This family consist of zinc finger protein ZPR1 and ZPR1-like proteins. The function of ZPR1 is not clear. ZPR1 is present in both the cytoplasm and nucleoplasma and its subcellular distribution changes during proliferation []. ZPR1 binds to the cytoplasmic tyrosine kinase domain of the epidermal growth factor receptor (EGFR) []and is a component of downstream signaling of both EGFR and FGFR signaling []. It has been associated with susceptibility to type 2 diabetes []and is downregulated in patients with spinal muscular atrophy [].
The zinc finger protein (ZPR1) is a eukaryotic protein that comprises tandem ZPR1 domains and which, in response to growth stimuli, binds to eukaryotic translation elongation factor 1A (eEF1A), assembles into multiprotein complexes with the survival motor neurons (SMN) protein, and accumulates in subnuclear structures, such as gems and Cajal bodies. ZPR1 has a conserved tandem architecture consisting of a duplicated module, the ZPR1 domain, comprised of two apparently modular domains: an elongation initiation factor 2-like zinc finger (Znf) and a double-stranded beta helix with a helical hairpin insertion (A/B domain). In consequence, the N- and C-terminal ZPR1 domains are referred to as the Znf1-A domain and Znf2-B domain modules, respectively. The Znf2-B domain module is required for viability, whilst the Znf1-A domain module is required for normal cell growth and proliferation [].This superfamily represents the A/B domain found inZPR1.
The zinc finger protein (ZPR1) is a eukaryotic protein that comprises tandem ZPR1 domains and which, in response to growth stimuli, binds to eukaryotic translation elongation factor 1A (eEF1A), assembles into multiprotein complexes with the survival motor neurons (SMN) protein, and accumulates in subnuclear structures, such as gems and Cajal bodies. ZPR1 has a conserved tandem architecture consisting of a duplicated module, the ZPR1 domain, comprised of two apparently modular domains: an elongation initiation factor 2-like zinc finger (Znf) and a double-stranded beta helix with a helical hairpin insertion (A/B domain). In consequence, the N- and C-terminal ZPR1 domains are referred to as the Znf1-A domain and Znf2-B domain modules, respectively. The Znf2-B domain module is required for viability, whilst the Znf1-A domain module is required for normal cell growth and proliferation [].This superfamily represents the zinc finger domain (Znf1/2) found in ZPR1.
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [, , , , ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents ZPR1-type zinc finger domains. An orthologous protein found once in each of the completed archaeal genomes corresponds to a zinc finger-containing domain repeated as the N-terminal and C-terminal halves of themouse protein ZPR1. ZPR1 is an experimentally proven zinc-binding protein that binds the tyrosine kinase domain of the epidermal growth factor receptor (EGFR); binding is inhibited by EGF stimulation and tyrosine phosphorylation, and activation by EGF is followed by some redistribution of ZPR1 to the nucleus. By analogy, other proteins with the ZPR1 zinc finger domain may be regulatory proteins that sense protein phosphorylation state and/or participate in signal transduction (see also ).Deficiencies in ZPR1 may contribute to neurodegenerative disorders. ZPR1 appears to be down-regulated in patients with spinal muscular atrophy (SMA), a disease characterised by degeneration of the alpha-motor neurons in the spinal cord that can arise from mutations affecting the expression of Survival Motor Neurons (SMN) []. ZPR1 interacts with complexes formed by SMN [], and may act as a modifier that effects the severity of SMA.
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [, , , , ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents ZPR1-type zinc finger domains. ZPR1 was shown experimentally to bind approximately two moles of zinc, and has two copies of a domain homologous to this protein, each containing a putative zinc finger of the form CXXCX(25)CXXC. ZPR1 bindsthe tyrosine kinase domain of epidermal growth factor receptor but is displaced by receptor activation and autophosphorylation after which it redistributes in part to the nucleus. The proteins described by this family by analogy may be suggested to play a role in signal transduction as proven for other Z-finger binding proteins.Deficiencies in ZPR1 may contribute to neurodegenerative disorders. ZPR1 appears to be down-regulated in patients with spinal muscular atrophy (SMA), a disease characterised by degeneration of the alpha-motor neurons in the spinal cord that can arise from mutations affecting the expression of Survival Motor Neurons (SMN) []. ZPR1 interacts with complexes formed by SMN [], and may act as a modifier that effects the severity of SMA.
