Domains InterPro

InterPro (http //www.ebi.ac.uk/interpro), database of protein families, domains, and functional sites allows prediction of the function or structure of a new protein on the basis of its sequence homology to sequences of known proteins. 

The EU funded Interpro project is a collaboration between many of the domain family databases and the SWISS-PROT sequence database. The Interpro collaboration aims to have a centralized annotation resources to reduce the amount of duplication between the database re-... 

There are many different domain database resources, each with their own priorities and strengths. There is currently no effective way to search them all with a single query. Several should be tested to get the most complete results possible. The Interpro collaboration should facilitate the creation of methods to query all the major domain databases in a single action. 

When a novel homology domain has been discovered, it is possible to store the corresponding domain descriptor (profile or HMM) in a number of dedicated domain databases, which can be used to analyze newly identified sequences for their domain content [9, 10]. Several competing domain- and motif-databases exist, including PROSITE, PFAM, SMART, and Superfam, which contain descriptors for most, if not all, of the known domains involved in the ubiquitin system [11-14]. Recently, a new meta-database named INTERPRO has been established, which tries to combine the descriptors of several domain databases under a single user interface [15]. Pointers to the very useful search engines of the domain databases are provided in Table 12.1. 

As mentioned in Chapter 2 for the description of our Y2H library screening procedure, what we obtained after a bioinformatics analysis is the location of the interacting domain within the bait or the prey protein. In reality, we do not measure interaction between full length proteins but between domains within proteins which is a closer representation of an in vivo interaction where only some key fragments of each protein interact with one another in space. These domains were called Selected Interacting Domain or SID. It is therefore clear that bioinformatics sequence analysis that compare SIDs obtained from Y2H experiments with Interpro domains can lead to very interesting observation regarding the domain keen to interact and can help to discriminate more specifically true and false positives. 

Figure 3. Hierarchical domain clustering of MASC proteins. Interpro domains in MASC proteins occurring more than once in the MASC dataset were clustered. Discrete clusters (grey boxes) were annotated with the protein class of which the majority proteins belonged to. Clusters are formed from co-occurrence of two or more domains characteristic of a protein class...

Databases for protein families, domains and functional sites InterPro 103... 

Apweiler, R., et al., InterPro - an integrated documentation resource for protein families, domains and functional sites. Bioinformatics, 2000. 16(12) p. 1145-50. 

Protein-pattern databases cover both motifs or functional domains and secondary structure. We have included the entire InterPro family of databases, as well as BLOCKS, CDD, and a description of patterns found in Swiss-Prot sequences. DSSP, ISSD, PSSD, and CATH are covered in the secondary-structure section. 

A comprehensive description of the databases and methods for domain, family, and pattern identification is available in chapter 2. Therefore, in this chapter, the discussion of the application of family and domain information to function assignment will be limited to Pfam, the virtual standard in protein domain/family classification, and to InterPro and CDD, two resources that integrate multiple domain databases. In addition, I discuss tools that can be used to scan those databases, namely HMMER,... 

Considering the large number of multidomain proteins in eukaryotes, the association of domains is expected to generate a dense and complex network of interactions. Studies conducted on yeast MIPS, MYGD, and DIP protein-interacting databases extracted the domains defined in InterPro [64] that are involved in these interactions to infer conclusions. Another method considers proteins as collections of domains in which each domain is responsible for a specific interaction with another domain. This methodology is done in order to estimate the probabilities of interaction between the corresponding proteins [60,65]. 

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