Enzymes

NogoA is a member of a family of integral membrane proteins termed reticulons that are thought to be involved in numerous disorders including neurodegenerative diseases. Reticulon proteins are known to regulate many cellular processes and interact with multiple proteins and receptors such as BACE. NogoA was initially identified as a myelin-associated neurite outgrowth inhibitor.

MAPKAP1 was initially identified as the human homolog of S. pombe SIN1. Recent evidence has shown that it identical to Mip1, a protein that interacts with MEKK2, a member of the mitogen-activated protein kinase (MAPK) intracellular signaling network. MAPKAP1 is thought to prevent MEKK2 activation and dimerization by forming a complex with the inactive and non-phosphorylated MEKK2, thereby blocking the JNK1/2, ERK1/2, p38 and ERK5 MAPKs.

DARC, also known as the Duffy antigen/chemokine receptor, is a seven-transmembrane protein homologous to the classical chemokine G-protein coupled receptors (GPCRs) with the exception of the motif required for G protein coupling. DARC can bind with high affinity several chemokines without transducing any signal, suggesting it may modulate the signals normally induced by these chemokines. Recently, DARC was found to interact with KAI1, a four transmembrane protein recently identified as a tumor metastasis suppressor protein.

Cell-mediated immune responses are initiated by T lymphocytes that are themselves stimulated by cognate peptides bound to MHC molecules on antig en-presenting cells (APC). T-cell activation is generally self-limited as activated T cells express receptors such as PD-1 (also known as PDCD-1) that mediate inhibitory signals from the APC. PD-1 can bind two different but related ligands, PDL-1 and PDL-2.

Antigen stimulation of immune cells triggers Ca++ entry through Ca++ release-activated Ca++ (CRAC) channels. ORAI1 is a recently identified four-transmembrane spanning protein that is an essential component of CRAC. A missense mutation in this protein in humans is the cause of one form of hereditary severe combined immune deficiency (SCID) which results in ablated T-cell Ca++ entry. It has been suggested that ORAI1 functions as a highly selective Ca++ plasma membrane channel that is gated through interactions with STIM1, the store-activated endoplasmic reticulum Ca++ sensor.