Enzymes

Replication protein A (RPA) is a single-stranded-DNA binding protein involved in numerous eukaryotic DNA processes including replication, repair and recombination. RPA interacting protein (RPA IP) has been identified as an adapter protein that is involved in RPA nuclear import instead of the prototypical importin proteins that normally mediate nuclear import. Multiple isoforms of RPA IP are known to exist, with the longest isoform localized to the cytoplasm. Isoform 2 is sumoylated and is located in the PML nuclear body within the nucleus.

The human trans-activation response (TAR) RNA binding protein 1 (TRBP1) was initially identified as a protein that binds to the HIV-1 TAR RNA and activates the long terminal repeat (LTR) expression in the absence and presence of the viral trans-activator Tat. This binding is enhanced by the presence of co-factors such as elongation factor 1alpha (EF-1alpha), polypyrimidine tract-binding protein (PTB), and the chaperonin-like protein stimulator of TAR RNA-binding proteins (SRB).

APH1 was initially identified as a component of the Notch pathway in C. elegans. Along with nicastrin, PEN2, and presenilin-1 APH1 is an essential component of the gamma-secretase complex which cleave the amyloid precursor protein (APP) at what are known as the gamma- and epsilon-sites and can lead to the accumulation of the Amyloid beta peptide (Abeta) cleavage product that is associated with Alzheimer’s disease. APH1 exists in at least three distinct isoforms with APH1a as the principal isoform present in the gamma-secretase complex.

TMP21 is a ubiquitously expressed protein that is involved in vesicular targeting and protein transport. More recent experiments have shown that it is also a component in the presenilin complex and modulates the gamma-secretase but not the epsilon-secretase cleavage activity of the amyloid precursor protein. The presenilin complex is composed of the proteins APH1, nicastrin, and PEN2 in addition to presenilin-1.

The LKB1 serine/threonine protein kinase was initially identified as a tumor suppressor gene mutated in human Peutz-Jeghers syndrome (PJS), a condition resulting in the growth of numerous intestinal polyps classed as hamartomas. LKB1 exists as a heterotrimeric complex with two other proteins, Ste20-related adaptor protein (STRAD) and MO25. Together, this complex can phsophorylate and activate the AMP-activate protein kinase (AMPK).