HACE1 Rabbit mAb

HACE1 Rabbit mAb recognizes endogenous levels of total HACE1 protein.

The HACE1 (HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1) gene is located on chromosome 6 and encodes a protein composed of 909 amino acids. HACE1 is strongly expressed in various human tissues, including the heart, brain, placenta, pancreas, and both fetal and adult kidneys. HACE1 mRNA is ubiquitously expressed across normal human tissues. Reduced expression levels of HACE1 are strongly associated with hypermethylation of two CpG islands located upstream of its gene locus, suggesting epigenetic regulation plays a role in its silencing. HACE1 is frequently downregulated in several types of cancer, including natural killer/T-cell lymphoma (NKTCL), colorectal cancer, and gastric cancer. Subcellularly, HACE1 localizes mainly to the endoplasmic reticulum and cytosol, although only low levels of endogenous protein are typically detected. Functionally, HACE1 acts as an E3 ubiquitin ligase and partners with the E2 enzyme UBCH7 to catalyze ubiquitination of target proteins. It is notably involved in phosphorylation-dependent degradation of cyclin D1, thereby playing a role in inhibiting cell cycle progression. HACE1 also preferentially binds to the active, GTP-bound form of the small GTPase Rac1 and promotes its polyubiquitination. This activity is essential for Rac1 degradation in response to cytotoxic necrotizing factor 1 (CNF1), facilitating bacterial invasion of endothelial cell monolayers, and highlighting a role for HACE1 in innate immune defense mechanisms. loss of HACE1 leads to the spontaneous development of late-onset tumors, further supporting its function as a tumor suppressor. The gene lies within the 6q21 chromosomal region which is a hotspot implicated in multiple human cancers, underscoring its clinical significance in tumorigenesis.