PRUNE1 (prune exopolyphosphatase)
2013-07-01 Massimo Zollo   AffiliationDepartment 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).
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 8640222 | 1996 | Identification and mapping of human cDNAs homologous to Drosophila mutant genes through EST database searching. | Banfi S et al |
| 23448979 | 2013 | Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction. | Carotenuto M et al |
| 15254413 | 2004 | Unraveling genes and pathways influenced by H-prune PDE overexpression: a model to study cellular motility. | D'Angelo A et al |
| 19390954 | 2009 | The Nm23-H1-h-Prune complex in cellular physiology: a 'tip of the iceberg' protein network perspective. | Galasso A et al |
| 17906697 | 2008 | Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility. | Garzia L et al |
| 16428445 | 2006 | Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions. | Kobayashi T et al |
| 10602478 | 1999 | Evidence for interaction between human PRUNE and nm23-H1 NDPKinase. | Reymond A et al |
| 18700747 | 2008 | Human metastasis regulator protein H-prune is a short-chain exopolyphosphatase. | Tammenkoski M et al |
| 23059542 | 2012 | Novel pyrimidopyrimidine derivatives for inhibition of cellular proliferation and motility induced by h-prune in breast cancer. | Virgilio A et al |
| 15671547 | 2005 | Overexpression 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
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Purine metabolism | KEGG | ko00230 |
| Purine metabolism | KEGG | hsa00230 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37666675 | 2023 | PRUNE1 (located on chromosome 1q21.3) promotes multiple myeloma with 1q21 Gain by enhancing the links between purine and mitochondrion. | 1 |
| 37666675 | 2023 | PRUNE1 (located on chromosome 1q21.3) promotes multiple myeloma with 1q21 Gain by enhancing the links between purine and mitochondrion. | 1 |
| 35379233 | 2022 | Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 gene. | 3 |
| 35379233 | 2022 | Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies in a consanguineous Iranian family is associated with a homozygous start loss variant in the PRUNE1 gene. | 3 |
| 33105479 | 2021 | NMIHBA results from hypomorphic PRUNE1 variants that lack short-chain exopolyphosphatase activity. | 7 |
| 34111303 | 2021 | An identical-by-descent novel splice-donor variant in PRUNE1 causes a neurodevelopmental syndrome with prominent dystonia in two consanguineous Sudanese families. | 2 |
| 33105479 | 2021 | NMIHBA results from hypomorphic PRUNE1 variants that lack short-chain exopolyphosphatase activity. | 7 |
| 34111303 | 2021 | An identical-by-descent novel splice-donor variant in PRUNE1 causes a neurodevelopmental syndrome with prominent dystonia in two consanguineous Sudanese families. | 2 |
| 30556349 | 2019 | A homozygous canonical splice acceptor site mutation in PRUNE1 is responsible for a rare childhood neurodegenerative disease in Manitoba Cree families. | 6 |
| 32134588 | 2019 | Bi-allelic mutations in PRUNE lead to neurodegeneration with spinal motor neuron involvement and hyperCKaemia. | 2 |
| 30556349 | 2019 | A homozygous canonical splice acceptor site mutation in PRUNE1 is responsible for a rare childhood neurodegenerative disease in Manitoba Cree families. | 6 |
| 32134588 | 2019 | Bi-allelic mutations in PRUNE lead to neurodegeneration with spinal motor neuron involvement and hyperCKaemia. | 2 |
| 29490009 | 2018 | Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1-TGF-β-OTX2-SNAIL via PTEN inhibition. | 18 |
| 29797509 | 2018 | PRUNE1-related disorder: Expanding the clinical spectrum. | 6 |
| 29940663 | 2018 | PRUNE1 Deficiency: Expanding the Clinical and Genetic Spectrum. | 6 |
Citation
Massimo Zollo
PRUNE1 (prune exopolyphosphatase)
Atlas Genet Cytogenet Oncol Haematol. 2013-07-01
Online version: http://atlasgeneticsoncology.org/gene/40895/prune1-(prune-exopolyphosphatase)
