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Small family with key contacts: par14 and par17 parvulin proteins, relatives of pin1, now emerge in biomedical research.

Mueller JW, Bayer P - Perspect Medicin Chem (2008)

Bottom Line: Parvulin has been proposed to function as Pin1 complementing enzyme in cell cycle regulation and in chromatin remodelling.Moreover, the Par17 protein that has been shown to be confined to anthropoid primate species only might provide a deeper understanding for human-specific brain development.This review aims at stimulating further research on Par14 and Par17 that are overlooked drug targets in the shadow of an overwhelming plethora of Pin1 literature by summarising all current knowledge on these parvulin proteins.

View Article: PubMed Central - PubMed

Affiliation: Institute for Structural and Medicinal Biochemistry, Centre for Medical Biotechnology-ZMB, University of Duisburg-Essen, 45117 Essen, Germany.

ABSTRACT
The parvulin-type peptidyl-prolyl cis/trans isomerase Pin1 is subject of intense biochemical and clinical research as it seems to be involved in the pathogenesis of certain cancers and protein folding illnesses like Alzheimer's and Parkinson's disease. In addition to Pin1, the human genome only contains a single other parvulin locus encoding two protein species-Par14 and Par17. Much less is known about these enzymes although their sequences are highly conserved in all metazoans. Parvulin has been proposed to function as Pin1 complementing enzyme in cell cycle regulation and in chromatin remodelling. Pharmaceutical modulation of Par14 might therefore have benefits for certain types of cancer. Moreover, the Par17 protein that has been shown to be confined to anthropoid primate species only might provide a deeper understanding for human-specific brain development. This review aims at stimulating further research on Par14 and Par17 that are overlooked drug targets in the shadow of an overwhelming plethora of Pin1 literature by summarising all current knowledge on these parvulin proteins.

No MeSH data available.


Related in: MedlinePlus

Schematic overview on different parvulin proteinsBacterial, plant and human parvulin representatives are depicted with their domain structure. E. coli SurA contains two PPIase domains (blue and gray) and large N- and C-terminal extensions. E. coli Par10 does not contain any extensions or additional loops—as one of the scarce parvulin sequences from Archaea, PinA from Cenarchaeum symbiosum (SwissProt: O74049). There are phospho-specific parvulins (indicated with the ribbon-like loop) both with and without WW domain. The WW domain is connected to the catalytic domain by a flexible linker in human Pin1.66 Par14-like parvulins contain an N-terminal basic domain (+++) and a five amino acid insertion (loop) between the C-terminal helix and beta-strand of the PPIase domain. An alpha-helical extension (barrel) to this sequence is hominid-specific.
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f1-pmc-2008-011: Schematic overview on different parvulin proteinsBacterial, plant and human parvulin representatives are depicted with their domain structure. E. coli SurA contains two PPIase domains (blue and gray) and large N- and C-terminal extensions. E. coli Par10 does not contain any extensions or additional loops—as one of the scarce parvulin sequences from Archaea, PinA from Cenarchaeum symbiosum (SwissProt: O74049). There are phospho-specific parvulins (indicated with the ribbon-like loop) both with and without WW domain. The WW domain is connected to the catalytic domain by a flexible linker in human Pin1.66 Par14-like parvulins contain an N-terminal basic domain (+++) and a five amino acid insertion (loop) between the C-terminal helix and beta-strand of the PPIase domain. An alpha-helical extension (barrel) to this sequence is hominid-specific.

Mentions: Besides Par14, a second protein species is encoded by the parvulin gene on chromosome Xq13 with an elongated N-terminus.13 The extended mRNA of Par17 is only transcribed in low copy numbers compared to Par14 with about 0.5% of total parvulin mRNA in skeletal muscle and liver tissues and up to 1.5% in brain and epithelial tissues.13 The Par17 protein is targeted to the mitochondrial matrix with the N-terminal domain acting as mitochondrial targeting peptide.14 As this mitochondrial targeting signal is only encoded within the genomes of great apes and humans, this might be the most recently evolved cellular targeting peptide known to date.14 The domain structure of different parvulin proteins is shown in Figure 1.


Small family with key contacts: par14 and par17 parvulin proteins, relatives of pin1, now emerge in biomedical research.

Mueller JW, Bayer P - Perspect Medicin Chem (2008)

Schematic overview on different parvulin proteinsBacterial, plant and human parvulin representatives are depicted with their domain structure. E. coli SurA contains two PPIase domains (blue and gray) and large N- and C-terminal extensions. E. coli Par10 does not contain any extensions or additional loops—as one of the scarce parvulin sequences from Archaea, PinA from Cenarchaeum symbiosum (SwissProt: O74049). There are phospho-specific parvulins (indicated with the ribbon-like loop) both with and without WW domain. The WW domain is connected to the catalytic domain by a flexible linker in human Pin1.66 Par14-like parvulins contain an N-terminal basic domain (+++) and a five amino acid insertion (loop) between the C-terminal helix and beta-strand of the PPIase domain. An alpha-helical extension (barrel) to this sequence is hominid-specific.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2746571&req=5

f1-pmc-2008-011: Schematic overview on different parvulin proteinsBacterial, plant and human parvulin representatives are depicted with their domain structure. E. coli SurA contains two PPIase domains (blue and gray) and large N- and C-terminal extensions. E. coli Par10 does not contain any extensions or additional loops—as one of the scarce parvulin sequences from Archaea, PinA from Cenarchaeum symbiosum (SwissProt: O74049). There are phospho-specific parvulins (indicated with the ribbon-like loop) both with and without WW domain. The WW domain is connected to the catalytic domain by a flexible linker in human Pin1.66 Par14-like parvulins contain an N-terminal basic domain (+++) and a five amino acid insertion (loop) between the C-terminal helix and beta-strand of the PPIase domain. An alpha-helical extension (barrel) to this sequence is hominid-specific.
Mentions: Besides Par14, a second protein species is encoded by the parvulin gene on chromosome Xq13 with an elongated N-terminus.13 The extended mRNA of Par17 is only transcribed in low copy numbers compared to Par14 with about 0.5% of total parvulin mRNA in skeletal muscle and liver tissues and up to 1.5% in brain and epithelial tissues.13 The Par17 protein is targeted to the mitochondrial matrix with the N-terminal domain acting as mitochondrial targeting peptide.14 As this mitochondrial targeting signal is only encoded within the genomes of great apes and humans, this might be the most recently evolved cellular targeting peptide known to date.14 The domain structure of different parvulin proteins is shown in Figure 1.

Bottom Line: Parvulin has been proposed to function as Pin1 complementing enzyme in cell cycle regulation and in chromatin remodelling.Moreover, the Par17 protein that has been shown to be confined to anthropoid primate species only might provide a deeper understanding for human-specific brain development.This review aims at stimulating further research on Par14 and Par17 that are overlooked drug targets in the shadow of an overwhelming plethora of Pin1 literature by summarising all current knowledge on these parvulin proteins.

View Article: PubMed Central - PubMed

Affiliation: Institute for Structural and Medicinal Biochemistry, Centre for Medical Biotechnology-ZMB, University of Duisburg-Essen, 45117 Essen, Germany.

ABSTRACT
The parvulin-type peptidyl-prolyl cis/trans isomerase Pin1 is subject of intense biochemical and clinical research as it seems to be involved in the pathogenesis of certain cancers and protein folding illnesses like Alzheimer's and Parkinson's disease. In addition to Pin1, the human genome only contains a single other parvulin locus encoding two protein species-Par14 and Par17. Much less is known about these enzymes although their sequences are highly conserved in all metazoans. Parvulin has been proposed to function as Pin1 complementing enzyme in cell cycle regulation and in chromatin remodelling. Pharmaceutical modulation of Par14 might therefore have benefits for certain types of cancer. Moreover, the Par17 protein that has been shown to be confined to anthropoid primate species only might provide a deeper understanding for human-specific brain development. This review aims at stimulating further research on Par14 and Par17 that are overlooked drug targets in the shadow of an overwhelming plethora of Pin1 literature by summarising all current knowledge on these parvulin proteins.

No MeSH data available.


Related in: MedlinePlus