The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins

Uversky, Vladimir N

d GARP2 purified from bovine rod photoreceptors were shown to be typical IDPs. 208 MGARP. Mitochondria-localized glutamic acid-rich protein [MGARP, which is also known as ovary-specific acidic protein (OSAP), corneal endothelium-specific protein 1 (CESP-1) and hypoxia upregulated mitochondrial movement regulator protein (HUMMR)] is one of the highly expressed proteins in retina. 209 MGARP is highly enriched in steroidogenic tissues and the visual system, and early in development, this protein is mainly detected in the retina and adrenal gland. 210 During the estrous cycle, MGARP levels correlate with estrogen levels in the ovaries. Furthermore, the expression of MGARP is regulated by estrogen in a tissue-specific manner and through a feedback regulatory mechanism. 210 As it follows from a long list of names, this protein has numerous important functions. In fact, among functions listed for this protein in the UniProt are (1) plays a role in the trafficking of mitochondria along microtubules, (2) regulates the kinesin-mediated axonal transport of mitochondria to nerve terminals along microtubules during hypoxia, (3) participates in the translocation of TRAK2/GRIF1 from the cytoplasm to the mitochondrion and (4) plays a role in steroidogenesis through maintenance of mitochondrial abundance and morphology. 211, 212 There are 283 residues in mouse MGARP, 49 of which are glutamic acids exclusively located in the Glu-rich region (residues 79-277). Based on the spectroscopic analysis of this protein, it has been concluded that mouse GARP is an IDP. 209 Some other GARPs. The life cycle of the phytopathogenic fungus Verticillium dahliae Kleb causing wilt disease in a wide range of crops, including cotton, includes three vegetative phases: parasitic, saprophytic and dormant. 213 One of the genes tagged in a pathogenicity encoded a glutamic acid-rich protein (VdGARP1), which shared no significant similarity to any known proteins. 213 linked to a glutamic acid and alanine repeat (EG-EA repeat). 235 There are 171, 83 and 43 glutamic acids, glycines and alanines in this latency associated nuclear antigen. Although there is low sequence identity between LANA1, EBNA1 and ORF73, all three proteins determine the poor recognition of viruses by CD8 + cytotoxic T lymphocytes (CTL). However, the mechanisms of their action are rather different. In the Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus the repeat domains were shown to enhance the stability of EBNA1 and LANA1 and decrease their translation rates, whereas the EG-EA repeat has no effect on the stability of HVS ORF73 or its rate of translation, but results in decreased steady-state levels of ORF73 mRNA. 235 Intriguingly, the motif EEAEEAEEE of HVS ORF73 was sufficient to cause a reduction in recognition of ORF73 by CD8 + CTL, suggesting that the EG-EA repeat of HVS ORF73 is crucial for the immune evasion. 235 Nsp3a. The N-terminal domain of the severe acute respiratory syndrome coronavirus (SARS-CoV) nonstructural protein 3 (nsp3a) is a typical IDP of 183 residues characterized by the presence of an ubiquitin-like globular domain (residues 1-112) and a flexible, highly extended Glu-rich domain (residues . 236 Nsp3a is a highly acidic protein (pH 3.72) that contains 40 glutamic acids, 28 of which are located within the C-terminal Glu-rich domain.