ARAP Protein Hypothesis
The ARAP protein is a novel adopter protein that is considered to be a protein-coding gene. The protein contains SAM, ARF-GAP, RHO-GAP (GTPase-activator protein (GAP), and pleckstrin homology (PH) domains (1). The proteins exhibitions RHO-GAP in vitro and ARF-GAP activity. The protein Is encoded, and associates with the Golgi and changes in the Golgi and are mediated by the ARF-GAP activity leading to the formation of filopodia. The protein also encodes various isoforms, and it is involved in apoptosis. Several diseases are associated with the protein. Some of the common illnesses include maturity-onset diabetes of the young and Kidney hypertrophy. The ARAP protein is referred to as the centaurin deltas and contains double GTPases activating proteins for the Rho and Arf family GTPases (2). They also contain the PH domain as well as the ankyrin repeat ras-associating besides the ARF-GAP and the Rho-GAP domains. The ARF-GAP activity of the ARAP protein depends on the PIP3, making them be considered as phosphoinositide Rho and Arf signaling integration points.
The PH domains help to bind the phosphoinositides with high affinity and are common in the human proteome. The PH domain consists of about 120 amino acids that are present in different proteins and are responsible for signaling (3). The ability of the PH domains to bind phosphoinositide is restricted by the pair of adjacent phosphates in the inositol headgroup. Where both the phosphoinositide and relevant Arfs are present such as in the Golgi apparatus, the PH domains act as coincidence detectors. The hypothesis in this paper is whether the receptor protein involved in apoptosis is regulated by the encoded proteins associated with the Golgi apparatus and the ARF-gap activity.
References
- Jung SH, Yoo EH, Yu MJ, Song HM, Kang HY, Cho JY, Lee JR. ARAP, a Novel Adaptor Protein, Is Required for TCR Signaling and Integrin-Mediated Adhesion. The Journal of Immunology. 2016 Aug 1;197(3):942-52.
- Nguyen MK, Jaillet L, Redon S. Generating conformational transition paths with low potential-energy barriers for proteins. Journal of computer-aided molecular design. 2018 Aug 1;32(8):853-67.
- Sansom MS, Stansfeld PJ, Naughton FB, Domański J, Kalli AC, Yamamoto E, Best RB. Multiple lipid-binding sites determine the affinity of PH domains for phosphoinositide-containing membranes. Science Advances. 2020 Feb 19;6(8).