Research Progress of Histidine Triad Nucleotide-Binding Protein 1 and 2 in Relation to Diseases

HINT (histidine triad nucleoside-binding protein) belongs to the HIT protein superfamily. HINT1 and HINT2 genes are located in the 5q31.2 and 9p11 regions of human chromosome, respectively. The encoded products are proteins containing 126 and 163 amino acids, respectively. Their relative molecular masses are about 14 kDa and 17 kDa, respectively, and there is 61% sequence homology between HINT1 and HINT2. HINT1 is located in the cytoplasm and nucleus, and HINT2 is located in the mitochondria, both of which are widely distributed in tissues. The subtypes of HINT1 and HINT2 are tumor suppressor factors, which are involved in cell proliferation and apoptosis. HINT1 can suppress tumors by regulating Wnt/β-catenin signaling pathway, the activity of p27KIP1, AP1, TFIIH, MITF and other transcription factors. HINT2 can suppress tumors by mitochondrial autophagy and mitochondrial pathways of apoptosis. This article reviews the discovery, distribution, structure, enzyme activity, tumor mechanism and other related disease of HINT1 and HINT2. It lays a theoretical foundation for further revealing the molecular inhibitory mechanism of HINT1 and HINT2 in different types of tumors, as well as targeted therapy and drug development.