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PRUNE1 (prune exopolyphosphatase)

Written2013-07Massimo Zollo
Department of Molecular Medicine, Medical Biotechnology, Federico II, Naples, Italy, CEINGE, Biotecnologie Avanzate, Naples, Italy

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPRUNE
prune homolog (Drosophila)
Alias_symbol (synonym)DRES-17
HTCD37
H-PRUNE
Other aliasDRES17
HGNC (Hugo) PRUNE1
LocusID (NCBI) 58497
Atlas_Id 40895
Location 1q21.3  [Link to chromosome band 1q21]
Location_base_pair Starts at 150980867 and ends at 151008189 bp from pter ( according to hg19-Feb_2009)
Fusion genes
(updated 2016)
PRUNE (1q21.3) / C1orf54 (1q21.2)PRUNE (1q21.3) / PRUNE (1q21.3)
Note Prune stands for the human homologue of the Drosophila prune gene. Prune protein was initially identified in Drosophila, in which its mutation caused a brownish-purple "prune" eye color due to significant loss of drosopterins "red pigments", compared to the bright red eye of the wild-type fly, thus explaining its mutant name. Then the human homologue gene was identified (the human clone, DRES17).

DNA/RNA

Description The prune gene is approximately 1,4 kb in length, consisting of 8 exons and 7 introns.
Transcription 11 transcripts.
Pseudogene A Prune pseudogene, missing exon 4, is located in the 13q12 chromosomal region (acc. no. AF126025) (Reymond et al., 1999).

Protein

Description Prune, a 62 kDa protein, belongs to the DHH family phosphoesterase proteins including RecJ DNA repair exonucleases, pyrophosphatases (PPASEs) and exopolyphospatases (PPX). The DHH super-family can be divided into two main groups on the basis of a C-terminal motif that is very well conserved within each group, but not across the groups. All the members of this super-family possess four other motifs that contain highly conserved charged residues predicted to be responsible for binding ions and catalyzing the phosphoesterase reaction. The most characteristic of these is the third motif, with the signature DHH (Asp-His-His), after which this superfamily was named. Prune is a cyclic nucleotides phosphodiesterase. Due to its protein similarities, Prune might possess other biochemical functionalities within the DHH family of proteins.
The region between amino acids 353-370 of the h-Prune C-terminal is part of the h-Prune DHH2 domain, and in particular constitutes the second part of the last helix and a turned region that interacts with the preceding helix; accordingly, this region in the h-Prune C-terminal has a clear helical propensity. Therefore, the IDP h-Prune C-terminal domain that does not have specific interactions with the globular portions of the whole protein begins at residue 371 and retains the secondary structure propensities (α2 and α3) indicated by the NMR analysis, with a more compact C-terminal region (amino acids 410-440) (Carotenuto et al., 2013).
Expression H-prune overexpression in breast, colorectal and gastric cancers correlates with the degree of lymph-node and distant metastases.
Localisation Prune is localized intracellularly to the cytoplasm.
Function Prune has a role in the metastatic processes through specific inhibition of the anti-metastasis function of nm23-H1 in vivo. Acting as a cytoplasmic cyclic nucleotides phosphodiesterases (cNMP-PDE), Prune is involved in both promoting cellular mobility and stimulating expression of genes involved in metastatic pathways. An additional function has being discovered linking to the first mammalian exopolyphosphatase activity homologue protein, by degrading Poly-P in the cytoplasm, as a source of energy within the cell.
Homology The PRUNE gene is conserved in Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, S. cerevisiae, K. lactis, E. gossypii, S. pombe, M. oryzae, and N. crassa.

Implicated in

Note
  
Entity Various cancers
Note Prune participates in the complex network of interactions with proteins involved in cell cycle and cell motility. It is known that: (i) Prune together with glycogen synthase kinase-3 (GSK3β), a kinase involved in WNT signaling pathway, cooperatively regulates the disassembly of focal adhesions to promote cell migration; (ii) Prune via interaction with Gelsolin, an ATP-severing protein acting in focal adhesions, leads to invasive properties for cancer cells. (iii) the h-prune interaction with NM23 in breast cells results in an increase in h-prune PDE activity, thus inducing negative regulation of nm23-H1 antimetastatic function.
  
  
Entity Colorectal and gastric cancers
Note H-Prune overexpression correlates with T and N stages in colorectal cancer and its expression is an independent predictor of survival of patients with gastric cancer.
  
  
Entity Breast cancer
Note In breast carcinoma, the overexpression of h-prune is accociated with lymph node status and metastasis formation.
  
  
Entity Brain development
Note Interestingly, Prune has also been shown to be highly expressed in brain development together with nm23-H1, expression was observed in cortex, hippocampus, midbrain and during cerebellum development.
  

Bibliography

Identification and mapping of human cDNAs homologous to Drosophila mutant genes through EST database searching.
Banfi S, Borsani G, Rossi E, Bernard L, Guffanti A, Rubboli F, Marchitiello A, Giglio S, Coluccia E, Zollo M, Zuffardi O, Ballabio A.
Nat Genet. 1996 Jun;13(2):167-74.
PMID 8640222
 
Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction.
Carotenuto M, Pedone E, Diana D, de Antonellis P, Dzeroski S, Marino N, Navas L, Di Dato V, Scoppettuolo MN, Cimmino F, Correale S, Pirone L, Monti SM, Bruder E, Zenko B, Slavkov I, Pastorino F, Ponzoni M, Schulte JH, Schramm A, Eggert A, Westermann F, Arrigoni G, Accordi B, Basso G, Saviano M, Fattorusso R, Zollo M.
Sci Rep. 2013;3:1351. doi: 10.1038/srep01351.
PMID 23448979
 
Unraveling genes and pathways influenced by H-prune PDE overexpression: a model to study cellular motility.
D'Angelo A, Zollo M.
Cell Cycle. 2004 Jun;3(6):758-61. Epub 2004 Jun 14. (REVIEW)
PMID 15254413
 
The Nm23-H1-h-Prune complex in cellular physiology: a 'tip of the iceberg' protein network perspective.
Galasso A, Zollo M.
Mol Cell Biochem. 2009 Sep;329(1-2):149-59. doi: 10.1007/s11010-009-0115-4. Epub 2009 Apr 24. (REVIEW)
PMID 19390954
 
Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility.
Garzia L, D'Angelo A, Amoresano A, Knauer SK, Cirulli C, Campanella C, Stauber RH, Steegborn C, Iolascon A, Zollo M.
Oncogene. 2008 Mar 20;27(13):1853-64. Epub 2007 Oct 1.
PMID 17906697
 
Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions.
Kobayashi T, Hino S, Oue N, Asahara T, Zollo M, Yasui W, Kikuchi A.
Mol Cell Biol. 2006 Feb;26(3):898-911.
PMID 16428445
 
Evidence for interaction between human PRUNE and nm23-H1 NDPKinase.
Reymond A, Volorio S, Merla G, Al-Maghtheh M, Zuffardi O, Bulfone A, Ballabio A, Zollo M.
Oncogene. 1999 Dec 2;18(51):7244-52.
PMID 10602478
 
Human metastasis regulator protein H-prune is a short-chain exopolyphosphatase.
Tammenkoski M, Koivula K, Cusanelli E, Zollo M, Steegborn C, Baykov AA, Lahti R.
Biochemistry. 2008 Sep 9;47(36):9707-13. doi: 10.1021/bi8010847. Epub 2008 Aug 14.
PMID 18700747
 
Novel pyrimidopyrimidine derivatives for inhibition of cellular proliferation and motility induced by h-prune in breast cancer.
Virgilio A, Spano D, Esposito V, Di Dato V, Citarella G, Marino N, Maffia V, De Martino D, De Antonellis P, Galeone A, Zollo M.
Eur J Med Chem. 2012 Nov;57:41-50. doi: 10.1016/j.ejmech.2012.08.020. Epub 2012 Aug 23.
PMID 23059542
 
Overexpression of h-prune in breast cancer is correlated with advanced disease status.
Zollo M, Andre A, Cossu A, Sini MC, D'Angelo A, Marino N, Budroni M, Tanda F, Arrigoni G, Palmieri G.
Clin Cancer Res. 2005 Jan 1;11(1):199-205.
PMID 15671547
 

Citation

This paper should be referenced as such :
Zollo, M
PRUNE (prune exopolyphosphatase)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(2):110-111.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PRUNEID40895ch1q21.html


External links

Nomenclature
HGNC (Hugo)PRUNE   13420
Cards
AtlasPRUNEID40895ch1q21
Entrez_Gene (NCBI)PRUNE1  58497  prune exopolyphosphatase
AliasesDRES-17; DRES17; HTCD37
GeneCards (Weizmann)PRUNE1
Ensembl hg19 (Hinxton)ENSG00000143363 [Gene_View]  chr1:150980867-151008189 [Contig_View]  PRUNE1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000143363 [Gene_View]  chr1:150980867-151008189 [Contig_View]  PRUNE1 [Vega]
ICGC DataPortalENSG00000143363
TCGA cBioPortalPRUNE1
AceView (NCBI)PRUNE1
Genatlas (Paris)PRUNE1
WikiGenes58497
SOURCE (Princeton)PRUNE1
Genetics Home Reference (NIH)PRUNE1
Genomic and cartography
GoldenPath hg19 (UCSC)PRUNE1  -     chr1:150980867-151008189 +  1q21.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)PRUNE1  -     1q21.2   [Description]    (hg38-Dec_2013)
EnsemblPRUNE1 - 1q21.2 [CytoView hg19]  PRUNE1 - 1q21.2 [CytoView hg38]
Mapping of homologs : NCBIPRUNE1 [Mapview hg19]  PRUNE1 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF051907 AF123538 AF123539 AK027875 AK294154
RefSeq transcript (Entrez)NM_001303229 NM_001303242 NM_001303243 NM_021222
RefSeq genomic (Entrez)NC_000001 NC_018912 NT_004487 NW_004929293
Consensus coding sequences : CCDS (NCBI)PRUNE1
Cluster EST : UnigeneHs.78524 [ NCBI ]
CGAP (NCI)Hs.78524
Alternative Splicing GalleryENSG00000143363
Gene ExpressionPRUNE1 [ NCBI-GEO ]   PRUNE1 [ EBI - ARRAY_EXPRESS ]   PRUNE1 [ SEEK ]   PRUNE1 [ MEM ]
Gene Expression Viewer (FireBrowse)PRUNE1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)58497
GTEX Portal (Tissue expression)PRUNE1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ86TP1   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ86TP1  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ86TP1
Splice isoforms : SwissVarQ86TP1
Catalytic activity : Enzyme3.6.1.1 [ Enzyme-Expasy ]   3.6.1.13.6.1.1 [ IntEnz-EBI ]   3.6.1.1 [ BRENDA ]   3.6.1.1 [ KEGG ]   
PhosPhoSitePlusQ86TP1
Domains : Interpro (EBI)DDH_dom    DHHA2   
Domain families : Pfam (Sanger)DHH (PF01368)    DHHA2 (PF02833)   
Domain families : Pfam (NCBI)pfam01368    pfam02833   
Conserved Domain (NCBI)PRUNE1
DMDM Disease mutations58497
Blocks (Seattle)PRUNE1
SuperfamilyQ86TP1
Human Protein AtlasENSG00000143363
Peptide AtlasQ86TP1
HPRD15188
IPIIPI00166931   IPI00155261   IPI00895854   IPI00895809   IPI00645747   IPI00929544   IPI00028177   IPI00645222   
Protein Interaction databases
DIP (DOE-UCLA)Q86TP1
IntAct (EBI)Q86TP1
FunCoupENSG00000143363
BioGRIDPRUNE1
STRING (EMBL)PRUNE1
ZODIACPRUNE1
Ontologies - Pathways
QuickGOQ86TP1
Ontology : AmiGOinorganic diphosphatase activity  protein binding  nucleus  cytoplasm  focal adhesion  metabolic process  metal ion binding  
Ontology : EGO-EBIinorganic diphosphatase activity  protein binding  nucleus  cytoplasm  focal adhesion  metabolic process  metal ion binding  
Pathways : KEGGPurine metabolism   
NDEx NetworkPRUNE1
Atlas of Cancer Signalling NetworkPRUNE1
Wikipedia pathwaysPRUNE1
Orthology - Evolution
OrthoDB58497
GeneTree (enSembl)ENSG00000143363
Phylogenetic Trees/Animal Genes : TreeFamPRUNE
HOVERGENQ86TP1
HOGENOMQ86TP1
Homologs : HomoloGenePRUNE1
Homology/Alignments : Family Browser (UCSC)PRUNE1
Gene fusions - Rearrangements
Fusion : MitelmanPRUNE/C1orf54 [1q21.3/1q21.2]  
Fusion: TCGAPRUNE 1q21.3 C1orf54 1q21.2 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPRUNE1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PRUNE1
dbVarPRUNE1
ClinVarPRUNE1
1000_GenomesPRUNE1 
Exome Variant ServerPRUNE1
ExAC (Exome Aggregation Consortium)PRUNE1 (select the gene name)
Genetic variants : HAPMAP58497
Genomic Variants (DGV)PRUNE1 [DGVbeta]
DECIPHER (Syndromes)1:150980867-151008189  ENSG00000143363
CONAN: Copy Number AnalysisPRUNE1 
Mutations
ICGC Data PortalPRUNE 
TCGA Data PortalPRUNE 
Broad Tumor PortalPRUNE
OASIS PortalPRUNE [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDPRUNE
BioMutasearch PRUNE1
DgiDB (Drug Gene Interaction Database)PRUNE1
DoCM (Curated mutations)PRUNE1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PRUNE1 (select a term)
intoGenPRUNE1
NCG5 (London)PRUNE1
Cancer3DPRUNE1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM
Orphanet
MedgenPRUNE1
Genetic Testing Registry PRUNE1
NextProtQ86TP1 [Medical]
TSGene58497
GENETestsPRUNE1
Huge Navigator PRUNE [HugePedia]
snp3D : Map Gene to Disease58497
BioCentury BCIQPRUNE1
ClinGenPRUNE1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD58497
Chemical/Pharm GKB GenePA134939749
Clinical trialPRUNE1
Miscellaneous
canSAR (ICR)PRUNE1 (select the gene name)
Probes
Litterature
PubMed25 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePRUNE1
EVEXPRUNE1
GoPubMedPRUNE1
iHOPPRUNE1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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