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SwissPalm: Protein Palmitoylation database.

Blanc M, David F, Abrami L, Migliozzi D, Armand F, Bürgi J, van der Goot FG - F1000Res (2015)

Bottom Line: Systems analysis of the palmitoyl-proteome screens indicate that 10% or more of the human proteome is susceptible to S-palmitoylation.Moreover, ontology and pathway analyses of the human palmitoyl-proteome reveal that key biological functions involve this reversible lipid modification.Through the compilation of data and continuous updates, SwissPalm will provide a powerful tool to unravel the global importance of protein S-palmitoylation.

View Article: PubMed Central - PubMed

Affiliation: Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.

ABSTRACT
Protein S-palmitoylation is a reversible post-translational modification that regulates many key biological processes, although the full extent and functions of protein S-palmitoylation remain largely unexplored. Recent developments of new chemical methods have allowed the establishment of palmitoyl-proteomes of a variety of cell lines and tissues from different species.  As the amount of information generated by these high-throughput studies is increasing, the field requires centralization and comparison of this information. Here we present SwissPalm ( http://swisspalm.epfl.ch), our open, comprehensive, manually curated resource to study protein S-palmitoylation. It currently encompasses more than 5000 S-palmitoylated protein hits from seven species, and contains more than 500 specific sites of S-palmitoylation. SwissPalm also provides curated information and filters that increase the confidence in true positive hits, and integrates predictions of S-palmitoylated cysteine scores, orthologs and isoform multiple alignments. Systems analysis of the palmitoyl-proteome screens indicate that 10% or more of the human proteome is susceptible to S-palmitoylation. Moreover, ontology and pathway analyses of the human palmitoyl-proteome reveal that key biological functions involve this reversible lipid modification. Comparative analysis finally shows a strong crosstalk between S-palmitoylation and other post-translational modifications. Through the compilation of data and continuous updates, SwissPalm will provide a powerful tool to unravel the global importance of protein S-palmitoylation.

No MeSH data available.


Related in: MedlinePlus

S-palmitoylation of mammalian protein complexes.A andB: Human and mouse protein complexes enriched in S-palmitoylation hits using the CORUM database. Proteins complexes containing more than 6 proteins and enriched by at least 50% of S-palmitoylation hits were selected.C: Representation of the TRiC complex subunits. Color circles represent the species in which each CCT subunit was identified as S-palmitoylated. The star indicated proteins identified by 2 independent techniques.D: Palmitoylation of the subunits was validated by Acyl-RAC on CCT1, CCT2, CCT3, CCT4 and CCT5 subunits and by3H-palmitate labelling on CCT1 and CCT2 subunits. (TCE: Total cell extract, NH2OH: Hydroxylamine treatment,3H-palm: radioactive palmitate signal, WB: Western blot signal).
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f7: S-palmitoylation of mammalian protein complexes.A andB: Human and mouse protein complexes enriched in S-palmitoylation hits using the CORUM database. Proteins complexes containing more than 6 proteins and enriched by at least 50% of S-palmitoylation hits were selected.C: Representation of the TRiC complex subunits. Color circles represent the species in which each CCT subunit was identified as S-palmitoylated. The star indicated proteins identified by 2 independent techniques.D: Palmitoylation of the subunits was validated by Acyl-RAC on CCT1, CCT2, CCT3, CCT4 and CCT5 subunits and by3H-palmitate labelling on CCT1 and CCT2 subunits. (TCE: Total cell extract, NH2OH: Hydroxylamine treatment,3H-palm: radioactive palmitate signal, WB: Western blot signal).

Mentions: Enrichment in protein complexes. Intrigued by the presence of a large number of protein complexes enriched in S-palmitoylated proteins, we analysed the human and mouse palmitoyl proteome dataset using CORUM, a database of manually curated and validated mammalian protein complexes60. A clear enrichment of S-palmitoylated proteins in protein complexes was observed: 18% (463/2558) of the human and 23% (217/938) of the mouse S-palmitoylation hits were part of a complex compared to the 6.8% (1455/21267) of human and 9.5% (1747/18402) of S-palmitoylation hits in their corresponding proteomes. 27 human and 20 mouse complexes possess more than 50% of their subunits S-palmitoylated (Figure 7A andFigure 7B). Intriguingly, the majority of the components of the CCT micro complex, also called TCP-1 ring complex (TRiC), appeared to be S-palmitoylated in both human and mouse analyses (Figure 7C). The TRiC complex is a cytosolic molecular chaperone that promotes folding of 10 to 15 percent of cellular proteins75. It is composed of two identical stacked rings, each of which contains eight different subunits. We were able to experimentally confirm the S-palmitoylation of CCT components; CCT1 and CCT2 could be labeled with3H-palmitate in a hydroxylamine-dependent manner (Figure 7D). These subunits, as well as CCT3, CCT4 and CCT5, also were positive for S-palmitoylation by Acyl-RAC. CCT subunits assemble into the TRiC complex but independent roles as individual subunits proteins have also been proposed76. What the functional consequence of this S-palmitoylation is remains to be established.


SwissPalm: Protein Palmitoylation database.

Blanc M, David F, Abrami L, Migliozzi D, Armand F, Bürgi J, van der Goot FG - F1000Res (2015)

S-palmitoylation of mammalian protein complexes.A andB: Human and mouse protein complexes enriched in S-palmitoylation hits using the CORUM database. Proteins complexes containing more than 6 proteins and enriched by at least 50% of S-palmitoylation hits were selected.C: Representation of the TRiC complex subunits. Color circles represent the species in which each CCT subunit was identified as S-palmitoylated. The star indicated proteins identified by 2 independent techniques.D: Palmitoylation of the subunits was validated by Acyl-RAC on CCT1, CCT2, CCT3, CCT4 and CCT5 subunits and by3H-palmitate labelling on CCT1 and CCT2 subunits. (TCE: Total cell extract, NH2OH: Hydroxylamine treatment,3H-palm: radioactive palmitate signal, WB: Western blot signal).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4544385&req=5

f7: S-palmitoylation of mammalian protein complexes.A andB: Human and mouse protein complexes enriched in S-palmitoylation hits using the CORUM database. Proteins complexes containing more than 6 proteins and enriched by at least 50% of S-palmitoylation hits were selected.C: Representation of the TRiC complex subunits. Color circles represent the species in which each CCT subunit was identified as S-palmitoylated. The star indicated proteins identified by 2 independent techniques.D: Palmitoylation of the subunits was validated by Acyl-RAC on CCT1, CCT2, CCT3, CCT4 and CCT5 subunits and by3H-palmitate labelling on CCT1 and CCT2 subunits. (TCE: Total cell extract, NH2OH: Hydroxylamine treatment,3H-palm: radioactive palmitate signal, WB: Western blot signal).
Mentions: Enrichment in protein complexes. Intrigued by the presence of a large number of protein complexes enriched in S-palmitoylated proteins, we analysed the human and mouse palmitoyl proteome dataset using CORUM, a database of manually curated and validated mammalian protein complexes60. A clear enrichment of S-palmitoylated proteins in protein complexes was observed: 18% (463/2558) of the human and 23% (217/938) of the mouse S-palmitoylation hits were part of a complex compared to the 6.8% (1455/21267) of human and 9.5% (1747/18402) of S-palmitoylation hits in their corresponding proteomes. 27 human and 20 mouse complexes possess more than 50% of their subunits S-palmitoylated (Figure 7A andFigure 7B). Intriguingly, the majority of the components of the CCT micro complex, also called TCP-1 ring complex (TRiC), appeared to be S-palmitoylated in both human and mouse analyses (Figure 7C). The TRiC complex is a cytosolic molecular chaperone that promotes folding of 10 to 15 percent of cellular proteins75. It is composed of two identical stacked rings, each of which contains eight different subunits. We were able to experimentally confirm the S-palmitoylation of CCT components; CCT1 and CCT2 could be labeled with3H-palmitate in a hydroxylamine-dependent manner (Figure 7D). These subunits, as well as CCT3, CCT4 and CCT5, also were positive for S-palmitoylation by Acyl-RAC. CCT subunits assemble into the TRiC complex but independent roles as individual subunits proteins have also been proposed76. What the functional consequence of this S-palmitoylation is remains to be established.

Bottom Line: Systems analysis of the palmitoyl-proteome screens indicate that 10% or more of the human proteome is susceptible to S-palmitoylation.Moreover, ontology and pathway analyses of the human palmitoyl-proteome reveal that key biological functions involve this reversible lipid modification.Through the compilation of data and continuous updates, SwissPalm will provide a powerful tool to unravel the global importance of protein S-palmitoylation.

View Article: PubMed Central - PubMed

Affiliation: Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.

ABSTRACT
Protein S-palmitoylation is a reversible post-translational modification that regulates many key biological processes, although the full extent and functions of protein S-palmitoylation remain largely unexplored. Recent developments of new chemical methods have allowed the establishment of palmitoyl-proteomes of a variety of cell lines and tissues from different species.  As the amount of information generated by these high-throughput studies is increasing, the field requires centralization and comparison of this information. Here we present SwissPalm ( http://swisspalm.epfl.ch), our open, comprehensive, manually curated resource to study protein S-palmitoylation. It currently encompasses more than 5000 S-palmitoylated protein hits from seven species, and contains more than 500 specific sites of S-palmitoylation. SwissPalm also provides curated information and filters that increase the confidence in true positive hits, and integrates predictions of S-palmitoylated cysteine scores, orthologs and isoform multiple alignments. Systems analysis of the palmitoyl-proteome screens indicate that 10% or more of the human proteome is susceptible to S-palmitoylation. Moreover, ontology and pathway analyses of the human palmitoyl-proteome reveal that key biological functions involve this reversible lipid modification. Comparative analysis finally shows a strong crosstalk between S-palmitoylation and other post-translational modifications. Through the compilation of data and continuous updates, SwissPalm will provide a powerful tool to unravel the global importance of protein S-palmitoylation.

No MeSH data available.


Related in: MedlinePlus