PRUNE1 (prune exopolyphosphatase)

2013-07-01   Massimo Zollo 

Department of Molecular Medicine, Medical Biotechnology, Federico II, Naples, Italy, CEINGE, Biotecnologie Avanzate, Naples, Italy

Identity

HGNC
LOCATION
1q21.3
LOCUSID
ALIAS
DRES-17,DRES17,H-PRUNE,HTCD37,NMIHBA,PRUNE
FUSION GENES

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).

Proteins

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

Entity name
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 name
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 name
Breast cancer
Note
In breast carcinoma, the overexpression of h-prune is accociated with lymph node status and metastasis formation.
Entity name
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

Pubmed IDLast YearTitleAuthors
86402221996Identification and mapping of human cDNAs homologous to Drosophila mutant genes through EST database searching.Banfi S et al
234489792013Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction.Carotenuto M et al
152544132004Unraveling genes and pathways influenced by H-prune PDE overexpression: a model to study cellular motility.D'Angelo A et al
193909542009The Nm23-H1-h-Prune complex in cellular physiology: a 'tip of the iceberg' protein network perspective.Galasso A et al
179066972008Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility.Garzia L et al
164284452006Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions.Kobayashi T et al
106024781999Evidence for interaction between human PRUNE and nm23-H1 NDPKinase.Reymond A et al
187007472008Human metastasis regulator protein H-prune is a short-chain exopolyphosphatase.Tammenkoski M et al
230595422012Novel pyrimidopyrimidine derivatives for inhibition of cellular proliferation and motility induced by h-prune in breast cancer.Virgilio A et al
156715472005Overexpression of h-prune in breast cancer is correlated with advanced disease status.Zollo M et al

Other Information

Locus ID:

NCBI: 58497
MIM: 617413
HGNC: 13420
Ensembl: ENSG00000143363

Variants:

dbSNP: 58497
ClinVar: 58497
TCGA: ENSG00000143363
COSMIC: PRUNE1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000143363ENST00000271620Q86TP1
ENSG00000143363ENST00000368934Q86TP1
ENSG00000143363ENST00000368935Q86TP1
ENSG00000143363ENST00000368936Q86TP1
ENSG00000143363ENST00000368937Q86TP1
ENSG00000143363ENST00000431193Q5SZG1
ENSG00000143363ENST00000450884Q5SZF2
ENSG00000143363ENST00000650332A0A3B3ITN0

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
50

Pathways

PathwaySourceExternal ID
Purine metabolismKEGGko00230
Purine metabolismKEGGhsa00230

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
164284452006Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions.42
189786782008Candidate gene/loci studies in cleft lip/palate and dental anomalies finds novel susceptibility genes for clefts.21
156715472005Overexpression of h-prune in breast cancer is correlated with advanced disease status.11
250262782014H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC.11
234489792013Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction.9
283349562017PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.7
283349562017PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.7
270375262016h-Prune is associated with poor prognosis and epithelial-mesenchymal transition in patients with colorectal liver metastases.6
207358412010Molecular alterations in key-regulator genes among patients with T4 breast carcinoma.4
294900092018Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1-TGF-β-OTX2-SNAIL via PTEN inhibition.4

Citation

Massimo Zollo

PRUNE1 (prune exopolyphosphatase)

Atlas Genet Cytogenet Oncol Haematol. 2013-07-01

Online version: http://atlasgeneticsoncology.org/gene/40895/prune1