This entry represents a group of plant proteins, including TAP1 from Antirrhinum majus and THNL1/2 from Arabidopsis. THNL1/2 belongs to the plant thionin (PR-13) family and may be involved in plant defense [].
The ABC transporter family is a group of membrane proteins that use the hydrolysis of ATP to power the translocation of a wide variety of substrates across cellular membranes. ABC transporters minimally consist of two conserved regions: a highly conserved nucleotide-binding domain (NBD) and a less conserved transmembrane domain (TMD). Eukaryotic ABC proteins are usually organised either as full transporters (containing two NBDs and two TMDs), or as half transporters (containing one NBD and one TMD), that have to form homo- or heterodimers in order to constitute a functional protein [].This entry represents Tap1 (also known as antigen peptide transporter 1), which is a vertebrate protein belonging to the ABC-B subfamily of the ABC transporter family. It plays a crucial role in the processing and presentation of the MHC class I-restricted antigens. It is a half transporter that forms a complex with Tap2. This complex translocates antigens from the cytoplasm to the endoplasmic reticulum for loading onto MHC class I molecules []. The structure of Tap1 has been solved [].Mutations in the Tap1 gene cause Bare lymphocyte syndrome 1 (BLS1), which is characterised by class I antigen deficiencies that are not accompanied by particular pathologic manifestations during the first years of life, although chronic lung disease develops in late childhood.
This family has members such as US6 () found in HCMV (Human cytomegalovirus). US6 is a unique short region glycoprotein found in the ER. It blocks the binding of ATP by TAP1 (Transporter associated with Antigen Processing 1) through a conformational change and subsequently inhibits TAP-mediated peptide translocation to the ER. It also down regulates MHC class I []. Inhibition of US6 of TAP has been shown to require residues 89 to 108 of the HCMV US6 luminal domain, whereas sequences that flank this region stabilize the binding of the viral protein to TAP. Residues 81 to 90 and the C-terminal 39 residues of HCMV US6 may also contributeto the stabilization of the interaction between US6 and TAP [].
This is a family of potent toxins that function as ion-channel inhibitors. Omega-Grammotoxin SIA is a VSCC antagonist that inhibits neuronal N- and P-type VSCC responses []. Huwentoxin-IV, from the Chinese bird spider, is a highly potent neurotoxin that specifically inhibits the neuronal tetrodotoxin-sensitive voltage-gated sodium channel in rat dorsal root ganglion neurons []. Hainantoxin-4, from the venom of spider Selenocosmia hainana, adopts an inhibitor cystine knot structural motif like huwentoin-IV, and is a potent antagonist that acts at site 1 on tetrodotoxin-sensitive (TTX-S) sodium channels []. Study of the molecular nature of toxin-receptor interactions has helped elucidate the functioning of many ion-channels []. Some members of this family, Tap1 and Tap2, can modulate the activity of both voltage-gated sodium and calcium channels which are implicated in the etiology of chronic pain, being interesting for chronic pain treatment [, ].
This entry represents a group acetyltransferases, including NSI from Arabidopsis, SNAT1/2 from rice and Histone acetyltransferase TAP1/2 from Glycine max (Soybean). NSI is a vascular-expressed acetyltransferase that interacts with NSP, which is a nuclear shuttle protein []. It has been shown to regulate the nuclear export of the viral genome and potentially other non transcriptional nuclear events in plant cells []. SNAT1 catalyses the N-acetylation of serotonin into N-acetylserotonin, the penultimate step in the synthesis of melatonin [, , , ]. TAP1 acts as a susceptibility factor that is hijacked by Avh52 in order to promote acetylation of histones H2A and H3 during early infection by Phytophtora sojae [].This entry also includes predicted N-acetyltransferases from bacteria.
Major histocompatibility complex (MHC) class I molecules present antigenic peptides to CD8 T cells. The majority of peptides found associated with class I molecules are derived from nuclear and cytosolic proteins, and they are generated largely by the proteasome complex. These peptides are transported from cytosol into the lumen of the endoplasmic reticulum (ER) by a peptide transporter, which is known as the transporter associated with antigen processing (TAP). TAP is a trimeric complex consisting of TAP1, TAP2 and tapasin (TAP-A). TAP1 and TAP2 are required for peptide transport. Tapasin, which actually serves as a docking site on the TAP complex specific for interaction with class I MHC molecules, is essential for peptide loading (up to four MHC class I-tapasin complexes have beenfound to bind to each TAP molecule). However, since the exact mechanisms oftapasin functions are still unknown, it has also been speculated thattapasin may regulate the MHC class I release from the ER rather than directly loading peptides onto MHC class I molecules [, , , ].In studies of the interaction between MHC class I and TAP, it was found that TAP1, but not TAP2, is required for the association of TAP with class I molecules. Because tapasin is essential for the association of MHC class I to TAP, tapasin may directly interact with TAP1. Thus the predicted order of interaction between different molecules in the TAP complex is TAP2 to TAP1, TAP1 to tapasin, and tapasin to MHC class I molecules. Thus, by these linked events, the translocation and loading of peptides rapidly and efficientlyproceed in the same microenvironment [, ].Tapasin is a type I transmembrane (TM) glycoprotein with a double lysinemotif that is thought to be involved with mediating the retrieval of proteins back from the cis-Golgi, thus maintaining membrane proteins in theER []. It is encoded by an MHC-linked gene and is a member of theimmunoglobulin superfamily. Binding to TAP is mediated by the C-terminalregion, whereas its N-terminal 50 residues constitute the key element thatconverts the MHC class I molecules and TAP weak interactions into a stablecomplex [, ].
