ATP7B

This gene is a member of the P-type cation transport ATPase family and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least 2 putative copper-binding sites. This protein functions as a monomer, exporting copper out of the cells, such as the efflux of hepatic copper into the bile. Alternate transcriptional splice variants, encoding different isoforms with distinct cellular localizations, have been characterized. Mutations in this gene have been associated with Wilson disease (WD). [provided by RefSeq, Jul 2008]

Full Name

ATPase Copper Transporting Beta

Function

Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into the bile in response to copper overload.

Biological Process

Cellular copper ion homeostasis Source: GO_Central
Copper ion export Source: GO_Central
Copper ion import Source: UniProtKB
Copper ion transport Source: UniProtKB
Ion transmembrane transport Source: Reactome
Response to copper ion Source: UniProtKB
Sequestering of calcium ion Source: UniProtKB
Xenobiotic detoxification by transmembrane export across the plasma membrane Source: GO_Central

Cellular Location

Late endosome; Trans-Golgi network membrane. Predominantly found in the trans-Golgi network (TGN). Localized in the trans-Golgi network under low copper conditions, redistributes to cytoplasmic vesicles when cells are exposed to elevated copper levels, and then recycles back to the trans-Golgi network when copper is removed (PubMed:10942420).
Isoform 1: Golgi apparatus membrane
Isoform 2: Cytoplasm
WND/140 kDa: Mitochondrion

Involvement in disease

Wilson disease (WD): An autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis.

Topology

Cytoplasmic: 1-653 aa
Helical: 654-675 aa
Extracellular: 676-697 aa
Helical: 698-717 aa
Cytoplasmic: 718-724 aa
Helical: 725-745 aa
Extracellular: 746-764 aa
Helical: 765-785 aa
Cytoplasmic: 786-919 aa
Helical: 920-942 aa
Extracellular: 943-972 aa
Helical: 973-994 aa
Cytoplasmic: 995-1322 aa
Helical: 1323-1340 aa
Extracellular: 1341-1351 aa
Helical: 1352-1371 aa
Cytoplasmic: 1372-1465 aa

PTM

Isoform 1 may be proteolytically cleaved at the N-terminus to produce the WND/140 kDa form.