Type I transmembrane proteins

APP is a type-I transmembrane protein that is part of an evolutionarily conserved protein family, including the amyloid precursor-like proteins 1 (APLP1) and 2 (APLP2). APP and APLPs are functionally redundant and form homo- and hetero-oligomers. The absence of the A 3 sequence in the APLPs underlines the importance of APP that can only give rise to the A 3 species. Decreasing the formation of soluble A 3... 

Both tumor necrosis factor receptors (TNFR) are type I transmembrane proteins, also belonging to a large family of proteins, the TNFR superfamily... 

Cell membrane spanning proteins contain a luminal/ extracellular domain, a transmembrane region and a cytosolic domain. In a type I transmembrane protein the N-terminus is the extracellular/luminal part of the protein, whereas the C-terminus comprises the cytosolic region of the membrane protein. 

Figure 46-5. Variations in the way in which proteins are inserted into membranes. This schematic representation, which illustrates a number of possible orientations, shows the segments of the proteins within the membrane as a-helicesand the other segments as lines. The LDL receptor, which crosses the membrane once and has its amino terminal on the exterior, is called a type I transmembrane protein. The asialoglycoprotein receptor, which also crosses the membrane once but has its carboxyl terminal on the exterior, is called a type II transmembrane protein. The various transporters indicated (eg, glucose) cross the membrane a number of times and are called type III transmembrane proteins they are also referred to as polytopic membrane proteins. (N, amino terminal C, carboxyl terminal.) (Adapted, with permission, from Wickner WT, Lodish HF Multiple mechanisms of protein insertion into and across membranes. Science 1985 230 400. Copyright 1985 by the American Association for the Advancement of Science.)...

A type I transmembrane protein called endothelial cell protein C receptor (EPCR), which is expressed at high levels exclusively on a subset of endothelial cells, has also been identified. EPCR has a role in the protein C pathway (30). EPCR binds to both protein C and activated protein C (APC) with equal affinity. Activation of protein C presumably requires interaction of the protein C-EPCR complex with the thrombin-thrombomodulin complex. APC that is formed as a result of this interaction is reversibly bound to EPCR until it dissociates to react subsequently with protein S. The APC-protein S complex inactivates activated factor V (Va). 

A relatively small minority of APP molecules enter the p-secretase pathway in which p-secretase cleaves APP and releases a soluble fragment, sAPPp. The C-terminal membrane-bound C99 peptide is then cleaved by y-secretase within the transmembrane domain, and two major isoforms of 40 and 42 amino acid lengths with different C-termini, Ap40 and Ap42, are generated. Based on the amino acid sequence, p-secretase is predicted to be a type I transmembrane protein with the active site on the lumenal side of... 

All identified TLRs are type I transmembrane proteins, whose intracellular domains contain regions homologous to the intracellular domains of IL-1R and are referred to as TIR domains (Takeda et ah, 2003). These intracellular domains are able to trigger signalling pathways known to activate the nuclear factor kappa B (NF-kB) (Medzhitov et ah, 1998 O Neill, 2000), which in turn leads to the secretion of pro-inflammatory cytokines such as TNF-a, IL-6 and IL-8. The membrane distribution of TLRs as well as their intracellular trafficking has only now beginning... 

The neurotrophin receptor p75 was first identified as a nerve growth factor (NGF)-binding protein and was subsequently shown to interact with each of the other neurotrophic factors, BDNF, neurotrophin-3, and neurotrophin-4/-5. It also modulates the activity of several members of the tropomyosin-related receptor tyrosine kinase family (Trk) (reviewed in Chao, 2003). p75, a member of the tumor necrosis factor superfamily, is a type I transmembrane protein with four cysteine-rich domains in its extracellular region and a Death domain in its cytoplasmic protein (Fig. 11). 

The tumor necrosis factor (TNF) receptor (TNFR) superfamily comprises more than 20 type-I transmembrane proteins that are structurally related in their extracellular domains and specifically activated by the corresponding superfamily of TNF-like ligands (Locksley et al, 2001). Members of this receptor superfamily are widely distributed and play important roles in many crucial biological processes such as lymphoid and neuronal development, innate and adaptive immunity, and maintenance of cellular homeostasis. Agents that manipulate the signaling of these receptors are being used or showing promise towards the treatment and prevention of many human diseases (Ashkenazi and Dixit, 1998 Leonen, 1998 Newton and Decicco, 1999). 

CD 11c is a type I transmembrane protein that is expressed on monocytes, granulocytes, a subset of B cells, dendritic cells, and macrophages and may be demonstrated on B-cell chronic lymphocytic leukemia, marginal zone lymphomas, and hairy cell leukemia. The amount of this antigen is varied with the antigen having dim to partial expression on chronic lymphocytic leukemia and a bright expression on hairy cell leukemia. CD 11c is abundantly expressed... 

Type I Proteins All type I transmembrane proteins possess an N-terminal signal sequence that targets them to the ER and an internal hydrophobic sequence that becomes the membrane-spanning a helix. The N-termlnal signal sequence on a nascent type I protein, like that of a secretory protein,... 

Some cell-surface proteins are anchored to the phospholipid bllayer not by a sequence of hydrophobic amino acids but by a covalently attached amphipathic molecule, gfyco sylphosphatidylinositol (GPI) (Figure 16-14a). These proteins are synthesized and initially anchored to the ER membrane exactly like type I transmembrane proteins, with a cleaved N-terminal signal sequence and Internal stop-transfer anchor sequence directing the process (see Figure... 

The CD-MPR is a 46 kDa type I transmembrane protein that has been cloned from bovine, human, and murine sources. As observed with the CI-MPR, the mammalian CD-MPRs share significant amino acid identity (>90%). The CD-MPR is... 

Calnexin, calreticulin, and the testis-specific homolog calmegin constitute a family of abundant ER proteins. Calnexin is a type I transmembrane protein that is pres-... 

TLRs are type I transmembrane proteins that consist of three major domains (1) a leucine-rich repeat (LRR) extracellular domain, (2) a transmembrane domain, and (3) a cytoplasmic TIR domain. There are 10 human TLRs (TLRl-10) and 13 murine TLRs (TLRl-13, although TLRIO is not functional in mice because of a retroviral insertion) that each have a different PAMP specificity. TLRl-10 are conserved between humans and mice, but TLRll-13 are not present in humans. Thus, despite some... 

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