APP secretase

Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Cleaves matrix extracellular phosphoglycoprotein MEPE. Involved in the solubilization of cross-linked TG thyroglobulin in the thyroid follicle lumen. Has also been implicated in tumor invasion and metastasis. Cathepsin B Protein, Human, Recombinant (GST) is expressed in E. coli expression system with N-GST tag. The predicted molecular weight is 54.6 kDa and the accession number is P07858.

Cathepsin B is an enzymatic protein belonging to the peptidase (or protease) families. The protein encoded by this gene is a lysosomal cysteine protease composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. It is a member of the peptidase C1 family. At least five transcript variants encoding the same protein have been found for this gene. Cystatin-B CSTB is an intracellular thiol proteinase inhibitor. Tightly binding reversible inhibitor of cathepsins L, H and B. Cystatin-B CSTB is able to form a dimer stabilized by noncovalent forces, inhibiting papain and cathepsins l, h and b. Cystatin-B CSTB is also thought to play a role in protecting against the proteases leaking from lysosomes.

Amyloid precursor protein (APP) is a type I membrane protein with several isoforms due to alternative splicing, performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Of the three major splice isoforms of APP (APP695, APP751, and APP770) APP695 is the predominant neuronal form from which Amyloid beta peptide and transcriptionally-active cleaved intracellular domain of APP (AICD) are preferentially generated by selective processing through the amyloidogenic pathway. Human APP695 consists of a 17 amino acid (aa) signal sequence, a 607 aa extracellular domain (ECD), a 24 aa transmembrane domain, and a 47 aa cytoplasmic domain. Within the ECD, human APP695 shares 97% aa sequence identity with mouse and rat APP695. Amyloid beta is a major molecule implicated in pathogenesis of Alzheimer's disease (AD) and related dementias. AICD regulates expression by direct promoter binding of multiple genes, including APP itself, the beta-secretase, BACE-1 and the Amyloid beta-degrading enzyme, Neprilysin. As such, APP695 plays an important role in brain development, learning and memory, synaptic plasticity, and neurodegeneration including AD.

Tumor necrosis factor receptor superfamily member 21(DR6) is a single-pass type I membrane protein and contains 1 death domain and 4 TNFR-Cys repeats. The protein may activate NF-kappa-B and promote apoptosis and it may activate JNK and be involved in T-cell differentiation.It is required for both normal cell body death and axonal pruning. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP). N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).