Human genome contains three separate genes that encode HINT1, HINT2 and HINT3 gene products. HINT1 and HINT2 share a 61 % sequence similarity and exist as a homodimer, while HINT3 forms a distinct branch of HIT superfamily proteins with 31 % sequence homology (Fig. 1a) and exists as multimeric species. HINT1 is mainly expressed and localized in the cytoplasm of the cell. A PPI network of HINT1 with NMDAR, RGS-z and mu-opioid receptors in the central nervous system (CNS) have been found to be critical in the regulation of the mu-opioid signaling pathway, while it’s multiprotein interaction complex with Lysyl-tRNA synthetase and microthalmia transcription factor (MITF) has been found to be vital in the transcriptional regulation of the melanomic oncogenes. In a similar study, using pull down and co-immunoprecipitation, Wieske et al identified direct interaction of HI...
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...domain is essential to complement its phenotype. Both HINT2 and echinT knockout phenotype suggest their distinct role in carbohydrate metabolism, implying their potential evolutionary conservatory role from prokaryotic cell to eukaryotic organelle. echinT has been shown to form stable interaction with six proteins: a putative oxidoreductase and formate dehydrogenase (b1501), heat shock protein 70 (Hsp70), β subunit of DNA polymerase III (dnaN), a membrane-bound lytic murein transglycolyase D (dniR), Ef-Tu elongation factor (tufA) and a putative synthetase (yjhH). Nevertheless, there hasn’t been any reported evidence of their PPI network with proteins involved within the carbohydrate or lipid metabolism cycle. Hence, a deeper understanding of echinT protein-protein interaction is required to elucidate the role of HINT proteins regulation in carbohydrate metabolism.
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