Domain families extracellular proteins

FIGURE 24-10 Schematic structures of nonreceptor protein tyrosine phosphatases (NRPTPs) and receptor protein tyrosine phosphatases (RPTPs). NRPTPs contain a catalytic domain and various regulatory domains. RPTPs are composed of an extracellular domain, a transmembrane domain and an intracellular domain with one or two catalytic domains. Like receptor protein tyrosine kinases, the structural features of the extracellular domains divide the RPTPs into different families. (With permission from reference [12]). 

A domain family that is considerably expanded in nematodes, relative to vertebrates, is the zona pellucida (ZP) domain (Bork and Sander, 1992). In database searches this domain was found in C. elegans cuticlin-1 (cut-1), a component of the nematode cuticle (Sebastiano et al., 1991), and 33 other C. elegans proteins (Table II). On the basis of disulfide-linked domains that accompany the ZP domain in these proteins, it is likely that they localize to the worm s extracellular matrix. Indeed, it is possible that most of these proteins are components of the worm cuticle. The cuticle structure is the multilayered elastic exoskeleton that determines the worm s body shape. Although vertebrates lack an equivalent... 

Although many typically extracellular domains are entirely absent from intracellular proteins, and vice versa, there is no absolute partitioning of domain families into separate cellular localizations. Several domain families, such as VWA (see Section II,B,1), PDZ (Wu et al, 1999), C2... 

Many different receptor types are coupled to G proteins, including receptors for norepinephrine and epinephrine (a- and p-adrenoceptors), 5-hydroxytrypta-mine (serotonin or 5-HT receptors), and muscarinic acetylcholine receptors. Figure 2.1 presents the structure of one of these, the uz-adrenoceptor from the human kidney. All members of this family of G protein-coupled receptors are characterized by having seven membrane-enclosed domains plus extracellular and intracellular loops. The specific binding sites for agonists occur at the extracellular surface, while the interaction with G proteins occurs with the intracellular portions of the receptor. The general term for any chain of events initiated by receptor activation is signal transduction. 

Several families of integral proteins in the plasma membrane provide specific points of attachment between cells, or between a cell and extracellular matrix proteins. Integrins are heterodimeric proteins (two unlike subunits, a and /3) anchored to the plasma membrane by a single hydrophobic transmembrane helix in each subunit (Fig. 11-22 see also Fig. 7-30). The large extracellular domains of the a and /3 subunits combine to form a specific binding site for extracellular proteins... 

Comparison of the primary structures of the auxihary jSl and fi2, subunits to those of other proteins revealed a clear structural relationship to the family of proteins that contain immunoglobuhn-hke folds (Isom et al 1995). The extracellular domains of the 1 and jS2 subunits are predicted to fold in a similar... 

The purpose of this review is to discuss what is currently known about the different functions of metalloprotease-disintegrins, and to highlight some of the most interesting and pressing questions that have now been raised about this intriguing protein family. A brief summary of the known properties of snake venom disin-tegrins and metalloproteases is followed by a discussion of the role of membrane-anchored metalloprotease-disintegrins in cell-cell interactions and proteolysis of extracytoplasmic or extracellular protein domains. 

SMART (Simple Modular Architecture Research Tool) [12-14] is a Web-based resource used for the annotation of protein domains and the analysis of domain architectures, with particular emphasis on mobile eukaryotic domains. Extensive annotation for each domain family is available, providing information relating to function, subcellular localization, phyletic distribution and tertiary structure. The January 2002 release has added more than 200 hand-curated domain models. This brings the total to over 600 domain families that are widely represented among nuclear, signalling and extracellular proteins. Annotation now includes links to the Online Mendelian Inheritance in Man (OMIM) database in cases where a human disease is associated with one or more mutations in a particular domain, (http //smart, embl-heidelberg. de/help/smart about. shtml)... 

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