Domain-containing proteins

PH domains consist of about 120 amino acid residues. They do not interact with other proteins, but associate with specific polyphosphoinositides. Consequently, PH domains appear to be important for localizing target proteins to the plasma membrane. Examples of PH domain-containing proteins include phospholipase C andpl20/RasGAP (Fig. 1). 

Noncatalytic phosphotyrosine binding (PTB) domains are 100-150 residue modules, which bind Asn-Pro-X-Tyr motifs. PTB-domain binding specificity is determined by residues at the amino-terminal side of the phosphotyrosine. In most cases, the tyrosine residue must be phosphorylated in order to mediate binding. PTB domain containing proteins are often found in signal transduction pathways. 

Pleckstrin homology domain (PH-domain) was first identified at the amino and carboxyl termini of a haematopoietic protein called pleckstrin. PH-domain, a protein region of approximately 120 amino acids, by binding to phosphatidylinositol lipids of the biological membranes induces the translocation of the PH-domain containing protein to membrane compartment. Various PH-domains possess specificities for phosphoinositides phosphorylated at different sites within the inositol ring. 

IL-10 inhibits CD28 and ICOS costimulations of T 127 cells via Src homology 2 domain-containing protein tyrosine phosphatase 1. J Allergy Chn Immunol 2007 120 76-83. 

Perret D, Shields M, Saxon A, Kehry MR A mouse Fey Fee protein that inhibits mast cells through activation of FcyRIIB, SH2 domain-containing inositol SS phosphatase 1, and SH2 domain-containing protein tyrosine phosphatases. J Allergy Chn Immunol 2008 121 441-447. 

The major 3 -phosphoinositide products of class I PI3Ks are phosphati-dylinositol 3,4,5-trisphosphate [PI(3,4,5)P3, which is formed primarily from phosphorylation of PI(4,5)P2) and its metabolite phosphatidylinositol 3,4-bisphosphate, PI(3,4)P2]. The basal levels of PI(3,4)P2 and PI(3,4,5)P3 in cells are usually in low abundance but can rise sharply after cell stimulation to interact with an array of protein effectors via pleckstrin homology (PH) domains, modular segments of about 100 amino acids found in many signaling proteins. It is these PH-domain-containing proteins that are able to propagate and drive downstream signaling events. 

Hung TJ, Kemphues KJ 1999 PAR-6 is a conserved PDZ domain-containing protein that colocalizes with PAR-3 in Caenorhabditit elegant embryos. Development 126 127—135 Izumi Y, Hirose T, Tamai Y et al 1998 An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditit elegant polarity protein PAR-3. J Cell Biol 143 95-106... 

Dong, H., O Brien, R. J., Fung, E. T., Fanahan, A. A., Worley, P. F., and Huganir, R. L. (1997) GRIP a synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature 386, 279-284. 

VASP, vasodilator stimulated phosphoprotein hsp27, heat shock protein hsp27 LASP, LIM and SH3 domain containing protein Tx, thromboxane IP3, inositol triphosphate ADP, adenosine 5 -diphosphate. Adapted from Refs. [44] and [116]. 

A class of DUBs only identified since 2002 is the OTU (ovarian tumor protein) DUB class. The OTU domain was originally identified in an ovarian tumor protein from Drosophila mdanogaster, and over 100 proteins from organisms ranging from bacteria to humans are annotated as having an OTU domain. The members of this protein superfamily were annotated as cysteine proteases, but no specific function had been demonstrated for any of these proteins. The first hint of a role for OTU proteins in the ubiquitin pathway was afforded by the observation that an OTU-domain-containing protein, HSPC263, reacted with ubiquitin vinyl sulfone (an active-site-directed irreversible inhibitor of DUBs) [41]. 

Haetmann-Peteesen, R., Semple, C., Ponting, C. P., Hendil, K. B., and Goedon, C. UBA domain containing proteins in fission yeast. Inter. J. Biochem. Cdl Biol. 2003, 35, 629-636. 

Chinnaiyan, A. M., O Rourke, K., Tewari, M., and Dixit, V. M., 1995, FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell SI 505-512. 

Pesesse, X., Deleu, S., De Smedt, F., Drayer, L., Emeux, C., 1997, Identification of a second SH2-domain containing protein closely related to the phosphatidyl inositol polyphosphate 5-phosphatase SHIP. Biochem. Biophys. Res. Common. 239 697-700. 

Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439 811-816 van Holde K, Yager T (2003) Models for chromatin remodeling a critical comparison. Biochem Cell Biol 81 169-172... 

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