PF03367

ZPR1 zinc-finger domain

Pfam entry
Member databasePfam
Pfam typedomain
Short namezf-ZPR1
ClanZn_Beta_Ribbon
Author Mifsud W;0000-0002-9805-6461
Sequence Ontology0000417

Description

This entry represents the zinc-ribbon domain found in ZPR1 family. The zinc-finger protein ZPR1 is ubiquitous among eukaryotes. It is indeed known to be an essential protein in yeast. In quiescent cells, ZPR1 is localised to the cytoplasm. But in proliferating cells treated with EGF or with other mitogens, ZPR1 accumulates in the nucleolus. ZPR1 interacts with the cytoplasmic domain of the inactive EGF receptor (EGFR) and is thought to inhibit the basal protein tyrosine kinase activity of EGFR. This interaction is disrupted when cells are treated with EGF, though by themselves, inactive EGFRs are not sufficient to sequester ZPR1 to the cytoplasm
[1, 4, 3]
. Upon stimulation by EGF, ZPR1 directly binds the eukaryotic translation elongation factor-1alpha (eEF-1alpha) to form ZPR1/eEF-1alpha complexes
[1]
. These move into the nucleus, localising particularly at the nucleolus. Indeed, the interaction between ZPR1 and eEF-1alpha has been shown to be essential for normal cellular proliferation
[1]
, and ZPR1 is thought to be involved in pre-ribosomal RNA expression
[4]
. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis
[2]
. The alignment for the ZPR1 family shows a duplicated set composed of a zinc-ribbon domain (this entry) followed by a jelly-roll domain. This family also includes several hypothetical archaeal proteins (from both Crenarchaeota and Euryarchaeota). This similarity between ZPR1 and archaeal proteins was not previously noted.

References

1.Interaction of ZPR1 with translation elongation factor-1alpha in proliferating cells. Gangwani L, Mikrut M, Galcheva-Gargova Z, Davis RJ. J. Cell Biol. 143, 1471-84, (1998). View articlePMID: 9852145

2.Structural insights into the interaction of the evolutionarily conserved ZPR1 domain tandem with eukaryotic EF1A, receptors, and SMN complexes. Mishra AK, Gangwani L, Davis RJ, Lambright DG. Proc. Natl. Acad. Sci. U.S.A. 104, 13930-5, (2007). View articlePMID: 17704259

3.Binding of zinc finger protein ZPR1 to the epidermal growth factor receptor. Galcheva-Gargova Z, Konstantinov KN, Wu IH, Klier FG, Barrett T, Davis RJ. Science 272, 1797-802, (1996). View articlePMID: 8650580

4.The cytoplasmic zinc finger protein ZPR1 accumulates in the nucleolus of proliferating cells. Galcheva-Gargova Z, Gangwani L, Konstantinov KN, Mikrut M, Theroux SJ, Enoch T, Davis RJ. Mol. Biol. Cell 9, 2963-71, (1998). View articlePMID: 9763455

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