With the advent of new generation of sequencing techno- logies (44,45), genome sequences of large number of or- ganisms are available. Using conserved sequence motifs and the internal sequence similarity as constraints, we have previously searched genome sequences of plants to identify and characterize the MIP proteins (15,16). We have extended this approach to genomes of other organism groups and identiﬁed more than 1000 MIP sequences in diverse organisms. The wealth of information on MIP se- quences is now stored in a database called MIPModDB and various details about the substitutions in the con- served NPA motif, gene structure and the features obtained from structural models are available for each MIP sequence. With diverse MIP sequences, one can also obtain structure-based sequence alignment and evo- lutionary relationship for a given set of MIP sequences. DATABASE CONSTRUCTION MIP genes were identiﬁed using BLAST (46) from com- pleted and partial genomes available in NCBI database and the protocol used for this purpose is the same as de- scribed in our previous studies (15,16). Thirteen human aquaporins and ﬁve plant MIPs belonging to the ﬁve major plant subfamilies were used as query sequences. Sequences of short length and those sequences with missing trans- membrane segments and important loop regions were dis- carded. We also found that some MIPs have been wrongly annotated. For example, an MIP from Salinispora tropica is annotated as ‘low molecular weight phosphotyrosine protein phosphatase’ (NCBI accession: YP_001157491). MIPs from plants identiﬁed from previous work (13–16,47) were also included. We have also searched the motif-oriented database, MIPDB (48), and considered those MIP sequences not identiﬁed in the above BLAST search. The ﬁnal data set contained 1008 MIP sequences from 341 different organisms. For each MIP sequence, presence of conserved NPA sequence motif and internal sequence similarity were examined and the sequences were also conﬁrmed by pattern databases like Pfam (49) and PROSITE (50). The three-dimensional structure of each MIP sequence was modeled by hom- ology modeling procedure using the same protocol that was applied earlier for plant MIPs (15,16). Structures of bovine AQP1, E. coli GlpF and archeal AQPM were used as template structures and their PDB (51) IDs are 1J4N, 1FX8 and 2F2B, respectively. The channel radius proﬁle was calculated using the HOLE program (52) as described previously (16). Thus the contents of this data- base can be largely categorized into sequence and struc- tural data and are explained in more details in the following sections. The important statistics related to sequence and structure data of MIPModDB is given in Table 1. Both the sequence and structure data for a rep- resentative MIP sequence is shown in Figure 1. MIP SEQUENCE DATA In general, only a single MIP has been identiﬁed in most of the microbial genomes. Plants have large number of Nucleic Acids Research, 2012, Vol. 40, Database issue D363 Table 1. Important statistics of MIPModDB Number of MIP sequences Number of organisms Substitutions in the NPA motifs Only in the ﬁrst NPA motif (loop B) Only in the second NPA motif (loop E) Both NPA motifs MIPs with selectivity ﬁlter similar to water-channelsa (FHTR+FHAR+FHCR+FHSR) MIPs with selectivity ﬁlter similar to glycerol channelsa (WGYR+WGFR+WGWR) Experimentally determined MIP structures 1008 341 219 74 82 63 349 170 38 aThe selectivity ﬁlter is formed by four residues and the corresponding amino acids are given in one letter codes. The ﬁrst and second residues come from the second and the ﬁfth transmembrane segments, respect- ively. The other two residues are contributed by the loop E. See text for details. MIPs in comparison to animals. For each MIP, its source and the NCBI accession ID are given. Each MIP sequence is also given a unique identiﬁer derived from its scientiﬁc name. The ﬁrst two characters are taken from its genus and the next four characters are from its species name followed by a four digit unique number. Wherever it is available, UNIPROT (53) accession ID is also provided. Apart from the primary structure information, sequence data includes exon–intron organization of the gene, substitution (if any) in the conserved NPA motif and percentage sequence similarity with the template se- quences that are used in the homology modeling proced- ure to build three-dimensional models. Sequence similarity between a given MIP sequence and the template sequences was calculated using the program NEEDLE as available in the EMBOSS suite of programs (54). Only the modeled part of the target MIP sequence was considered for this purpose. Gene structure For each MIP, gene structure is represented in the form of a graphical diagram. It gives the length and the positions of the introns with respect to the secondary structures of the corresponding MIP. The red and blue vertical bars indicate the starting positions of helices and loops B/E, respectively. The information regarding the positions of each individual introns was extracted from the NCBI database annotations. Transmembrane segments are marked based on the modeled structures (see below). Knowledge of intron–exon organization helps to under- stand the evolution of MIPs across different organisms and MIP subfamilies within a same species. For example, in plants it has been shown that the number and positions of introns are conserved within a given MIP subfamily (14–16). Substitutions in NPA motif In addition to its role in solute transport and selectivity (36,55–57), substitutions in the highly conserved NPA motifs seem to be important in other functional roles such as protein targeting (58) and full expression of the protein (59). In our data set, substitutions in only the ﬁrst