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作者

Xiaoqian Zhang, Yanping Zhang, Zhenguo Zhai, Xietong Wang

作者单位

Affiliations ¹ Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Healthcare Hospital Affiliated to Qingdao University, Jinan, China. ² Department of Obstetrics and Gynaecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. ³ School of Clinical and Basic Medicine, (Institute of Basic Medicine), Shandong First Medical University, (Shandong Academy of Medical Sciences), Jinan, China.

刊名

Frontiers in molecular biosciences

年份

2026

卷号

Vol.13

页码

1751599

ISSN

2296-889X

关键词

DUF716 ECM TMEM45A TMEM45B endomembrane endoplasmic reticulum.

摘要

The Transmembrane protein 45 family comprises multi-pass transmembrane proteins that harbor the ancient DUF716 domain and are predominantly localized to the endomembrane system . In mammals, TMEM45 members exhibit highly tissue-specific expression patterns and their functions are tightly linked to endomembrane activities. TMEM45A directly binds prolyl-4-hydroxylase to modulate extracellular matrix synthesis, thereby contributing to fibrosis and corneal disorders. TMEM45B participates in the G...更多

The Transmembrane protein 45 family comprises multi-pass transmembrane proteins that harbor the ancient DUF716 domain and are predominantly localized to the endomembrane system . In mammals, TMEM45 members exhibit highly tissue-specific expression patterns and their functions are tightly linked to endomembrane activities. TMEM45A directly binds prolyl-4-hydroxylase to modulate extracellular matrix synthesis, thereby contributing to fibrosis and corneal disorders. TMEM45B participates in the Golgi processing and trafficking of nociceptive signaling molecules and also influences viral replication. Another paralog, TEDDM1, is implicated in sperm maturation. Expression of TMEM45 proteins is stringently regulated by upstream signaling cascades including TGF-β1/Smad, hypoxia/HIF-1α, calcium signaling, and JAK2/STAT3. In turn, these proteins serve as regulatory nodes that modulate downstream pathways such as Jagged1/Notch, Rho/ROCK, unfolded protein response , NF-κB, AKT/mTOR, Wnt/β-catenin, DNA-damage repair, and apoptosis. This review integrates current knowledge on the tissue distribution and upstream/downstream signaling networks of TMEM45 proteins to clarify endomembrane protein function and provide new perspectives on intracellular signal transduction mechanisms.收起

文献类型

期刊