The Copper Toxicosis Gene Product Murr1 Directly Interacts with the Wilson Disease Protein

Distinct Wilson’s Disease Mutations in ATP7B Are Associated With Enhanced Binding to COMMD1 and Reduced Stability of ATP7B

“…Analysis of glutathione-sepharose precipitates from lysates of these cells ( Figure 2A) indicated that the amino terminal region of ATP7B is sufficient for interaction with COMMD1, as shown previously 13 . Within its amino terminal region, ATP7B contains six copper binding sequences, through which it receives copper by a transient copper-dependent interaction with the copper chaperone ATOX1 7,8 .…”

“…Subsequent identification of COMMD1 as an interacting partner of ATP7B further supports the role of COMMD1 in copper homeostasis 13 , and suggests that these two proteins cooperate to facilitate excretion of copper from the hepatocyte into the bile canaliculus. Although COMMD1 has been postulated as a candidate gene for non-Wilsonian copper overload disorders, and as a modifier gene for the clinical presentation of WD, no disease associated mutations in COMMD1 have been detected in patients with these disorders, but a silent missense mutation in COMMD1 was possibly associated with an earlier onset of the disorder in patients with known ATP7B mutations 14 -18.…”

“…In addition, knockdown of COMMD1 by RNA interference in several cell lines results in increased cellular copper levels 25,28 . COMMD1 interacts with the copper transport protein ATP7B, which is mutated in WD, suggesting that these two proteins cooperate in the excretion of copper 13 . Consequentially, these observations suggest that COMMD1 could play a role in the development of WD.…”

Posttranslational regulation of copper transporters

“…Although it has been reported that COMMD1 binds Cu 2? [112], a direct and copper-independent interaction between the amino terminus of ATP7B and COMMD1 has been characterized [113,114]. Transient knockdown of COMMD1 by RNA interference results in increased cellular copper levels in HEK293T cells [115][116][117].…”

XIAP: Cell death regulation meets copper homeostasis

“…Using positional cloning, MURR1 (now referred to as COMMD1) was identified as the gene responsible for this disorder [70]. Its protein product binds to the amino-terminus of ATP7B and presumably regulates its function by a mechanism yet to be identified [71]. COMMD1 is the prototypical member of a family of ten homologous and highly conserved proteins known as COMMD1 to 10 [72].…”