Ask about this productRelated genes to: HINT2 Blocking Peptide
- Gene:
- HINT2 NIH gene
- Name:
- histidine triad nucleotide binding protein 2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 9p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-03-07
- Date modifiied:
- 2016-10-05
Related products to: HINT2 Blocking Peptide
Related articles to: HINT2 Blocking Peptide
- Acute pancreatitis (AP) is a life-threatening inflammatory disorder with limited therapeutic options. The mitochondrial protein HINT2 has been identified as a promising therapeutic target, but specific agonists remain unexplored. - Source: PubMed
Publication date: 2026/01/12
Peng YangYao Jia-QiLi Hong-YingWang Yu-XuanHu Feng-JiaoYang Ming-YuChen YongGao Chong-YongMo Jun-FengMiao Yi-FanJin Wei - Acute liver failure (ALF) is a life-threatening condition marked by high mortality, poor prognosis, and limited treatment options. Excessive neutrophil infiltration and NETosis are key drivers of hepatic inflammation and injury, yet the underlying molecular mechanisms remain unclear. This study identifies histidine triad nucleotide-binding protein 2 (Hint2) as a pivotal regulator of neutrophil chemotaxis and NETosis during ALF. - Source: PubMed
Publication date: 2026/01/21
Guo JinZhang XiaoyaZhang DanmeiShi ChunxiaWang LuwenGong Zuojiong - This study investigated the role of histidine triad nucleotide-binding protein 2 (HINT2) in regulating mitochondrial dysfunction and oxidative stress in the context of ischemic stroke associated with alcohol use disorder (AUD), and examined whether the neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) are partially dependent on HINT2 signaling. AUD was modeled in male Sprague-Dawley rats using the two-bottle choice paradigm. Focal cerebral ischemia was induced via middle cerebral artery occlusion (MCAO) using the intraluminal filament technique. HINT2 expression was downregulated through administration of small interfering RNA. Animals were randomized into five experimental groups: Sham, AUD, MCAO, G-CSF treatment, and HINT2 inhibition. Mitochondrial membrane potential was assessed via JC-1 staining, and reactive oxygen species (ROS) levels were quantified using 2',7'-dichlorodihydrofluorescein diacetate. Protein expression of HINT2 was evaluated by western blotting. Infarct volume was measured using 2,3,5-triphenyltetrazolium chloride staining, and histopathological changes were analyzed using hematoxylin and eosin staining. Neurological function was evaluated using standardized behavioral assessments. G-CSF administration significantly reduced cerebral infarct volume and improved neurological outcomes in both the AUD and MCAO groups (p < 0.05). G-CSF also partially restored mitochondrial membrane potential and attenuated ROS production (p < 0.05). Under conditions of HINT2 suppression, the effects of G-CSF on ROS reduction and mitochondrial membrane potential were attenuated (p < 0.05). HINT2 expression was downregulated following ischemic insult but was partially restored by G-CSF treatment (p < 0.05). Neurological scores indicated improved functional recovery in G-CSF-treated animals, whereas outcomes were significantly impaired in the HINT2-inhibited group. The findings indicate that HINT2 contributes to the neuroprotective effects of G-CSF in AUD-related ischemic stroke by modulating mitochondrial function and reducing oxidative stress. The G-CSF-HINT2-mitochondrial axis may represent a potential therapeutic target for patients with ischemic stroke and comorbid AUD. Further investigation is warranted to elucidate the underlying mechanisms and therapeutic potential. - Source: PubMed
Publication date: 2025/11/10
Guo Zhi-ChenZhang Hong-WeiZhao Hai-JianZhao Zhi-LiShen DanLi Xiao-FangXi Hui-FangFan TengYin JieAn NingYue Xiu-QinWang Wei-Wei - Mitochondrial dysfunction, particularly involving energy metabolism, oxidative stress, and structural integrity, is recognized as a critical factor in the pathogenesis of hearing loss. However, evidence regarding a potential association between mitochondrial function and sudden sensorineural hearing loss (SSNHL) remains limited. This study aims to explore the potential causal relationship between mitochondrial biological function and SSNHL using Mendelian randomization (MR) analysis. We utilized genome-wide association study data on SSNHL from the FinnGen database, along with mitochondria-related genome-wide association study summary statistics from previously published studies. Inverse variance weighting served as the primary MR method, using genetic instruments associated with mitochondrial biological function to estimate their effects on SSNHL risk. Sensitivity analyses-including MR-Egger regression, MR-PRESSO, and leave-one-out analysis-were conducted to assess the robustness of the findings and to exclude potential biases. Three mitochondrial proteins were found to exhibit potential causal effects on SSNHL. MUL1 was identified as a potential risk factor, whereas HINT2 and GRPEL1 appeared to serve as potential protective factors. This study provides evidence supporting a potential causal role of mitochondrial biological function in SSNHL. The findings offer novel insights into the mechanistic underpinnings of SSNHL and emphasize the importance of mitochondrial pathways in its pathophysiology. These results may encourage otolaryngologists to consider targeting mitochondrial energy metabolism in the development of more effective clinical prevention and treatment strategies for SSNHL. - Source: PubMed
Chen JialeiHao ChangTang XuYao HongbingSu Shuping - Human HINT3 belongs to the histidine triad (HIT) superfamily of hydrolases and transferases, and some of its cellular functions have already been discovered. However, the endogenous substrates of HINT3 and the three-dimensional structure of the protein have not been identified yet. We used a fusion variant of the human HINT3 protein: MBP-HINT3-His6, which contains maltose-binding protein (MBP) at its N-terminus and His-tag at the C-terminus. We tested the hydrolytic activity of MBP-HINT3-His6 towards various adenosine, guanosine, and 2'-deoxyguanosine 5'-O-phosphate derivatives with different leaving groups. The binding affinity data of MBP-HINT3-His6 towards various ligands were also investigated. Structure modeling of HINT3 was performed and a docking simulation with an AMP ligand at the active site of HINT3. HINT3 shows hydrolase activity towards synthetic mononucleotide derivatives of different types (e.g. nucleoside phosphoramidates), similar to HINT1, HINT2 and Aprataxin, and dinucleotide polyphosphate, similar to FHIT and Aprataxin, the enzymes of different branches of the HIT superfamily. HINT3 favors adenosine over guanosine derivatives, as shown by biochemical experiments (substrate screening) and K determination. Structure modeling of the HINT3(Gly36) variant revealed that the enzyme exists mainly in monomeric form and that an helix α3 is present (similar to Aprataxin), which is absent in the structures of HINT1 and HINT2. Analysis of the HINT3 structure shows that there are two potential disulfide bond sites. These results, presented for the first time, show that HINT3 is more similar to Aprataxin than HINT1 and HINT2, suggesting that Aprataxin and HINT3 may belong to the same branch. - Source: PubMed
Publication date: 2025/10/25
Dolot RafałSierant MałgorzataMikołajczyk AleksandraKaczmarek RenataNawrot BarbaraKrakowiak Agnieszka