更新于：2024-11-01

TCN1

更新于：2024-11-01

基本信息

别名

Haptocorrin、HC、Protein R

+ [8]

简介

Binds vitamin B12 with femtomolar affinity and protects it from the acidic environment of the stomach.

关联

项与 TCN1 相关的药物

US20220184218

专利挖掘

靶点

TCN1

作用机制-

在研机构

Syracuse University

原研机构

Syracuse University

在研适应症

恶心

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TCN1 相关的临床结果

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100 项与 TCN1 相关的转化医学

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0 项与 TCN1 相关的专利（医药）

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396

项与 TCN1 相关的文献（医药）

2024-10-01·Human Genetics

Protein-centric omics integration analysis identifies candidate plasma proteins for multiple autoimmune diseases

Article

作者: Gong, Weiming ; Yuan, Zhongshang ; Xue, Fuzhong ; Guo, Ping ; Wang, Shukang ; Zhou, Xiang ; Liu, Shuai ; Chen, Yingxuan

AbstractIt remains challenging to translate the findings from genome-wide association studies (GWAS) of autoimmune diseases (AIDs) into interventional targets, presumably due to the lack of knowledge on how the GWAS risk variants contribute to AIDs. In addition, current immunomodulatory drugs for AIDs are broad in action rather than disease-specific. We performed a comprehensive protein-centric omics integration analysis to identify AIDs-associated plasma proteins through integrating protein quantitative trait loci datasets of plasma protein (1348 proteins and 7213 individuals) and totally ten large-scale GWAS summary statistics of AIDs under a cutting-edge systematic analytic framework. Specifically, we initially screened out the protein-AID associations using proteome-wide association study (PWAS), followed by enrichment analysis to reveal the underlying biological processes and pathways. Then, we performed both Mendelian randomization (MR) and colocalization analyses to further identify protein-AID pairs with putatively causal relationships. We finally prioritized the potential drug targets for AIDs. A total of 174 protein-AID associations were identified by PWAS. AIDs-associated plasma proteins were significantly enriched in immune-related biological process and pathways, such as inflammatory response (P = 3.96 × 10–10). MR analysis further identified 97 protein-AID pairs with potential causal relationships, among which 21 pairs were highly supported by colocalization analysis (PP.H4 > 0.75), 10 of 21 were the newly discovered pairs and not reported in previous GWAS analyses. Further explorations showed that four proteins (TLR3, FCGR2A, IL23R, TCN1) have corresponding drugs, and 17 proteins have druggability. These findings will help us to further understand the biological mechanism of AIDs and highlight the potential of these proteins to develop as therapeutic targets for AIDs.

2024-05-01·Journal of Biological Chemistry

The structure of the rat vitamin B12 transporter TC and its complex with glutathionylcobalamin

Article

作者: Kawamura, Takashi ; Okumura, Hideo ; Werner, Stefan ; Klimyuk, Victor ; Goto, Sawako ; Saito, Akihiko ; Kumasaka, Takashi ; Kawano, Yoshiaki ; Bokhove, Marcel ; Jarczowski, Franziska

Vitamin B₁₂ (cobalamin or Cbl) functions as a cofactor in two important enzymatic processes in human cells, and life is not sustainable without it. B₁₂ is obtained from food and travels from the stomach, through the intestine, and into the bloodstream by three B₁₂-transporting proteins: salivary haptocorrin (HC), gastric intrinsic factor, and transcobalamin (TC), which all bind B₁₂ with high affinity and require proteolytic degradation to liberate Cbl. After intracellular delivery of dietary B₁₂, Cbl in the aquo/hydroxocobalamin form can coordinate various nucleophiles, for example, GSH, giving rise to glutathionylcobalamin (GSCbl), a naturally occurring form of vitamin B₁₂. Currently, there is no data showing whether GSCbl is recognized and transported in the human body. Our crystallographic data shows for the first time the complex between a vitamin B₁₂ transporter and GSCbl, which compared to aquo/hydroxocobalamin, binds TC equally well. Furthermore, sequence analysis and structural comparisons show that TC recognizes and transports GSCbl and that the residues involved are conserved among TCs from different organisms. Interestingly, haptocorrin and intrinsic factor are not structurally tailored to bind GSCbl. This study provides new insights into the interactions between TC and Cbl.

2024-04-01·Animal Bioscience

Integrated analysis of transcriptome and milk metagenome in subclinical mastitic and healthy cows

Article

作者: Li, Wenlong ; Usman, Tahir ; Tang, Yongjie ; Liu, Xueqin ; Zhang, Jinning ; Yu, Ying ; Mi, Siyuan ; Yang, Mengyou

Objective: Abnormally increased somatic cell counts (SCCs) in milk is usually a sign of bovine subclinical mastitis. Mutual interaction between the host and its associated microbiota plays an important role in developing such diseases. The main objective of this study was to explore the difference between cows with elevated SCCs and healthy cattle from the perspective of host-microbe interplay.Methods: A total of 31 milk samples and 23 bovine peripheral blood samples were collected from Holstein dairy cattle to conduct an integrated analysis of transcriptomic and metagenomics.Results: The results showed that Ralstonia and Sphingomonas were enriched in cows with subclinical mastitis. The relative abundance of the two bacteria was positively correlated with the expression level of bovine transcobalamin 1 and uridine phosphorylase 1 encoding gene. Moreover, functional analysis revealed a distinct alternation in some important microbial biological processes.Conclusion: These results reveal the relative abundance of Ralstonia and Sphingomonas other than common mastitis-causing pathogens varied from healthy cows to those with subclinical mastitis and might be associated with elevated SCCs. Potential association was observed between bovine milk microbiota composition and the transcriptional pattern of some genes, thus providing new insights to understand homeostasis of bovine udder.