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A single PDZ domain protein interacts with the Menkes copper ATPase, ATP7A. A new protein implicated in copper homeostasis.
J Biol Chem. 2005 Sep 30; 280(39):33270-9.JB

Abstract

The homeostatic regulation of essential elements such as copper requires many proteins whose activities are often mediated and tightly coordinated through protein-protein interactions. This regulation ensures that cells receive enough copper without intracellular concentrations reaching toxic levels. To date, only a small number of proteins implicated in copper homeostasis have been identified, and little is known of the protein-protein interactions required for this process. To identify other proteins important for copper homeostasis, while also elucidating the protein-protein interactions that are integral to the process, we have utilized a known copper protein, the copper ATPase ATP7A, as a bait in a yeast two-hybrid screen of a human cDNA library to search for interacting partners. One of the ATP7A-interacting proteins identified is a novel protein with a single PDZ domain. This protein was recently identified to interact with the plasma membrane calcium ATPase b-splice variants. We propose a change in name for this protein from PISP (plasma membrane calcium ATPase-interacting single-PDZ protein) to AIPP1 (ATPase-interacting PDZ protein) and suggest that it represents the protein that interacts with the class I PDZ binding motif identified at the ATP7A C terminus. The interaction in mammalian cells was confirmed and an additional splice variant of AIPP1 was identified. This study represents an essential step forward in identifying the proteins and elucidating the network of protein-protein interactions involved in maintaining copper homeostasis and validates the use of the yeast two-hybrid approach for this purpose.

Authors+Show Affiliations

Centre for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, Burwood, Victoria 3125, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16051599

Citation

Stephenson, Sarah E M., et al. "A Single PDZ Domain Protein Interacts With the Menkes Copper ATPase, ATP7A. a New Protein Implicated in Copper Homeostasis." The Journal of Biological Chemistry, vol. 280, no. 39, 2005, pp. 33270-9.
Stephenson SE, Dubach D, Lim CM, et al. A single PDZ domain protein interacts with the Menkes copper ATPase, ATP7A. A new protein implicated in copper homeostasis. J Biol Chem. 2005;280(39):33270-9.
Stephenson, S. E., Dubach, D., Lim, C. M., Mercer, J. F., & La Fontaine, S. (2005). A single PDZ domain protein interacts with the Menkes copper ATPase, ATP7A. A new protein implicated in copper homeostasis. The Journal of Biological Chemistry, 280(39), 33270-9.
Stephenson SE, et al. A Single PDZ Domain Protein Interacts With the Menkes Copper ATPase, ATP7A. a New Protein Implicated in Copper Homeostasis. J Biol Chem. 2005 Sep 30;280(39):33270-9. PubMed PMID: 16051599.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A single PDZ domain protein interacts with the Menkes copper ATPase, ATP7A. A new protein implicated in copper homeostasis. AU - Stephenson,Sarah E M, AU - Dubach,Daphne, AU - Lim,Chris M, AU - Mercer,Julian F B, AU - La Fontaine,Sharon, Y1 - 2005/07/28/ PY - 2005/7/30/pubmed PY - 2005/12/13/medline PY - 2005/7/30/entrez SP - 33270 EP - 9 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 280 IS - 39 N2 - The homeostatic regulation of essential elements such as copper requires many proteins whose activities are often mediated and tightly coordinated through protein-protein interactions. This regulation ensures that cells receive enough copper without intracellular concentrations reaching toxic levels. To date, only a small number of proteins implicated in copper homeostasis have been identified, and little is known of the protein-protein interactions required for this process. To identify other proteins important for copper homeostasis, while also elucidating the protein-protein interactions that are integral to the process, we have utilized a known copper protein, the copper ATPase ATP7A, as a bait in a yeast two-hybrid screen of a human cDNA library to search for interacting partners. One of the ATP7A-interacting proteins identified is a novel protein with a single PDZ domain. This protein was recently identified to interact with the plasma membrane calcium ATPase b-splice variants. We propose a change in name for this protein from PISP (plasma membrane calcium ATPase-interacting single-PDZ protein) to AIPP1 (ATPase-interacting PDZ protein) and suggest that it represents the protein that interacts with the class I PDZ binding motif identified at the ATP7A C terminus. The interaction in mammalian cells was confirmed and an additional splice variant of AIPP1 was identified. This study represents an essential step forward in identifying the proteins and elucidating the network of protein-protein interactions involved in maintaining copper homeostasis and validates the use of the yeast two-hybrid approach for this purpose. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/16051599/A_single_PDZ_domain_protein_interacts_with_the_Menkes_copper_ATPase_ATP7A__A_new_protein_implicated_in_copper_homeostasis_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=16051599 DB - PRIME DP - Unbound Medicine ER -