CASTp is an online tool that identifies and measures pockets and voids on 3D protein structures. The new version of CASTp includes functional annotations of specific residues from the Protein Data Bank (PDB), Swiss-Prot, and Online Mendelian Inheritance in Man (OMIM). Annotations from these sources are mapped to surface pockets, interior voids, or other regions of PDB structures. The tool uses a semi-global pair-wise sequence alignment method to align sequences from Swiss-Prot, OMIM, and PDB. The updated CASTp web server allows users to study surface features, functional regions, and the roles of key residues in proteins. The paper describes the mapping of annotated residues from Swiss-Prot and OMIM onto PDB structures. It also details updates to the CASTp web server for visualizing annotated functional residues, with a focus on mapping to surface pockets and interior voids. Additional updates to the CASTp web server are also described. The mapping results show that there are 113,928 annotated residues in 4,922 PDB structures. The transfer of 241,913 Swiss-Prot annotations added 226,177 unique annotations to 15,913 PDB structures. Of these, 13,094 structures did not previously have any annotations. The mapping of OMIM disease mutations added 2128 annotated residues on 310 PDB structures. Of these, 254 were mapped onto annotations from PDB or Swiss-Prot. CASTp allows for interactive visualization of biologically important annotated residues by querying the server using a four-letter PDB protein name, Swiss-Prot or GenBank identification. A new database of CASTp calculations of single chains of a multiple chain complex can also be queried by adding the chain identifier to the PDB protein name. The user is also presented with a corresponding sequence map, where residues in highlighted pockets are highlighted in the same color as in the structural visualization. The user has finer control over the visualization, including changing pocket colorings, display styles, and sending customized rasmol scripts to the Chime visualization. The CASTp web server and the associated mapping database are freely accessible at http://cast.engr.uic.edu. Funding for the Open Access publication was provided by grants from the National Science Foundation, National Institute of Health, and Office of Naval Research.CASTp is an online tool that identifies and measures pockets and voids on 3D protein structures. The new version of CASTp includes functional annotations of specific residues from the Protein Data Bank (PDB), Swiss-Prot, and Online Mendelian Inheritance in Man (OMIM). Annotations from these sources are mapped to surface pockets, interior voids, or other regions of PDB structures. The tool uses a semi-global pair-wise sequence alignment method to align sequences from Swiss-Prot, OMIM, and PDB. The updated CASTp web server allows users to study surface features, functional regions, and the roles of key residues in proteins. The paper describes the mapping of annotated residues from Swiss-Prot and OMIM onto PDB structures. It also details updates to the CASTp web server for visualizing annotated functional residues, with a focus on mapping to surface pockets and interior voids. Additional updates to the CASTp web server are also described. The mapping results show that there are 113,928 annotated residues in 4,922 PDB structures. The transfer of 241,913 Swiss-Prot annotations added 226,177 unique annotations to 15,913 PDB structures. Of these, 13,094 structures did not previously have any annotations. The mapping of OMIM disease mutations added 2128 annotated residues on 310 PDB structures. Of these, 254 were mapped onto annotations from PDB or Swiss-Prot. CASTp allows for interactive visualization of biologically important annotated residues by querying the server using a four-letter PDB protein name, Swiss-Prot or GenBank identification. A new database of CASTp calculations of single chains of a multiple chain complex can also be queried by adding the chain identifier to the PDB protein name. The user is also presented with a corresponding sequence map, where residues in highlighted pockets are highlighted in the same color as in the structural visualization. The user has finer control over the visualization, including changing pocket colorings, display styles, and sending customized rasmol scripts to the Chime visualization. The CASTp web server and the associated mapping database are freely accessible at http://cast.engr.uic.edu. Funding for the Open Access publication was provided by grants from the National Science Foundation, National Institute of Health, and Office of Naval Research.