D366 Nucleic Acids Research, 2012, Vol. 40, Database issue for all the TM segments and the functionally important loops B and E is provided for all the MIPs present in the same organism along with the template sequences. We have also previously identiﬁed 17 positions that occur in the helix–helix interface. They are small and weakly polar residues and have been shown to be highly conserved if the amino acids Ala, Thr, Ser, Cys and Gly are considered as a group (15,16). These positions along with the residues that form the ar/R selectivity ﬁlter are highlighted in the structure-based sequence alignment. An example of structure-based sequence alignment as obtained from the MIPModDB database is shown in Figure 3. Construction of phylogenetic tree for selected MIPs The database provides an interface whereby the user will be able to analyze the evolutionary relationship among the selected group of MIPs. For constructing a phylogenetic tree, the user needs to select at least three sequences. The user will have the option to choose one of the three dif- ferent methods, namely, neighbor-joining method, max- imum likelihood method and maximum parsimony method to construct a phylogenetic tree. In addition to the complication in generating a multiple sequence align- ment of diverse MIP sequences, many MIPs have long N- and C-termini as well as long loops connecting the TM segments. Hence to avoid errors, while constructing the evolutionary tree, the input used for this purpose is the structure-based sequence alignment of TM helical regions and the loops B and E. The program PHYLIP which is part of the EMBOSS suite of programs (54) is being utilized by the server to create the phylogenetic trees (Figure 2D). IMPLEMENTATION The information content on MIPs is maintained as a re- lational database using MySQL (http://www.mysql.com). This allows easy access and storage. The database is hosted on a web server running apache (http://www .apache.org/) on Fedora Core Linux platform and can be queried through the web interface which is imple- mented in PHP (v5.2) scripting language (http://www .php.net/). ACCESS TO MIP DATA MIPModDB allows the users to browse, retrieve and query the database. The Statistics page lists all the MIPs in three different categories: (i) based on the NPA sequence motif, (ii) selectivity ﬁlter residues and (iii) organism-wise grouping. Users can browse MIPs ac- cording to the conservation or substitutions that are found in the NPA boxes. One can also look for MIPs with par- ticular residues that form the selectivity ﬁlter. MIPs are also organized as per the organism in which they occur. They are arranged in the descending order in which the model tree Populus tricocarpa is present on the top with the maximum number of 55 MIPs. The database interface allows the user to retrieve and identify MIPs using various features of MIPs as query. It can be searched by unique accession and complete or partial amino acid sequence. The search facility also allows the user to select MIP(s) with particular residues in the selectivity ﬁlter. Alternatively, MIPs with speciﬁc substitutions in the NPA motif also can be queried. A query based on an organism name will retrieve all MIP sequences from a particular species. More than one MIP features can also be used to narrow down the search. More detailed information can be retrieved by following the associated links. In addition to searching speciﬁc MIPs, the database enables users to download all the MIP sequences from a given organism or all the sequences that have the same ar/R selectivity ﬁlter residues in FASTA format. MIP sequences with speciﬁc substitutions in the NPA motif can also be downloaded. Sequence alignments used to generate the three-dimensional models can be downloaded in PIR or PAP format. For each MIP, the coordinates of the model are available in the PDB format. Similarly, the phylogenetic tree for a selected set of MIPs can be downloaded. COMPARISON WITH OTHER TRANSPORTER DATABASES There are databases which are developed speciﬁcally for membrane proteins that are involved in transporting the solutes across the membranes. The database TransportDB (66) provides information about the complete list of trans- porters for a given organism. For example, in the case of humans, the type of transporters listed include those that are ATP-dependent, ion channels, secondary transporters and unclassiﬁed. It also lists all outer membrane porins and channels from different organisms. The other database TCDB is a Transporter Classiﬁcation Database (67) and is a classiﬁcation system for membrane transporters. The superfamilies of transporters in this database include channel-forming toxins and peptides, transporters, sympor- ters, antiporters, porins, carriers and ion channels. Both the above databases do not include all the MIP super- family members whose members are known to predom- inantly transport neutral solutes. For example, while TransportDB lists human MIPs, MIP members in other organisms are not found. TCDB does not seem to include MIP superfamily although some MIP sequences are found. Moreover, while the above two databases largely contain sequence information and known PDB structures, MIPModDB provides structural models and associated information for more than 1000 MIP sequences. FUTURE DIRECTIONS Few MIPs have been functionally very well characterized and experimental studies are being carried out to deter- mine the solute transport properties of many more MIPs. In the next version of MIPModDB database, whenever it is available, functional properties of MIPs, post- translational modiﬁcation and cellular localization will be annotated and the related literature will be linked through PUBMED. As new MIPs are being recognized,