组织转酰胺酶（TG2）是一种广泛分布、多功能的蛋白质，在各种细胞间隔中执行广泛的细胞和代谢功能。除了酰胺化作用外，TG2还作为Gα信号蛋白、蛋白质二硫化异构酶（PDI）、蛋白激酶和蛋白骨架蛋白发挥作用。在细胞核中，TG2修饰组蛋白和转录因子。PDI功能催化核中热休克因子-1的三聚化和激活，并调节几种线粒体复合物的氧化状态。细胞质中的TG2通过添加血清素或其他一级胺修饰蛋白质，从而影响细胞信号传导。蛋白质和谷氨酰胺修饰降低了泛素依赖性蛋白酶体降解。在细胞膜上，TG2与GPCR相关，在跨膜信号中发挥作用。TG2也存在于细胞外空间，在蛋白质交联和细胞外基质稳定中发挥作用。最近关于TG2在基因表达、蛋白质稳态、细胞信号转导、自身免疫、炎症和缺氧方面的研究发现尤为重要。因此，TG2在多个细胞间隔中扮演多种功能，使其成为最多功能的细胞蛋白质之一。额外的证据将TG2与多种人类疾病，包括子痫前期、高血压、心血管疾病、器官纤维化、癌症、神经退行性疾病和腹腔疾病联系起来。总之，TG2对生理应激提供了多功能和多地点的响应。

Tissue transglutaminase (TG2) is a widely distributed multifunctional protein involved in a broad range of cellular and metabolic functions carried out in a variety of cellular compartments. In addition to transamidation, TG2 also functions as a Gα signaling protein, a protein disulphide isomerase (PDI), a protein kinase and a scaffolding protein. In the nucleus, TG2 modifies histones and transcription factors. The PDI function catalyzes the trimerization and activation of heat shock factor-1 in the nucleus and regulates the oxidation state of several mitochondrial complexes. Cytosolic TG2 modifies proteins by the addition of serotonin or other primary amines and in this way affects cell signaling. Modification of protein bound glutamines reduces ubiquitin-dependent proteasomal degradation. At the cell membrane, TG2 is associated with GPCRs, where it functions in transmembrane signaling. TG2 is also found in the extracellular space where it functions in protein cross-linking and extracellular matrix stabilization. Of particular importance in transglutaminase research are recent findings concerning the role of TG2 in gene expression, protein homeostasis, cell signaling, autoimmunity, inflammation, and hypoxia. Thus, TG2 performs a multitude of functions in multiple cellular compartments making it one of the most versatile cellular proteins. Additional evidence links TG2 with multiple human diseases including preeclampsia, hypertension, cardiovascular disease, organ fibrosis, cancer, neurodegenerative diseases and celiac disease. In conclusion, TG2 provides a multifunctional and multisite response to physiological stress.