Protein sequence families

ZT Zhang. Relations of the numbers of protein sequences, families and folds. Protein Eng 10 757-761, 1997. 

Despite these advances, Oberai et al. (3) estimate that if no acceleration of membrane protein structure determination occurs, then it will take more than three decades to determine at least one structural representative of 90% of the a-helical membrane protein sequence families (3). 

The protein sequence database is also a text-numeric database with bibliographic links. It is the largest public domain protein sequence database. The current PIR-PSD release 75.04 (March, 2003) contains more than 280 000 entries of partial or complete protein sequences with information on functionalities of the protein, taxonomy (description of the biological source of the protein), sequence properties, experimental analyses, and bibliographic references. Queries can be started as a text-based search or a sequence similarity search. PIR-PSD contains annotated protein sequences with a superfamily/family classification. 

To gain the most predictive utility as well as conceptual understanding from the sequence and structure data available, careful statistical analysis will be required. The statistical methods needed must be robust to the variation in amounts and quality of data in different protein families and for structural features. They must be updatable as new data become available. And they should help us generate as much understanding of the determinants of protein sequence, structure, dynamics, and functional relationships as possible. 

The four major classes or families of mammalian G proteins (Gj, G, G, and G,2) are based on protein sequence homology. Representative members of each are shown, along with known stimuli, effectors, and well-defined biologic effects. Nine isoforms of adenylyl cyclase have been identified (isoforms l-IX). All isoforms are stimulated by a inhibit types V and Vi, and Oq inhibits types I and V. At least 16 different a subunits have been identified. 

Kayano, T., et al. Evidence for a family of human glucose transporterlike proteins. Sequence and gene localization of a protein expressed in fetal skeletal muscle and other tissues. J. Biol. Chem. 1988, 263, 15245-15248. 

The protein sequence databases are the most comprehensive source of information on proteins. The goal of this chapter is to describe the different protein sequence databases available to researchers. It is necessary to distinguish between universal databases that cover proteins from all species and specialized data collections that store information about specific families or groups of proteins, or about the proteins of a specific organism. Two categories of universal protein sequence databases can be discerned simple archives of sequence data and annotated databases in which additional information has been added to the sequence record. The next section describes the Protein Information Resource (PIR), the oldest protein sequence database SWISS-PROT, an annotated universal sequence database and TrEMBL, the supplement of... 

The SBASE database is a collection of annotated protein sequence segments (Murvai et al., 1999). SBASE avoids using consensus methods such as profile-HMMs and uses pairwise methods to detect domains. The database includes more than 130,000 annotated sequence segments that have been clustered into groups on the basis of BLAST similarities. SBASE currently contains 1038 domain families. 

The use of sequence information to frame structural, functional, and evolutionary hypotheses represents a major challenge for the postgeno-mic era. Central to an understanding of the evolution of sequence families is the concept of the domain a structurally conserved, genetically mobile unit. When viewed at the three-dimensional level of protein structure, a domain is a compact arrangement of secondary structures connected by linker polypeptides. It usually folds independently and possesses a relatively hydrophobic core (Janin and Chothia, 1985). The importance of domains is that they cannot be divided into smaller units— they represent a fundamental building block that can be used to understand the evolution of proteins. 

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