript (Entrez)NM_001145524 NM_031477
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)YPEL3
Cluster EST : UnigeneHs.513491 [ NCBI ]
CGAP (NCI)Hs.513491
Alternative Splicing GalleryENSG00000090238
Gene ExpressionYPEL3 [ NCBI-GEO ]   YPEL3 [ EBI - ARRAY_EXPRESS ]   YPEL3 [ SEEK ]   YPEL3 [ MEM ]
Gene Expression Viewer (FireBrowse)YPEL3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)83719
GTEX Portal (Tissue expression)YPEL3
Protein : pattern, domain, 3D structure
UniProt/SwissProtP61236   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP61236  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP61236
Splice isoforms : SwissVarP61236
PhosPhoSitePlusP61236
Domaine pattern : Prosite (Expaxy)YIPPEE (PS51792)   
Domains : Interpro (EBI)Yippee/Mis18/Cereblon   
Domain families : Pfam (Sanger)Yippee-Mis18 (PF03226)   
Domain families : Pfam (NCBI)pfam03226   
Conserved Domain (NCBI)YPEL3
DMDM Disease mutations83719
Blocks (Seattle)YPEL3
SuperfamilyP61236
Human Protein AtlasENSG00000090238
Peptide AtlasP61236
HPRD15683
IPIIPI00640143   IPI00873358   
Protein Interaction databases
DIP (DOE-UCLA)P61236
IntAct (EBI)P61236
FunCoupENSG00000090238
BioGRIDYPEL3
STRING (EMBL)YPEL3
ZODIACYPEL3
Ontologies - Pathways
QuickGOP61236
Ontology : AmiGOnucleolus  metal ion binding  positive regulation of cellular senescence  
Ontology : EGO-EBInucleolus  metal ion binding  positive regulation of cellular senescence  
NDEx NetworkYPEL3
Atlas of Cancer Signalling NetworkYPEL3
Wikipedia pathwaysYPEL3
Orthology - Evolution
OrthoDB83719
GeneTree (enSembl)ENSG00000090238
Phylogenetic Trees/Animal Genes : TreeFamYPEL3
HOVERGENP61236
HOGENOMP61236
Homologs : HomoloGeneYPEL3
Homology/Alignments : Family Browser (UCSC)YPEL3
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerYPEL3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)YPEL3
dbVarYPEL3
ClinVarYPEL3
1000_GenomesYPEL3 
Exome Variant ServerYPEL3
ExAC (Exome Aggregation Consortium)YPEL3 (select the gene name)
Genetic variants : HAPMAP83719
Genomic Variants (DGV)YPEL3 [DGVbeta]
DECIPHER (Syndromes)16:30103637-30107537  ENSG00000090238
CONAN: Copy Number AnalysisYPEL3 
Mutations
ICGC Data PortalYPEL3 
TCGA Data PortalYPEL3 
Broad Tumor PortalYPEL3
OASIS PortalYPEL3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICYPEL3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDYPEL3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch YPEL3
DgiDB (Drug Gene Interaction Database)YPEL3
DoCM (Curated mutations)YPEL3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)YPEL3 (select a term)
intoGenYPEL3
NCG5 (London)YPEL3
Cancer3DYPEL3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM609724   
Orphanet
MedgenYPEL3
Genetic Testing Registry YPEL3
NextProtP61236 [Medical]
TSGene83719
GENETestsYPEL3
Huge Navigator YPEL3 [HugePedia]
snp3D : Map Gene to Disease83719
BioCentury BCIQYPEL3
ClinGenYPEL3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD83719
Chemical/Pharm GKB GenePA134985092
Clinical trialYPEL3
Miscellaneous
canSAR (ICR)YPEL3 (select the gene name)
Probes
Litterature
PubMed14 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineYPEL3
EVEXYPEL3
GoPubMedYPEL3
iHOPYPEL3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Sat Jan 21 16:48:43 CET 2017

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